If you are preparing for USMLE Step 1 questions , the official NBME “Free 120” sample test questions are the closest free preview you will get of the real exam interface, question style, and difficulty. The catch is that the official PDF gives you only an answer key, a single letter per item, with no reasoning. This explanation guide from IMG Helping Hands Corp fixes that. Below you will find a complete, high-yield walkthrough of all 119 Free 120 USMLE Step 1 answers and explanations, plus one bonus item (Question 120), each explained the way a strong tutor would explain it at the whiteboard.
For every question we do four things:
The explanations are organized to mirror the exam exactly: Block 1 through Block 6, so you can read alongside the official PDF.
Whether you are an international medical graduate (IMG) building your Step 1 free 120 strategy, a first-time test-taker doing a final content pass, or a repeat examiner closing knowledge gaps, this Free 120 answer NBME explanation guide is built to be your single, clean reference.
Work a block, check your answers here, and lock in the concept before moving on.
Download the official Free 120 (Step 1 Sample Test Questions):
• Sample test questions page: usmle.org/exam-resources/step-1-materials/step-1-sample-test-questions
• Direct PDF: Step_1_Sample_Items.pdf (free, official, and the exact set explained here).
Cardiology, immunology, neurology, behavioral science, and the high-yield basics.
The clue: Sudden dyspnea + hypoxia after a long flight + a swollen, tender calf = a DVT that has thrown a pulmonary embolism (PE).
Correct answer B Factor V Leiden mutation
Tachycardia, tachypnea, an oxygen saturation of 89% with clear lungs, and a unilaterally swollen calf are the classic fingerprints of venous thromboembolism. Long-haul travel provides venous stasis; the question is asking what made this young woman hypercoagulable in the first place.
Factor V Leiden is the single most common inherited thrombophilia in people of European descent. A point mutation makes factor Va resistant to cleavage by activated protein C (“APC resistance”), so the clot brake fails and thrombin generation continues unchecked. It is by far the most likely heritable cause of an unprovoked DVT/PE in a young patient.
Why the other options are wrong
Memory hook Most common inherited hypercoagulable state = Factor V Leiden = APC resistance (factor Va cannot be inactivated).
The clue: Six years of symmetric hand stiffness and pain with deforming joint changes in a middle-aged woman = rheumatoid arthritis (RA).
Correct answer A Anti-citrullinated peptide antibody (anti-CCP / ACPA)
RA is a chronic autoimmune synovitis that favours the small joints of the hands and feet, producing morning stiffness lasting more than 30 minutes and, over years, ulnar deviation, swan-neck, and boutonnière deformities, the kind of deformity shown in the photograph.
Anti-citrullinated peptide antibodies (ACPA, detected as anti-CCP) are the most specific serologic marker for RA. They appear early, predict more aggressive erosive disease, and confirm the diagnosis when the clinical picture is suggestive. Rheumatoid factor is sensitive but far less specific.
Memory hook Anti-CCP = SPECIFIC for RA (and prognostic). Rheumatoid factor = sensitive but not specific.
The clue: Failure of the left eye to abduct on left gaze + right hemiparesis + right loss of vibration/2-point = a lesion of the caudal, ventromedial pons.
Correct answer B Asymmetric smile
The shaded ventromedial/ventrolateral caudal pons contains the corticospinal tract and medial lemniscus (giving contralateral right hemiparesis and right dorsal-column sensory loss) plus the exiting fibers of CN VI (failed left eye abduction).
Sitting right beside CN VI in the caudal pons are the fascicles of the facial nerve (CN VII). Damaging them produces an ipsilateral peripheral facial palsy, a drooping, asymmetric smile. This “alternating” pattern (contralateral body, ipsilateral cranial nerve) localises the stroke to a basilar pontine branch.
Why the other options are wrong
Memory hook Caudal pons = CN VI + CN VII neighbours → lateral gaze palsy + peripheral facial palsy (asymmetric smile).
The clue: Two weeks of fever, exudative pharyngitis, GENERALIZED lymphadenopathy, plus pancytopenia and a NEGATIVE monospot.
Correct answer C HIV infection
Bilateral tonsillar exudate with diffuse lymphadenopathy in the neck, axillae and groin looks like infectious mononucleosis, but the negative heterophile (Monospot) antibody test argues against EBV.
The combination of a mono-like illness, generalized lymphadenopathy, and tri-lineage cytopenias (low hemoglobin, leukopenia, thrombocytopenia) is the classic acute retroviral syndrome of primary HIV infection. On Step 1, a mono-like picture with a negative heterophile should trigger the differential of CMV, Toxoplasma, and HIV.
Memory hook Mono symptoms + NEGATIVE heterophile → think CMV, Toxoplasma, HIV.
The clue: Fever + rash + AKI + eosinophilia + WBC casts and urine eosinophils, three weeks into a beta-lactam (oxacillin).
Correct answer C Interstitial inflammatory infiltrate
Acute interstitial nephritis (AIN) is a hypersensitivity reaction to drugs, beta-lactams are textbook offenders. The triad of fever, rash, and eosinophilia, plus AKI with sterile pyuria, WBC casts, and urine eosinophils, is the giveaway.
The lesion is an inflammatory infiltrate of the renal interstitium (lymphocytes and eosinophils), not a glomerular or tubular process. Stopping the drug is the treatment.
Memory hook AIN = Fever + Rash + Eosinophilia + WBC casts; classic culprits: penicillins, NSAIDs, PPIs, sulfa, rifampin.
The clue: Progressive arm weakness + cape-like loss of pain sensation + a central cervical syrinx on MRI.
Correct answer D Trauma
A syrinx is a fluid-filled cavity in the central cord. As it expands it first interrupts the crossing spinothalamic fibers (loss of pain and temperature in a cape distribution) and the anterior horns (lower-motor-neuron weakness and atrophy of the hands), while sparing the dorsal columns (fine touch, vibration) until late.
Syrinx formation is strongly associated with prior spinal cord trauma (and with Chiari malformations). Asking specifically about trauma is the highest-yield additional history.
Memory hook Syringomyelia = cape-like pain/temp loss + LMN hands, dorsal columns spared; ask about TRAUMA / Chiari.
The clue: Intermittent claudication (leg pain with walking, relieved by rest) + cool, hairless, atrophic skin + absent pedal pulses.
Correct answer E Vascular obstruction by lipid-rich plaques
This is classic peripheral artery disease (PAD). The chronic ischemic skin changes and absent posterior tibial/dorsalis pedis pulses point to fixed obstruction of medium and large arteries.
The underlying mechanism is atherosclerosis, progressive luminal narrowing by lipid-rich (atheromatous) plaques. Management centres on risk-factor control (high-intensity statin, BP control, antiplatelet), supervised exercise, and cilostazol for refractory claudication.
Memory hook PAD = atherosclerosis. Claudication + absent pulses + dependent rubor; treat with statin, antiplatelet, exercise ± cilostazol.
The clue: A smoker who is NOT ready to quit: the task is to evoke his own motivation, not to lecture.
Correct answer A “Are there any reasons why you might want to quit smoking?”
Motivational interviewing is patient-centred. With a patient in the pre-contemplation/contemplation stage, open-ended questions that let him voice his own reasons for change are the most effective opener, they build rapport and strengthen intrinsic motivation.
Asking what reasons he might have to quit invites him to argue for change himself, which is exactly the goal.
Memory hook Motivational interviewing = OARS: Open-ended questions, Affirmations, Reflective listening, Summaries.
The clue: Length tracking at the 25th percentile while weight has crossed down below the 5th, weight drops first.
Correct answer B Caloric insufficiency
When caloric intake is inadequate, the body protects linear (bone) growth and brain development at the expense of fat stores, so weight falls before length. A diet of mostly milk-based formula with little solid food is a recipe for inadequate calories.
This pattern, weight percentile falling well below length percentile in an otherwise well child, is nonorganic failure to thrive. Management is dietary (structured meals, calorie-dense foods, limiting excess milk), not an immediate lab workup.
Memory hook Caloric FTT: weight ↓ first, then length. Endocrine (GH/hypothyroid) FTT: length ↓ first.
The clue: Adding a major missing calcium source (yogurt) to a food-frequency questionnaire captures exposure more completely.
Correct answer A Internal validity
If yogurt is omitted, true calcium intake is systematically under-measured, a form of exposure misclassification (information bias). Adding it lets the questionnaire measure what it is supposed to measure.
Accurately capturing the exposure improves internal validity: the degree to which the study’s observed association truly reflects cause and effect within the sample, free of systematic measurement error.
Memory hook Less measurement error → less bias → better INTERNAL validity (truth within the study).
The clue: Asymptomatic Trypanosoma cruzi on a blood-donor screen in a woman from El Salvador.
Correct answer D Reduviid bug
Chagas disease (T. cruzi) is endemic to Central and South America and is transmitted by the reduviid (“kissing”) bug, which feeds at night and defecates near the bite; scratching rubs the infectious feces into the wound or mucosa.
