A 58-year-old man with a 15-year history of gastroesophageal reflux disease treated with a daily proton pump inhibitor undergoes upper endoscopy because of persistent heartburn. He has no dysphagia or weight loss. Endoscopy shows a 4-cm segment of salmon-colored mucosa extending proximally from the gastroesophageal junction. A biopsy specimen of the distal esophagus is shown. The pathologist reports intestinal metaplasia with no dysplasia, confirmed by a second pathologist. Which of the following is the most appropriate next step in management?
ASurveillance endoscopy with biopsies in 3 to 5 years
BRepeat endoscopy with biopsies in 6 months
CEndoscopic radiofrequency ablation of the segment
DEsophagectomy with gastric pull-through reconstruction
ENo further endoscopic surveillance
Answer: A Surveillance endoscopy with biopsies in 3 to 5 years is the appropriate next step. The biopsy shows columnar epithelium with goblet cells (intestinal metaplasia) replacing squamous epithelium, which is Barrett esophagus. Nondysplastic Barrett esophagus carries a low annual risk of progression to adenocarcinoma, so management is continued acid suppression and periodic surveillance; guidelines recommend every 5 years for segments shorter than 3 cm and every 3 years for segments of 3 cm or longer. Contrast: repeat endoscopy in 6 months is for indefinite or low-grade dysplasia when ablation is not chosen; radiofrequency ablation is reserved for confirmed dysplasia, not metaplasia alone; esophagectomy is no longer first-line even for high-grade dysplasia; stopping surveillance ignores the established cancer risk of Barrett mucosa.
A 24-year-old man who smokes one pack of cigarettes daily comes to the emergency department because of 2 weeks of cough productive of blood-streaked sputum, fatigue, and dark urine. Blood pressure is 152/94 mm Hg. Crackles are heard at both lung bases. Urinalysis shows 3+ blood with dysmorphic red cells and red cell casts. Serum creatinine is 3.1 mg/dL; it was 1.0 mg/dL at a visit 2 weeks ago. Chest radiograph shows bilateral alveolar infiltrates. Serum anti-glomerular basement membrane antibody is positive; ANCA, ANA, and anti-dsDNA antibodies are negative, and serum C3 is normal. He has no purpuric rash, abdominal pain, or arthralgia. A renal biopsy is performed, and a light micrograph of a glomerulus is shown. Immunofluorescence microscopy is most likely to show which of the following?
AGranular deposits of IgG and C3 along the subepithelial side of the basement membrane
BLinear deposition of IgG along the glomerular basement membrane
CMesangial deposits of IgA with C3 in a granular pattern
DFew or no immunoglobulin or complement deposits
EGranular full-house deposits of IgG, IgA, IgM, C3, and C1q
Answer: B Linear deposition of IgG along the glomerular basement membrane is the expected finding. The micrograph shows a cellular crescent filling Bowman space, the lesion of rapidly progressive glomerulonephritis. A young male smoker with hemoptysis plus nephritic urine and creatinine doubling within 2 weeks has anti-glomerular basement membrane disease (Goodpasture syndrome): autoantibodies against the alpha-3 chain of type IV collagen bind uniformly along the GBM and alveolar basement membrane, producing a smooth linear ribbon of IgG (often with C3) on immunofluorescence. Contrast: granular subepithelial IgG and C3 indicates immune-complex disease such as postinfectious glomerulonephritis, in which C3 would be low; mesangial IgA is IgA nephropathy or IgA vasculitis, excluded by the absence of purpuric rash, abdominal pain, and arthralgia and by the positive anti-GBM antibody; pauci-immune (few or no deposits) crescentic disease is ANCA-associated vasculitis, excluded by the negative ANCA; full-house deposits indicate lupus nephritis, excluded by negative ANA and anti-dsDNA with normal C3.
A 36-year-old woman is brought to the emergency department because of 2 days of fever, headache, and confusion. Temperature is 38.6°C. She is disoriented and has scattered petechiae over both legs. Laboratory studies show: Hemoglobin 8.1 g/dL Platelet count 14,000/mm3 Serum lactate dehydrogenase 1,420 U/L Serum creatinine 1.6 mg/dL Prothrombin time 12 seconds Partial thromboplastin time 30 seconds Fibrinogen 320 mg/dL Direct antiglobulin (Coombs) test negative A peripheral blood smear is shown. Which of the following is the characteristic microscopic lesion in the affected organs of this patient?
AAntibody-coated red cells cleared by splenic macrophages
BFibrin-rich thrombi with widespread consumption of coagulation factors
CPlatelet-rich hyaline microthrombi in arterioles and capillaries
DLeukocytoclastic immune-complex vasculitis of small vessels
ECholesterol crystal emboli lodged in small arteries and arterioles
Answer: C Platelet-rich hyaline microthrombi in arterioles and capillaries are the characteristic lesion. The smear shows schistocytes (helmet and fragmented cells) with very few platelets, indicating microangiopathic hemolysis. Fever, neurologic change, thrombocytopenia, Coombs-negative hemolysis with high LDH, and mild renal impairment in a young woman with normal PT, PTT, and fibrinogen is thrombotic thrombocytopenic purpura. Deficient ADAMTS13 leaves ultralarge von Willebrand factor multimers on the endothelium; platelets adhere and form hyaline microthrombi that occlude arterioles and capillaries in brain, kidney, and heart and shear passing red cells. Contrast: fibrin-rich thrombi with factor consumption describe disseminated intravascular coagulation, which would prolong PT and PTT and lower fibrinogen; antibody-coated red cells cleared by the spleen is warm autoimmune hemolysis, which is Coombs-positive and does not fragment cells; immune-complex vasculitis and cholesterol emboli do not produce schistocytes with profound thrombocytopenia.
Q4 · Cardiovascular · Pathology · ecg
A 62-year-old man is brought to the emergency department 1 hour after the onset of crushing substernal chest pain and diaphoresis. He has hypertension and a 40-pack-year smoking history. Pulse is 54/min and blood pressure is 82/50 mm Hg. Jugular venous pressure is markedly elevated and rises with inspiration. The lungs are clear to auscultation bilaterally, and there is no peripheral edema. A 12-lead ECG is shown. Aspirin is given and the cardiac catheterization laboratory is activated. Which of the following is the most appropriate immediate management step?
ASublingual nitroglycerin every 5 minutes for three doses
BIntravenous furosemide bolus followed by continuous infusion
CIntravenous metoprolol titrated to the heart rate
DIntravenous fluid bolus and avoidance of nitroglycerin
EIntravenous morphine titrated to relief of pain
Answer: D An intravenous fluid bolus with avoidance of nitroglycerin is the appropriate immediate step. The ECG shows ST elevation in leads II, III, and aVF with reciprocal depression in I and aVL, an inferior STEMI from right coronary artery occlusion. The triad of hypotension, elevated jugular venous pressure with Kussmaul sign, and clear lungs identifies right ventricular involvement: the failing right ventricle cannot fill the left ventricle, so cardiac output depends on preload. A crystalloid bolus restores RV filling while reperfusion is arranged, and preload-reducing drugs are withheld. Contrast: nitroglycerin, furosemide, and morphine all reduce venous return and can precipitate profound hypotension in RV infarction; intravenous metoprolol worsens the bradycardia and hypotension already present and is contraindicated in hemodynamically unstable STEMI.
A 29-year-old man is intubated and mechanically ventilated in the intensive care unit after a motor vehicle collision in which he sustained multiple right-sided rib fractures and a pulmonary contusion. On the second hospital day, his blood pressure abruptly falls to 70/40 mm Hg and oxygen saturation decreases to 82% on an FiO2 of 0.6. Peak airway pressures have risen sharply. Examination shows distended neck veins, deviation of the trachea to the left, and absent breath sounds over the right hemithorax. A portable chest radiograph is shown. Which of the following best explains how this patient's initial pleural air leak progressed to the condition shown?
ARupture of a subpleural bleb producing a persistent pleural defect through which air moves freely in both directions
BA bronchopleural fistula allowing unrestricted bidirectional flow of air between the airway and pleural space with each breath
CLoss of surfactant from the contused lung causing diffuse alveolar collapse and markedly reduced compliance
DProgressive accumulation of blood in the pleural space compressing the ipsilateral lung and mediastinum
EA one-way valve admitting air into the pleural space on inspiration that cannot escape on expiration
Answer: E A one-way valve that admits air into the pleural space on inspiration but does not let it escape on expiration converts a simple pneumothorax into a tension pneumothorax. The radiograph shows a large hyperlucent right hemithorax without lung markings and shift of the mediastinum and trachea to the left. With each positive-pressure breath, air is pumped through the flap-like pleural tear and trapped, so intrapleural pressure rises above atmospheric pressure throughout the cycle; the mediastinum is pushed contralaterally, the venae cavae are kinked, venous return falls, and obstructive shock follows. Contrast: a bleb rupture or bronchopleural fistula with free bidirectional flow lets pleural pressure equilibrate and produces a simple pneumothorax without progressive tension; surfactant loss causes atelectasis with increased opacity, not a hyperlucent hemithorax; a hemothorax compresses the lung but appears as a dense opacity with a fluid level, not an air-filled hemithorax.
