Free USMLE Step 1 Exam Flashcards

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.

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

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

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.

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.

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

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.

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.

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.

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.

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

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

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.

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.

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

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.

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.

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.

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

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.

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.

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.

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

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.

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

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

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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

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.

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

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.

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

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.

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

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

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.

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

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

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.

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.

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.