Most patients are asymptomatic for years; chronic disease can produce dilated cardiomyopathy, apical aneurysm, megacolon, and megaesophagus.
Memory hook Chagas = Reduviid/“kissing” bug → cardiomyopathy, megacolon, megaesophagus.
The clue: A patient who keeps returning yet refuses standard therapy, first understand what he actually wants.
Correct answer A “Help me to understand what you are hoping I can do for you today.”
With repeated visits but ongoing refusal of treatment, the most productive first move is open-ended, non-judgmental exploration of the patient’s goals and expectations. This honours autonomy, uncovers hidden agendas or fears, and keeps the therapeutic relationship intact.
Understanding why he keeps coming, and what he hopes to get, lays the groundwork for shared decision-making.
Memory hook Persistent nonadherence → start with open-ended questions about the patient’s own goals.
The clue: Older man with frequency, nocturia, weak stream + a diffusely enlarged, symmetric prostate = benign prostatic hyperplasia (BPH).
Correct answer B α1-Adrenergic antagonism
First-line therapy for rapid symptom relief in BPH is an α1-adrenergic antagonist (tamsulosin, doxazosin). These drugs relax the smooth muscle of the prostatic urethra and bladder neck, lowering dynamic outflow resistance and improving flow within days.
5-α-reductase inhibitors (finasteride) shrink the gland over months by blocking testosterone→DHT conversion, but they work slowly.
Memory hook BPH: “-osins” relax the prostate (fast relief); “-asterides” shrink it (slow).
The clue: Pressured speech, loose associations, no sleep, grandiose delusions AND hallucinations = mania with psychosis.
Correct answer A Bipolar disorder, manic, with psychotic features
The manic core, rapid, hard-to-interrupt speech, loose associations, and a dramatically reduced need for sleep, plus grandiose delusions (married to the president’s twin) and auditory hallucinations defines a manic episode with psychotic features.
Because the psychosis occurs in the context of a prominent mood (manic) episode, the diagnosis is bipolar disorder, not a primary psychotic disorder. Psychosis confined to mood episodes distinguishes it from schizoaffective disorder.
Memory hook Mood episode + psychosis only DURING the episode → mood disorder with psychotic features.
The clue: Both drugs raise gastric pH; the proton-pump inhibitor raises it more and longer than the H2 blocker.
Correct answer B Cimetidine → B, Omeprazole → A
Omeprazole irreversibly blocks the H+/K+-ATPase, the final common pathway of acid secretion, producing the greatest, most sustained rise in pH (curve A).
Cimetidine blocks only the histamine pathway (H2 receptor), leaving gastrin and acetylcholine partially active, so the pH rise is more modest (curve B). Curves that fall over time represent acid stimulants, not suppressants.
Memory hook PPI shuts the final common pathway → highest, longest pH rise. H2 blocker = partial, modest.
The clue: Right-colon cancer that has reached the liver AND the lungs, trace the venous path.
Correct answer B Inferior vena cava
The right colon drains via the superior mesenteric vein into the portal vein and then the liver (first-pass metastasis). To reach the lungs, tumor cells must leave the liver through the hepatic veins into the inferior vena cava, travel to the right heart, and embolise to the pulmonary arteries.
The structure that carries cells from liver to lungs is therefore the inferior vena cava.
Memory hook Right colon → SMV → portal → liver → hepatic veins → IVC → right heart → lungs.
The clue: Intense itching (worse at night) with thin serpiginous burrows in finger webs, waistline, and inner thighs.
Correct answer E Scabies
Sarcoptes scabiei mites tunnel through the superficial epidermis, leaving short, thin, elevated serpiginous tracks, burrows, with a tiny vesicle where the female mite resides. The web spaces, axillae, waist, and inner thighs are favoured sites.
Severe pruritus that worsens at night with this burrow pattern is diagnostic of scabies.
Memory hook Burrows in web spaces + nighttime itch = scabies (treat with permethrin / ivermectin).
The clue: Sickle cell disease + RUQ pain radiating to the shoulder + gallstones on ultrasound.
Correct answer E Overload of unconjugated bilirubin
Chronic extravascular hemolysis in sickle cell disease floods the liver with unconjugated bilirubin. When bilirubin exceeds bile’s solubility, calcium bilirubinate precipitates as black pigment stones, a classic complication of any chronic hemolytic anemia.
So the underlying cause here is an unconjugated bilirubin overload from hemolysis.
Memory hook Chronic hemolysis (SCD) → ↑ unconjugated bilirubin → black PIGMENT gallstones.
The clue: Medullary thyroid carcinoma (parafollicular C cells) + prior pheochromocytoma + parathyroid disease in mother.
Correct answer D Proto-oncogene
A neck mass of parafollicular-cell origin is medullary thyroid carcinoma. Combined with a personal pheochromocytoma and a parathyroid tumor in the mother, the syndrome is MEN2A (medullary thyroid carcinoma, pheochromocytoma, parathyroid hyperplasia).
MEN2A is caused by a germline gain-of-function mutation in the RET proto-oncogene.
Memory hook MEN2A = Medullary thyroid CA + Pheo + Parathyroid (“MPP”), driven by RET proto-oncogene.
The clue: A 6-years old with breast buds, pubic hair, vaginal bleeding AND elevated FSH/LH plus estradiol.
Correct answer A Central activation of neurons
Secondary sexual development before age 8 in a girl is precocious puberty. The key discriminator is the gonadotropins: FSH and LH are elevated alongside estradiol, indicating activation of the hypothalamic-pituitary-gonadal axis, central (GnRH-dependent) precocious puberty.
This reflects premature maturation of hypothalamic GnRH-secreting neurons.
Memory hook High estradiol + HIGH FSH/LH = CENTRAL (GnRH-dependent). High estradiol + LOW FSH/LH = peripheral.
Endocrine, renal, pharmacology, microbiology, and embryology favorites.
The clue: Delayed puberty, tall/eunuchoid habitus, gynecomastia, small firm testes, with HIGH FSH/LH and LOW testosterone.
Correct answer E Nondisjunction of the X chromosome during meiosis
Small testes with primary hypogonadism (low testosterone, high gonadotropins from lost negative feedback), tall stature, long extremities, and gynecomastia describe Klinefelter syndrome.
The cause is meiotic nondisjunction producing a 47,XXY karyotype, the most common cause of primary hypogonadism in males.
Memory hook Klinefelter 47,XXY: tall, small testes, gynecomastia, ↑LH/FSH, ↓testosterone (primary hypogonadism).
The clue: Ambiguous genitalia + hyponatremia + hyperkalemia + hypoglycemia + metabolic acidosis in a newborn = salt-wasting 21-hydroxylase deficiency.
Correct answer B Aldosterone (mineralocorticoid) receptor
21-hydroxylase deficiency (the most common CAH) blocks cortisol and aldosterone synthesis while shunting precursors into androgens. The result is salt-wasting (low Na+, high K+, acidosis), hypoglycemia, and virilization.
Treatment replaces what is missing: a glucocorticoid (which also suppresses ACTH and androgen overproduction) plus a mineralocorticoid: fludrocortisone, acting at the aldosterone receptor.
Memory hook Salt-wasting CAH: replace glucocorticoid + mineralocorticoid (fludrocortisone → aldosterone receptor).
The clue: Advanced CKD with marked uremia (BUN 65), which complication forces urgent dialysis?
Correct answer C Pericardial friction rub
The mnemonic AEIOU lists absolute indications for dialysis: severe Acidosis, Electrolyte disturbance (refractory hyperkalemia), Intoxications, Overload (refractory pulmonary edema), and Uremia (pericarditis or encephalopathy).
A pericardial friction rub signals uremic pericarditis, a life-threatening uremic complication and a definitive indication for immediate hemodialysis.
Memory hook Dialyze now (AEIOU): Acidosis, Electrolytes (K+), Intoxication, Overload, Uremia (pericarditis/encephalopathy).
The clue: Anterolateral STEMI (ST elevation V4-V6, new Q waves, ↑troponin) acutely drops contractility.
Correct answer C W → Z
Loss of contracting myocardium reduces contractility, so stroke volume and cardiac output fall while end-diastolic volume rises (blood the weakened ventricle cannot eject). On the ventricular function graph this is a downward shift onto a LOWER contractility curve at a HIGHER end-diastolic volume, the transition W → Z.
Staying on the same curve (e.g., W → Y) would mean unchanged contractility; an acute infarct instead drops the ventricle to a new, depressed curve.
Memory hook ↓Contractility (MI) = shift DOWN to a lower curve + ↑EDV (W→Z).
The clue: On-off freezing on carbidopa-levodopa, the adjunct enzyme to inhibit prolonged dopamine action.
Correct answer C Monoamine oxidase B
MAO-B inhibitors (selegiline, rasagiline) block central breakdown of dopamine to DOPAC, prolonging dopaminergic signalling and smoothing the motor fluctuations (“on-off”, freezing) of advancing Parkinson disease.