A 42-year-old man comes to the physician because of itchy, scaly skin lesions on his elbows and knees that have persisted for 3 years and worsen each winter. He has no joint pain. Examination shows well-demarcated erythematous plaques with silvery scale over the extensor surfaces of both elbows and knees; a photograph of the left elbow is shown. Several fingernails show pitting. Gentle removal of scale from a plaque produces pinpoint bleeding. The lesions cover approximately 4% of the body surface area. The physician prescribes topical calcipotriene to be applied twice daily and advises him not to exceed 100 g per week. Which of the following best describes the mechanism of action of the prescribed agent?
AInhibition of calcineurin phosphatase in activated T lymphocytes
BInhibition of phosphodiesterase-4 in inflammatory cells
CNeutralization of circulating interleukin-17A cytokine
DInhibition of dihydrofolate reductase in proliferating cells
EVitamin D analog that inhibits keratinocyte proliferation
Answer: E Calcipotriene is a synthetic vitamin D3 analog that binds the vitamin D receptor and inhibits keratinocyte proliferation while promoting normal differentiation. The image shows the classic chronic plaque psoriasis: sharply demarcated erythematous plaques with silvery scale on extensor surfaces, with nail pitting and the Auspitz sign (pinpoint bleeding on scale removal) confirming the diagnosis. Psoriatic epidermis is hyperproliferative with a shortened keratinocyte transit time, which is why a vitamin D analog that slows proliferation and restores differentiation clears plaques; the 100 g/week limit exists because systemic absorption can cause hypercalcemia. Contrast: calcineurin inhibition (tacrolimus) and phosphodiesterase-4 inhibition (roflumilast, apremilast) act on T cells and inflammatory cytokine production rather than directly on keratinocyte proliferation and are not the mechanism of calcipotriene; interleukin-17A neutralization describes secukinumab, an injectable biologic; dihydrofolate reductase inhibition is methotrexate, a systemic agent for extensive disease.
A 58-year-old man is brought to the emergency department because of fever, headache, and confusion for 12 hours. He has alcohol use disorder and has had a cough productive of purulent sputum for 4 days. His temperature is 39.4°C, pulse is 112/min, and blood pressure is 108/70 mm Hg. He is somnolent and has nuchal rigidity. Lumbar puncture is performed. Cerebrospinal fluid analysis shows: Opening pressure: 320 mm H2O Leukocyte count: 2,400/mm3 (92% neutrophils) Protein: 210 mg/dL Glucose: 18 mg/dL (serum glucose 110 mg/dL) A Gram stain of the cerebrospinal fluid is shown. Sheep blood agar grows catalase-negative colonies with a zone of greenish discoloration. The isolate does not grow in 6.5% sodium chloride and is bile-esculin negative. Which of the following laboratory properties best identifies the causal organism?
ABacitracin susceptibility and pyrrolidonyl arylamidase positivity
BCAMP test positivity and hippurate hydrolysis
CGrowth in 6.5% sodium chloride and bile esculin hydrolysis
DOptochin susceptibility and bile solubility
ENovobiocin resistance and coagulase negativity
Answer: D Streptococcus pneumoniae is identified by optochin susceptibility and bile solubility. The Gram stain shows Gram-positive, lancet-shaped diplococci among neutrophils, and the CSF profile (marked neutrophilic pleocytosis, high protein, very low glucose) is that of acute bacterial meningitis. Alpha-hemolysis (green discoloration on blood agar) with catalase negativity narrows the field to streptococci; among alpha-hemolytic streptococci, pneumococcus is distinguished from viridans streptococci by lysis in bile salts (autolysin activation) and a zone of inhibition around an optochin disk. Preceding pneumonia and alcohol use disorder are classic settings for pneumococcal meningitis in adults. Contrast: bacitracin susceptibility with PYR positivity identifies Streptococcus pyogenes, and CAMP positivity with hippurate hydrolysis identifies Streptococcus agalactiae, but both are beta-hemolytic, which the greenish (alpha) hemolysis excludes; growth in 6.5% NaCl with bile esculin hydrolysis identifies Enterococcus, excluded here because the isolate fails to grow in 6.5% NaCl and is bile-esculin negative; novobiocin resistance with coagulase negativity identifies Staphylococcus saprophyticus, a catalase-positive coccus in clusters.
A 27-year-old woman comes to the physician because of daily headaches for 2 months. The headaches are worse in the morning and when lying down, with brief episodes of dimming of vision on standing. She has bilateral pulsatile tinnitus. BMI is 38 kg/m2. Blood pressure is 128/80 mm Hg. Visual acuity is 20/20 bilaterally with normal color vision and no afferent pupillary defect; visual fields show enlarged blind spots. Erythrocyte sedimentation rate and C-reactive protein are normal. Funduscopic examination is shown. Orbital ultrasonography shows widened optic nerve sheaths bilaterally with normal ophthalmic artery flow velocities. Contrast-enhanced MRI of the brain and MR venography are normal, with patent dural venous sinuses and no mass, hydrocephalus, or vascular abnormality. Which of the following is the most appropriate next step in diagnosis?
CLumbar puncture with measurement of opening pressure
DTemporal artery biopsy
EColor Doppler ultrasonography of the ophthalmic artery
Answer: C Lumbar puncture with measurement of opening pressure is the next step. The fundus shows bilateral optic disc swelling with blurred margins (papilledema), and the history of an obese young woman with positional headache, transient visual obscurations, pulsatile tinnitus, and enlarged blind spots is characteristic of idiopathic intracranial hypertension. The diagnosis requires excluding a mass lesion and venous sinus thrombosis with MRI and MR venography (already done and normal) and then documenting an elevated CSF opening pressure with normal CSF composition; the lumbar puncture is deliberately performed after imaging to avoid herniation. Contrast: CT angiography evaluates arterial lesions, but contrast-enhanced MRI and MR venography have already shown no vascular abnormality and patent sinuses; visual evoked potentials assess optic nerve conduction in optic neuritis, excluded by 20/20 acuity, normal color vision, and no afferent pupillary defect, and do not measure intracranial pressure; temporal artery biopsy is for giant cell arteritis, excluded by her age of 27 years and normal ESR and CRP; ophthalmic artery Doppler has no role in confirming raised intracranial pressure, and ophthalmic artery flow has already been assessed by orbital ultrasonography and is normal.
A 29-year-old woman comes to the physician because of a painless neck lump she noticed 2 months ago. At the age of 7 years she received mantle-field radiation therapy for Hodgkin lymphoma. Her diet has always been iodine-sufficient. Her mother is euthyroid with no history of thyroid disease; there is no family history of thyroid cancer or pheochromocytoma. Examination shows a firm, 2-cm nodule in the right thyroid lobe that moves with swallowing. Serum TSH and calcitonin concentrations are normal; anti-thyroid peroxidase antibodies are present at low titer. Radionuclide scan shows a cold nodule. Right lobectomy is performed; a photomicrograph of the nodule is shown, and the pathologist reports papillae, optically clear nuclei, and psammoma bodies. Which of the following is an established risk factor for this tumor?
CLong-standing Hashimoto thyroiditis with hypothyroidism
DGermline RET proto-oncogene mutation
EMaternal Graves disease during pregnancy
Answer: B Ionizing radiation to the neck during childhood is the established risk factor for papillary thyroid carcinoma. The photomicrograph shows papillary carcinoma: overlapping nuclei with optically clear (Orphan Annie eye) chromatin, nuclear grooves, and laminated calcified psammoma bodies. External radiation to the head and neck in childhood, including mantle-field therapy for Hodgkin lymphoma, is the best-established environmental cause, typically with a latency of a decade or more, and papillary carcinoma is the histologic type it produces. Contrast: iodine deficiency is associated with follicular (not papillary) carcinoma and is excluded by her iodine-sufficient diet; Hashimoto thyroiditis is linked to thyroid lymphoma and only weakly to papillary carcinoma, and her low-titer antibodies with normal TSH do not represent long-standing hypothyroid disease; germline RET mutations cause medullary carcinoma (MEN 2), which arises from C cells, shows nests of cells in amyloid stroma rather than papillae with clear nuclei, raises serum calcitonin, and runs in families with pheochromocytoma, none of which is present; maternal Graves disease confers no risk of thyroid carcinoma in the offspring, and her mother has never had thyroid disease.
