USMLE Step 1 Exam Flashcards

Q: What do these USMLE Step 1 flashcards cover?

These cards focus on high-yield active recall from local Step 1 content: biochemical enzyme defects, genetics patterns, immunology mechanisms, microbiology anchors, pathology distinctions, physiology formulas, pharmacology mechanisms, biostatistics, and ethics basics.

Q: Are these flashcards copied from live USMLE questions?

No. The cards use original prompts and explanations based on local project content and stable foundational science concepts. They are not copied from live exams, recalled questions, leaked materials, or proprietary question banks.

Q: How many questions are on USMLE Step 1?

Local exam metadata follows the official USMLE format: Step 1 has up to 280 multiple-choice questions across 7 blocks, with up to 40 questions per block, administered in one testing day of approximately 8 hours.

Q: Is USMLE Step 1 scored pass/fail?

Yes. Step 1 is reported as Pass/Fail. USMLE still reports an equivalent passing standard of 196 on the prior 3-digit scale for reference.

Q: How should these flashcards fit into Step 1 prep?

Use them for daily active recall and rapid weak-area repair, then apply the same concepts in timed question blocks. Flashcards are best for mechanisms and distinctions; practice questions are still needed for vignette interpretation and pacing.

Question 1

Which bilirubin-processing enzyme is deficient in Gilbert syndrome and Crigler-Najjar syndrome?

Accepted Answer

UDP-glucuronosyltransferase. Low activity impairs hepatic conjugation of bilirubin, producing unconjugated hyperbilirubinemia. Hemolysis can also raise indirect bilirubin, but the primary conjugation defect is in this enzyme.

Question 2

What is the enzyme defect and dietary treatment in classic phenylketonuria?

Accepted Answer

Phenylalanine hydroxylase deficiency, most often. Treat with phenylalanine restriction and adequate tyrosine, because tyrosine becomes conditionally essential when phenylalanine cannot be converted efficiently.

Question 3

Which glycogen storage disease causes severe fasting hypoglycemia, lactic acidosis, hyperuricemia, and hepatomegaly?

Accepted Answer

Von Gierke disease, caused by glucose-6-phosphatase deficiency. The liver cannot release free glucose from glycogenolysis or gluconeogenesis, so fasting produces marked hypoglycemia.

Question 4

Which enzyme is deficient in classic galactosemia?

Accepted Answer

Galactose-1-phosphate uridyltransferase. Infants exposed to lactose can develop vomiting, jaundice, hepatomegaly, cataracts, and developmental injury unless galactose and lactose are removed from the diet.

Question 5

Which vitamin-derived cofactor is required by pyruvate dehydrogenase?

Accepted Answer

Thiamine pyrophosphate from vitamin B1. Pyruvate dehydrogenase also uses lipoic acid, CoA, FAD, and NAD+, but thiamine deficiency is the classic Step 1 anchor for impaired pyruvate to acetyl-CoA conversion.

Question 6

What is the rate-limiting enzyme in cholesterol synthesis and what drug class targets it?

Accepted Answer

HMG-CoA reductase is the rate-limiting enzyme, and statins inhibit it. The consequence is decreased hepatic cholesterol synthesis and increased LDL receptor expression.

Question 7

What genetic mechanism causes fragile X syndrome?

Accepted Answer

CGG trinucleotide repeat expansion in the FMR1 gene on the X chromosome. Expansion causes methylation and reduced FMR1 expression, classically producing inherited intellectual disability, long face, large ears, and macroorchidism in males.

Question 8

How do Prader-Willi and Angelman syndromes differ at chromosome 15q11-q13?

Accepted Answer

Prader-Willi results from loss of paternal expression; Angelman results from loss of maternal expression. Prader-Willi classically features hypotonia followed by hyperphagia, while Angelman features severe developmental delay, seizures, ataxia, and frequent laughter.