They are a standard adjunct to levodopa for exactly this problem.
Memory hook PD adjuncts that raise dopamine: MAO-B inhibitors (-giline) and COMT inhibitors (-capone).
The clue: Bullet entering the posterior LEFT 10th intercostal space; CT shows the metallic fragment in the left upper abdomen.
Correct answer E Spleen
The spleen sits in the left upper quadrant, lateral to the stomach, beneath the left 9th-11th ribs near the left 10th intercostal space, exactly where this bullet entered. It is the abdominal organ most often injured by left lower thoracic/upper abdominal trauma.
The fragment lodged in this solid LUQ organ is in the spleen.
Memory hook Left lower rib / 10th intercostal trauma → think SPLEEN (LUQ, ribs 9-11).
The clue: Days after starting olanzapine: high fever, autonomic instability, and altered mental status.
Correct answer B Muscle rigidity
Neuroleptic malignant syndrome (NMS) is an idiosyncratic, life-threatening reaction to antipsychotics. The tetrad is altered mental status, autonomic instability (tachycardia, hypertension, tachypnea), hyperthermia, and generalized “lead-pipe” muscle rigidity.
Expect diffuse rigidity on exams, often with sluggish reflexes.
Memory hook NMS = antipsychotic + Fever + Autonomic instability + “lead-pipe” Rigidity + AMS (slow reflexes). Serotonin syndrome = clonus/hyperreflexia.
The clue: Painless hematuria + occupational naphthylamine + heavy smoking + a mass in the renal pelvis.
Correct answer E Urothelial carcinoma
Painless hematuria with a renal pelvis mass and the two heaviest risk factors: aromatic amines (naphthylamine, benzidine) and cigarette smoking, points to urothelial (transitional cell) carcinoma of the upper urinary tract.
A resected kidney implies a malignant process; benign oncocytomas are usually left in place.
Memory hook Painless hematuria + smoking + aromatic amines (naphthylamine/dyes/rubber) = urothelial carcinoma.
The clue: Recurrent central facial erythema, flushing, and burning with monthly flares, and weekly red wine.
Correct answer A Effect of alcohol on the condition
Centrofacial erythema with flushing and a burning sensation describes rosacea. Flares are precipitated by stress, heat, spicy food, and alcohol, especially red wine, which this patient drinks weekly.
Asking specifically how alcohol affects the rash establishes a known lifestyle trigger and supports the diagnosis.
Memory hook Rosacea triggers: stress, heat, spicy food, ALCOHOL (red wine), sun.
The clue: An unvaccinated child stays healthy because most of the surrounding community is vaccinated.
Correct answer B Herd immunity
Herd immunity occurs when enough of a population is immune that transmission chains break, indirectly protecting susceptible (unvaccinated) individuals.
Her good health despite refusing vaccines is best explained by the immunity of those around her.
Memory hook Unvaccinated but protected because OTHERS are vaccinated = herd immunity.
The clue: Rh-negative mother, Rh-positive partner; the prophylactic drug is Rho(D) immune globulin (anti-D).
Correct answer A Binding to the D antigen on fetal erythrocytes
Rho(D) immune globulin contains anti-D IgG. Given to an Rh-negative mother, these antibodies bind the D antigen on any Rh-positive fetal red cells in maternal circulation and trigger their clearance before the mother’s own immune system can mount a primary response, preventing alloimmunization and hemolytic disease of the newborn.
The mechanism is binding to the D antigen on fetal erythrocytes (opsonization and splenic clearance).
Memory hook RhIg = anti-D IgG → coats/clears Rh+ fetal cells → blocks maternal sensitization.
The clue: Acute podagra (red, swollen, exquisitely tender great toe) after beer and shellfish.
Correct answer D Purine degradation pathway
Acute gouty arthritis results from monosodium urate crystal deposition driven by hyperuricemia. Uric acid is the end product of purine degradation; purine-rich foods (lobster) raise production and alcohol reduces renal urate excretion, a perfect storm.
So intermediates accumulate in the purine degradation pathway.
Memory hook Gout = end-product of PURINE degradation (uric acid). Beer + shellfish + diuretics raise it.
The clue: A patient discloses a DUI, explores problematic drinking with a non-judgmental, open question.
Correct answer A “Do you have any concerns about your alcohol use?”
After a substance-related event such as a DUI, the best first step is an open-ended, non-judgmental question that gauges insight and readiness to change while preserving rapport.
Asking whether she has concerns about her alcohol use invites reflection without confrontation.
Memory hook Substance disclosure → open-ended, non-judgmental question first (assess readiness).
The clue: Progressive leg swelling in a young child with anomalous lymphatic vessels on lymphoscintigraphy.
Correct answer C Mesoderm
The entire cardiovascular system: blood vessel endothelium, lymphatic vessels, microcirculation, and spleen, derives from embryonic mesoderm.
Congenitally malformed lymphatics (primary lymphedema) therefore arise from a mesodermal defect.
Memory hook Vessels + lymphatics + blood + spleen = MESODERM.
The clue: BMI 63, daytime somnolence, cyanosis, and an ABG with respiratory acidosis (pH 7.31, PCO₂ 70, PO₂ 50).
Correct answer B Increased hemoglobin concentration
Obesity hypoventilation syndrome causes chronic hypoxemia and CO₂ retention. Chronic hypoxia drives erythropoietin release (via HIF), expanding red-cell mass, so hemoglobin/hematocrit rise (secondary polycythemia).
Increased hemoglobin concentration is the expected additional finding.
Memory hook Chronic hypoxia → ↑EPO → ↑Hgb (secondary polycythemia). Cor pulmonale = RV hypertrophy.
The clue: Bloody diarrhea → days later anemia + thrombocytopenia + acute kidney injury = HUS.
Correct answer B Escherichia coli
Hemolytic uremic syndrome follows infection with Shiga toxin–producing E. coli (O157:H7). The toxin injures glomerular endothelium, triggering microthrombi (consuming platelets), microangiopathic hemolysis (schistocytes, low hemoglobin), and acute kidney injury (rising creatinine, hypertension).
The classic course is bloody diarrhea followed within a week by the HUS triad, exactly this child.
Memory hook HUS triad = microangiopathic hemolytic anemia + thrombocytopenia + AKI; cause = Shiga-toxin E. coli O157:H7 (avoid antibiotics).
The clue: Uncontrolled HTN (154/100) with ECG left ventricular hypertrophy (tall R in V5-V6).
Correct answer C Increased synthesis of contractile filaments
Chronic pressure overload makes existing cardiac myocytes hypertrophy by synthesizing more contractile filaments (actin and myosin) and adding sarcomeres in parallel, concentric LVH. Myocytes are terminally differentiated and do not multiply.
Hence increased synthesis of contractile filaments.
Memory hook Pressure overload → sarcomeres in PARALLEL → concentric LVH (hypertrophy, not hyperplasia).
The clue: Benzene + smoking; a polymorphism in a metabolic-ACTIVATION enzyme raises cancer risk.
Correct answer B Cytochrome P450
Benzene and polycyclic aromatic hydrocarbons are pro-carcinogens, harmless until bioactivated. Phase I cytochrome P450 enzymes (e.g., CYP2E1) oxidize them into reactive electrophilic intermediates (like benzene oxide) that bind DNA and cause mutations.
An activating polymorphism in CYP therefore increases cancer risk.
Memory hook Pro-carcinogen → ACTIVATED by Phase I CYP450 (e.g., CYP2E1). Phase II (GST, methyltransferase) = detox.
The clue: Maximum tolerated dose, safety, and pharmacokinetics in a small group of healthy volunteers.
Correct answer B Phase 1
Phase 1 trials test safety, toxicity, maximum tolerated dose, and pharmacokinetics in a small cohort (typically healthy volunteers).
Assessing MTD and PK in 80 healthy volunteers is the definition of phase 1.
Memory hook Phase 0 micro-dose → 1 Safety (healthy) → 2 Efficacy (patients) → 3 RCT vs standard → 4 post-market.
The clue: Marathon trainee with type 1 diabetes, glucose 25, and NO response to glucagon.
Correct answer A Depletion of glycogen stores
Glucagon raises glucose by stimulating hepatic glycogenolysis. After prolonged, intense exercise (marathon training), hepatic glycogen stores are exhausted, so glucagon has no substrate to mobilize, glucose stays at 25 mg/dL.
The lack of response is due to depleted glycogen stores.
Memory hook No glycogen, no glucagon effect, glucagon needs hepatic glycogen to work.
Hematology-oncology, communication, and classic single-best-answer pattern recognition.
The clue: A pancreatic head mass with liver lesions, be honest, clear, and compassionate.
Correct answer B “I’m concerned the mass could be cancer. The biopsy will provide more information.”
When findings are highly suspicious for cancer, the physician should deliver an honest but empathetic “warning shot” using plain language, then offer the next step. This respects autonomy and prepares the patient for the likely diagnosis without false reassurance.
“I’m concerned the mass could be cancer; the biopsy will provide more information” strikes that balance perfectly.