A 4-year-old boy is brought to the physician because of painful swelling of both hands for 2 days. He has had two similar episodes involving his feet during the past year. His parents emigrated from West Africa. He appears pale. Examination shows tender, swollen dorsa of both hands. The spleen, which was palpable at a visit 2 years ago, is no longer palpable. Hemoglobin concentration is 7.2 g/dL, reticulocyte count is 12%, and mean corpuscular volume is 82 fL. A peripheral blood smear is shown; the laboratory also reports target cells and Howell-Jolly bodies. Hemoglobin electrophoresis shows 85% hemoglobin S, no hemoglobin A, and an increased proportion of hemoglobin F. Which of the following molecular events is most directly responsible for the abnormal erythrocyte shape seen on the smear?
APolymerization of deoxygenated hemoglobin S into fibers
BOxidative denaturation of hemoglobin with Heinz body formation
CLoss of spectrin tethering to the membrane skeleton
DReduced beta-globin synthesis with alpha-chain precipitation
EComplement-mediated injury to the erythrocyte membrane
Answer: A Polymerization of deoxygenated hemoglobin S into rigid fibers produces the sickled shape. The smear shows elongated, crescent-shaped sickle cells; the reported target cells and Howell-Jolly bodies indicate loss of splenic function (autosplenectomy from repeated infarction, explaining the spleen that is no longer palpable). The Glu6Val substitution on the beta-globin chain creates a hydrophobic patch that, when hemoglobin S is deoxygenated, allows tetramers to stack into long fibers that deform the cell; dactylitis, hemolytic anemia with reticulocytosis, and the electrophoresis pattern confirm sickle cell anemia. Contrast: oxidative denaturation with Heinz bodies produces bite cells in G6PD deficiency rather than sickle forms; loss of spectrin tethering produces spherocytes in hereditary spherocytosis; reduced beta-globin synthesis with alpha-chain precipitation is beta thalassemia, which gives microcytosis and absent or reduced hemoglobin S rather than 85% hemoglobin S; complement-mediated membrane injury is the mechanism of paroxysmal nocturnal hemoglobinuria and does not change cell shape.
Q11 · Cardiovascular · Pathology · ecg
A 22-year-old man is evaluated for recurrent episodes of palpitations and near-syncope that begin and terminate abruptly. He has had three such episodes in the past 18 months, each lasting 10–30 minutes. Echocardiography shows no structural abnormality. An electrocardiogram during sinus rhythm demonstrates a PR interval of 100 ms, a slurred upstroke on the initial portion of the QRS complex with no R′ wave in lead V1, and a total QRS duration of 120 ms. An ECG is shown. Which of the following mechanisms best explains these findings?
AConduction through an accessory atrioventricular pathway
BDelayed conduction through the atrioventricular node
CRe-entrant circuit confined within the atrioventricular node
DRight bundle branch conduction delay
ETriggered activity from delayed afterdepolarizations
Answer: A Conduction through an accessory atrioventricular pathway (bundle of Kent) produces the ECG findings of Wolff-Parkinson-White syndrome. Pre-excitation occurs when the accessory pathway conducts the atrial impulse directly to the ventricle, bypassing AV nodal delay and producing a short PR interval (100 ms); the initial slurred QRS deflection (delta wave) represents slow myocardial activation before the normal His-Purkinje wavefront arrives. The total QRS duration is widened by the fusion of pre-excited and normally conducted beats. Contrast: Delayed AV nodal conduction (option B) would prolong, not shorten, the PR interval; AVNRT (option C) causes narrow-complex tachycardia without altering the resting ECG; RBBB (option D) widens the terminal QRS and creates an R′ in V1, not an initial delta wave; and triggered activity from DADs (option E) produces ventricular ectopy, not the pre-excitation pattern.
A 41-year-old man with untreated HIV infection (CD4 count 85 cells/μL) presents with a 5-week history of fever, drenching night sweats, progressive weight loss, and a nonproductive cough. Temperature is 38.9°C. Auscultation reveals diffuse fine crackles bilaterally. A chest radiograph is shown demonstrating innumerable 1–3 mm nodular opacities distributed uniformly throughout both lung fields. Sputum acid-fast smear is positive. Which of the following mechanisms is most responsible for this radiographic pattern?
ADirect extension of a Ghon focus into the adjacent pleural space
BHematogenous seeding of both lungs from a blood-borne bacillemia
CEndobronchial spread from rupture of a cavitary upper-lobe lesion
DLymphatic dissemination through hilar nodes to contiguous lung segments
EAspiration of infected secretions into the dependent lung fields
Answer: B Hematogenous seeding of both lungs from mycobacteremia produces the miliary radiographic pattern. Mycobacterium tuberculosis enters the bloodstream via erosion of a granuloma into a vessel, disseminating uniformly to both lungs and other organs; each bacillus seeds a new granuloma, producing the countless discrete 1–3 mm nodules that resemble millet seeds on chest radiograph. The symmetric, random distribution is the hallmark of hematogenous spread. Contrast: Direct pleural extension (option A) causes a localized effusion or focal consolidation, not bilateral miliary nodularity; endobronchial spread (option C) produces patchy asymmetric consolidation, not uniform tiny nodules; lymphatic dissemination (option D) causes a lymphangitic pattern along bronchovascular bundles rather than random miliary seeding; and aspiration (option E) produces dependent lower-lobe disease, not the diffuse symmetric distribution shown.
A 35-year-old man with poorly controlled HIV (CD4 count 62 cells/μL, not on antiretroviral therapy) presents with a 3-week history of worsening headache, photophobia, and neck stiffness. Lumbar puncture shows an opening pressure of 290 mmH₂O, glucose 32 mg/dL, protein 68 mg/dL, and 8 cells/μL (90% lymphocytes). An India ink preparation of the CSF is shown, demonstrating round budding organisms each surrounded by a clear unstained halo. Which of the following best explains this appearance?
ALaccase-mediated melanin production renders the cell wall impermeable to ink particles
BUrease activity alkalinizes the CSF, precipitating India ink around the capsule
CA thick polysaccharide capsule repels India ink particles, creating a clear halo
DCapsular antigen shed into the CSF depletes ink particles from the surrounding field
Eβ-Glucan in the cell wall physically excludes India ink molecules from the organism
Answer: C The thick polysaccharide capsule of Cryptococcus neoformans physically excludes India ink particles, producing a clear unstained halo around each organism. The glucuronoxylomannan capsule is impenetrable to the carbon particles in India ink, so the background stains dark while the capsular space remains clear, revealing the encapsulated yeast without culture. Contrast: Laccase-mediated melanin (option A) darkens the yeast cell wall but does not produce an external capsular halo; urease activity (option B) is a virulence factor that facilitates cerebral invasion but plays no role in ink exclusion; capsular antigen shedding throughout the CSF (option D) would uniformly reduce ink staining rather than create a discrete per-cell halo around each organism; and cell-wall β-glucan (option E) is an intracellular structural component that cannot account for an external extracellular capsular halo.
A 16-year-old girl is referred for episodic jaundice since childhood. Her spleen is palpable 3 cm below the left costal margin. Laboratory results: hemoglobin 9.8 g/dL (ref 12.0–16.0), MCV 78 fL (ref 80–100), MCHC 37.2 g/dL (ref 31.5–35.5), reticulocytes 8% (ref 0.5–1.5), total bilirubin 3.4 mg/dL, direct bilirubin 0.2 mg/dL, LDH 310 U/L (ref 100–190). Osmotic fragility test is abnormal. A peripheral blood smear is shown. Which of the following proteins is most likely deficient in this patient?
Answer: D Spectrin deficiency disrupts the vertical linkage of the erythrocyte cytoskeleton to the lipid bilayer, causing hereditary spherocytosis. Loss of cytoskeletal support leads to progressive membrane loss, spheroidization, and osmotic fragility; spherocytes are then sequestered and destroyed by splenic macrophages, producing chronic extravascular hemolysis. The elevated MCHC (37.2 g/dL) reflects the densely hemoglobinated, dehydrated spherocyte and is a key diagnostic clue. Contrast: G6PD deficiency (option A) and pyruvate kinase deficiency (option C) both cause hemolytic anemia but produce normal osmotic fragility and normal or low MCHC; hemoglobin β-chain mutations (option B) cause sickling or thalassemic changes with target cells, not spherocytes with elevated MCHC; and Von Willebrand factor deficiency (option E) is a platelet-adhesion coagulopathy with no effect on red cell morphology.
