TL;DR
The USMLE Step 1 “Free 120” is the official set of sample items published by the USMLE, and the booklet currently posted at usmle.org (updated April 2026) contains 119 items in six blocks, available as a PDF and in the interactive testing experience that mirrors the real interface. It is the only practice material written by the people who write the exam, which makes it the best final-week calibration you can get for free. The PDF includes a bare answer key but no explanations. Below is an item-by-item key with the reasoning for each answer and why the main distractors are wrong. We do not reproduce the question stems (they are NBME copyright); each entry has a short descriptor so you can match it to the item in front of you. Do the set under timed conditions first, then work through this page with your incorrects.
How to use the Free 120 (and this key)
Treat the Free 120 as a dress rehearsal, not as study material. The items are easier on average than a real Step 1 form and the set is small, so your percentage on it is a loose signal at best; what it does tell you reliably is how the interface feels, how the newer item styles read, and which content areas you still reason through slowly. Take it in the interactive testing experience about a week before your exam, in timed blocks matching the current format (since May 2026, Step 1 runs fourteen 30-minute blocks of up to 20 items). Then use the key below to review every item you missed or guessed on, including the ones you got right by elimination. The explanations here are written to teach the tested concept rather than just defend the letter, so the ones you got right are worth a skim too. If a particular topic keeps appearing in your misses, that is the signal to generate more practice on it rather than to re-read the explanation.
Note on versions: USMLE revises the sample set periodically. This key matches the booklet marked “updated April 2026” (119 items). If your copy has a different item count or ordering, check the date on its first page.
Block 1: Items 1–20
1. 27-year-old woman, sudden dyspnea after a cross-country flight, tender swollen right calf. Answer: B, Factor V Leiden mutation. This is a DVT with pulmonary embolism in a young patient with only a mild provoking factor, and the question asks for the most likely underlying cause. Factor V Leiden is by far the most common inherited thrombophilia (about 5% of people of European ancestry carry it), so it is the statistically correct choice over antithrombin III, protein C or protein S deficiency, which are all much rarer. Glanzmann thrombasthenia and von Willebrand disease are bleeding disorders, not clotting disorders.
2. 53-year-old woman, six years of hand stiffness and trouble buttoning clothes, hand photograph. Answer: A, anti-citrullinated peptide antibody. Chronic symmetric small-joint stiffness with functional loss and a photograph of deformed hands is rheumatoid arthritis, and anti-CCP is the most specific confirmatory antibody. Antimitochondrial antibody is for primary biliary cholangitis; HLA-DQ2 is associated with celiac disease; the marrow precursor options are distractors with no role in confirming an inflammatory arthritis.
3. 80-year-old woman after stroke: left eye cannot abduct, right hemiparesis, right posterior-column loss. Answer: B, asymmetric smile. Failure of left abduction with intact right gaze is a left abducens (CN VI) lesion; contralateral hemiparesis and loss of vibration and two-point discrimination localize the lesion to the left medial pons (corticospinal tract and medial lemniscus). The facial nerve fascicle loops around the abducens nucleus in the same territory, so the expected additional finding is an ipsilateral lower-motor-neuron facial weakness, which shows up as an asymmetric smile. Facial anesthesia (CN V) is a lateral pontine finding; hoarseness and tongue paralysis are medullary; loss of accommodation is midbrain.
4. 32-year-old man, two weeks of fever and pharyngitis, generalized lymphadenopathy, pancytopenia, heterophile antibody negative. Answer: C, HIV infection. A mononucleosis-like illness with lymphadenopathy in multiple regions, a negative heterophile (Monospot) test and cytopenias in a young adult is acute HIV seroconversion. EBV would typically give a positive heterophile antibody and does not usually cause this degree of pancytopenia. Streptococcal and gonococcal pharyngitis do not produce generalized adenopathy and marrow suppression; lymphogranuloma venereum causes inguinal buboes, not pharyngitis.
5. 60-year-old woman three weeks into IV oxacillin: fever, rash, eosinophilia, rising creatinine, urine eosinophils and WBC casts. Answer: C, interstitial inflammatory infiltrate. Fever, rash, peripheral eosinophilia and acute kidney injury with eosinophiluria and white-cell casts after a beta-lactam is drug-induced acute interstitial nephritis. The histology is an interstitial infiltrate of lymphocytes and eosinophils with tubulitis. Collapsing FSGS is seen with HIV; glomerular necrosis suggests a rapidly progressive glomerulonephritis; mesangial expansion with GBM thickening is diabetic nephropathy; tubular dilation with brush-border loss is acute tubular necrosis, which does not cause eosinophiluria or a drug-allergy picture.
6. 20-year-old woman with progressive arm weakness and a central cervical syrinx on MRI. Answer: D, trauma. Syringomyelia classically presents with a cape-like loss of pain and temperature and weakness in the upper extremities; the two common causes are Chiari I malformation and prior spinal cord injury. Of the history options, trauma is the one that bears on etiology. Diet, travel, family illness and weight loss do not point to any cause of a syrinx.
7. 68-year-old man with diabetes, coronary disease and calf claudication; absent pedal pulses, hairless atrophic skin. Answer: E, vascular obstruction by lipid-rich plaques. Intermittent claudication with absent distal pulses and trophic skin changes is peripheral arterial disease, and in a patient with this risk-factor profile the mechanism is atherosclerosis. Hyaline arteriosclerosis affects small arterioles (the lesion of benign hypertension and diabetes in the kidney), not the large conduit arteries that cause claudication. Fibromuscular dysplasia affects renal and carotid arteries in young women; giant cell arteritis involves the aorta and cranial branches; segmental inflammation of medium vessels is polyarteritis nodosa.
8. 58-year-old man with COPD who is not ready to quit smoking; his wife’s cough. Answer: A, “Are there any reasons why you might want to quit smoking?” A patient in the precontemplation stage responds best to motivational interviewing that elicits his own reasons for change. The other options lecture (B, D), guilt-trip (C) or interrogate (E), all of which increase resistance. The exam consistently rewards open-ended, nonjudgmental questions that let the patient voice ambivalence.
9. 18-month-old girl whose weight has fallen from the 25th to below the 5th percentile; two bottles of formula a day plus a little table food. Answer: B, caloric insufficiency. Weight falls first and length is preserved, which is the pattern of inadequate intake rather than endocrine disease (where length falls first or alongside weight). Two 8-ounce bottles plus “small amounts” of table food is well short of the calories a toddler needs. Familial short stature and constitutional delay affect length, not weight velocity, and her parents are tall. Growth hormone deficiency and adrenal insufficiency are not suggested by the history.
10. Prospective cohort of dietary calcium and osteoporosis; investigators add yogurt to the food questionnaire. Answer: A, internal validity. Omitting a major calcium source would systematically misclassify exposure, a measurement bias. Fixing the instrument improves how accurately the study measures what it claims to measure, which is internal validity. Inter-rater reliability concerns agreement between observers; response rate is unaffected by questionnaire content; type I error is about the significance threshold, not measurement.
11. 40-year-old woman from El Salvador whose donated blood is positive for Trypanosoma cruzi. Answer: D, reduviid bug. Chagas disease is transmitted by the triatomine (“kissing”) bug, a reduviid, which defecates into the bite wound. Mosquitoes carry malaria and arboviruses, black flies carry Onchocerca, ticks carry Borrelia and Babesia, and bedbugs are not vectors of T. cruzi.
12. 40-year-old man with irritable bowel syndrome on his third visit, using his grandmother’s herbal tea and declining medication. Answer: A, “Help me to understand what you are hoping I can do for you today.” The patient keeps returning, so something is unmet; the best move is to elicit his agenda without judging his choices. B pushes the physician’s agenda, C and E are dismissive, and D redirects to the tea before understanding why he is there.
13. 72-year-old man with urinary frequency, nocturia and slow stream; smooth symmetric prostate enlargement. Answer: B, α1-adrenergic antagonism. Benign prostatic hyperplasia with lower urinary tract symptoms is treated first-line with an α1 blocker such as tamsulosin, which relaxes prostatic and bladder-neck smooth muscle. α1 agonism would worsen obstruction, α2 agents act centrally on blood pressure, and β1 drugs act on the heart.