Memory hook Bad news = warning shot + plain language + empathy; no false reassurance, no withholding.
The clue: Headache, fatigue, splenomegaly, and panmyelosis (Hgb 19.5, Hct 59%, high platelets).
Correct answer B Janus kinase 2
Elevations across multiple myeloid lines (erythrocytosis, thrombocytosis) with splenomegaly point to polycythemia vera, a myeloproliferative neoplasm.
>95% of PV cases carry a gain-of-function JAK2 V617F mutation, which makes hematopoietic growth-factor receptors fire independently of erythropoietin.
Memory hook Polycythemia vera, essential thrombocythemia, primary myelofibrosis → JAK2 (V617F).
The clue: Olfactory aura (“burning rubber”) + lip-smacking automatisms = mesial temporal lobe seizures.
Correct answer E Hippocampus (label E)
Focal seizures with olfactory auras, automatisms (lip smacking), and emotional features localise to the mesial temporal lobe, the hippocampus and amygdala. In refractory cases, intracranial electrodes target the hippocampal region to map a resectable focus.
On the coronal section, the hippocampus is labeled E.
Memory hook Olfactory aura + lip smacking = mesial temporal lobe (hippocampus/amygdala).
The clue: Parotid/submandibular swelling, eroded teeth, Russell sign, and “worthless/fat” self-talk = bulimia nervosa.
Correct answer A Binding to muscarinic acetylcholine receptors
Recurrent self-induced vomiting causes reflex salivary gland hypertrophy (sialadenosis), producing the bilateral parotid/submandibular swelling seen here, along with dental erosion and knuckle scarring (Russell sign).
A drug acting at muscarinic acetylcholine receptors (an antimuscarinic such as glycopyrrolate) reduces salivary secretion and can relieve the painful glandular swelling, the symptom being treated.
Memory hook Purging → parotid sialadenosis; saliva is muscarinic-driven → antimuscarinic reduces it.
The clue: Severely itchy vesicular rash one day after handling weeds (urushiol/poison ivy).
Correct answer D Type IV (delayed)
Allergic contact dermatitis to urushiol is a delayed (Type IV) hypersensitivity. Sensitized T lymphocytes recognise the antigen on re-exposure and release cytokines that recruit macrophages, producing the itchy, vesicular rash 24-48 hours later.
The 1-day delay after exposure is the tell of a T-cell-mediated reaction.
Memory hook Poison ivy / nickel / PPD = Type IV delayed (T-cell) hypersensitivity (24-72 h).
The clue: Two years at 10,000 ft → right-heart failure (JVD, pedal edema) from chronic hypoxic pulmonary hypertension.
Correct answer E Right ventricular diastolic compliance (decreased)
Chronic high-altitude hypoxia triggers hypoxic pulmonary vasoconstriction, raising pulmonary vascular resistance and pressure. The pressure-loaded right ventricle hypertrophies and stiffens, so its diastolic compliance DECREASES, impairing filling and causing systemic venous congestion (JVD, edema).
The parameter that decreased is right ventricular diastolic compliance.
Memory hook Chronic hypoxia → pulmonary HTN → RVH → stiff RV → ↓ diastolic compliance → cor pulmonale.
The clue: Upper-extremity hypertension (135/85) with low leg pressure (80/40) and an interscapular murmur.
Correct answer A Delayed femoral pulses
Coarctation is a narrowing of the aorta just distal to the left subclavian artery. It causes upper-extremity hypertension with hypoperfusion below the narrowing, classically producing a brachial-femoral delay, weak, delayed femoral pulses.
The interscapular systolic murmur and arm-leg BP gradient seal the diagnosis.
Memory hook Coarctation: arm BP > leg BP + radio-femoral delay; associated with Turner syndrome & bicuspid aortic valve.
The clue: Fatigue, constipation, polyuria + hypercalcemia with LOW PTH + bilateral hilar lymphadenopathy.
Correct answer A Calcitriol production by activated macrophages
Bilateral hilar lymphadenopathy with interstitial infiltrates and hypercalcemia is sarcoidosis. Activated macrophages within granulomas express 1-α-hydroxylase, converting 25-OH vitamin D to active calcitriol (1,25-OH₂D), which raises calcium and suppresses PTH.
So the hypercalcemia is from macrophage-derived calcitriol.
Memory hook Sarcoid/granulomas → macrophage 1-α-hydroxylase → ↑calcitriol → ↑Ca²⁺ with ↓PTH.
The clue: Recurrent pancreatitis + steatorrhea + weight loss = exocrine pancreatic insufficiency.
Correct answer C Lipase
Chronic pancreatitis destroys exocrine tissue, reducing digestive enzyme output. Fat malabsorption dominates because lipase is the most vulnerable enzyme, producing the oily, foul-smelling, floating stools (steatorrhea) and weight loss described.
Pancreatic enzyme replacement centred on lipase is most beneficial.
Memory hook Pancreatic insufficiency → steatorrhea → replace LIPASE (fat-soluble vitamin A,D,E,K loss too).
The clue: RUQ pain + hypoechoic liver lesion after travel to India = Entamoeba histolytica liver abscess.
Correct answer C Eradication of intestinal organisms
Amebic liver abscess needs a two-drug strategy: metronidazole kills invasive tissue trophozoites, but it is absorbed in the upper gut and fails to reach luminal cysts. A non-absorbable luminal amebicide: paromomycin, is added to eradicate intestinal cysts and prevent relapse.
Paromomycin’s role is eradication of intestinal organisms (luminal cysts).
Memory hook Amebic abscess: metronidazole (tissue) + paromomycin (luminal cysts → prevent relapse).
The clue: Proptosis in a young child with a biopsy showing malignant cells with striations.
Correct answer D Rhabdomyosarcoma
Rapid orbital proptosis without trauma in a child, with malignant cells showing cross-striations (skeletal muscle origin), is orbital rhabdomyosarcoma, the most common soft-tissue sarcoma of childhood. Immunohistochemistry is positive for desmin and myogenin.
Striations point straight to a muscle-derived tumor.
Memory hook Child + proptosis + striated malignant cells + desmin = rhabdomyosarcoma.
The clue: Carpenter with a puncture wound now necrotic + fever, tachycardia, hypotension = wound sepsis.
Correct answer E Staphylococcus aureus
A puncture wound that becomes diffusely swollen, erythematous, and necrotic with systemic signs of sepsis (fever, tachycardia, hypotension, respiratory alkalosis with low PCO₂) most likely harbours Staphylococcus aureus, the classic skin/soft-tissue and wound pathogen.
S. aureus readily produces necrotizing wound infections and sepsis.
Memory hook Necrotic wound + sepsis (post-trauma) → Staphylococcus aureus.
The clue: Atrophy/weakness of intrinsic hand muscles (T1) + sensory loss below the clavicles (T2) + UMN signs in legs.
Correct answer C T1
The intrinsic hand muscles are innervated by T1; their weakness and atrophy place the lower limit of motor injury there. Sensory loss beginning at the clavicle corresponds to the T2 dermatome, and the leg hyperreflexia/Babinski indicates corticospinal (UMN) involvement below the lesion.
All findings converge on a T1 cord lesion.
Memory hook Hand intrinsics = T1; sensory level at clavicle = T2. Lower the level → more distal the deficit.
The clue: BMI 46 with exertional dyspnea, clear lungs, extrapulmonary restriction with intact gas exchange.
Correct answer D FEV₁ 84%, FVC 78%, TLC 78%, DLCO 92%
Massive obesity mechanically restricts chest-wall and diaphragmatic excursion, producing a restrictive pattern: low TLC and FVC (<80%), with a normal or high FEV₁/FVC ratio because airflow is unobstructed.
Crucially, the alveolar-capillary membrane is healthy, so DLCO is preserved (≥80%). Option D, reduced volumes with normal DLCO and ratio, matches.
Memory hook Obesity/neuromuscular restriction = low volumes, NORMAL DLCO. Intrinsic lung restriction = low DLCO.
The clue: Postmenopausal woman with low libido and no psychosocial cause = vulvovaginal atrophy from estrogen loss.
Correct answer C Decreased vaginal rugation
Loss of ovarian estrogen thins the vaginal epithelium and reduces submucosal collagen and elasticity, producing a pale, dry vaginal wall with decreased rugation, the genitourinary syndrome of menopause.
Decreased vaginal rugation is the expected pelvic-exam finding.
Memory hook Menopause → low estrogen → atrophic, pale, dry vagina with ↓ rugae (GSM).
The clue: A1c of 12% with patient frustration, assess her baseline knowledge first, non-judgmentally.
Correct answer E “What is your understanding of what your hemoglobin A1c should be?”
With chronic disease mismanagement, the best initial response is open-ended and assesses the patient’s understanding of the data and goals. This identifies knowledge gaps and builds rapport before introducing changes.
Asking what she understands her A1c target to be does exactly that.
Memory hook Chronic mismanagement → first assess the patient’s understanding (open-ended, non-judgmental).