A 24-year-old woman presents with a 4-month history of painless cervical lymphadenopathy, low-grade fever, drenching night sweats, and a 5-kg weight loss. CT chest shows an anterior mediastinal mass. Peripheral WBC is 8,400/μL with a normal differential; hemoglobin and platelet counts are normal. A lymph node biopsy is performed; a histologic image is shown demonstrating large binucleate cells with prominent eosinophilic nucleoli on a background of small lymphocytes and eosinophils. These large cells classically co-express which of the following surface markers?
Answer: E Classic Reed-Sternberg cells in Hodgkin lymphoma co-express CD15 and CD30. The combination of an anterior mediastinal mass, constitutional B symptoms, bimodal age distribution (young adults), and large binucleate 'owl-eye' cells in a mixed eosinophil-rich background is pathognomonic for classic Hodgkin lymphoma; the RS cells express CD15 and CD30 but are typically CD20-negative and CD45-negative. Contrast: CD3/CD8 marks cytotoxic T lymphocytes, which are small mononuclear cells incapable of the binucleate giant-cell morphology shown (option A); CD10/CD20/BCL-2 identifies follicular lymphoma B cells, which form follicles without eosinophilic stroma (option B); CD14/CD64 marks macrophages and monocytes, not neoplastic lymphoid cells (option C); and CD19/CD20/CD138 marks plasma cells or mature B cells—RS cells lack CD138, and the eosinophil-rich stroma is incompatible with a plasma cell neoplasm (option D).
A 48-year-old woman with a 22-year history of type 1 diabetes mellitus (HbA1c 9.2%) is referred to ophthalmology after noting floaters in her right eye for 3 weeks. Visual acuity is 20/40 right eye and 20/25 left eye. Intraocular pressure is normal. A fundus photograph of the right eye is shown, demonstrating new vessels arising from the optic disc that extend across the vitreous face with associated punctate hemorrhages. Which of the following best explains the formation of these new vessels?
BRelease of angiopoietin-2 from activated pericytes
CProliferation of pericytes driven by PDGF signaling
DStimulation of endothelial migration by basic FGF
EInhibition of angiogenesis by TGF-β from astrocytes
Answer: A Upregulation of vascular endothelial growth factor (VEGF) in ischemic retinal cells is the primary molecular driver of neovascularization in proliferative diabetic retinopathy. Chronic hyperglycemia damages retinal pericytes and capillaries, producing focal ischemia; the ischemic retina activates HIF-1α, which transcribes VEGF, and VEGF diffuses to the vitreous cavity where it stimulates endothelial cell proliferation and migration, forming new fragile vessels at the disc and elsewhere. This is the molecular target of intravitreal anti-VEGF therapy. Contrast: Angiopoietin-2 (option B) destabilizes existing vessel walls and is a permissive co-factor, not the principal angiogenic signal; PDGF signaling (option C) recruits and stabilizes pericytes on mature vessels rather than generating new ones; basic FGF (option D) has angiogenic activity but plays a secondary role relative to VEGF in diabetic retinopathy; and TGF-β from astrocytes (option E) inhibits rather than promotes angiogenesis and cannot explain the new vessel formation shown.
A 52-year-old man presents with painful oral erosions for 4 weeks followed by the appearance of multiple flaccid blisters and erosions on the trunk and proximal extremities. The blisters rupture with minimal lateral pressure (positive Nikolsky sign). He takes no new medications. Skin biopsy shows intraepidermal acantholysis with suprabasal cleft formation on light microscopy and IgG deposits along the surfaces of individual keratinocytes on direct immunofluorescence. Antibodies directed against which of the following targets are responsible for this disease?
Answer: B Autoantibodies against desmoglein 3 (Dsg3), a desmosomal cadherin required for keratinocyte cell-cell adhesion, cause pemphigus vulgaris. IgG antibodies bind Dsg3 on the keratinocyte surface, disrupting desmosomal junctions and causing intraepidermal acantholysis; because Dsg3 is expressed in oral mucosa, mucosal erosions typically precede skin blisters, and the IgG deposits appear in an intercellular (chicken-wire) pattern rather than at the basement membrane. Contrast: Collagen XVII (option A) and BP180/BPAG2 (option C) are subepidermal targets—antibodies to these cause bullous pemphigoid with tense blisters and linear IgG at the dermal-epidermal junction, not the intraepidermal acantholysis shown; Dsg1 (option D) is targeted in pemphigus foliaceus, which spares mucous membranes because Dsg1 is absent from oral epithelium (the oral erosions shown here exclude this option); and laminin-332 (option E) is a subepidermal anchoring protein targeted in epidermolysis bullosa acquisita, producing subepidermal separation, not acantholysis.
Q18 · Cardiovascular · Pathology · ecg
A 68-year-old man with hypertension and type 2 diabetes presents with fatigue and exertional dyspnea. He has not seen a physician in 3 years. Pulse is 88 beats/min and irregularly irregular. Blood pressure is 146/92 mmHg. An ECG is shown, demonstrating absent P waves, an irregularly irregular ventricular rate, narrow QRS complexes, and a fibrillatory isoelectric baseline. Which of the following is the most likely serious complication of this arrhythmia if it remains untreated?
ASudden cardiac death from ventricular fibrillation
BSyncope from third-degree atrioventricular block
CCardioembolic stroke from left atrial appendage thrombus
DSystemic hypertension from renin-angiotensin-aldosterone activation
EAortic valve regurgitation from turbulent transvalvular flow
Answer: C Cardioembolic stroke from thrombus formation in the left atrial appendage is the most serious complication of untreated atrial fibrillation. Disorganized, ineffective atrial contraction causes blood stasis in the left atrial appendage, creating a nidus for thrombus; embolization to the cerebral circulation produces ischemic stroke. This patient's age, hypertension, and diabetes confer a high CHA₂DS₂-VASc score, making anticoagulation essential. Contrast: Degeneration to ventricular fibrillation (option A) requires an accessory pathway—absent here given the narrow QRS complexes; complete heart block (option B) would produce bradycardia, not a pulse of 88/min; hypertension (option D) is a risk factor that predisposes to AF rather than a complication of it, and the patient already has hypertension; and aortic regurgitation (option E) has no established causal link to atrial fibrillation.
A 38-year-old woman presents with acute gingival bleeding, epistaxis, and petechiae on her arms and legs. She has no prior bleeding history and takes no medications. CBC: WBC 35,000/μL (78% blasts), hemoglobin 7.8 g/dL, platelets 22,000/μL. Coagulation studies: PT 22 s (ref 11–13), aPTT 48 s (ref 25–35), fibrinogen 89 mg/dL (ref 200–400), D-dimer markedly elevated. A peripheral blood smear is shown, demonstrating myeloblasts containing elongated purple cytoplasmic inclusions. Which of the following is the most likely complication responsible for the coagulopathy?
AImmune thrombocytopenic purpura from platelet autoantibodies
BThrombotic thrombocytopenic purpura from ADAMTS13 enzyme deficiency
CHemolytic uremic syndrome from Shiga-like toxin and endothelial injury
DDisseminated intravascular coagulation from blast granule release
EVitamin K-dependent clotting factor depletion by hepatic failure
Answer: D Disseminated intravascular coagulation (DIC) triggered by procoagulant material released from leukemic blast granules is responsible for this patient's coagulopathy. The elongated cytoplasmic inclusions are Auer rods, pathognomonic for AML; acute promyelocytic leukemia (AML M3) blasts harbor t(15;17) and release tissue factor and annexin II from their hypergranular cytoplasm, activating the coagulation cascade systemically and consuming fibrinogen (89 mg/dL), platelets (22,000/μL), and other factors while elevating D-dimer. Contrast: ITP (option A) causes isolated thrombocytopenia with normal PT, aPTT, and fibrinogen; TTP (option B) and HUS (option C) feature microangiopathic hemolytic anemia with characteristically normal coagulation studies—the prolonged PT, prolonged aPTT, and low fibrinogen shown here are incompatible with both; and vitamin K-dependent factor depletion (option E) prolongs PT and aPTT but does not lower fibrinogen (factor I is not vitamin K-dependent) or elevate D-dimer as seen here.