Question 9

Which proliferative signaling pathway is typically downstream of receptor tyrosine kinases?

Accepted Answer

The Ras-MAPK pathway. Receptor tyrosine kinase activation commonly promotes growth and proliferation through Ras, while cAMP, IP3, and nitric oxide are anchors for other receptor systems.

Question 10

What does p53 do after DNA damage?

Accepted Answer

p53 promotes cell-cycle arrest, DNA repair, and apoptosis when damage is severe. Loss of p53 removes a major checkpoint and allows damaged cells to keep dividing.

Question 11

What is the core defect in chronic granulomatous disease?

Accepted Answer

Defective NADPH oxidase impairs the respiratory burst. Neutrophils cannot generate superoxide efficiently, leading to recurrent infections with catalase-positive organisms and granuloma formation.

Question 12

What immune defect follows thymic aplasia in DiGeorge syndrome?

Accepted Answer

T-cell deficiency. Failed development of the third and fourth pharyngeal pouches can cause thymic aplasia, hypocalcemia from parathyroid hypoplasia, and conotruncal cardiac defects.

Question 13

Which SCID form is caused by IL2RG mutation and how is it inherited?

Accepted Answer

X-linked recessive SCID due to common gamma chain mutation. It disrupts multiple interleukin receptor signals, causing severe T-cell and NK-cell dysfunction with profound susceptibility to infection.

Question 14

What cell and antibody drive type I hypersensitivity reactions?

Accepted Answer

IgE bound to mast cells. Re-exposure cross-links IgE, triggering mast-cell degranulation and release of mediators that cause urticaria, bronchospasm, hypotension, or anaphylaxis.

Question 15

Deficiency of terminal complement components C5-C9 predisposes to which infections?

Accepted Answer

Recurrent Neisseria infections. The terminal complement pathway forms the membrane attack complex, which is especially important for defense against encapsulated Neisseria species.

Question 16

What is the adhesion defect in leukocyte adhesion deficiency type 1?

Accepted Answer

Defective CD18 integrins. Neutrophils cannot adhere and migrate into tissue effectively, causing recurrent bacterial infections, impaired pus formation, poor wound healing, and delayed umbilical cord separation.

Question 17

Which MHC class presents antigen to CD4 helper T cells?

Accepted Answer

MHC class II presents extracellular antigen to CD4 T cells. MHC class I presents intracellular antigen to CD8 cytotoxic T cells, so the class tells you both the source of antigen and the responding T-cell type.

Question 18

Which Staphylococcus aureus feature distinguishes it from coagulase-negative staphylococci?

Accepted Answer

Coagulase positivity. S. aureus is catalase positive and coagulase positive, helping it form fibrin barriers around infection; coagulase-negative staphylococci include S. epidermidis and S. saprophyticus.

Question 19

Which two lab anchors help identify Streptococcus pneumoniae?

Accepted Answer

Optochin sensitivity and bile solubility. S. pneumoniae is an encapsulated, alpha-hemolytic, lancet-shaped diplococcus that commonly causes pneumonia, meningitis, otitis media, and sinusitis.

Question 20

What is the classic cause of multiple ring-enhancing brain lesions in AIDS with CD4 count below 100?

Accepted Answer

Toxoplasma gondii. It often causes focal neurologic deficits and multiple lesions, especially in the basal ganglia. Primary CNS lymphoma is an important differential but is usually solitary.

Question 21

Which hepatitis B viral protein is linked to hepatocellular carcinoma risk?

Accepted Answer

HBx protein. It can disrupt tumor-suppressor control and promote oncogenic signaling, while chronic inflammation and regeneration from persistent HBV infection add additional cancer risk.

Question 22

Which HIV cell target explains progressive loss of adaptive immune coordination?

Accepted Answer

CD4 T helper cells. HIV entry depends on CD4 plus a chemokine coreceptor such as CCR5 or CXCR4, and CD4 decline weakens macrophage activation, B-cell help, and cytotoxic T-cell responses.