The clue: Adding 1000 patients to a trial increases statistical power.
Correct answer D Less chance of a Type II error
A Type II error (β) is failing to detect a true effect. Increasing the sample size raises statistical power (1 – β), so the study is more likely to detect a real effect, reducing the chance of a Type II error.
Larger n → more power → fewer false negatives.
Memory hook ↑ Sample size → ↑ Power (1-β) → ↓ Type II error. α (Type I) is unchanged.
The clue: Hydronephrosis with a dilated renal pelvis but a NON-dilated ureter.
Correct answer D Ureteropelvic junction
In obstruction, the segment proximal to the block dilates while the distal segment stays normal. Dilation of the renal pelvis without ureteral dilation localises the obstruction to the ureteropelvic junction (UPJ), the most common site of congenital obstruction.
So the block is at the UPJ.
Memory hook Dilated pelvis + normal ureter = UPJ obstruction (most common congenital site).
The clue: Invasive Mycobacterium avium complex (osteomyelitis + septic joint) in a child with a NEGATIVE HIV test.
Correct answer E Dysfunctional interferon-γ receptors
Clearing intracellular mycobacteria depends on the IL-12 / IFN-γ axis between macrophages and Th1 cells. A congenital defect in IFN-γ receptors prevents macrophage activation, leaving the patient uniquely vulnerable to disseminated infection with low-virulence environmental mycobacteria like MAC, despite a normal HIV test.
The most likely abnormality is dysfunctional IFN-γ receptors.
Memory hook Disseminated atypical mycobacteria in non-HIV → IL-12 / IFN-γ axis defect.
The clue: Enlarging subcutaneous mass at a prior surgical site, with thick hyalinized collagen bundles.
Correct answer G Myofibroblasts
A keloid is an abnormal wound-healing response that extends beyond the original injury borders, with dense, hyalinized type I/III collagen. The excess matrix is laid down by overactive, persistently differentiated myofibroblasts driven by TGF-β.
Myofibroblasts are the cell type responsible.
Memory hook Keloid = TGF-β-driven MYOFIBROBLASTS depositing collagen beyond wound margins.
Reproductive, GI, pulmonary, and genetics, plus the must-know ethics items.
The clue: “Early menopause” that is actually a 24-week pregnancy, on lisinopril, with oligohydramnios + Potter-sequence features.
Correct answer C Fetal renal hemodynamics
ACE inhibitors are teratogenic in the 2nd/3rd trimesters. By blocking angiotensin II, they impair fetal renal hemodynamics and urine output, causing oligohydramnios. Low amniotic fluid then produces Potter sequence: pulmonary hypoplasia, limb deformities, and the cranial/facial changes described.
The drug interferes with fetal renal hemodynamics.
Memory hook ACE inhibitors in pregnancy → ↓ fetal renal perfusion → oligohydramnios → Potter sequence.
The clue: Sudden fatal respiratory distress; lung histology shows intra-alveolar pale-pink transudate with congested capillaries.
Correct answer C Massive myocardial infarction
Acellular, homogeneous pale-pink intra-alveolar fluid with engorged capillaries is acute pulmonary edema. Sudden death from cardiogenic pulmonary edema implies acute left-ventricular failure, a massive myocardial infarction abruptly raising pulmonary venous pressure and flooding the alveoli.
The underlying cause is a massive MI.
Memory hook Pink, acellular alveolar transudate = cardiogenic pulmonary edema → acute LV failure (massive MI).
The clue: Doubling warfarin but INR stays ~1, the patient is on rifampin.
Correct answer E Induction of cytochrome enzymes
Rifampin is a potent inducer of hepatic cytochrome P450 enzymes. It accelerates warfarin metabolism, lowering plasma levels so the INR remains subtherapeutic even after doubling the dose.
The cause is enzyme induction by rifampin.
Memory hook Inducers (rifampin, phenytoin, carbamazepine, St John’s wort, chronic alcohol) → ↓ warfarin effect → ↓ INR.
The clue: Progressive painless central vision loss + soft drusen around the macula = dry AMD.
Correct answer A Age
Yellowish subretinal deposits (soft drusen) at the macula with central vision loss while reading/driving define dry age-related macular degeneration. The single strongest, non-modifiable risk factor is advanced age, via cumulative oxidative stress and lipofuscin accumulation in the retinal pigment epithelium.
Age most increased her risk.
Memory hook Dry AMD: soft drusen + central vision loss; #1 risk = AGE (then smoking).
The clue: Induction chemo for ALL + fever + gum ulcers + gram-negative bacteremia.
Correct answer E Neutropenia
Induction chemotherapy profoundly suppresses the marrow, dropping the absolute neutrophil count. Neutropenia predisposes to bacterial (especially gram-negative rods) and fungal infections, and neutropenic fever is an emergency requiring immediate broad-spectrum antibiotics.
The mechanism is neutropenia.
Memory hook Chemo → neutropenia → gram-negative & fungal infection; neutropenic fever = emergency.
The clue: Compare event rates: 18 per 1000 (Procedure B) vs 12 per 1000 (Procedure A).
Correct answer A (18/1000) – (12/1000)
Absolute risk reduction (ARR) is simply the difference in absolute event rates between the two groups: risk in B minus risk in A = 18/1000 – 12/1000.
Only patients enrolled in the study count toward these risks.
Memory hook ARR = risk(control) − risk(treatment). NNT = 1/ARR.
The clue: Fever, bleeding gums, ecchymoses, pancytopenia with circulating blasts containing Auer rods.
Correct answer B Acute myelogenous leukemia
Marrow failure (anemia, profound thrombocytopenia, bleeding) plus large myeloid blasts with Auer rods (fused azurophilic granules) is diagnostic of acute myelogenous leukemia (AML).
Auer rods are pathognomonic of myeloblasts.
Memory hook Auer rods = AML (esp. APL). Smudge cells = CLL.
The clue: Tendinous xanthomas + total cholesterol 410 + MI before 50 + strong family history.
Correct answer D LDL receptor
Familial hypercholesterolemia is an autosomal-dominant defect in the LDL receptor, impairing LDL clearance. The result is markedly elevated LDL cholesterol, tendinous (Achilles) xanthomas, and premature coronary disease.
The deficiency is of the LDL receptor.
Memory hook FH = LDL-receptor defect → ↑↑LDL, tendinous xanthomas, early MI (autosomal dominant).
The clue: A healthy 5-year-old with isolated nighttime bed-wetting, normal exam and urinalysis.
Correct answer C Delayed maturation of detrusor and sphincter control
Primary nocturnal enuresis is nighttime wetting in a child ≥5 who never achieved sustained dryness, with an otherwise normal evaluation. It reflects delayed physiologic maturation of detrusor/sphincter control and nocturnal arousal (often with low nighttime ADH).
The cause is delayed maturation, and most children outgrow it.
Memory hook Isolated nighttime wetting, normal exam/UA = primary nocturnal enuresis (maturational; reassure).
The clue: Hard “pebble” stools every 5 days + bright red blood on tissue + protruding rectal mucosa.
Correct answer A Constipation
Infrequent, hard pebble-like stools with painful defecation and bright-red blood on the tissue indicate constipation complicated by an anal fissure (and minor rectal mucosal prolapse). No features point to a specific organic disease.
Constipation is the unifying diagnosis.
Memory hook Hard pebble stools + fissure (bright-red blood on tissue) = simple constipation.
The clue: Unaffected sister of a CF patient; both parents are obligate carriers.
Correct answer D 2 of 3
Because an affected brother (aa) means both parents are carriers (Aa × Aa), offspring are 1 AA : 2 Aa : 1 aa. Since this woman is phenotypically unaffected, the aa option is eliminated, leaving AA, Aa, Aa.
Of those three equally likely genotypes, two are carriers, a 2/3 carrier probability.
Memory hook Unaffected child of two carriers → conditional carrier risk = 2/3.
The clue: STEMI with hypotension (70 systolic) AND tachycardia (136), raise BP WITHOUT raising heart rate.
Correct answer A α-Adrenergic agonist
Phenylephrine is a pure α1-agonist that increases systemic vascular resistance and blood pressure through vasoconstriction. Because it has no β1 activity, it raises pressure without further increasing heart rate or myocardial oxygen demand.
An α-adrenergic agonist meets the goal.
Memory hook Need ↑BP without ↑HR → pure α1-agonist (phenylephrine).
The clue: Recurrent UTIs + one large U-shaped kidney on ultrasound.
Correct answer D Fusion of the inferior poles of the metanephros during ascent
A horseshoe kidney forms when the inferior poles of the metanephros fuse; during ascent the fused kidney is caught beneath the inferior mesenteric artery, leaving it low and predisposing to UTIs and stones. It is associated with Turner syndrome.
The embryologic origin is fusion of the inferior poles.
Memory hook Horseshoe kidney = fused lower poles, trapped under the IMA; linked to Turner syndrome.