A 28-year-old woman presents with a 6-month history of intermittent diarrhea, bloating, and a 7-kg weight loss despite a normal appetite. Her sister has type 1 diabetes mellitus. Laboratory values show a microcytic anemia, hypoalbuminemia, elevated fecal fat, and anti-tissue transglutaminase (anti-tTG) IgA antibodies above the upper limit of normal. A small intestinal biopsy is performed, and a histologic image is shown. Which of the following immunologic mechanisms best explains the mucosal changes demonstrated?
AEosinophil-mediated epithelial injury via IL-5 signaling
BIgE-mediated hypersensitivity to wheat proteins at mucosal mast cells
CNeutrophil-rich inflammation from bacterial exotoxin-mediated epithelial injury
DIgG immune complex deposition along the villous basement membrane
ET-cell-mediated destruction of gliadin-sensitized enterocytes
Answer: E CD4+ T-cell-mediated destruction of enterocytes sensitized by gliadin peptides is the primary immunologic mechanism of celiac disease. Gliadin is deamidated by tissue transglutaminase, creating modified peptides that are presented by HLA-DQ2/DQ8 molecules to CD4+ T cells; activated T cells release IFN-γ and other cytokines that damage enterocytes and recruit intraepithelial lymphocytes, producing the villous atrophy and crypt hyperplasia visible on biopsy. Anti-tTG IgA antibodies confirm the diagnosis. Contrast: IgE-mediated mast cell activation (option B) causes acute-onset allergic reactions within minutes, not the 6-month malabsorptive syndrome shown; eosinophil-IL-5 signaling (option A) characterizes eosinophilic esophagitis, not celiac disease; bacterial exotoxin-driven neutrophilic inflammation (option C) causes acute gastroenteritis incompatible with this chronic course and autoimmune serology; and IgG immune complex deposition (option D) is inconsistent with the anti-tTG IgA seropositivity and the villous atrophy pattern of a T-cell-mediated process.
Q21 · Human Development · Genetics · other
A 32-year-old woman at 16 weeks of gestation presents for prenatal screening. Triple analyte screening shows elevated serum hCG, decreased alpha-fetoprotein, and decreased unconjugated estriol. Her obstetrician recommends amniocentesis for definitive diagnosis. The resulting karyotype is shown above, revealing 47 chromosomes. The fetus has no other structural anomalies on ultrasound. Which of the following most likely accounts for this chromosomal finding?
DRobertsonian translocation between chromosomes 14 and 21
EDeletion at chromosome 21q22.3
Answer: A Nondisjunction during maternal meiosis I is the most common mechanism producing trisomy 21 in Down syndrome. The karyotype shows three copies of chromosome 21 (47,XX+21). When homologous chromosome 21 pairs fail to separate during maternal meiosis I, both copies enter the same secondary oocyte; fertilization by a normal sperm produces trisomy 21. This accounts for approximately 95% of Down syndrome cases and is more common in advanced maternal age. Contrast: Meiosis II nondisjunction (option B) also yields trisomy 21 but arises from sister chromatid failure and is far less frequent; Robertsonian translocation (option D) accounts for ~4% of cases and produces a 46-chromosome karyotype with a fused 14;21 marker—not a free trisomy; paternal nondisjunction (option C) is responsible for <5% of all cases; deletion at 21q22.3 (option E) would cause partial monosomy 21, not trisomy.
A 58-year-old man presents with a 6-week history of progressive headaches, cognitive slowing, and right arm weakness. MRI shows a ring-enhancing lesion in the left parietal lobe with surrounding vasogenic edema. Stereotactic biopsy is performed and the specimen is shown above. Intraoperative frozen sections confirm a high-grade glial neoplasm. Which histologic feature is most characteristic of this diagnosis and distinguishes it from lower-grade gliomas?
BNecrosis with peripheral pseudopalisading of tumor cells
CPerivascular lymphocytic cuffing with reactive gliosis
DRosenthal fiber formation within the tumor stroma
EHomer Wright pseudorosette formation by tumor cells
Answer: B Necrosis with peripheral pseudopalisading of tumor cells is the pathognomonic histologic feature of glioblastoma (WHO grade 4 astrocytoma). Pseudopalisading necrosis refers to hypercellular bands of viable tumor cells lining areas of central necrosis; it reflects a hypoxic tumor microenvironment that drives HIF-1α and VEGF upregulation, producing the characteristic microvascular proliferation. Contrast: Geographic necrosis without palisading (option A) is seen in high-grade lymphomas and some carcinomas but lacks the defining palisade of viable cells; perivascular lymphocytic cuffing (option C) is characteristic of viral encephalitis or CNS vasculitis, not neoplasm; Rosenthal fibers (option D) are eosinophilic protein aggregates found in low-grade pilocytic astrocytomas; Homer Wright pseudorosettes (option E) are characteristic of medulloblastoma and primitive neuroectodermal tumors, not glioblastoma.
A 26-year-old man presents with 8 months of crampy right lower quadrant pain, intermittent non-bloody diarrhea, and 8 kg unintentional weight loss. Colonoscopy reveals a cobblestone mucosal pattern with linear ulcers in the terminal ileum and two discrete involved segments separated by normal-appearing bowel. Biopsy from an involved area is shown above. Which histologic finding most specifically distinguishes this condition from its closest clinical and endoscopic mimicker?
ACrypt abscesses confined to the mucosa and submucosa
BLoss of goblet cells with continuous mucosal architectural distortion
CTransmural inflammation with skip lesions
DContinuous mucosal involvement extending from the rectum proximally
EPseudopolyp formation from mucosal bridging over ulcerated segments
Answer: C Transmural inflammation with skip lesions is the histologic hallmark that distinguishes Crohn disease from ulcerative colitis. In Crohn disease, the inflammatory infiltrate extends through all layers of the bowel wall—mucosa, submucosa, muscularis propria, and serosa—and diseased segments are separated by endoscopically normal skip areas. Non-caseating granulomas, when present, further confirm the diagnosis. Contrast: Crypt abscesses confined to mucosa and submucosa (option A) are the classic histologic feature of ulcerative colitis; loss of goblet cells with continuous architectural distortion (option B) also characterizes UC's chronic mucosal injury pattern; continuous involvement from the rectum proximally (option D) is the defining endoscopic and pathologic distribution of UC, not Crohn disease; pseudopolyp formation (option E) occurs in both conditions and is not discriminating.
Q24 · Cardiovascular · Physiology · ecg
A 67-year-old man with type 2 diabetes mellitus and CKD stage 3b presents with 3 days of progressive generalized muscle weakness. Medications include metformin, lisinopril 10 mg daily, and insulin glargine. Blood pressure is 138/86 mmHg. Serum sodium 139 mEq/L, potassium 6.4 mEq/L, creatinine 2.6 mg/dL. An ECG is shown above, demonstrating peaked T waves. Which medication most directly caused this patient's electrolyte abnormality?
Answer: D Lisinopril, an ACE inhibitor, most directly caused this patient's hyperkalemia by suppressing the renin-angiotensin-aldosterone axis. ACE inhibitors block conversion of angiotensin I to angiotensin II, thereby reducing aldosterone secretion. Aldosterone normally drives potassium excretion in the distal nephron via the principal cell ENaC/ROMK pathway; its reduction causes potassium retention. The risk is compounded by underlying CKD, which independently impairs renal potassium handling. The ECG shows peaked T waves, a classic early sign of hyperkalemia. Contrast: Metformin (option A) has no direct effect on potassium homeostasis; hydrochlorothiazide (option B) and furosemide (option C) are kaliuretic diuretics that cause hypokalemia rather than hyperkalemia; insulin glargine (option E) promotes cellular potassium uptake via Na/K-ATPase and acutely lowers serum potassium.
A 45-year-old woman with a history of multiple blistering sunburns during childhood presents for evaluation of a changing lesion on her upper back. Examination shows a pigmented lesion with asymmetry, irregular borders, color variation (tan, brown, black, and focal red areas), and diameter 9 mm. A clinical photograph is shown above. Dermoscopy reveals regression structures and atypical vascular patterns consistent with malignant transformation. Molecular analysis of the resected specimen most commonly reveals which of the following alterations?
EBRAF V600E mutation activating the MAPK signaling pathway
Answer: E BRAF V600E mutation activating the MAPK signaling pathway is the most commonly identified driver alteration in UV-induced cutaneous melanoma. The V600E valine-to-glutamate substitution at codon 600 constitutively activates BRAF kinase independent of upstream RAS signaling, driving continuous phosphorylation of MEK and ERK to promote cell proliferation and survival. BRAF V600E is present in approximately 40–50% of cutaneous melanomas and is the target of vemurafenib and dabrafenib. Contrast: CDKN2A loss (option A) affects cell cycle regulation via p16/Rb and p14ARF/p53 but is a secondary/cooperating event rather than the most common initiating driver; PTEN deletion (option C) cooperates with BRAF mutation but is not the primary driver; CDH1 methylation (option B) is characteristic of lobular breast and gastric cancer; KIT mutations (option D) drive mucosal and acral lentiginous melanoma, not UV-induced superficial spreading melanoma.