14. 33-year-old woman with two months of stalking the president, pressured speech, no sleep, grandiosity and a voice. Answer: A, bipolar disorder, manic, with psychotic features. Pressured speech, decreased need for sleep, grandiosity and loose associations over weeks define a manic episode; the delusion and hallucination are mood-congruent psychotic features. Schizophrenia requires six months of illness and the prominent mood symptoms argue against it. Brief psychotic disorder lasts under a month; delusional disorder lacks the manic features; nothing suggests a medical cause.
15. 63-year-old woman with reflux in a gastric-pH study; match curves to cimetidine and omeprazole. Answer: B, cimetidine = curve B, omeprazole = curve A. Cimetidine is a competitive, reversible H2 blocker: it raises pH quickly but only partially, and the effect plateaus at a modest level (curve B). Omeprazole irreversibly inhibits the parietal-cell H+/K+ ATPase; it needs active pumps to work, so its onset is slower, but once the pumps are covalently blocked acid secretion falls almost completely and stays suppressed until new pumps are synthesized, giving the curve that climbs highest and stays there (curve A). Curves C and D fall over time, which no acid suppressant does.
16. 65-year-old woman one year after right colectomy for colon cancer; new liver and lung metastases. Answer: B, inferior vena cava. Colon cancer spreads first to the liver through the portal circulation (superior mesenteric vein for a right-sided tumor). From the liver, tumor emboli travel through the hepatic veins into the inferior vena cava, through the right heart and into the pulmonary arteries, which is how lung metastases arise. The inferior mesenteric and left colic veins drain the left colon; arteries do not carry metastatic emboli from the primary; the pulmonary veins would carry tumor away from the lungs, not to them.
17. 4-year-old boy with three weeks of itching; thin serpiginous tracks in the webspaces, axillae, waist and inner thighs. Answer: E, scabies. Linear burrows in intertriginous areas and finger webs with intense pruritus are diagnostic of Sarcoptes scabiei. Pediculosis causes nits on hair shafts, not burrows; Lyme disease produces erythema migrans; chickenpox gives vesicles in crops on the trunk; ehrlichiosis is a febrile tick-borne illness.
18. 18-year-old woman with sickle cell disease and biliary colic; gallstones on ultrasound. Answer: E, overload of unconjugated bilirubin. Chronic hemolysis delivers more unconjugated bilirubin to the bile than the liver can conjugate efficiently, producing black pigment stones. A high cholesterol-to-bile-acid ratio is the mechanism of cholesterol stones; β-glucuronidase-secreting infection produces brown pigment stones in biliary infection; lecithin and bile-salt reabsorption are not the issue in hemolytic disease.
19. 34-year-old man with prior pheochromocytoma, a mother with a parathyroid tumor, and a C-cell neoplasm of the thyroid. Answer: D, proto-oncogene. Medullary thyroid carcinoma plus pheochromocytoma plus parathyroid disease is MEN 2A, caused by a germline gain-of-function mutation in RET, a receptor tyrosine kinase proto-oncogene. Tumor suppressors (MEN1, RB, p53) cause other familial syndromes; mismatch-repair genes cause Lynch syndrome.
20. 6-year-old girl with vaginal bleeding, breast buds, pubic hair; elevated FSH and LH, high estradiol. Answer: A, central activation of neurons. Elevated gonadotropins alongside sex-steroid elevation mean the hypothalamic-pituitary axis has switched on: central (GnRH-dependent) precocious puberty. Peripheral causes (McCune-Albright with its GNAS mutation, exogenous steroids, 21-hydroxylase deficiency) suppress FSH and LH through negative feedback, so they do not fit elevated gonadotropins. Prolactin does not drive puberty.
Block 2: Items 21–40
21. 16-year-old boy, tall with long limbs, gynecomastia, small testes; high FSH and LH, low testosterone. Answer: E, nondisjunction of the X chromosome during meiosis. Hypergonadotropic hypogonadism in a tall adolescent with gynecomastia and small firm testes is Klinefelter syndrome (47,XXY), which arises from meiotic nondisjunction. Constitutional delay and GnRH neuron hypoplasia (Kallmann) give low gonadotropins; an FSH-receptor mutation would not raise LH or produce this phenotype; 21-hydroxylase deficiency causes androgen excess, not deficiency.
22. Newborn with ambiguous genitalia, poor feeding, hyponatremia, hyperkalemia and hypoglycemia. Answer: B, aldosterone receptor. This is salt-wasting congenital adrenal hyperplasia (21-hydroxylase deficiency): cortisol and aldosterone are both deficient. Treatment is hydrocortisone plus fludrocortisone, and of the receptors listed, the one targeted by that therapy is the mineralocorticoid (aldosterone) receptor, which fludrocortisone agonizes to correct the sodium loss and potassium retention. Glucocorticoid therapy lowers ACTH indirectly by feedback; it does not act at the ACTH receptor.
23. 59-year-old man with diabetes and chronic kidney disease, BUN 65 and creatinine 4.2. Answer: C, pericardial friction rub. Uremic pericarditis is an absolute indication for urgent dialysis because of the risk of hemorrhagic effusion and tamponade. Anemia, edema, hypertension and hypoglycemia are managed medically; none of them by itself mandates immediate dialysis.
24. 65-year-old woman with an anterior STEMI; cardiac output versus end-diastolic volume graph labeled W, X, Y, Z. Answer: C, W → Z. The graph shows two Frank-Starling curves; W sits on the upper (higher contractility) curve and Z on the lower one at a larger end-diastolic volume. In the first seconds of acute ischemia, contractility falls, so the heart drops to the lower curve: stroke volume and cardiac output fall and the ventricle incompletely empties, so end-diastolic volume rises. That is a move down and to the right, from W to Z. Transitions ending at Y describe increased contractility; those ending at X describe reduced preload, which is the wrong direction for a failing ventricle with JVD and crackles.
25. 66-year-old man with Parkinson disease on carbidopa-levodopa who has freezing episodes. Answer: C, monoamine oxidase B. MAO-B inhibitors (selegiline, rasagiline) prolong the action of dopamine in the striatum and are standard adjuncts to levodopa. Inhibiting aromatic L-amino acid decarboxylase is what carbidopa already does peripherally; dopamine β-hydroxylase converts dopamine to norepinephrine; tyrosine hydroxylase inhibition would reduce dopamine synthesis; PNMT makes epinephrine.
26. 25-year-old man shot in the back at the left posterior 10th intercostal space, hypotensive and tachycardic. Answer: E, spleen. The spleen sits posterolaterally under the left 9th to 11th ribs, so a posterior left 10th-intercostal-space wound with hemorrhagic shock points to splenic injury. The left kidney lies lower and more medially (roughly T12 to L3), the colon is anterior, and the adrenal is small and medial. The lung is possible but would present with pneumothorax or hemothorax rather than this abdominal CT finding.
27. 33-year-old man five days after starting olanzapine: confusion, fever 40.3°C, tachycardia, hypertension. Answer: B, muscle rigidity. Hyperthermia, autonomic instability and altered mental status within days of starting an antipsychotic is neuroleptic malignant syndrome, whose hallmark exam finding is “lead-pipe” rigidity (with elevated creatine kinase). Hyperreflexia and mydriasis point to serotonin syndrome, which this patient’s medications do not explain; a petechial rash suggests meningococcemia; hemiparesis suggests stroke.
28. 68-year-old former naphthylamine-plant worker and heavy smoker with painless hematuria and a renal pelvic mass. Answer: E, urothelial carcinoma. Aromatic amines (naphthylamine, benzidine) and tobacco are the classic carcinogens for urothelial (transitional cell) carcinoma, which can arise anywhere from the renal pelvis to the urethra. Angiomyolipoma is a benign tumor of tuberous sclerosis; nephroblastoma is a pediatric tumor; oncocytoma is benign and not linked to these exposures.