The clue: An anxious 16-year-old worried about an STI, validate first, then take the history.
Correct answer C “I’m glad you came in today and told me about this.”
Adolescents face stigma seeking sexual-health care. The best initial response creates a safe, non-judgmental space by affirming that he came in. This builds rapport and encourages honest disclosure before moving to the detailed sexual history.
Validating his initiative comes first.
Memory hook Adolescent + sensitive concern → validate & ensure confidentiality FIRST, then the 5 P’s.
The clue: Overweight woman, BP 140/90, fasting glucose 102, family history of T2DM = insulin resistance.
Correct answer D Increased fasting insulin concentration
Insulin resistance forces the pancreas to secrete more insulin to overcome reduced tissue responsiveness, so fasting insulin is elevated (compensatory hyperinsulinemia) in prediabetes/metabolic syndrome.
Increased fasting insulin is the expected abnormality.
Memory hook Early insulin resistance: glucose high → pancreas compensates → ↑ fasting insulin (later it fails).
The clue: Episodic full-body weakness after high-carbohydrate, salty meals and exercise, resolving spontaneously.
Correct answer D Potassium
Hypokalemic periodic paralysis features transient muscle weakness triggered by carbohydrate-rich meals and rest after exercise, when insulin/catecholamines drive potassium into cells and drop serum K+. Episodes resolve on their own and labs are normal between attacks.
Serum potassium is the value most likely abnormal during an episode.
Memory hook Carb/exercise-triggered transient paralysis = hypokalemic periodic paralysis (K+ shifts into cells).
The clue: Polyuria + polydipsia + dilute urine that CONCENTRATES after desmopressin (ADH).
Correct answer F Supraoptic nucleus
Dilute urine that responds to exogenous ADH indicates central diabetes insipidus, deficient ADH production. ADH (vasopressin) is synthesized in the hypothalamic supraoptic (and paraventricular) nuclei and released from the posterior pituitary.
The dysfunctional structure is the supraoptic nucleus.
Memory hook Central DI: ADH made in supraoptic/paraventricular nuclei; urine concentrates WITH desmopressin (vs nephrogenic = no response).
The clue: Young man, painless firm testicular mass; histology shows clear-cytoplasm cells with central nuclei (“fried egg”).
Correct answer B Seminoma
A painless solid testicular mass in a young adult with uniform cells, clear (glycogen-rich) cytoplasm, and prominent central nuclei in lobules separated by fibrous septa is the classic seminoma, the most common pure germ-cell tumor and very radiosensitive.
The “fried-egg” appearance is the giveaway.
Memory hook Young man + painless testicular mass + “fried-egg” cells = seminoma (radiosensitive; ↑hCG sometimes).
The clue: Heavy maternal alcohol use throughout pregnancy.
Correct answer D Short palpebral fissures
Prenatal alcohol exposure disrupts neural-crest migration and other processes, producing fetal alcohol syndrome: short palpebral fissures, a smooth philtrum, a thin vermilion border, growth restriction, and neurodevelopmental impairment.
Short palpebral fissures are the classic facial finding.
Memory hook FAS face: short palpebral fissures + smooth philtrum + thin upper lip + growth/CNS deficits.
The clue: Postpartum thyrotoxicosis (palpitations, heat intolerance, lid lag, undetectable TSH, high T₄/T₃) with NO exophthalmos.
Correct answer D Lymphocytic infiltration of the thyroid
Postpartum thyroiditis is a subacute lymphocytic (painless) thyroiditis occurring within 12 months of delivery. Autoimmune lymphocytic infiltration damages follicles, releasing preformed hormones (thyrotoxic phase), often followed by transient hypothyroidism and recovery.
The mechanism is destructive lymphocytic infiltration releasing stored hormones.
Memory hook Postpartum thyroiditis = destructive lymphocytic thyroiditis → leaks preformed hormone (no exophthalmos, low uptake). Graves = TSH-R antibodies + eye disease.
Biostatistics, neuroanatomy, pathology, and infectious disease.
The clue: Compute false positives when a test is applied to 100,000 people with prevalence 80/100,000.
Correct answer D 9992
From the validation data, the false-positive rate = 100 false positives / 1000 non-diseased = 0.1. In the new population of 100,000, the number WITHOUT disease is 100,000 – 80 = 99,920.
Expected false positives = 0.1 × 99,920 = 9,992.
Memory hook False positives = FPR × (number WITHOUT disease). Here 0.1 × 99,920 = 9,992.
The clue: Ignoring the left side + tactile extinction on the left + left lower quadrantanopia, no motor/language deficit.
Correct answer E Right parietal
The non-dominant (right) parietal lobe governs spatial attention. A right parietal lesion produces contralateral (left) hemispatial neglect, bumping into the left, ignoring left stimuli, and tactile extinction on bilateral simultaneous stimulation. A left lower quadrantanopia fits parietal optic radiation involvement.
Intact motor, language, and proprioception localise the lesion to the right parietal lobe.
Memory hook Left neglect + extinction = RIGHT parietal lobe (non-dominant).
The clue: Conotruncal defect (interrupted aortic arch) + hypocalcemic tetany + hypertelorism/short philtrum/micrognathia.
Correct answer E 22
Failed development of the 3rd/4th pharyngeal pouches causes thymic and parathyroid hypoplasia. The result: cardiac conotruncal anomalies, neonatal hypocalcemia, dysmorphic facies, and T-cell immunodeficiency, is DiGeorge syndrome, a 22q11.2 microdeletion.
The defect is on chromosome 22.
Memory hook DiGeorge = 22q11.2 deletion → CATCH-22: Cardiac, Abnormal facies, Thymic aplasia, Cleft, Hypocalcemia.
The clue: Palpitations with a sawtooth ECG pattern.
Correct answer E Right atrium
Typical atrial flutter arises from a macro-reentrant circuit around the tricuspid valve annulus in the right atrium, with the cavotricuspid isthmus as the critical slow zone. The sawtooth flutter waves are the hallmark.
The abnormal activity originates in the right atrium.
Memory hook Sawtooth flutter waves = right-atrial reentry around the cavotricuspid isthmus.
The clue: Hematemesis + epigastric tenderness + positive occult blood on chronic ibuprofen.
Correct answer D Inhibition of cyclooxygenase-1
Non-selective NSAIDs inhibit COX-1, the enzyme that makes protective gastric prostaglandins (PGE₂, PGI₂). Loss of these prostaglandins reduces mucus/bicarbonate secretion and mucosal blood flow while acid output rises, predisposing to erosions, ulcers, and upper-GI bleeding.
The mechanism is systemic COX-1 inhibition.
Memory hook NSAID ulcers = ↓ COX-1 prostaglandins → ↓ mucus/bicarbonate/blood flow → erosions/bleed.
The clue: Oligohydramnios → intrauterine crowding → clubfoot (talipes equinovarus).
Correct answer A Deformation
A deformation is an extrinsic mechanical force distorting a normally formed structure. Oligohydramnios removes the protective fluid cushion, so intrauterine compression bends the otherwise normal fetal feet into the clubfoot position.
This is a deformation.
Memory hook Outside mechanical force on normal tissue = DEFORMATION (oligohydramnios → clubfoot/Potter).
The clue: Knife wound to the chest with the trachea shifted away, air in the pleural space.
Correct answer B Decreased fremitus, hyperresonant, decreased breath sounds
A pneumothorax fills the pleural space with air. Air transmits sound poorly (decreased tactile fremitus and decreased breath sounds) and is resonant to percussion (hyperresonant). Tracheal shift away from the side signals a tension pneumothorax.
Decreased fremitus, hyperresonance, and decreased breath sounds is the correct combination.
Memory hook Pneumothorax = ↓fremitus, hyperresonant, ↓breath sounds (± tracheal shift away in tension).
The clue: Ten days after losing 20% of blood volume, the marrow is regenerating.
Correct answer D Polychromasia
Acute hemorrhage triggers erythropoietin-driven marrow erythroid hyperplasia. By ~10 days the blood shows polychromasia, large, blue-gray immature red cells (reticulocytes) carrying residual ribosomal RNA.
Polychromasia reflects a healthy regenerative response.
Memory hook Post-bleed marrow response = reticulocytosis = polychromasia on smear.
The clue: Steatorrhea (floating, bulky stools) + weight loss + a dry, scaly rash.
Correct answer B Vitamin A
Fat malabsorption depletes fat-soluble vitamins (A, D, E, K). Vitamin A deficiency classically causes dry, scaly skin (follicular hyperkeratosis/xerosis) and night blindness.
The dry scaly rash with steatorrhea points to vitamin A deficiency.
Memory hook Steatorrhea → lose fat-soluble vitamins (ADEK). Dry scaly skin + night blindness = vitamin A.
The clue: Painless gross hematuria + papillary necrosis in sickle cell disease.
Correct answer C Decreased oxygen tension, Increased osmolality
The renal medulla is uniquely hostile: low oxygen tension (from countercurrent exchange) and high osmolality (from the countercurrent multiplier). Both conditions promote HbS polymerization and red-cell sickling, occluding the vasa recta and causing ischemic papillary necrosis.