A 55-year-old man with a 3-year history of seropositive rheumatoid arthritis presents with 2 weeks of progressive dyspnea and right-sided pleuritic chest pain. Examination reveals decreased tactile fremitus and dullness to percussion at the right base. A chest radiograph is shown above, demonstrating blunting of the right costophrenic angle. Thoracentesis yields 650 mL of straw-colored fluid: pleural protein 4.2 g/dL, serum protein 6.8 g/dL, pleural LDH 280 U/L, serum LDH 350 U/L. Which laboratory result best classifies this effusion as an exudate?
APleural fluid LDH-to-serum LDH ratio greater than 0.6
BPleural fluid protein-to-serum protein ratio less than 0.5
CPleural fluid glucose concentration greater than 60 mg/dL
DPleural fluid pH greater than 7.3
EPleural fluid total nucleated cell count less than 1,000/µL
Answer: A A pleural fluid LDH-to-serum LDH ratio greater than 0.6 classifies this effusion as an exudate by Light's criteria. This patient's LDH ratio is 280/350 = 0.80, which exceeds the 0.6 threshold. Light's criteria define an exudate when at least one of the following is met: pleural fluid LDH/serum LDH >0.6, pleural fluid protein/serum protein >0.5, or pleural fluid LDH >2/3 the upper normal serum LDH. Rheumatoid arthritis is a well-recognized cause of exudative pleural effusion. Contrast: A protein ratio less than 0.5 (option B) would indicate a transudate; this patient's ratio is 4.2/6.8 = 0.62, also consistent with an exudate by that criterion, but option B as written states the transudate threshold; glucose >60 mg/dL (option C) and pH >7.3 (option D) reflect effusion characteristics not used in Light's classification; cell count <1,000/µL (option E) is not a Light's criterion.
A 24-year-old Peace Corps volunteer returns from 18 months in sub-Saharan Africa with a 4-day history of high-grade fever reaching 40.1°C, shaking chills, and frontal headache. Examination shows splenomegaly and scleral icterus. Laboratory studies: hemoglobin 9.2 g/dL, platelet count 68,000/µL. A Giemsa-stained peripheral blood smear is shown above. The patient is admitted to the ICU. Which finding on this smear most specifically identifies the infecting Plasmodium species?
ASingle large ring form per erythrocyte with Schüffner dots and marked erythrocyte enlargement
BMultiple ring-form trophozoites per erythrocyte without erythrocyte enlargement
CLarge ameboid trophozoites filling an enlarged, pale erythrocyte with Schüffner dots
DBand-form trophozoite spanning the full equatorial diameter of the erythrocyte
ECompact oval ring form with Maurer clefts in a normal-to-enlarged erythrocyte
Answer: B Multiple ring-form trophozoites per erythrocyte without erythrocyte enlargement is the distinguishing blood smear feature of Plasmodium falciparum. P. falciparum characteristically parasitizes erythrocytes of all ages without enlarging them and can infect multiple ring forms per cell (including appliqué or 'headphone' ring forms with double chromatin dots). Gametocytes appear as banana/crescent shaped forms. High parasitemia with multi-organ dysfunction is typical. Contrast: A single ring with Schüffner dots and cell enlargement (option A) describes P. vivax or P. ovale; large ameboid trophozoites in enlarged cells with Schüffner dots (option C) is P. vivax at the trophozoite stage; band-form trophozoites spanning the RBC diameter (option D) are pathognomonic of P. malariae; compact oval rings with Maurer clefts in normal-sized RBCs (option E) may partially reflect P. falciparum features, but Maurer clefts alone do not provide species identification as reliably as multiple rings per cell without enlargement.
A 34-year-old African American woman is referred for evaluation of mild anemia identified on routine complete blood count. Hemoglobin is 10.4 g/dL, MCV 78 fL, reticulocyte count 4.2%. Splenomegaly is noted on physical examination. A peripheral blood smear is shown above. Hemoglobin electrophoresis reveals greater than 90% hemoglobin C with no sickle hemoglobin detected. Which mechanism best explains the characteristic morphology of the erythrocytes seen on this smear?
ADecreased intracellular ionic osmolarity causing passive water efflux, cellular dehydration, and progressive volume contraction
BIntravascular hemolysis causing free hemoglobin release into plasma with resultant hemoglobinuria and schistocyte formation
CRelative excess of red cell membrane surface area compared with intracellular hemoglobin content
DOxidative denaturation of hemoglobin beta-chains forming precipitated Heinz body inclusions along the inner membrane
EIgG autoantibody-mediated opsonization of erythrocytes triggering accelerated extravascular phagocytosis by splenic macrophages
Answer: C A relative excess of red cell membrane surface area compared with intracellular hemoglobin content is the mechanism underlying target cell (codocyte) formation in hemoglobin C disease. HbC polymerizes into intracellular crystals, reducing the osmotically active intracellular content and allowing membrane lipid redistribution; the result is a cell with excess surface area relative to volume, producing the characteristic bull's-eye target cell appearance on Giemsa-stained smear. Splenomegaly reflects trapping of poorly deformable, dehydrated HbC erythrocytes. Contrast: Cellular dehydration from osmolarity changes (option A) produces echinocytes in uremia or dehydration, not target cells; intravascular hemolysis with schistocytes (option B) characterizes TMA or mechanical heart valves; Heinz body formation (option D) results from G6PD deficiency or unstable hemoglobins, not HbC; IgG opsonization (option E) is the mechanism of warm autoimmune hemolytic anemia, which would show spherocytes on smear.
Q29 · Gastrointestinal · Pathology · radiology
A 68-year-old woman with prior open cholecystectomy and appendectomy presents with 18 hours of colicky periumbilical pain, multiple episodes of bilious vomiting, and inability to pass flatus or stool. Abdomen is distended with high-pitched, tinkling bowel sounds; no rebound or guarding. An upright abdominal radiograph is shown above, demonstrating dilated small bowel loops with air-fluid levels and a paucity of distal bowel gas. Among adults presenting with this radiographic pattern, which etiology is most common?
Answer: D Postoperative adhesions are the most common cause of small bowel obstruction in adults, accounting for approximately 60–75% of cases in developed countries. Peritoneal injury during prior abdominal or pelvic surgery leads to fibrous adhesion formation that can kink, compress, or angulate bowel loops, producing mechanical obstruction. This patient's prior open cholecystectomy and appendectomy place her at substantial risk. The radiograph shows the classic SBO pattern of dilated small bowel with air-fluid levels. Contrast: Incarcerated hernias (option A) are the second most common cause (~10–15%) and would require careful examination for external defects; Crohn stricture (option C) is a recognized cause but requires a prior diagnosis and represents a smaller fraction of cases; intussusception (option B) is predominantly a pediatric condition; gallstone ileus (option E) is rare, accounts for <1% of SBO, and typically requires a cholecystoenteric fistula with air in the biliary tree on imaging.
A 28-year-old HIV-positive man presents with 3 weeks of bilateral leg swelling and frothy urine. Serum albumin is 2.0 g/dL, creatinine 2.4 mg/dL, BUN 40 mg/dL; blood pressure is 126/78 mmHg. Urinalysis shows 3+ protein; urine microscopy reveals waxy casts and oval fat bodies. A renal biopsy specimen is shown above. Which histologic finding on this biopsy most specifically distinguishes this diagnosis from minimal change disease?
AComplete global effacement of podocyte foot processes on transmission electron microscopy, shared with minimal change disease
BMesangial IgA immune complex deposits on immunofluorescence microscopy with associated mesangial hypercellularity
CSubepithelial electron-dense immune complex deposits appearing as humps on electron microscopy
DLinear continuous IgG deposition along the glomerular basement membrane on immunofluorescence
EFocal segmental collagenous sclerosis of glomerular tufts with sparing of adjacent glomeruli
Answer: E Focal segmental collagenous sclerosis of glomerular tufts with sparing of adjacent glomeruli is the light microscopy hallmark of FSGS that distinguishes it from minimal change disease. HIV-associated nephropathy (HIVAN) is the prototypical cause of FSGS in HIV-positive patients and presents with nephrotic-range proteinuria, waxy casts, oval fat bodies, and rapid progression to renal failure. On light microscopy, FSGS demonstrates segmental areas of collagenous sclerosis in a subset of glomeruli (focal), with adjacent and uninvolved glomeruli appearing histologically normal—a pattern absent in minimal change disease, which shows normal light microscopy. Contrast: Podocyte foot process effacement (option A) is seen in both FSGS and minimal change disease on electron microscopy and is therefore not distinguishing; mesangial IgA deposits (option B) characterize IgA nephropathy; subepithelial humps (option C) are characteristic of post-streptococcal GN; linear IgG along the GBM (option D) is the hallmark of anti-GBM disease.