29. 37-year-old woman with three years of episodic facial flushing and burning triggered by stress; drinks red wine. Answer: A, effect of alcohol on the condition. Episodic facial flushing with burning in a woman in her thirties, with a photograph of facial skin, is rosacea, and alcohol (especially red wine), heat and stress are its classic triggers, so the relevant history is whether alcohol provokes episodes. Sweating, adenoma family history and neuropathic symptoms are aimed at carcinoid or MEN syndromes that do not fit a three-year, stress-triggered facial pattern.
30. Healthy unvaccinated 5-year-old whose mother declined all vaccines. Answer: B, herd immunity. An unvaccinated child in a highly vaccinated community is protected because the pathogens have little opportunity to circulate. Maternal antibodies wane within the first year; “eradication” is true only of smallpox; a normal immune system does not prevent infection on first exposure.
31. 28-year-old Rh-negative woman at 12 weeks whose husband is Rh-positive; asks the mechanism of therapy to prevent newborn complications. Answer: A, binding to the D antigen on fetal erythrocytes. Anti-D immune globulin binds Rh(D)-positive fetal red cells that enter the maternal circulation and clears them before the maternal immune system can mount a primary response. It does not block complement, induce class switching, suppress fetal erythropoiesis or physically prevent fetomaternal hemorrhage. (A note the exam does not ask about: a mother who is already sensitized, as a positive antibody titer implies, is managed by fetal surveillance rather than prophylaxis; the mechanism question is still answered by A.)
32. 40-year-old man with acute first-MTP joint pain after lobster and beer. Answer: D, purine degradation pathway. Acute gout results from monosodium urate crystal deposition, and urate is the end product of purine catabolism (hypoxanthine to xanthine to uric acid via xanthine oxidase). Purine-rich food and alcohol raise the load. The pentose phosphate pathway, urea cycle, methionine salvage and chylomicron processing do not generate urate.
33. 34-year-old woman cited for driving under the influence; chart says “social drinker.” Answer: A, “Do you have any concerns about your alcohol use?” The initial response should be open and nonjudgmental and should invite the patient’s own view. B and D jump to quantification before rapport, C puts words in her mouth, and E presumes a diagnosis and a treatment plan.
34. 4-year-old girl with progressive unilateral leg lymphedema; anomalous lymphatic development. Answer: C, mesoderm. Lymphatic vessels, like blood vessels, derive from mesoderm. Ectoderm forms epidermis and nervous tissue; endoderm forms gut and respiratory epithelium; neural crest forms peripheral nerves, melanocytes and craniofacial bone.
35. 50-year-old man with BMI 63, obstructive sleep apnea, cyanosis; ABG pH 7.31, PCO2 70, PO2 50. Answer: B, increased hemoglobin concentration. Chronic hypoxemia from obesity hypoventilation drives erythropoietin release and secondary polycythemia. Bicarbonate is elevated, not decreased, as renal compensation for chronic hypercapnia; total lung capacity is reduced in massive obesity; the ventricle that hypertrophies from chronic hypoxic pulmonary hypertension is the right one.
36. 5-year-old girl with bloody diarrhea, then five days later oliguria, hypertension, anemia, thrombocytopenia and creatinine 3.3. Answer: B, Escherichia coli. Bloody diarrhea followed by microangiopathic hemolytic anemia, thrombocytopenia and acute kidney injury is hemolytic uremic syndrome, most often from Shiga toxin-producing E. coli O157:H7. Campylobacter is associated with Guillain-Barré and reactive arthritis, Salmonella with bacteremia and osteomyelitis, rotavirus with watery diarrhea, and Yersinia pestis with plague.
37. 52-year-old woman with hypertension; displaced PMI, left axis deviation, tall R waves in V5–V6. Answer: C, increased synthesis of contractile filaments. Pressure overload produces concentric left ventricular hypertrophy by adding sarcomeres in parallel within existing myocytes; adult cardiomyocytes do not divide, so hyperplasia is wrong. Glycogen accumulation describes Pompe disease; conduction-pathway fibrosis causes heart block; protein misfolding describes amyloid.
38. Investigator finds polymorphisms in metabolic activation enzymes raise benzene-related lung cancer risk. Answer: B, cytochrome P450. Phase I cytochrome P450 enzymes convert procarcinogens such as benzene and polycyclic hydrocarbons into reactive electrophilic intermediates; polymorphisms that speed this activation increase risk. Glutathione S-transferase and methyltransferases are detoxifying (phase II) enzymes; aldehyde dehydrogenase and succinate dehydrogenase are not activation steps for these compounds.
39. New malaria drug given to 80 healthy volunteers to find the maximum tolerated dose and pharmacokinetics. Answer: B, phase 1. Phase 1 trials test safety, tolerability, dosing and pharmacokinetics in a small number of healthy volunteers. Phase 2 tests efficacy in patients, phase 3 compares against standard of care in large trials, and phase 4 is post-marketing surveillance. Phase 0 is a microdosing exploratory study, not a dose-finding one.
40. 21-year-old marathon trainee with type 1 diabetes found unresponsive; glucose 25 mg/dL unchanged 20 minutes after glucagon. Answer: A, depletion of glycogen stores. Glucagon raises blood glucose by stimulating hepatic glycogenolysis, so it fails when liver glycogen has been exhausted by prolonged exercise and fasting. The fix is intravenous dextrose. Exercise does not downregulate glucagon receptors, catecholamines promote rather than impair glycogenolysis, and his insulin dose had been reduced.
Block 3: Items 41–60
41. 72-year-old woman with jaundice, weight loss, a pancreatic head mass and liver lesions; she knows about the mass but not the suspected cancer. Answer: B, “I’m concerned the mass could be cancer. The biopsy will provide more information.” Once a patient has been assessed as ready to hear information, the physician should disclose the suspected diagnosis honestly but without false certainty. A overstates certainty before the biopsy; C and E withhold what the physician actually suspects; D defers disclosure, which is paternalistic when the patient is ready.
42. 56-year-old man with headaches, splenomegaly, hemoglobin 19.5 and hematocrit 59%. Answer: B, Janus kinase 2. Polycythemia vera, a myeloproliferative neoplasm with erythrocytosis and splenomegaly, is driven by the JAK2 V617F mutation in more than 95% of cases. Thrombopoietin receptor (MPL) mutations occur in a minority of essential thrombocythemia and myelofibrosis; the retinoic acid receptor fusion defines acute promyelocytic leukemia; PDGF receptor rearrangements cause hypereosinophilic syndromes.
43. 34-year-old woman with refractory seizures preceded by a burning-rubber smell, lip smacking and emotional outbursts; labeled coronal brain section. Answer: E, the medial temporal lobe. Olfactory auras, oral automatisms and ictal emotion are the signature of mesial temporal lobe epilepsy, with the focus in the hippocampus and amygdala. On the coronal section, label E marks the medial temporal lobe (the hippocampal region adjacent to the temporal horn of the lateral ventricle); A and B are the superior frontal gyrus and cingulate, C the thalamic region, and D the insula. Olfactory hallucinations point to the uncus and amygdala, not to the frontal or parietal cortex.
44. 20-year-old woman hospitalized for an eating disorder: parotid swelling, eroded teeth, knuckle scars, two days of inner-cheek mouth pain. Answer: A, binding to muscarinic acetylcholine receptors. Parotid and submandibular enlargement in bulimia (sialadenosis) plus a dry, painful mouth, worsened by an SSRI’s anticholinergic dryness, is treated symptomatically with a muscarinic agonist sialagogue such as pilocarpine or cevimeline. The remaining options are antibiotic mechanisms (nicotinic blockade is a neuromuscular blocker; 50S inhibition, DNA disruption and cell-wall synthesis inhibition are antimicrobial) and there is no infection in the vignette.
45. 42-year-old man with a severely itchy rash one day after cutting weeds. Answer: D, type IV (delayed). Poison ivy (urushiol) contact dermatitis is a T-cell-mediated delayed hypersensitivity: the reaction appears 12 to 72 hours after exposure as pruritic, often linear vesicles. Type I is immediate IgE-mediated (urticaria, anaphylaxis); type II is antibody against cell surfaces; type III is immune-complex deposition (serum sickness, Arthus).