Decreased O₂ tension with increased osmolality drives the sickling.
Memory hook Renal medulla = LOW O₂ + HIGH osmolality → sickling → papillary necrosis (and hyposthenuria).
The clue: RLQ rebound tenderness + appendix histology dense with neutrophils.
Correct answer C Leukotriene
Acute appendicitis shows transmural neutrophilic infiltration of the muscularis. Neutrophil recruitment is driven by chemotactic mediators, leukotriene B₄ being a potent one (alongside IL-8, C5a, and bacterial f-Met peptides).
Leukotriene is the chemoattractant among the options.
Memory hook Neutrophil chemoattractants: LTB₄, IL-8, C5a, bacterial f-Met peptides (“Clean Up: C5a, LTB4, IL-8, f-Met”).
The clue: Acute hallucinations + delusions + disorganized speech after a stressor, <1 month, negative tox screen.
Correct answer B Brief psychotic disorder
Psychotic symptoms lasting more than a day but less than a month, triggered by a stressor, with eventual return to baseline and a negative toxicology screen, define brief psychotic disorder.
Duration <1 month is the key.
Memory hook Psychosis <1 month (often post-stressor) = brief psychotic disorder. 1-6 mo = schizophreniform; >6 mo = schizophrenia.
The clue: Summer-camp outbreak; CSF lymphocytosis with NORMAL glucose and mildly elevated protein.
Correct answer B Enterovirus
Viral (aseptic) meningitis shows lymphocytic pleocytosis, normal glucose, normal/slightly elevated protein, and normal opening pressure. In summer, among camp contacts, enteroviruses are the most common cause.
Enterovirus fits the season, exposure, and CSF profile.
Memory hook Viral meningitis: lymphocytes + NORMAL glucose; summer/camp → enterovirus.
The clue: Restrictive PFTs (low TLC/FVC, normal ratio) with NORMAL DLCO + cachexia + poor diaphragmatic excursion.
Correct answer B Decreased respiratory muscle strength
Low lung volumes with a normal/high FEV₁/FVC and a completely normal DLCO indicate EXTRApulmonary restriction, the lung parenchyma is intact. With cachexia and reduced diaphragmatic excursion, the cause is respiratory-pump failure from decreased respiratory muscle strength.
Normal DLCO rules out intrinsic lung disease.
Memory hook Restrictive + NORMAL DLCO = extrapulmonary (muscle weakness / chest wall). Restrictive + LOW DLCO = intrinsic (fibrosis).
The clue: Painful menses from day one, no pelvic pathology = primary dysmenorrhea.
Correct answer C Inhibition of prostaglandin synthesis
Primary dysmenorrhea is driven by excess endometrial prostaglandins causing uterine contractions and pain. First-line therapy is an NSAID, which inhibits prostaglandin synthesis (cyclooxygenase) and relieves the cramping.
The mechanism is inhibition of prostaglandin synthesis.
Memory hook Primary dysmenorrhea = prostaglandin-driven → NSAIDs (block prostaglandin synthesis) first-line.
The clue: Collapse after a marathon with volume depletion (low BP, tachycardia, dry membranes).
Correct answer D Increased aquaporin expression
Severe volume depletion and high plasma osmolality drive ADH release. ADH binds V2 receptors on collecting-duct principal cells, inserting aquaporin-2 channels into the apical membrane so water is reabsorbed and urine becomes concentrated.
The renal change is increased aquaporin expression.
Memory hook Dehydration → ADH → V2 receptor → insert aquaporin-2 → concentrated urine.
The clue: College freshman with fever, malaise, and parotid gland swelling.
Correct answer D Mumps virus
Fever with bilateral parotitis in a young adult (especially with waning vaccination) is classic mumps, a paramyxovirus. Complications include orchitis, aseptic meningitis, and pancreatitis.
Parotid swelling points to the mumps virus.
Memory hook Parotitis in a young adult = mumps (paramyxovirus); watch for orchitis & aseptic meningitis.
The clue: Unresectable metastatic melanoma, which molecule to block with antibody?
Correct answer D CTLA4
CTLA-4 is an inhibitory T-cell receptor that outcompetes CD28 for B7, switching off T-cell activation and letting tumors evade immunity. Blocking CTLA-4 (ipilimumab) restores co-stimulation and reinvigorates the anti-tumor T-cell response.
Antibody blockade of CTLA-4 helps most.
Memory hook Checkpoint inhibitors: anti-CTLA-4 (ipilimumab), anti-PD-1/PD-L1 (nivolumab) → unleash T cells.
The clue: Mandarin-speaking patient, no in-person interpreter; the husband offers to translate.
Correct answer D Use a telephone interpreter service
A professional interpreter (in person or by phone) is required when there is a language barrier, to ensure accurate, unbiased communication and informed consent. Family members should not interpret because of medical-terminology limits and potential bias.
Use a telephone interpreter service now.
Memory hook Language barrier → professional (phone/in-person) interpreter, not family.
The clue: Unvaccinated infant with paroxysmal coughing spells, post-tussive vomiting, and a whoop.
Correct answer C Macrolide
Paroxysmal coughing fits with a whoop and post-tussive emesis in an unvaccinated infant is whooping cough (Bordetella pertussis, a gram-negative coccobacillus). The drug of choice is a macrolide (azithromycin, erythromycin), which reduces severity and limits transmission.
Macrolide is correct.
Memory hook Pertussis (catarrhal → paroxysmal whoop → convalescent) → macrolide (azithromycin).
Pharmacology, valvular disease, immunology, and a bonus Question 120.
The clue: Known amphetamine user with sympathomimetic toxicity (tremor, palpitations, hypertension, tachycardia).
Correct answer F Increased release of biogenic amines
Amphetamines act primarily by driving release of biogenic amines (norepinephrine, dopamine): they enter the presynaptic neuron, block the vesicular monoamine transporter so amines accumulate in the cytosol, and reverse the membrane transporters to dump amines into the synapse (they also block reuptake).
The dominant mechanism is increased release of biogenic amines.
Memory hook Amphetamine = ↑ release of NE/dopamine (reverse transporters + block VMAT/reuptake).
The clue: Tall young man, sudden severe back pain, hypotension, and a NEW diastolic murmur = aortic dissection with aortic regurgitation.
Correct answer E Stretched aortic annulus
A very tall (Marfan-type) young man with tearing back pain and hemodynamic collapse has aortic dissection. When the dissection extends into the aortic root, it dilates and stretches the aortic annulus, rendering the valve incompetent, producing acute aortic regurgitation (the diastolic murmur).
The cause of the murmur is a stretched aortic annulus.
Memory hook Tall + tearing chest/back pain + diastolic murmur = dissection → aortic root dilation → aortic regurgitation.
The clue: Bronchogenic carcinoma + pre-op weakness + prolonged paralysis; LOW EPP but NORMAL MEPP and normal ACh response.
Correct answer E Myasthenic (Lambert-Eaton) syndrome
Read the electrophysiology: a normal MEPP and normal response to applied acetylcholine prove the postsynaptic membrane and receptors are intact. The markedly reduced EPP (with normal MEPP) means too few ACh vesicles are released per nerve impulse, a PREsynaptic defect.
This is Lambert-Eaton myasthenic syndrome: paraneoplastic antibodies (often with small-cell lung cancer) against presynaptic voltage-gated calcium channels reduce ACh release.
Memory hook LEMS = presynaptic (anti-VGCC, SCLC): ↓EPP, normal MEPP, improves with use. MG = postsynaptic: worsens with use.
The clue: Asymptomatic hypercalcemia + high-normal PTH + VERY LOW urine calcium (FECa <1%) + family history.
Correct answer C Calcium-sensing receptor
Familial hypocalciuric hypercalcemia (FHH) is an autosomal-dominant inactivating mutation of the calcium-sensing receptor (CaSR). In the parathyroid, the set-point shifts up so PTH isn’t suppressed despite hypercalcemia; in the kidney, calcium reabsorption rises, giving very low urinary calcium (FECa <1%).
It is benign and must be distinguished from primary hyperparathyroidism to avoid needless surgery.
Memory hook FHH = inactivated CaSR → high Ca²⁺, high-normal PTH, LOW urine Ca (FECa <1%); don’t operate.
The clue: Terminal stage IV cancer; the patient declines further invasive procedures.
Correct answer C “I’d like to hear about your goals for the time you have remaining.”
A terminally ill patient with capacity who declines burdensome interventions should have her autonomy respected and care shifted toward comfort and quality of life. Exploring her goals lets the physician build a values-based palliative/hospice plan.
Asking about her goals is the most appropriate response.
Memory hook Capacity + terminal illness declining interventions → respect autonomy, explore goals of care.
The clue: 46,XX newborn with virilized genitalia (phallus-like structure, urethra at vaginal base).