Q31 · Biostatistics & Epidemiology/Population Health · Biostatistics · other
Public health investigators are evaluating a foodborne illness outbreak affecting residents in a mid-sized city. Cases reported daily over a 3-week period are plotted in the figure shown. The onset curve demonstrates a gradual rise beginning on day 2, a prolonged plateau lasting approximately 10 days, and a gradual decline following removal of the contamination source. The implicated vehicle is a municipal water supply found to harbor Salmonella contamination; the supply was not removed from service until day 19. Which pattern does this epidemic curve most likely represent?
ESporadic case clustering with no unifying exposure
Answer: A Continuous common-source outbreak is characterized by a prolonged, plateau-shaped epidemic curve that reflects sustained exposure to a single contaminating source. When the exposure persists over days (as with a contaminated water supply kept in service), the curve rises gradually, sustains a plateau, and declines only after the source is removed. Contrast: a point-source outbreak produces a sharp unimodal bell-shaped curve bounded by the incubation period (exposure was brief and simultaneous); a propagated outbreak shows successive waves of increasing height separated by an incubation interval. Mixed patterns display an initial common-source peak with secondary person-to-person waves. Sporadic clustering lacks temporal coherence and no common source is identified.
A 72-year-old man presents with a 2-year history of progressive bilateral hearing loss and new-onset frontal headache. He denies bone pain. Physical examination reveals frontal bossing and mild sensorineural hearing loss bilaterally. Laboratory studies: alkaline phosphatase 890 U/L, serum calcium 9.1 mg/dL, phosphorus 3.7 mg/dL. A plain radiograph of the skull is shown, demonstrating characteristic changes. Serum protein electrophoresis reveals no M-spike. Bone scan demonstrates focal areas of markedly increased uptake. Which pathophysiologic mechanism best explains the radiographic findings in this patient?
ADecreased osteoblast activity with intact osteoclast function causing generalized osteopenia
BIncreased osteoclastic resorption followed by disorganized osteoblastic deposition of woven bone
CCortical tunneling and subperiosteal resorption from chronic elevation of parathyroid hormone
DReplacement of normal hematopoietic marrow by fibrotic stroma and reactive woven bone formation
EFailure of osteoid mineralization from vitamin D deficiency causing trabecular thinning and osteomalacia
Answer: B Increased osteoclastic resorption followed by disorganized osteoblastic deposition of woven bone is the hallmark pathophysiology of Paget disease of bone. The pagetic process begins with exaggerated osteoclastic activity, followed by a coupled but disorganized osteoblastic response that lays down structurally inferior woven (mosaic) bone, producing the classic 'cotton-wool' skull appearance and marked alkaline phosphatase elevation with normal calcium. Contrast: decreased osteoblast activity (option A) produces osteoporosis and does not explain the sclerotic foci; subperiosteal resorption with cortical tunneling (option C) is characteristic of hyperparathyroidism; marrow fibrosis with woven bone (option D) describes fibrous dysplasia; osteomalacia (option E) shows Looser zones and undermineralized osteoid, not sclerotic cotton-wool changes.
A 22-year-old sexually active man presents with a 5-day history of purulent urethral discharge and dysuria. He reports multiple sexual partners and inconsistent condom use over the past 6 months. He had a similar episode 8 months ago that resolved after antibiotic therapy. Vital signs are normal. A Gram stain of the urethral discharge is shown. Nucleic acid amplification testing confirms the diagnosis. Which property of this organism most directly explains why reinfection after successful treatment is common despite the development of antibodies during initial infection?
ABeta-lactamase production conferring resistance to penicillin-class antibiotics
BFormation of a polysaccharide capsule preventing complement-mediated opsonophagocytosis
CAntigenic variation of pili and outer membrane proteins prevents the development of protective immunity
DObligate intracellular lifestyle that enables persistent bacterial evasion of both humoral and cellular immunity
EProduction of IgA1 protease that cleaves secretory IgA at mucosal surfaces reducing local immunity
Answer: C Antigenic variation of pili and outer membrane proteins (Opa proteins) in Neisseria gonorrhoeae prevents the development of durable protective immunity, allowing reinfection with the same species. Gonococcal pili and Opa proteins undergo high-frequency phase and antigenic variation mediated by recombination; antibodies generated against one antigenic variant are ineffective against subsequent variants. Contrast: beta-lactamase production (option A) is a resistance mechanism, not an immune-evasion strategy, and does not explain susceptibility to reinfection in a treated patient; encapsulation (option B) is not a feature of N. gonorrhoeae; obligate intracellular lifestyle (option D) applies to Chlamydia trachomatis, not to this gram-negative diplococcus; IgA protease (option E) degrades local secretory IgA but does not explain the failure of systemic immune memory.
A 74-year-old woman presents with a 2-year history of gradually worsening central visual distortion and difficulty reading fine print. She notes that straight lines appear wavy when viewing an Amsler grid. Distance vision is relatively preserved. She has no history of elevated intraocular pressure, eye trauma, or eye surgery. Fundoscopic examination is shown. Best-corrected visual acuity is 20/100 in the right eye and 20/80 in the left eye. Which pathophysiologic mechanism best explains the origin of this patient's visual symptoms?
ANeovascularization of the iris causing elevated intraocular pressure
BProgressive optic nerve axon loss from chronically elevated intraocular pressure and ischemia
CCentral corneal haze from stromal collagen disorganization and irregular astigmatism
DAccumulation of drusen beneath the retinal pigment epithelium causing progressive photoreceptor atrophy
ESegmental demyelination of the optic nerve causing monocular vision loss and an afferent pupillary defect
Answer: D Accumulation of drusen beneath the retinal pigment epithelium (RPE), with secondary RPE dysfunction and progressive photoreceptor atrophy, is the core pathophysiology of age-related macular degeneration (AMD) and the cause of central scotoma and metamorphopsia. Drusen are focal deposits of lipid-rich extracellular material between the RPE and Bruch membrane; their accumulation disrupts RPE function and leads to overlying photoreceptor degeneration concentrated at the macula. The gradual central loss with preserved peripheral vision and metamorphopsia are hallmarks of dry AMD. Contrast: neovascular glaucoma from iris neovascularization (option A) elevates intraocular pressure and causes non-central field loss; glaucoma (option B) produces optic disc cupping and arcuate scotomas, not central distortion; corneal haze (option C) causes blurred vision globally, not isolated metamorphopsia; optic neuritis (option E) causes monocular vision loss with an afferent pupillary defect and pain on eye movement.
A 29-year-old woman presents with a 3-month history of symmetric small-joint arthritis, recurrent oral ulcers, and a facial rash that worsens with sun exposure. She also reports diffuse hair thinning and fatigue. Vital signs: temperature 37.2°C, blood pressure 118/74 mmHg. A photograph of her face is shown. Laboratory studies: ANA positive at 1:640 (speckled pattern), anti-dsDNA antibody positive, serum C3 32 mg/dL (reference 90–180 mg/dL). Urinalysis shows 2+ proteinuria. Which mechanism best explains why ultraviolet light exposure exacerbates this patient's skin findings?
CPhotosensitization of endogenous porphyrins generating reactive oxygen species and cutaneous tissue damage
DUVA-induced epidermal collagen cross-linking and keratinocyte hyperproliferation causing hyperkeratosis
EUV-induced keratinocyte apoptosis releases nuclear antigens that trigger autoantibody production
Answer: E UV-induced keratinocyte apoptosis releases intranuclear antigens (including dsDNA, histones, and Ro/SSA antigen) to the cell surface, where they become accessible to autoantibodies, activating complement and amplifying the local inflammatory response. In SLE, keratinocytes are abnormally sensitive to UV-induced apoptosis; the released nuclear material drives type I interferon production and amplifies the autoimmune cycle. Ultraviolet radiation and sun exposure increase cell apoptosis and are well-known triggers of SLE flare. Contrast: granuloma formation (option A) characterizes sarcoidosis or cutaneous tuberculosis, not SLE; IgE-mediated urticaria (option B) is immediate hypersensitivity unrelated to autoantibody generation; porphyria photosensitivity (option C) produces blistering, not a malar rash, and is caused by porphyrin accumulation rather than nuclear antigen release; collagen cross-linking and hyperkeratosis (option D) do not explain SLE photosensitivity.