46. 45-year-old park ranger living at 10,000 feet for two years, now with dyspnea, JVD and pedal edema. Answer: E, right ventricular diastolic compliance. Chronic hypoxic pulmonary vasoconstriction over two years raises pulmonary vascular resistance, thickens the right ventricle and eventually produces right heart failure. The parameter that falls as the ventricle hypertrophies is its diastolic compliance (a stiffer chamber). Hematocrit, PVR, RV wall thickness, R-wave height in V1 and P-wave height all increase in this setting.
47. 7-year-old boy with arm blood pressure 135/85 and leg pressure 80/40; systolic murmur at the left sternal border and between the scapulae. Answer: A, delayed femoral pulses. An arm-leg systolic gradient with an interscapular murmur is coarctation of the aorta; the femoral pulses are weak and delayed relative to the radial pulses. Elevated JVP implies right heart failure, a pulsatile abdominal mass implies aneurysm, pulsus paradoxus implies tamponade or severe airway obstruction, and an inguinal mass is unrelated.
48. 52-year-old woman with fatigue, constipation and polyuria; calcium 11.1 with suppressed PTH; bilateral hilar adenopathy. Answer: A, calcitriol production by activated macrophages. Hypercalcemia with low PTH and hilar lymphadenopathy is sarcoidosis, in which granuloma macrophages express 1α-hydroxylase and make 1,25-dihydroxyvitamin D independently of PTH. PTHrP secretion is the mechanism in squamous cell carcinomas, local osteolysis occurs with bony metastases, and PTH secretion is excluded by the low PTH.
49. 34-year-old man with recurrent pancreatitis since age 21, oily foul stools and an 11-kg weight loss. Answer: C, lipase. Chronic pancreatitis causes exocrine insufficiency, and fat malabsorption (steatorrhea) is the dominant clinical problem because lipase output falls earliest and most severely; pancreatic enzyme replacement is dosed by lipase units. Amylase deficiency is compensated by salivary and brush-border enzymes; protease deficiency causes less clinical malabsorption; lactase and tryptase are not pancreatic enzymes.
50. 46-year-old man from India with fever, RUQ pain and a 4-cm hypoechoic liver lesion, treated with metronidazole plus paromomycin. Answer: C, eradication of intestinal organisms. Amebic liver abscess is treated with metronidazole for the invasive tissue infection, followed by a luminal agent (paromomycin, iodoquinol or diloxanide) to clear intestinal cysts of Entamoeba histolytica that metronidazole does not reliably eradicate, preventing relapse and transmission. Paromomycin is poorly absorbed, so it is not for liver penetration, CNS prophylaxis or resistance prevention.
51. 3-year-old boy with rapid proptosis and an orbital mass; biopsy shows malignant cells with striations. Answer: D, rhabdomyosarcoma. Rhabdomyosarcoma is the most common soft-tissue sarcoma of childhood and the most common primary orbital malignancy in children; cross-striations or desmin/myogenin positivity mark the skeletal-muscle origin. Retinoblastoma arises inside the globe and causes leukocoria; neuroblastoma can metastasize to the orbit but is a small round blue cell tumor without striations.
52. 37-year-old carpenter with a necrotic hand puncture wound from four days ago, now febrile, hypotensive and tachypneic. Answer: E, Staphylococcus aureus. A rapidly progressive wound infection with systemic toxicity (fever, hypotension, hyperventilation) in an otherwise healthy adult is most likely S. aureus, the most common cause of skin and soft-tissue infection and of toxic-shock syndromes from wounds. Pasteurella follows animal bites, Pseudomonas classically follows a nail through a sneaker, Mycobacterium abscessus is indolent, and tetanus produces spasms rather than a septic wound.
53. 24-year-old woman one month after a car crash: intrinsic hand weakness and atrophy, spastic legs, normal biceps and triceps reflexes, sensory level at the clavicles. Answer: C, T1. Lower-motor-neuron findings in the intrinsic hand muscles (C8 to T1) with upper-motor-neuron findings below and a sensory level in the infraclavicular region (T1 to T2 dermatomes) localize the lesion to T1. Preserved biceps (C5 to C6) and triceps (C7) reflexes rule out the higher cervical levels; a T3 or T5 lesion would spare the hands.
54. 33-year-old man with BMI 46 and exertional dyspnea; clear lungs, normal oxygen saturation; choose the PFT pattern. Answer: D, FEV1 84%, FVC 78%, TLC 78%, DLCO 92%. Severe obesity produces a mild extrapulmonary restrictive pattern: proportionally reduced FEV1 and FVC (preserved ratio), modestly reduced total lung capacity, and a normal diffusing capacity because the lung parenchyma itself is healthy. Option A is severe obstruction with reduced DLCO (emphysema), B is severe intrinsic restriction with low DLCO (fibrosis), C is mild obstruction, and E is normal.
55. 67-year-old woman, 16 years postmenopausal, with decreased libido. Answer: C, decreased vaginal rugation. Long-standing estrogen deficiency causes genitourinary atrophy: thin, pale, smooth vaginal mucosa with loss of rugae and dryness, which contributes to dyspareunia and decreased desire. Palpable ovaries in a postmenopausal woman would be abnormal and suspicious; an 8-cm uterus would be enlarged for her age; vaginal wall prolapse is not suggested by the history.
56. 47-year-old woman with 35 years of type 1 diabetes and an A1c of 12% who apologizes for it. Answer: E, “What is your understanding of what your hemoglobin A1c should be?” The best initial response explores the patient’s understanding and goals in a nonjudgmental way before problem-solving. A, C and D jump to specific causes; B is punitive and shuts the conversation down.
57. Finasteride and prostate cancer study enlarged from 500 to 1500 patients. Answer: D, less chance of type II error. Increasing sample size increases statistical power, which is 1 minus β; a larger study is less likely to miss a true effect. The type I error rate is set by the chosen α and does not change with sample size.
58. 56-year-old woman with recurrent UTIs, left flank pain and left hydronephrosis on coronal MRI. Answer: D, ureteropelvic junction. The image shows a dilated left renal pelvis and calyces with a normal-caliber ureter below, which means the obstruction is at the junction between the pelvis and the ureter. If the ureter were dilated all the way down, the block would be at the ureterovesical junction or bladder neck; a mid-ureteral obstruction would show dilatation of the upper ureter. Congenital UPJ obstruction (a crossing vessel or an adynamic segment) presents in adults exactly like this, with intermittent flank pain and infections.
59. 13-year-old boy with Mycobacterium avium complex osteomyelitis and septic arthritis, HIV negative. Answer: E, dysfunctional interferon-γ receptors. Disseminated or invasive infection with nontuberculous mycobacteria in an HIV-negative child indicates Mendelian susceptibility to mycobacterial disease, most often a defect in the IL-12/IFN-γ axis (IFN-γ receptor or IL-12 receptor). Terminal complement deficiency predisposes to Neisseria; abnormal neutrophil granules (Chédiak-Higashi) and hypogammaglobulinemia predispose to pyogenic bacteria; CD8 counts are not the relevant defect.
60. 53-year-old woman with a slowly enlarging subcutaneous chest-wall nodule at the site of a lesion removed three years ago; photomicrographs. Answer: G, myofibroblasts. The sections show a dermal and subcutaneous nodule made of thick, glassy, haphazardly arranged collagen bundles with scattered spindle cells, which is a keloid, an exuberant scar that grows beyond the original wound and recurs after excision. The cells that lay down that collagen are myofibroblasts, the contractile fibroblast-like cells of wound healing. Melanocytic, mast-cell, macrophage, mesothelial, myeloblastic and myocyte lesions do not produce a hypocellular hyalinized collagen mass at a surgical site.
Block 4: Items 61–80
61. 36-year-old woman with hypertension on lisinopril, unexpectedly pregnant at 24 weeks; oligohydramnios, fetal hypocalvaria and small bladder. Answer: C, fetal renal hemodynamics. ACE inhibitors cross the placenta and block fetal angiotensin II, which the fetal kidney depends on to maintain glomerular filtration. The result is fetal renal failure, oligohydramnios and the downstream deformations (skull hypoplasia, limb contractures, pulmonary hypoplasia). The lung findings are secondary to the oligohydramnios, not to a direct effect on lung development.