Question 23

What type of necrosis is classically found in tuberculosis granulomas?

Accepted Answer

Caseating necrosis. TB often produces granulomas with central cheese-like necrosis, reflecting a type IV hypersensitivity response organized by T cells and activated macrophages.

Question 24

Which toxins cause Clostridioides difficile pseudomembranous colitis?

Accepted Answer

Toxins A and B. They inactivate Rho GTPases, disrupting the cytoskeleton and epithelial barrier, which causes watery diarrhea and pseudomembrane formation after antibiotic-associated dysbiosis.

Question 25

How do gout and pseudogout crystals differ under polarized light?

Accepted Answer

Gout has needle-shaped, negatively birefringent monosodium urate crystals. Pseudogout has rhomboid, positively birefringent calcium pyrophosphate crystals.

Question 26

What coagulation pattern is expected in hemophilia A?

Accepted Answer

Factor VIII deficiency causes prolonged PTT with normal PT and normal platelet count. Deep tissue bleeding and hemarthroses are more typical than mucosal bleeding.

Question 27

Which iron study best separates iron deficiency anemia from anemia of chronic disease?

Accepted Answer

Ferritin is low in iron deficiency anemia but normal or high in anemia of chronic disease. Both can have low serum iron, so ferritin and total iron-binding capacity help distinguish depleted stores from inflammatory iron sequestration.

Question 28

What finding distinguishes vitamin B12 deficiency from folate deficiency?

Accepted Answer

Neurologic dysfunction points to B12 deficiency. Both can cause megaloblastic anemia, but B12 deficiency can also cause demyelination with loss of vibration and proprioception plus upper motor neuron signs.

Question 29

Which leukocytes dominate acute versus chronic inflammation?

Accepted Answer

Neutrophils dominate acute inflammation, especially early bacterial injury. Macrophages, lymphocytes, and plasma cells dominate chronic inflammation, reflecting ongoing immune activation and tissue remodeling.

Question 30

What is the key difference between liquefactive and coagulative necrosis?

Accepted Answer

Liquefactive necrosis digests tissue into liquid material, classically in brain infarcts and abscesses. Coagulative necrosis preserves tissue architecture for days and is typical of ischemic infarcts in most solid organs except the brain.

Question 31

Which tumor suppressor is commonly lost early in the adenoma-carcinoma sequence of colorectal cancer?

Accepted Answer

APC. Loss of APC increases beta-catenin signaling and promotes adenoma formation; later changes often include KRAS activation and p53 loss as lesions progress toward carcinoma.

Question 32

What inheritance pattern is associated with BRCA1 and BRCA2 cancer predisposition?

Accepted Answer

Autosomal dominant cancer predisposition. A germline mutation in one allele increases risk, while tumor formation follows loss or inactivation of the remaining functional allele in affected tissue.

Question 33

What is the equation for renal clearance of a substance?

Accepted Answer

Clearance equals urine concentration times urine flow rate divided by plasma concentration: C = (U x V) / P. A clearance near GFR suggests free filtration with no net secretion or reabsorption.

Question 34

How does FEV1/FVC change in obstructive versus restrictive lung disease?

Accepted Answer

Obstructive disease decreases FEV1/FVC because expiratory flow is impaired. Restrictive disease usually has a normal or increased ratio because FEV1 and FVC fall together, with FVC reduced proportionally or more.

Question 35

What is the oxygenation consequence of a true pulmonary shunt?

Accepted Answer

A true shunt causes hypoxemia that responds poorly to supplemental oxygen because blood bypasses ventilated alveoli. Low V/Q units improve more with oxygen than a complete shunt does.

Question 36

Why do loop diuretics commonly cause hypokalemia?

Accepted Answer

They block Na+-K+-2Cl- transport in the thick ascending limb, increasing distal sodium delivery and tubular flow. Distal sodium reabsorption through ENaC creates a lumen-negative gradient that promotes potassium secretion.