A 52-year-old man with a 20-year history of heavy alcohol consumption presents with progressive abdominal distension and new-onset jaundice. Examination reveals spider angiomata on the anterior chest, palmar erythema, gynecomastia, splenomegaly, and shifting dullness on percussion. A liver biopsy specimen is shown. Laboratory results: prothrombin time 22 seconds (INR 2.1), serum albumin 2.3 g/dL, total bilirubin 5.4 mg/dL, platelet count 88,000/µL, ALT 54 U/L, AST 78 U/L. Which mechanism best explains this patient's elevated INR?
ADecreased synthesis of coagulation factors II, VII, IX, and X causing coagulopathy
BIncreased consumption of coagulation factors by disseminated intravascular coagulation
CNutritional vitamin K deficiency impairing gamma-carboxylation of clotting factor precursors
DAutoimmune hepatocyte destruction resulting in release of tissue thromboplastin
ESplenic sequestration and destruction of circulating coagulation factors due to portal hypertension
Answer: A Decreased hepatic synthesis of coagulation factors II, VII, IX, and X (and also V and fibrinogen) is the primary cause of coagulopathy and elevated INR in cirrhosis. The liver is the sole site of synthesis for these clotting proteins; as hepatocellular mass is lost to fibrosis and regenerative nodule formation, clotting factor production falls, prolonging PT/INR. Prothrombin time is elevated due to coagulation factor defects, while albumin is low as the liver synthesizes it and its functional capacity decreases. Contrast: DIC (option B) would be accompanied by thrombocytopenia out of proportion, elevated D-dimer, and fibrin degradation products; vitamin K deficiency (option C) would respond to vitamin K administration, which has limited effect in advanced cirrhosis; autoimmune hepatocyte destruction (option D) does not release thromboplastin in a clinically significant way; portal hypertension causes platelet sequestration but does not trap or destroy circulating coagulation factors (option E).
A 68-year-old man presents with a 4-month history of fatigue, lower back pain, and two hospitalizations for community-acquired pneumonia in the past year. Laboratory studies: hemoglobin 9.1 g/dL, total protein 10.2 g/dL, albumin 2.8 g/dL, serum calcium 11.4 mg/dL, creatinine 2.1 mg/dL. Serum protein electrophoresis shows a prominent M-spike in the gamma region. Urine protein electrophoresis demonstrates Bence Jones proteinuria. A peripheral blood smear is shown. Which mechanism best explains the appearance of the erythrocytes on this peripheral blood smear?
BParaprotein reduces the normal electrostatic repulsion between red blood cells
CHyperviscosity-induced mechanical deformation and elongation of erythrocytes within small capillaries
DComplement-mediated erythrocyte lysis leaving behind only the most rigid and osmotically resistant cells
EIron deficiency producing microcytic hypochromic erythrocytes that aggregate into pseudo-rouleaux chains
Answer: B Paraprotein (monoclonal immunoglobulin) reduces the normal negative surface charge (zeta potential) on red blood cells, eliminating electrostatic repulsion and allowing them to stack into rouleaux — the characteristic stacked-coin appearance seen in multiple myeloma. Rouleaux formation occurs with any increase in serum proteins, particularly immunoglobulins and fibrinogen; it is reversible and disappears when protein levels normalize. The RBCs here have stacked together in long chains — this is known as 'rouleaux formation' and it happens with increased serum proteins, particularly fibrinogen and globulins. Contrast: membrane cholesterol changes (option A) alter red cell shape but do not cause rouleaux; hyperviscosity deforms cells in capillaries but does not produce ordered stacking on a smear (option C); complement-mediated lysis (option D) is unrelated to rouleaux; iron deficiency (option E) produces hypochromic microcytes that do not stack in rouleaux.
Q38 · Cardiovascular · Pathology · ecg
A 78-year-old man with no prior cardiac history presents with two episodes of sudden loss of consciousness lasting 20–30 seconds with spontaneous recovery, as well as progressive exertional dyspnea over the past 3 months. Examination: pulse 38 beats/min and regular; cannon A waves visible in the jugular venous pulse with variable intensity; variable intensity of S1 on auscultation. An ECG is shown. Which hemodynamic consequence of this arrhythmia best explains this patient's syncopal episodes?
Answer: C Complete AV dissociation eliminates the atrial 'kick,' which normally contributes approximately 20–30% of ventricular end-diastolic volume; when atria and ventricles are completely dissociated, this contribution is lost and cardiac output falls enough to cause syncope. In third-degree (complete) heart block, no supraventricular impulses are conducted to the ventricles; the ventricles escape at an intrinsic rate of 30–45 bpm driven by a junctional or idioventricular pacemaker. Third-degree AV block is characterised by complete AV dissociation, with no supraventricular impulses conducted to the ventricles. Cannon A waves arise when the atrium contracts against a closed tricuspid valve (AV dissociation). Contrast: retrograde conduction and early mitral closure (option A) occur in nodal rhythms with retrograde P waves, not complete heart block; reduced diastolic filling time (option B) is important at fast rates; ANP loss (option D) is not a recognized hemodynamic cause of syncope; demand ischemia from rate-pressure product (option E) is more relevant to tachyarrhythmias.
An 82-year-old woman with a known history of osteoporosis is brought to the emergency department 1 hour after a ground-level fall while walking. She is unable to bear weight on her right lower extremity, which is held in external rotation and apparent shortening. Vital signs are stable. Distal pulses and sensation are intact. A pelvic radiograph is shown demonstrating a displaced fracture of the femoral neck. Which vascular complication most directly threatens this patient's long-term functional outcome?
AInjury to the common femoral artery in the femoral triangle causing acute lower extremity ischemia
BOcclusion of the obturator artery disrupting the only blood supply passing through the ligamentum teres
CVenous thrombosis of the femoral vein propagating to cause symptomatic pulmonary embolism
DDisruption of the medial femoral circumflex artery supplying the femoral head
EInjury to the lateral femoral cutaneous nerve causing permanent meralgia paresthetica
Answer: D Disruption of the medial femoral circumflex artery (MFCA), which provides the dominant blood supply to the femoral head via ascending cervical branches, is the vascular injury that leads to avascular necrosis of the femoral head — the most feared long-term complication of femoral neck fracture. The MFCA travels along the femoral neck and is vulnerable to tearing at the time of the fracture or during reduction; interruption leads to ischemic death of the femoral head articular segment. In patients with femoral neck fractures, risk of osteonecrosis is increased because the fracture often disrupts the blood supply to the femoral head. Contrast: the common femoral artery (option A) lies anterior in the femoral triangle, well away from the intracapsular fracture plane, and its injury would cause acute limb-threatening ischemia, which is absent here; the obturator artery via the ligamentum teres (option B) contributes negligible blood supply in adults; DVT/PE (option C) is a serious peri-operative risk but not a long-term functional threat to the hip joint itself; lateral femoral cutaneous nerve injury (option E) causes sensory paresthesia without affecting bone viability or hip mechanics.
Q40 · Human Development · Genetics · other
A couple seeks genetic counseling because two of their four children are affected by an autosomal recessive metabolic disorder. Both parents are phenotypically unaffected. The pedigree shown is consistent with autosomal recessive inheritance. One of the couple's two unaffected children, an 18-year-old daughter, wants to know the probability that she is a carrier of this condition. Assuming each unaffected sibling is equally likely to have been selected, what is the probability that this unaffected daughter is a carrier?
Answer: E 2/3 is the probability that an unaffected child of two carrier parents is a carrier of the autosomal recessive trait. From a carrier × carrier (Aa × Aa) cross the offspring probabilities are: 1/4 homozygous normal (AA), 2/4 carrier (Aa), and 1/4 affected (aa). Given that this child is known to be unaffected, the probability space is restricted to the unaffected genotypes: AA (1/4) or Aa (2/4), totaling 3/4 of all offspring. The conditional probability of being a carrier (Aa) given being unaffected = (2/4) ÷ (3/4) = 2/3. Contrast: 1/2 (option D) would be correct if the child's carrier status were calculated unconditionally (without conditioning on unaffected status); 1/4 (option B) is the unconditional probability of being homozygous normal; 0 (option A) would apply only if a carrier state were impossible for this condition.