62. 64-year-old woman who died 30 minutes after sudden respiratory distress; autopsy lung photomicrograph. Answer: C, massive myocardial infarction. The section shows alveoli filled with homogeneous pink proteinaceous fluid and engorged, congested capillaries, which is acute pulmonary edema, and sudden respiratory distress with death within half an hour in a 64-year-old is acute left ventricular failure from a massive infarction (flash pulmonary edema). Asthma would show mucus plugs, thickened basement membranes and eosinophils; bronchopneumonia would show neutrophils in bronchioles and alveoli; viral pneumonia would show interstitial lymphocytes. Option D is a distractor on two counts: pulmonary emboli lodge in pulmonary arteries, not bronchial arteries, and an embolus does not produce this histology.
63. 78-year-old man with a mechanical valve on warfarin whose INR stays at 1.1 despite a doubled dose, one week after starting rifampin and ciprofloxacin. Answer: E, induction of cytochrome enzymes. Rifampin is one of the most potent CYP inducers (CYP2C9 and CYP3A4), accelerating warfarin metabolism and abolishing its effect. Ciprofloxacin, alcohol and decreased protein binding would all raise the INR; eating more vegetables (vitamin K) lowers the INR but not to this degree in four days; gut-flora eradication reduces vitamin K synthesis and would raise the INR.
64. 80-year-old woman with progressive central vision loss; dilated fundus examination shown. Answer: A, age. Bilateral loss of reading and driving vision in an octogenarian with a fundus photograph is age-related macular degeneration, and age is the strongest risk factor by a wide margin. Smoking is the next most important modifiable factor (she never smoked). Hypertension and alcohol are minor contributors; her family history is of glaucoma and diabetes, not macular degeneration; and AMD is actually less common in Black patients than in White patients.
65. 4-year-old boy three weeks into ALL induction with fever and gram-negative bacteremia. Answer: E, neutropenia. Cytotoxic induction chemotherapy ablates the marrow, and gram-negative bacteremia from gut translocation is the signature infection of chemotherapy-induced neutropenia (gum ulcers are another clue). T-cell dysfunction from steroids predisposes to Pneumocystis and fungi over a longer course; hypogammaglobulinemia predisposes to encapsulated bacteria; complement deficiency predisposes to Neisseria.
66. Randomized trial of two cesarean wound closures: infection in 12/1000 with A and 18/1000 with B. Answer: A, (18/1000) − (12/1000). Absolute risk reduction is simply the difference in event rates between the two arms. The 85% figure describes the proportion of eligible patients enrolled and has no place in the calculation; option E is the relative risk reduction.
67. 67-year-old man with gum bleeding, petechiae, pneumonia; WBC 24,500 with 50% monocytes, platelets 18,000. Answer: B, acute myelogenous leukemia. Acute onset of cytopenias with bleeding, a high white count dominated by monocytoid cells and (on the smear) blasts, in an older smoker, is AML; gingival involvement and the monocytic predominance suggest the monocytic subtype. CLL would show mature lymphocytes and a chronic course; CML shows a left-shifted granulocytic series with basophilia; ALL is a disease of children and shows lymphoblasts.
68. 45-year-old man with an MI, tendon xanthomas, total cholesterol 410 and a family history of early MI. Answer: D, LDL receptor. Familial hypercholesterolemia is an autosomal dominant defect in the LDL receptor (or less commonly in apoB-100 or gain-of-function PCSK9), producing isolated severe LDL elevation, tendon xanthomas and premature coronary disease. Lipoprotein lipase and apoC-II deficiency produce chylomicronemia with very high triglycerides; apoB-48 is a chylomicron protein; HMG-CoA reductase deficiency would lower cholesterol.
69. 5-year-old boy who was never dry at night, with normal daytime continence and examination. Answer: C, delayed maturation of detrusor and sphincter control. Primary monosymptomatic nocturnal enuresis in a healthy child under about 7 is a normal developmental variant and needs no imaging or urodynamics. Reflux, ectopic ureter and neurologic lesions produce daytime symptoms, infections or abnormal findings; recurrent infection would show on urinalysis.
70. 5-year-old boy with painful hard stools, a bloody stool, and 1 cm of red mucosa protruding from the anus. Answer: A, constipation. Straining against hard, infrequent stools is the usual cause of minor rectal mucosal prolapse and streaky rectal bleeding in children, and the history here is textbook constipation. Cystic fibrosis is a classic association of rectal prolapse but presents with bulky greasy stools and poor weight gain rather than pebble-like stools. Hirschsprung presents in infancy with failure to pass meconium; intussusception causes colicky pain and currant-jelly stool; hookworm causes anemia.
71. 27-year-old woman whose brother has cystic fibrosis asks about her carrier risk. Answer: D, 2 of 3. Both parents are obligate carriers. Among their children the genotype ratio is 1 AA : 2 Aa : 1 aa, but because she is unaffected the aa possibility is excluded, leaving a 2/3 chance she is a carrier. The classic mistake is to answer 1/2 (the risk for a child of one carrier parent) or 1/4 (the untested prior for being affected).
72. 45-year-old woman with an anterior MI, heart rate 136 and systolic pressure 70; need to raise blood pressure without raising heart rate. Answer: A, α-adrenergic agonist. A pure α1 agonist such as phenylephrine raises blood pressure by vasoconstriction and, through the baroreceptor reflex, tends to slow rather than speed the heart. β agonists increase heart rate and myocardial oxygen demand; α and β blockers lower pressure; dopamine at pressor doses is also chronotropic.
73. 5-year-old girl with recurrent UTIs and a single U-shaped kidney. Answer: D, fusion of the inferior poles of the metanephros during ascent. A horseshoe kidney forms when the lower poles fuse; the fused isthmus then catches under the inferior mesenteric artery and the kidney cannot ascend past L3. The failure of ascent is a consequence, not the primary event. Malrotation and ureteric bud defects produce other anomalies (duplication, agenesis), not fusion.
74. 16-year-old boy with a scrotal “pimple” worried about a sexually transmitted infection. Answer: C, “I’m glad you came in today and told me about this.” The first move with an anxious adolescent is to affirm the decision to seek care and build trust; the sexual history (A, D, E) follows. Involving his mother (B) undermines confidentiality.
75. 54-year-old overweight woman with fasting glucose 102 and two parents with type 2 diabetes. Answer: D, increased fasting insulin concentration. Central adiposity produces insulin resistance, and the pancreas compensates with hyperinsulinemia; mildly impaired fasting glucose is the first crack in that compensation. Leptin is increased (not decreased) in obesity; estrone rises with aromatization in adipose tissue; growth hormone is lower; TSH is not characteristically altered.
76. 17-year-old boy with recurrent episodes of generalized weakness after football practice and carbohydrate-heavy meals, resolving in hours. Answer: D, potassium. Episodic flaccid weakness after exercise or a carbohydrate load with normal interval labs is hypokalemic periodic paralysis, a channelopathy (CACNA1S or SCN4A) in which insulin and catecholamine surges drive potassium into muscle. Serum potassium is low only during attacks, which is why the interval panels are normal.
77. 26-year-old man with polyuria and thirst, urine osmolality 50 that normalizes after vasopressin. Answer: F, supraoptic nucleus. Dilute urine that concentrates in response to exogenous ADH means the kidney works and the problem is deficient ADH production, central diabetes insipidus. ADH is synthesized in the supraoptic and paraventricular hypothalamic nuclei and released from the posterior pituitary. The anterior pituitary and hypophyseal portal system handle anterior pituitary hormones; the loop of Henle and glomerulus are nephron components that are functioning here.
78. 25-year-old man with a painless firm testicular mass; round cells with clear cytoplasm and central nuclei. Answer: B, seminoma. Sheets of large uniform cells with clear (glycogen-rich) cytoplasm, central nuclei and a lymphocytic infiltrate (“fried-egg” cells) are classic seminoma, the most common testicular germ cell tumor. Embryonal carcinoma is pleomorphic and hemorrhagic; yolk sac tumor shows Schiller-Duval bodies; teratoma has multiple tissue types; Sertoli cell tumors form tubules.