Question 37

What acid-base disorder follows prolonged vomiting or pyloric stenosis?

Accepted Answer

Metabolic alkalosis with volume depletion. Loss of gastric acid raises serum bicarbonate, while volume contraction activates aldosterone and can produce hypokalemia and paradoxical aciduria.

Question 38

What is the fastest baroreceptor response to acute blood loss?

Accepted Answer

Increased heart rate from decreased vagal tone and increased sympathetic output. Sympathetic vasoconstriction and increased contractility also help maintain pressure, but heart-rate change is a rapid early response.

Question 39

What stimulus causes BNP release in heart failure?

Accepted Answer

Ventricular wall stretch. BNP promotes natriuresis, diuresis, and vasodilation, so an elevated level reflects volume or pressure stress on the ventricles.

Question 40

What hemodynamic change causes pulsus paradoxus in cardiac tamponade?

Accepted Answer

Exaggerated inspiratory fall in systolic blood pressure. Increased venous return to the right heart shifts the septum leftward within a fixed pericardial space, reducing left ventricular filling during inspiration.

Question 41

What does the Henderson-Hasselbalch relationship say about metabolic acidosis compensation?

Accepted Answer

Lower bicarbonate lowers pH unless ventilation decreases PaCO2. Respiratory compensation is hyperventilation, which reduces PaCO2 and partially restores the bicarbonate-to-carbon dioxide ratio.

Question 42

Why does hypokalemia increase digoxin toxicity?

Accepted Answer

Potassium and digoxin compete at the Na+/K+-ATPase. Low potassium allows more digoxin binding, increasing pump inhibition and raising the risk of arrhythmias, visual symptoms, nausea, and confusion.

Question 43

What enzyme does methotrexate inhibit, and what reduces toxicity?

Accepted Answer

Methotrexate inhibits dihydrofolate reductase. Folinic acid, also called leucovorin, can rescue normal cells from folate depletion and reduce mucositis and myelosuppression.

Question 44

What adverse effects anchor ACE inhibitors on Step 1?

Accepted Answer

Dry cough, angioedema, hyperkalemia, and teratogenicity. ACE inhibitors reduce angiotensin II and aldosterone; cough and angioedema are linked to increased bradykinin.

Question 45

Why can beta blockers make diabetes management riskier?

Accepted Answer

They can mask adrenergic warning signs of hypoglycemia such as tremor, palpitations, and tachycardia. Nonselective beta blockers can also impair glycogenolysis and worsen bronchospasm in susceptible patients.

Question 46

What transporter does ezetimibe inhibit?

Accepted Answer

NPC1L1 on intestinal enterocytes. Blocking this transporter reduces cholesterol absorption, decreases hepatic cholesterol delivery, and increases LDL receptor expression.

Question 47

What lab pattern points to classic 21-hydroxylase deficiency?

Accepted Answer

Elevated 17-hydroxyprogesterone with cortisol deficiency, aldosterone deficiency, and androgen excess. Severe forms cause salt wasting, hypotension, hyperkalemia, and virilization of genetic females.

Question 48

What is the defective gene and primary accumulation site in Wilson disease?

Accepted Answer

ATP7B mutation causes impaired copper excretion into bile. Copper first accumulates in the liver, then can deposit in the brain and cornea, producing neurologic findings and Kayser-Fleischer rings.

Question 49

How do sensitivity and specificity differ?

Accepted Answer

Sensitivity is the proportion of diseased patients who test positive, so a highly sensitive test helps rule out disease when negative. Specificity is the proportion without disease who test negative, so a highly specific test helps rule in disease when positive.

Question 50

How do capacity and competence differ in medical decision-making?

Accepted Answer

Capacity is a clinical assessment of a patient's ability to understand, appreciate, reason, and communicate a choice for a specific decision. Competence is a legal determination made by a court.

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