How to use these: try each question on your own first, then expand it for the answer and a full explanation of why each wrong choice is wrong. Start with any topic — they're numbered for reference, not in difficulty order.
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Step 1 · Physiology
Q1. A patient receives a rapid IV fluid bolus. Which change best explains the resulting increase in stroke volume?
- Decreased afterload from vasodilation
- Increased preload stretching ventricular muscle fibers toward their optimal length
- Direct sympathetic stimulation of cardiac myocytes
- Reduced heart rate prolonging diastolic filling
Answer: B. The Frank-Starling mechanism: increased venous return raises end-diastolic volume (preload), stretching sarcomeres toward optimal overlap of actin and myosin, which increases the force of the next contraction and therefore stroke volume. A fluid bolus doesn't vasodilate (A), doesn't add sympathetic tone (C — and fluids don't directly stimulate myocytes), and typically raises rather than lowers heart rate (D). Test yourself: the same logic is why positive inotropes (digoxin, dobutamine) shift the whole Frank-Starling curve upward.
Step 1 · Biochemistry
Q2. An enzyme's kinetics are measured with and without a drug. With the drug, Vmax is unchanged but Km increases. The drug is best described as:
- A noncompetitive inhibitor
- A competitive inhibitor
- An uncompetitive inhibitor
- An irreversible activator
Answer: B. Competitive inhibitors bind the active site, so more substrate is needed to reach half-maximal velocity (Km rises), but at very high substrate concentrations the inhibitor is outcompeted and Vmax is preserved. Noncompetitive inhibitors (A) lower Vmax with Km unchanged; uncompetitive inhibitors (C) lower both Vmax and Km; (D) is a contradiction in terms here. Classic example: statins are competitive inhibitors of HMG-CoA reductase.
Step 1 · Genetics
Q3. Two healthy parents are each known carriers of the same autosomal recessive disease allele. What is the probability that their next child is affected?
- 100%
- 50%
- 25%
- 0% — carriers cannot have affected children
Answer: C. Each carrier parent (Aa) passes the disease allele with probability 1/2; the child needs both copies, so 1/2 × 1/2 = 1/4 (25%). The full Punnett breakdown: 25% affected (aa), 50% carriers (Aa), 25% unaffected non-carriers (AA). Watch for the common trap: if you already know a child is unaffected, the chance that child is a carrier becomes 2/3, not 1/2 — but that isn't what's asked here.
Step 1 · Renal
Q4. Which nephron segment is impermeable to water but actively reabsorbs NaCl, making it the key site of action for loop diuretics?
- Proximal convoluted tubule
- Descending limb of the loop of Henle
- Thick ascending limb of the loop of Henle
- Collecting duct
Answer: C. The thick ascending limb expresses the Na⁺-K⁺-2Cl⁻ cotransporter (NKCC2) — the target of furosemide and other loop diuretics — and is impermeable to water, which is how the medullary concentration gradient gets built. The proximal tubule (A) reabsorbs ~65% of filtered Na⁺ and water together; the descending limb (B) is water-permeable but salt-impermeable (the mirror image); the collecting duct (D) is where ADH-regulated water reabsorption and aldosterone-regulated Na⁺ reabsorption occur.
Step 1 · Metabolism
Q5. During a prolonged fast, which hormone change primarily drives hepatic ketogenesis, and what is the main substrate?
- Increased insulin; glucose
- Increased glucagon; fatty acids
- Increased cortisol; amino acids
- Decreased epinephrine; lactate
Answer: B. Fasting lowers insulin and raises glucagon, which drives lipolysis in adipose tissue; the released fatty acids undergo hepatic β-oxidation to acetyl-CoA, which is shunted into ketone-body synthesis when oxaloacetate is depleted (it's being used for gluconeogenesis). Insulin (A) does the opposite — it suppresses ketogenesis. Cortisol (C) rises in stress but glucagon is the primary fasting driver; amino acids feed gluconeogenesis, not ketogenesis. Epinephrine (D) increases, not decreases, during fasting stress.
Step 1 · Microbiology
Q6. Penicillin kills growing bacteria by interfering with which process?
- DNA replication via topoisomerase inhibition
- Protein synthesis at the 30S ribosomal subunit
- Peptidoglycan cross-linking by penicillin-binding proteins
- Folic acid synthesis via dihydropteroate synthase
Answer: C. β-lactams bind penicillin-binding proteins (transpeptidases), blocking the cross-linking of peptidoglycan in the bacterial cell wall; the weakened wall ruptures under osmotic pressure, which is why penicillin is bactericidal only against growing organisms. Topoisomerase inhibition (A) is the fluoroquinolones; 30S binding (B) is the aminoglycosides/tetracyclines; folate blockade (D) is the sulfonamides. Resistance most often comes from β-lactamase enzymes that cleave the drug's β-lactam ring.