79. 2-week-old boy whose mother drank heavily throughout pregnancy. Answer: D, short palpebral fissures. The cardinal facial features of fetal alcohol syndrome are short palpebral fissures, a smooth philtrum and a thin upper lip, with microcephaly and growth restriction. Limb hypoplasia suggests thalidomide or vascular disruption; neck webbing suggests Turner or Noonan syndrome; hypospadias and spasticity are not specific features.
80. 25-year-old woman three months postpartum with palpitations, heat intolerance, a nontender goiter, undetectable TSH and no exophthalmos. Answer: D, lymphocytic infiltration of the thyroid. Thyrotoxicosis in the first six months after delivery, with a painless goiter and no ophthalmopathy or dermopathy, is postpartum thyroiditis, an autoimmune lymphocytic thyroiditis in which stored hormone leaks from a damaged gland (low radioiodine uptake). Graves disease (TSH receptor antibodies) can also flare postpartum but is usually marked by eye findings and high uptake. Activating TSH receptor mutations cause toxic adenomas; thyroglobulin is a marker, not a mechanism.
Block 5: Items 81–100
81. Screening test positive in 250/1000 women with cancer and 100/1000 without; applied to 100,000 women with prevalence 80 per 100,000. Answer: D, 9,992. Specificity is 900/1000 = 90%, so the false-positive rate is 10%. Of 100,000 women, 80 have cancer and 99,920 do not; 10% of 99,920 is 9,992 false positives. Option A (20) is the number of true positives (25% sensitivity × 80); option B is the number of cases; E adds true and false positives together.
82. 73-year-old man walking into doorframes on his left; left lower quadrantanopia; extinguishes left-sided stimuli on double simultaneous stimulation. Answer: E, right parietal. Hemispatial neglect (sensory extinction) with a contralateral inferior quadrantanopia localizes to the right parietal lobe, through which the superior optic radiations pass. A temporal lesion would give a superior quadrantanopia (Meyer loop); frontal lesions do not cause visual field cuts or neglect of this type; the left-sided deficits mean the lesion is on the right.
83. Newborn with hypertelorism, micrognathia, interrupted aortic arch and hypocalcemic tetany on day 3. Answer: E, 22. Conotruncal cardiac defect plus hypocalcemia (absent parathyroids) plus facial dysmorphism is DiGeorge syndrome, a 22q11.2 microdeletion affecting third and fourth pharyngeal pouch derivatives, with T-cell deficiency from thymic aplasia to follow. Trisomies 13, 18 and 21 have distinct phenotypes without this triad.
84. 75-year-old man with alcohol use disorder, BMI 17, palpitations and lightheadedness; ECG shown. Answer: E, right atrium. The strip shows continuous sawtooth atrial activity with no normal P waves and narrow QRS complexes conducted irregularly: atrial flutter with variable AV block (atrial fibrillation, its cousin, is the other alcohol-triggered atrial arrhythmia). Typical flutter is a macro-reentrant circuit running around the tricuspid annulus in the right atrium, which is why the right atrium is the origin of the abnormal activity rather than the sinoatrial node (overridden), the AV node (merely conducting the atrial impulses), or the His-Purkinje system and ventricle (which would produce wide complexes). Alcohol and the electrolyte depletion of malnutrition are the setup.
85. 52-year-old woman with hematemesis and hypotension, taking oral ibuprofen and topical diclofenac for arthritis. Answer: D, inhibition of cyclooxygenase-1. NSAIDs cause gastric ulceration mainly by blocking COX-1-derived prostaglandins (PGE2, PGI2) that maintain mucosal blood flow, mucus and bicarbonate secretion; the effect is systemic, which is why even parenteral or topical NSAIDs carry risk. Prostaglandin production is decreased, not increased; direct topical injury is a minor contributor compared with the systemic prostaglandin loss; nitric oxide is protective.
86. Term newborn after oligohydramnios: small for gestational age, feet turned down and inward, otherwise normal. Answer: A, deformation. Clubfoot caused by uterine constraint in oligohydramnios is a deformation: a normally formed structure altered by mechanical force. A malformation is an intrinsic error of development, a disruption is destruction of a normally forming structure (for example by amniotic bands), and a dysplasia is abnormal tissue organization.
87. 19-year-old soldier with a right-chest stab wound, tachypnea, hypoxia and the trachea deviated to the left. Answer: B, decreased fremitus, hyperresonant percussion, decreased breath sounds. Contralateral tracheal deviation after penetrating chest trauma is tension pneumothorax: air in the pleural space transmits no vibration (decreased fremitus), is hyperresonant, and muffles breath sounds. Dullness with decreased fremitus and sounds would be hemothorax; increased fremitus with dullness and bronchial breath sounds is consolidation.
88. 22-year-old man ten days after losing 20% of his blood volume in a crash. Answer: D, polychromasia. Within a week of acute blood loss the marrow responds with reticulocytosis, and reticulocytes appear on a Wright-stained smear as larger, bluish-gray (polychromatophilic) cells. Hypochromia and microcytosis take months of iron deficiency to develop; spherocytes indicate hemolysis; Heinz bodies indicate oxidative damage; siderotic granules indicate iron-loading states.
89. 53-year-old man with a year-long dry scaly rash, 15-kg weight loss, BMI 17 and floating bulky stools. Answer: B, vitamin A. Steatorrhea causes malabsorption of fat-soluble vitamins, and vitamin A deficiency produces dry, scaly skin with follicular hyperkeratosis (along with night blindness and xerophthalmia). Zinc deficiency causes an acral and perioral erosive dermatitis with alopecia and diarrhea; vitamin C deficiency causes perifollicular hemorrhage and gum bleeding; B12 deficiency causes neuropathy and megaloblastic anemia; magnesium deficiency causes neuromuscular irritability.
90. 22-year-old woman with sickle cell disease and painless hematuria; CT suggests papillary necrosis. Answer: C, oxygen tension decreased, osmolality increased. The renal medulla is the perfect environment to provoke sickling: it is relatively hypoxic (low oxygen tension from countercurrent exchange) and hypertonic (high osmolality draws water out of red cells, concentrating hemoglobin S). The result is microvascular occlusion of the vasa recta, papillary infarction and hematuria.
91. 34-year-old woman with acute appendicitis; photomicrograph of the appendix. Answer: C, leukotriene. The microscopic hallmark of acute appendicitis is a transmural neutrophilic infiltrate, and leukotriene B4 is the major lipid chemoattractant that recruits neutrophils. Histamine and bradykinin mediate vasodilation and pain; thromboxane promotes platelet aggregation; lipoxins are anti-inflammatory and signal resolution.
92. 15-year-old boy, previously well, with hallucinations and paranoid fears one week after a school shooting; brought in with knives. Answer: B, brief psychotic disorder. Sudden psychotic symptoms lasting less than a month after a marked stressor in a previously healthy adolescent, with negative toxicology, is brief psychotic disorder. Schizophrenia requires six months; PTSD does not include frank hallucinations and delusions of this kind; adjustment disorder lacks psychosis; schizotypal personality is a lifelong pattern.
93. 10-year-old camper in summer with headache, photophobia and mild meningismus; CSF lymphocytes 43/mm³, glucose 65, protein 70. Answer: B, enterovirus. Summer outbreaks of aseptic meningitis among children in close quarters, with a lymphocytic pleocytosis, normal glucose and mildly elevated protein, are enteroviral (echovirus, coxsackievirus). Bacterial causes give neutrophils and low glucose; HSV meningitis is usually sporadic and encephalitic; adenovirus causes respiratory and conjunctival disease.
94. 85-year-old woman with BMI 15 and progressive dyspnea: FEV1 and FVC both 26%, ratio 1.0, TLC 54%, RV 120%, DLCO 100%, limited diaphragmatic excursion. Answer: B, decreased respiratory muscle strength. A restrictive pattern with a normal DLCO, elevated residual volume and poor diaphragmatic excursion means the lungs are intrinsically normal and the bellows are weak: the patient cannot inhale fully (low TLC) or exhale fully (high RV), and chronic hypoventilation produces the hypercapnia. Parenchymal fibrosis (decreased compliance) would lower DLCO; surfactant and surface-tension options describe neonatal disease; increased compliance and mucus describe obstructive disease.