Correct answer C Maternal androgen exposure
A 46,XX infant with virilization was exposed to excess androgens in utero. With CAH being one possibility, the option provided is maternal androgen exposure (e.g., a maternal androgen-secreting tumor or exogenous androgens), which virilizes a genetically female fetus.
Maternal androgen exposure explains the intersex findings.
Memory hook 46,XX + virilization → excess androgens (CAH or maternal androgen source).
The clue: Dishwasher in wet shoes/socks with itchy, burning scaly feet = tinea pedis (dermatophyte).
Correct answer D Squalene monooxygenase
Tinea pedis is a dermatophyte infection. The preferred treatment is terbinafine, which inhibits squalene monooxygenase (squalene epoxidase), blocking ergosterol synthesis and causing toxic squalene accumulation in the fungal cell.
The enzyme inhibited is squalene monooxygenase.
Memory hook Terbinafine (tinea pedis) → inhibits squalene epoxidase → ↓ ergosterol + toxic squalene.
The clue: Left eye fails to adduct on rightward gaze; leftward gaze is normal.
Correct answer B Left medial longitudinal fasciculus
The medial longitudinal fasciculus (MLF) links the abducens nucleus to the contralateral oculomotor nucleus to coordinate horizontal gaze. Failure of the LEFT eye to adduct on rightward gaze indicates a lesion of the LEFT MLF, internuclear ophthalmoplegia, classically from multiple sclerosis in a young woman.
The damaged structure is the left MLF.
Memory hook INO: the ADDUCTING eye fails → lesion of the MLF on that SAME side (left eye can’t adduct = left MLF).
The clue: Poorly controlled hypertension (180/105) with headache.
Correct answer A Arteriovenous nicking
Chronic, severe hypertension produces hypertensive retinopathy. The classic funduscopic sign is arteriovenous nicking, the thickened arteriole compressing the vein where they cross, along with flame hemorrhages and cotton-wool spots.
Expect AV nicking.
Memory hook Hypertensive retinopathy: AV nicking, flame hemorrhages, cotton-wool spots, ± papilledema.
The clue: 16-day-old with jaundice + dark urine + CONJUGATED hyperbilirubinemia (direct 14 of 20) and mildly high liver enzymes.
Correct answer D Obstruction of bile flow
Conjugated (direct) hyperbilirubinemia in a newborn is always pathologic and means cholestasis. Dark urine confirms water-soluble conjugated bilirubin is being excreted renally, which only happens when bile flow is obstructed (e.g., biliary atresia), backing conjugated bilirubin into the blood and mildly elevating enzymes.
The cause is obstruction of bile flow.
Memory hook Neonatal CONJUGATED hyperbilirubinemia + dark urine = biliary obstruction (rule out biliary atresia urgently).
The clue: Young woman, severe HTN (220/100), abdominal bruit, LVH, NORMAL creatinine/electrolytes.
Correct answer B Fibromuscular dysplasia
Severe secondary hypertension with an abdominal bruit in a young woman is classic renovascular hypertension from fibromuscular dysplasia, a non-atherosclerotic, non-inflammatory arterial disease (“string of beads” on angiography) that narrows the renal arteries and activates the renin-angiotensin system.
Fibromuscular dysplasia is the cause.
Memory hook Young woman + severe HTN + abdominal bruit = fibromuscular dysplasia (“string of beads”).
The clue: Mean leukocyte count 7500 in a normal (Gaussian) distribution, where do 50% fall?
Correct answer D <7500/mm³
A normal distribution is symmetric about its mean, so exactly 50% of values lie below the mean and 50% above it. With a mean of 7500, half the individuals have counts below 7500.
The 50% group is <7500/mm³.
Memory hook Normal curve: 68% within ±1 SD, 95% within ±2 SD, 99.7% within ±3 SD; 50% below the mean.
The clue: Mucocutaneous bleeding + normal platelet count + normal ristocetin but NO aggregation to thrombin.
Correct answer C Glycoprotein IIb-IIIa
GpIIb/IIIa binds fibrinogen to cross-link platelets, the final step of aggregation. In Glanzmann thrombasthenia this receptor is defective: platelets adhere normally (normal ristocetin/vWF-GpIb pathway) but fail to AGGREGATE to agonists like thrombin/ADP. Platelet count and morphology are normal, and PT/PTT are normal.
The defect is in glycoprotein IIb-IIIa.
Memory hook Glanzmann = GpIIb/IIIa defect (no aggregation, normal ristocetin). Bernard-Soulier = GpIb defect (abnormal ristocetin, big platelets).
The clue: A single BRCA2 founder mutation (999del5) accounts for 9% of Icelandic breast cancers.
Correct answer C Geographically isolated population
Iceland was settled by a small founding population and remained geographically isolated with little immigration, so a few founder alleles became over-represented, the founder effect. The 999del5 BRCA2 allele is one such over-represented mutation.
The explanation is a geographically isolated (founder) population.
Memory hook One mutation over-represented in an isolated population = FOUNDER effect.
The clue: Syncope + a pedunculated intracardiac mass; histology shows stellate cells in a myxoid stroma.
Correct answer B Left atrium
Stellate/spindle cells in a myxoid stroma define a cardiac myxoma, the most common primary cardiac tumor in adults. About 80% arise in the LEFT atrium, where a pedunculated mass can intermittently obstruct the mitral valve and cause syncope (a “ball-valve” effect).
The lesion came from the left atrium.
Memory hook Cardiac myxoma = stellate cells in myxoid stroma; 80% in the LEFT ATRIUM (ball-valve syncope, ↑IL-6).
The clue: Transplanted kidney becomes swollen and hemorrhagic within 10 minutes of reperfusion.
Correct answer D Preformed antibodies in the recipient
Rejection within minutes of reperfusion is hyperacute rejection, mediated by PREformed recipient antibodies (anti-ABO or anti-HLA) that immediately bind donor endothelium, activate complement, and cause widespread thrombosis and ischemic necrosis.
The cause is preformed antibodies in the recipient.
Memory hook Minutes = hyperacute (performed antibodies). Weeks = acute (T cells). Months-years = chronic.
The clue: Non-traumatic (pathologic) femoral fracture in a patient with multiple myeloma.
Correct answer A Bone remodeling
Myeloma plasma cells secrete RANKL and IL-6 to activate osteoclasts while suppressing osteoblasts (via DKK1/Wnt inhibition). This uncoupling of bone remodeling causes lytic lesions and mechanical weakness, predisposing to pathologic fractures.
The underlying abnormality is dysregulated bone remodeling.
Memory hook Myeloma bone disease = ↑RANKL/IL-6 osteoclast activity + ↓osteoblasts → lytic lesions, fractures, ↑Ca²⁺.
The clue: Twisted ankle with tenderness JUST DISTAL to the lateral malleolus.
Correct answer C Inversion
A lateral ankle sprain is caused by inversion of the plantar-flexed foot, which stretches/tears the lateral ligaments, most often the anterior talofibular ligament (ATFL), then the calcaneofibular ligament. Tenderness just below/in front of the lateral malleolus localises the injury there.
The mechanism is inversion.
Memory hook Inversion injury → lateral ligaments (ATFL first). Eversion → medial deltoid ligament.
The clue: Choking on candy + decreased left breath sounds + bronchial obstruction on x-ray + O₂ sat 93%.
Correct answer E Ventilation-perfusion mismatch
A foreign body lodged in the left main bronchus blocks ventilation to that lung while perfusion continues, a low V/Q (shunt-effect) region. Deoxygenated blood from the unventilated lung mixes with normal blood and lowers systemic oxygen saturation.
The hypoxemia is from ventilation-perfusion mismatch.
Memory hook Airway obstruction → ventilated-but-not-perfused becomes perfused-but-not-ventilated → V/Q mismatch/shunt → hypoxemia.
The clue: Progressive dyspnea + pulmonary congestion years after a childhood febrile illness with “heart trouble,” in a woman from Nigeria.
Correct answer D Fused commissures
A history of acute rheumatic fever (untreated Streptococcus pyogenes pharyngitis) at age 10, followed years later by exertional dyspnea and pulmonary congestion, is the classic story of chronic rheumatic heart disease causing mitral stenosis.
Recurrent immune-mediated inflammation fibroses and calcifies the mitral leaflets, fusing the commissures and shortening the chordae tendineae. The valve narrows into the classic “fish-mouth” orifice, elevating left atrial and pulmonary pressures. Auscultation gives the triad of a loud S1, an opening snap, and a low-pitched mid-diastolic rumble best heard at the apex in the left lateral decubitus position.
The pathologic hallmark is fused commissures.
Memory hook Rheumatic MS: Strep pharyngitis → rheumatic fever → fibrosis → FUSED commissures (“fish-mouth” valve) → loud S1 + opening snap + diastolic rumble.
Note: This guide is an independent educational resource and is not affiliated with or endorsed by the NBME, FSMB, or USMLE. Answer letters follow the official 2026 Step 1 Sample Test Questions answer key. We double-checked every item, but if you spot anything to improve, let us know.
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