Step 1 · Neurophysiology
Q7. During the absolute refractory period of a neuronal action potential, no stimulus — however strong — can trigger another action potential. The best explanation is:
- Voltage-gated K⁺ channels are closed
- Voltage-gated Na⁺ channels are inactivated
- The membrane is hyperpolarized below threshold
- Intracellular Ca²⁺ is depleted
Answer: B. After opening, voltage-gated Na⁺ channels enter an inactivated state from which they cannot reopen until the membrane repolarizes — no amount of stimulus overrides this. Hyperpolarization (C) describes the relative refractory period, when a stronger-than-normal stimulus can still fire the neuron (K⁺ channels open, Na⁺ channels merely recovering). K⁺ channels being closed (A) is the resting state, not the refractory mechanism; Ca²⁺ (D) matters for neurotransmitter release at the terminal, not the axonal action potential.
Step 1 · Cardiovascular
Q8. A patient with right-sided heart failure develops ankle edema. According to Starling forces, the direct cause of fluid leaving the capillaries is:
- Decreased plasma oncotic pressure
- Increased capillary hydrostatic pressure
- Increased interstitial oncotic pressure
- Decreased capillary permeability
Answer: B. Failing right-sided forward flow backs up into the venous system, raising venous (and therefore capillary) hydrostatic pressure, which pushes fluid out of capillaries faster than lymphatics can return it. Decreased plasma oncotic pressure (A) causes edema in nephrotic syndrome or liver failure — not here. Increased interstitial oncotic pressure (C) would pull fluid out but isn't the heart-failure mechanism. Capillary permeability (D) rises in inflammation, not in hydrostatic edema.
Step 2 · Pulmonary / ID
Q9. A healthy 34-year-old with no recent antibiotics develops community-acquired pneumonia and will be treated as an outpatient. Which organism is the most likely cause, and what is guideline-preferred first-line therapy?
- Mycoplasma pneumoniae; azithromycin
- Streptococcus pneumoniae; amoxicillin
- Pseudomonas aeruginosa; ciprofloxacin
- Staphylococcus aureus; vancomycin
Answer: B. S. pneumoniae remains the most common cause of community-acquired pneumonia overall, and for healthy outpatients without recent antibiotic exposure, guidelines prefer amoxicillin (or doxycycline, or a macrolide in areas of low resistance) — amoxicillin covers pneumococcus with the narrowest spectrum. Mycoplasma (A) is the classic "walking pneumonia" of young adults but is not the most common cause overall. Pseudomonas (C) is a concern in bronchiectasis or prior colonization, not healthy outpatients; MRSA pneumonia (D) follows influenza or in specific risk groups.
Step 2 · Endocrine
Q10. A 22-year-old with type 1 diabetes presents with vomiting, abdominal pain, Kussmaul respirations, glucose 480 mg/dL, and a high anion gap metabolic acidosis with ketonemia. What is the first management step?
- IV regular insulin bolus
- Isotonic IV fluid resuscitation
- Oral potassium supplementation
- IV sodium bicarbonate
Answer: B. Diabetic ketoacidosis management starts with aggressive isotonic fluid resuscitation (typically normal saline or balanced crystalloid) — these patients are profoundly volume-depleted, and restoring perfusion comes before insulin. Insulin (A) follows fluids (and only after potassium is checked: insulin drives K⁺ intracellularly, so hypokalemia must be corrected first). Bicarbonate (D) is reserved for severe acidemia (pH < 6.9) and isn't routine. The full sequence to memorize: fluids → check/replace K⁺ → insulin infusion → find and treat the precipitant (infection, missed insulin, new diagnosis).
Step 2 · OB
Q11. A pregnant patient at 28 weeks has chronic hypertension. Which antihypertensive is contraindicated in pregnancy?
- Methyldopa
- Nifedipine
- Lisinopril
- Labetalol
Answer: C. ACE inhibitors like lisinopril are teratogenic — they cause fetal renal dysgenesis, oligohydramnios, limb contractures, and calvarial hypoplasia, classically in the second and third trimesters. The safe first-line agents in pregnancy are methyldopa (A), nifedipine (B), and labetalol (D). This is a favorite test point because the mechanism question sometimes follows: ACE inhibitors block angiotensin II, and the fetal kidney depends on an intact renin-angiotensin system for development.
Step 2 · Cardiology
Q12. A 58-year-old man has 45 minutes of crushing substernal chest pain. ECG shows ST-segment elevations in leads II, III, and aVF. The most appropriate immediate next step is:
- Order troponins and wait for the result before acting
- Emergent coronary angiography with intent for percutaneous coronary intervention
- Start a heparin infusion and admit for observation
- Obtain an echocardiogram to confirm wall-motion abnormality
Answer: B. ST elevations in contiguous inferior leads (II, III, aVF = right coronary artery territory) define a STEMI, which is a clinical + ECG diagnosis — you do not wait for troponins (A) or confirmatory echo (D). The standard of care is emergent reperfusion, preferably primary PCI within 90 minutes of first medical contact (fibrinolytics if PCI is unavailable within 120 minutes). Heparin alone (C) is the treatment for NSTEMI/unstable angina, not STEMI. Also note: inferior MIs can involve the right ventricle — check right-sided leads and be cautious with nitrates if RV infarct is suspected.
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