95. 25-year-old woman with severe pain on the first day of each menstrual period. Answer: C, inhibition of prostaglandin synthesis. Primary dysmenorrhea is driven by endometrial prostaglandin F2α and E2 release, which cause uterine hypercontractility and ischemia; first-line therapy is an NSAID started at or just before onset. Combined oral contraceptives are second-line and work by suppressing ovulation and thinning the endometrium, not by blocking estrogen synthesis.
96. 60-year-old marathon runner who collapsed in 90°F heat; hypotensive, dry mucous membranes, poor skin turgor. Answer: D, increased aquaporin expression. Hypovolemia from sweating triggers ADH release, which inserts aquaporin-2 channels into collecting-duct principal cells to maximize water reabsorption, raising urine osmolality. Renin rises, not falls; GFR falls with hypotension; ADH receptors are not downregulated acutely; albumin reabsorption is unrelated.
97. 19-year-old college freshman with fever, malaise and parotid swelling. Answer: D, mumps virus. Parotitis in an adolescent or young adult in a congregate setting is mumps, a paramyxovirus still seen in outbreaks among under- or incompletely vaccinated college students; orchitis and aseptic meningitis are the complications to warn about. EBV causes pharyngitis and cervical adenopathy rather than parotid swelling; measles and rubella produce characteristic rashes; hepatitis B does not cause parotitis.
98. 64-year-old man with unresectable metastatic melanoma; which molecule to block with an antibody. Answer: D, CTLA4. CTLA-4 is an inhibitory checkpoint receptor on T cells; blocking it (ipilimumab) releases the brake on antitumor immunity and was the first checkpoint inhibitor approved for melanoma. Blocking B7 or CD28 would prevent T-cell costimulation and suppress the response; CD40 and Fcγ receptors are not checkpoint targets.
99. 78-year-old Mandarin-speaking woman facing a biopsy; husband insists on interpreting, hospital interpreter unavailable until morning. Answer: D, use a telephone interpreter service. Patients are entitled to a trained medical interpreter, and family members should not interpret for consent or diagnostic discussions because of accuracy, bias and confidentiality concerns. A telephone or video service meets the standard immediately; delaying all communication until morning is unnecessary; an ethics consult is not needed for a routine access problem.
100. 5-month-old unvaccinated boy with ten days of paroxysmal coughing spells ending in a gasp and vomiting, well between spells. Answer: C, macrolide. Paroxysms of cough followed by an inspiratory whoop and post-tussive emesis in an unimmunized infant is pertussis, and a macrolide (azithromycin) is the treatment of choice; it shortens contagiousness and, given early, blunts the course, and it is also used for household prophylaxis. Beta-lactams and fluoroquinolones have no role against Bordetella pertussis in infants; trimethoprim-sulfamethoxazole is a second-line alternative for older children but is avoided under two months of age.
Block 6: Items 101–119
101. 25-year-old amphetamine user with four hours of restlessness, tremor, tachycardia and hypertension. Answer: F, increased release of biogenic amines. Amphetamines are indirect sympathomimetics: they enter the presynaptic terminal through the monoamine transporter and reverse it, forcing release of norepinephrine and dopamine into the synapse (and they weakly inhibit MAO as a secondary effect). The clinical picture is the resulting excess of synaptic catecholamines. Decreased MAO activity alone describes MAO inhibitors; altered presynaptic receptor activation does not produce this syndrome.
102. 19-year-old, 196 cm tall, with sudden severe upper back pain, hypotension, weak carotid pulses and a new diastolic murmur. Answer: E, stretched aortic anulus. A very tall young man with tearing back pain and shock has an acute aortic dissection from a connective-tissue disorder such as Marfan syndrome; when the dissection extends proximally it dilates the aortic root and separates the valve commissures, producing acute aortic regurgitation, the diastolic murmur heard here. Papillary muscle rupture causes a systolic murmur of mitral regurgitation; mitral stenosis is a chronic rheumatic lesion; an atrial septal defect gives a systolic flow murmur; a perforated tricuspid valve is not a feature of dissection.
103. 78-year-old woman with lung cancer and prior weakness who has profound residual block after pancuronium; EPP reduced to 3 mV, MEPP and acetylcholine response normal. Answer: E, myasthenic (Lambert-Eaton) syndrome. A small end-plate potential with normal miniature end-plate potentials and a normal response to applied acetylcholine means the postsynaptic receptors work fine; the problem is that each nerve impulse releases fewer vesicles. That is a presynaptic defect, which in a patient with bronchogenic carcinoma is Lambert-Eaton syndrome (antibodies against presynaptic voltage-gated calcium channels). Myasthenia gravis and a residual pancuronium effect are postsynaptic and would reduce the MEPP and the acetylcholine response; cholinergic crisis produces depolarizing block with excess acetylcholine, not reduced release.
104. 28-year-old asymptomatic man with familial hypercalcemia: calcium 11.3, PTH 112, urine calcium 42 mg/day, fractional excretion under 1%. Answer: C, calcium-sensing receptor. Mild hypercalcemia with an inappropriately normal-to-high PTH and very low urinary calcium in multiple family members is familial hypocalciuric hypercalcemia, an autosomal dominant loss-of-function mutation in the calcium-sensing receptor that resets the parathyroid set point and increases renal calcium reabsorption. Primary hyperparathyroidism would show hypercalciuria and symptoms; the other receptors listed do not produce this pattern. Recognizing FHH matters because parathyroidectomy does not help.
105. 32-year-old woman with stage IV breast cancer and recurrent malignant effusions who says she is “done” with the hospital. Answer: C, “I’d like to hear about your goals for the time you have remaining.” A patient with incurable disease declining further burdensome procedures is opening a goals-of-care conversation, and the physician’s job is to explore those goals, not to label the decision as giving up (A), guilt her with her family (B), presume depression (D) or offer a platitude (E). Depression screening may follow, but it is not the first response to a reasoned statement of preference.
106. Vigorous newborn with a vagina and a phallic structure with the urethra at its base; karyotype 46,XX. Answer: C, maternal androgen exposure. A virilized 46,XX newborn has been exposed to androgens in utero, and among the options the source is maternal: an androgen-secreting ovarian or adrenal tumor, or exogenous androgenic drugs. (Congenital adrenal hyperplasia from 21-hydroxylase deficiency is the most common cause overall, but it is not offered; option A describes a deficiency of 17-hydroxyprogesterone, which is the opposite of CAH, where it accumulates.) SRY presence would make a 46,XX testicular DSD with testes, not this picture; müllerian-inhibiting substance excess would eliminate the vagina and uterus; 5α-reductase deficiency undervirilizes 46,XY infants.
107. 37-year-old dishwasher with three weeks of itchy, burning, scaling feet; photograph of maceration between the toes. Answer: D, squalene monooxygenase. Interdigital scaling and maceration in chronically wet feet is tinea pedis, a dermatophyte infection, and the first-line topical and oral agent class for dermatophytes is the allylamines (terbinafine), which inhibit squalene epoxidase (squalene monooxygenase) and block ergosterol synthesis upstream of the azole target. β-glucan synthase inhibitors are echinocandins for Candida and Aspergillus; thymidylate synthase inhibition is flucytosine’s mechanism; chitin synthase and phospholipase D are not targets of marketed antifungals.
108. 27-year-old woman with diplopia: the left eye does not adduct on rightward gaze, leftward gaze is normal. Answer: B, left medial longitudinal fasciculus. Failure of adduction of one eye on horizontal gaze with normal abduction of the other eye is internuclear ophthalmoplegia, caused by a lesion in the MLF on the side of the eye that cannot adduct (the MLF carries the signal from the contralateral abducens nucleus to the ipsilateral oculomotor nucleus). Convergence is preserved, which distinguishes it from a third-nerve palsy. In a young woman this is multiple sclerosis until proven otherwise. An abducens lesion would impair abduction, not adduction.
109. 50-year-old man with two months of headache and exertional dyspnea, blood pressure 180/105 on a thiazide. Answer: A, arteriovenous nicking. Chronic hypertension thickens retinal arteriolar walls, and where a stiffened arteriole crosses a vein it compresses it, producing arteriovenous nicking (along with copper or silver wiring, and in more severe disease flame hemorrhages, cotton-wool spots and papilledema). Tractional detachment and posterior subcapsular cataracts belong to diabetes and steroids; optic neuritis is a demyelinating or inflammatory process; uveal melanocytes are normal.
110. 16-day-old boy born at 36 weeks with two days of jaundice and dark urine; total bilirubin 20 with direct 14, elevated GGT and alkaline phosphatase. Answer: D, obstruction of bile flow. Conjugated (direct) hyperbilirubinemia in the first weeks of life with dark urine and cholestatic enzymes (GGT and alkaline phosphatase elevated out of proportion to the transaminases) is biliary obstruction, and in a neonate the diagnosis that must be made urgently is biliary atresia, because the Kasai portoenterostomy works best before 60 days of age. UDP-glucuronosyltransferase deficiency (Crigler-Najjar, Gilbert) and hemolysis cause unconjugated hyperbilirubinemia; a canalicular MRP2 defect (Dubin-Johnson) causes mild conjugated hyperbilirubinemia with normal enzymes, not this cholestatic picture.
111. 21-year-old woman with blood pressure 220/100, a faint abdominal bruit, LVH and normal renal function. Answer: B, fibromuscular dysplasia. Severe hypertension with a renal-artery bruit in a young woman is renovascular hypertension from fibromuscular dysplasia, the noninflammatory, nonatherosclerotic arteriopathy that produces the “string of beads” appearance on angiography and is correctable with angioplasty. Atherosclerotic renal artery stenosis is a disease of older smokers; mid-aortic syndrome and extrinsic compression are rare; spontaneous dissection presents acutely with flank pain.
112. Leukocyte counts in 100 people: mean 7,500, standard deviation 1,000, normally distributed; which range contains 50% of individuals. Answer: D, below 7,500/mm³. In a normal distribution the mean equals the median, so exactly half of the population lies below it. The range 6,500 to 8,500 (mean ± 1 SD) holds about 68%; 5,500 to 9,500 (± 2 SD) holds about 95%; outside ± 1 SD is about 32%; above 9,500 is about 2.5%.
113. 10-year-old boy and his brother with mucosal bleeding; normal platelet count and morphology, normal ristocetin response, no aggregation with thrombin, normal PT and PTT. Answer: C, glycoprotein IIb-IIIa. Normal platelet numbers and shape with failure of aggregation to physiologic agonists (thrombin, ADP, collagen) but a normal ristocetin response is Glanzmann thrombasthenia, an autosomal recessive deficiency of the GpIIb/IIIa fibrinogen receptor that platelets need to bind one another. Bernard-Soulier (GpIb) and von Willebrand disease fail the ristocetin test; storage pool disease gives a milder, mixed defect; factor VII and fibrinogen deficiencies prolong the coagulation tests.
114. 36-year-old Icelandic woman with breast cancer and a BRCA2 999del5 mutation that accounts for 9% of Icelandic breast cancers. Answer: C, geographically isolated population. A single specific mutation reaching high frequency in one population is a founder effect: Iceland was settled by a small group and remained isolated, so a mutation carried by one early settler spread through the descendants. A bottleneck caused by breast cancer deaths would select against the mutation, not for it; heterozygote advantage has not been shown for BRCA2; random mating in a large population would dilute a single mutation.
115. 65-year-old woman with syncope, S3 and S4, and a pedunculated intracardiac mass; photomicrograph of stellate cells in a myxoid stroma. Answer: B, left atrium. The histology (scattered stellate and spindle cells in abundant loose mucopolysaccharide matrix) is a cardiac myxoma, the most common primary cardiac tumor in adults, and about three-quarters arise from the left atrium, typically on a stalk from the fossa ovalis. The pedunculated mass intermittently obstructs the mitral valve, causing positional syncope, a “tumor plop” and mitral-stenosis-like physiology. The other chambers are far less common sites.
116. 45-year-old woman receiving a kidney transplant whose graft becomes swollen and hemorrhagic within ten minutes of reperfusion. Answer: D, preformed antibodies in the recipient. Graft failure within minutes of restoring blood flow is hyperacute rejection, mediated by preexisting recipient antibodies against donor ABO or HLA antigens (from prior transfusions, pregnancies or transplants) that bind the graft endothelium, activate complement and cause thrombosis and hemorrhage. T-cell-mediated acute rejection takes days to weeks; chronic rejection takes months; “donor” antibodies and perfusate hypersensitivity are distractors.
117. 65-year-old man with multiple myeloma on a bisphosphonate who sustains an atraumatic midshaft femoral fracture. Answer: A, bone remodeling. A transverse midshaft femoral fracture after minimal or no trauma in a patient on prolonged bisphosphonate therapy is an atypical femoral fracture, a consequence of oversuppressed bone turnover: bisphosphonates inhibit osteoclasts so completely that microdamage is not repaired and the bone becomes brittle. Myeloma itself causes lytic lesions, but a diaphyseal atraumatic fracture on this drug points to the remodeling defect. Serum calcium, vitamin D and PTH abnormalities are not the mechanism, and osteoblast generation is not what bisphosphonates target.
118. 45-year-old man who twisted his foot, cannot bear weight, with tenderness just distal to the lateral malleolus. Answer: C, inversion. Tenderness below the lateral malleolus after a twisting injury is a lateral ankle sprain of the anterior talofibular ligament, the most common ankle injury, and it results from inversion of a plantar-flexed foot. Eversion injures the medial (deltoid) ligament; pure dorsiflexion and plantar flexion are not the usual mechanisms of ligamentous ankle injury.
119. 3-year-old boy with sudden coughing and gagging while eating candy, decreased breath sounds on the left, saturation 93%; chest x-ray shown. Answer: E, ventilation-perfusion mismatch. The film shows a hyperlucent, hyperinflated left lung, the classic air-trapping picture of a foreign body acting as a check valve in the left mainstem bronchus. Those alveoli are perfused but poorly ventilated, so blood passes through them without being fully oxygenated: a low V/Q region, which is why his saturation is reduced. There is no diffusion barrier, no cardiac shunt, and the chest wall is normal; a complete obstruction with atelectasis would move the physiology toward an intrapulmonary shunt, but the hyperinflation here means air is still moving in.
What to do with your misses
Sort your incorrects into two piles. The first is knowledge gaps: you did not know the fact (the vector for Chagas disease, the mechanism of fludrocortisone), and a flashcard fixes it. The second is reasoning errors: you knew the facts but misread the vignette, anchored on the first finding, or picked the “most dramatic” answer over the “most likely” one. Those are the misses that cost points on the real exam, and they only improve with more vignettes on the same topic under time. The Free 120 gives you one pass at each concept; when a topic shows up twice in your second pile, you need ten more questions on it, not a re-read. If your question bank is exhausted on that topic, a grounded generator such as Neural Consult’s Question Generator can build board-style items by topic and difficulty with explanations (it scored a perfect score on this exact Step 1 sample set, along with the Step 2 CK and Step 3 sets), and the Flashcard Hub turns the first pile into spaced-repetition cards you can export to Anki. For a complete dedicated-period plan built around UWorld, NBME self-assessments and this kind of targeted practice, see How to Build a Step 1 Dedicated Study Schedule with AI.
The bottom line
The Free 120 is the closest you can get to the real Step 1 without sitting it, and the official answer key tells you what, not why. Use this page for the why, be honest about which misses were knowledge and which were reasoning, and spend the final week on timed mixed blocks rather than new content. If you want more practice on the topics this set exposed, try Neural Consult. Good luck on test day.
This key reflects our reading of the current official sample items and is provided for study purposes. The questions and the official answer key are the property of the Federation of State Medical Boards and the National Board of Medical Examiners; download them directly from usmle.org.