NBME 26 208 Exam (USMLE Step 1) 2026/2027 Complete Certification Prep and Advanced Study Guide: Detailed Topic Modules, Extensive Test Bank Review, Practice Questions, and Final Exam Readiness Manual

A child presenting with intellectual disability, self-mutilating behaviors (such as lip and finger biting), choreoathetosis, and hyperuricemia/gout is diagnosed with LeschNyhan syndrome. Which metabolic pathway is primarily defective? • A. Pyrimidine de novo synthesis pathway • B. Purine salvage pathway • C. Anaerobic glycolysis pathway • D. Urea cycle pathway • E. Mitochondrial fatty acid oxidation Correct Answer: B. Purine salvage pathway Rationale: Lesch-Nyhan syndrome is an X-linked recessive disorder caused by a severe deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRT), a key enzyme in the purine salvage pathway. Without HGPRT, hypoxanthine and guanine cannot be salvaged into IMP and GMP, leading to excess accumulation of phosphoribosyl pyrophosphate (PRPP), up-regulation of de novo purine synthesis, and hyperuricemia. Question 2 A patient involved in a crush injury with a tibial fracture develops severe leg pain, dark tea-colored urine, and acute kidney injury. Urinalysis shows a positive dipstick result for blood, but microscopic examination reveals no red blood cells (RBCs). What is the most likely renal pathology? • A. Acute post-infectious glomerulonephritis B. Acute tubular necrosis (ATN) secondary to rhabdomyolysis C. Minimal change nephrotic syndrome D. Acute bacterial pyelonephritis • E. Atherosclerotic renal artery stenosis Correct Answer: B. Acute tubular necrosis (ATN) secondary to rhabdomyolysis Rationale: Muscle crush injury causes compartment syndrome and rhabdomyolysis, releasing massive amounts of myoglobin into the bloodstream. Myoglobin is filtered by the glomerulus and causes direct tubular toxicity and intratubular cast obstruction, precipitating acute tubular necrosis. Reagent dipsticks detect the heme moiety in both hemoglobin and myoglobin; thus, a positive dipstick for blood in the absence of intact RBCs on microscopy is diagnostic of myoglobinuria. Question 3 A patient presenting with ascites is evaluated for cardiac vs. hepatic pathology. Which physical examination finding most strongly points to constrictive pericarditis rather than liver cirrhosis? • A. Marked hypoalbuminemia • B. Esophageal varices on endoscopy • C. Elevated jugular venous pressure (JVP) with Kussmaul sign • D. Splenomegaly • E. Distended abdomen with fluid wave Correct Answer: C. Elevated jugular venous pressure (JVP) with Kussmaul sign Rationale: Both cirrhosis and constrictive pericarditis can cause ascites and peripheral fluid overload. However, constrictive pericarditis is a disease of right-heart filling failure, which leads to elevated JVP (often displaying a Kussmaul sign—a paradoxical rise in JVP during inspiration). Cirrhosis causes portal hypertension with normal or reduced central venous pressure / JVP. Question 4 A newborn infant presents with fragile skin and widespread friction-induced bullae. Skin biopsy demonstrates defective anchoring fibrils within the basement membrane zone. What is the primary clinical manifestation of this condition? • A. Fragile skin with blister formation (epidermolysis bullosa) B. Extensive ecchymosis and easy bruising C. Diffuse cutaneous hyperpigmentation D. Thickened, hyperkeratotic skin plaques • E. Absent eccrine sweat glands Correct Answer: A. Fragile skin with blister formation (epidermolysis bullosa) Rationale: Anchoring fibrils are composed of type VII collagen, which anchors the basal lamina of the epidermis to the underlying dermis. Genetic mutations in type VII collagen (COL7A1) cause dystrophic epidermolysis bullosa, leading to extreme skin fragility and sub-epidermal blistering following mild mechanical trauma. Question 5 A barium contrast small bowel series demonstrates prominent circular mucosal folds resulting in a characteristic "feathery" radiologic appearance in the proximal small intestine. Which anatomical structure is primarily responsible for this appearance? • A. Peyer patches in the terminal ileum • B. Selective loss of circular smooth muscle layer • C. Global villous atrophy • D. Increased mucosal surface area via plicae circulares (valvulae conniventes) • E. Decreased mesenteric arterial blood flow Correct Answer: D. Increased mucosal surface area via plicae circulares (valvulae conniventes) Rationale: The jejunum features dense, tall, circular folds of mucosa and submucosa called plicae circulares (valvulae conniventes). These structures maximize surface area for nutrient absorption and produce the classic "feathery" or "accordion" pattern on barium contrast radiography. Question 6 A client diagnosed with Chronic Lymphocytic Leukemia (CLL) develops progressive fatigue, anemia, spherocytes on peripheral blood smear, and an elevated unconjugated (indirect) bilirubin level. What is the underlying mechanism of this complication? • A. Pure red cell aplasia • B. Warm autoimmune hemolytic anemia (AIHA) C. Microcytic iron deficiency anemia D. Glucose-6-phosphate dehydrogenase (G6PD) deficiency E. Microangiopathic hemolytic anemia (MAHA) Correct Answer: B. Warm autoimmune hemolytic anemia (AIHA) Rationale: Patients with CLL are at high risk of developing warm autoimmune hemolytic anemia (mediated by IgG autoantibodies against RBC antigens). Partial phagocytosis of antibody-coated RBC membranes by splenic macrophages generates spherocytes. Extravascular destruction of RBCs in the spleen leads to elevated unconjugated bilirubin and jaundice. Question 7 A client with cerebral edema receives an intravenous infusion of mannitol. What is the expected physiological response regarding serum osmolality and antidiuretic hormone (ADH) secretion? • A. Decreased serum osmolality and decreased ADH secretion • B. Increased serum osmolality and increased ADH secretion • C. Decreased serum osmolality and increased ADH secretion • D. Increased serum osmolality and decreased ADH secretion • E. No significant change in serum osmolality Correct Answer: B. Increased serum osmolality and increased ADH secretion Rationale: Mannitol is an non-reabsorbable osmotic diuretic that remains in the intravascular space, thereby increasing plasma osmolality. Hyperosmolality is detected by hypothalamic osmoreceptors, which trigger the release of antidiuretic hormone (ADH / vasopressin) to promote renal water retention in an attempt to restore osmotic equilibrium. Question 8 Following an acute inferior wall myocardial infarction, a client suddenly develops acute pulmonary edema and a new holosystolic murmur heard best at the apex. Severe mitral regurgitation is diagnosed. Which cardiac structure was most likely disrupted by ischemic necrosis? • A. Aortic valve cusps • B. Papillary muscles or chordae tendineae C. Interventricular septum D. Sinoatrial (SA) node E. Pulmonary valve leaflets Correct Answer: B. Papillary muscles or chordae tendineae Rationale: The posteromedial papillary muscle has a single blood supply (typically from the posterior descending artery), making it highly susceptible to ischemic rupture following an acute inferior myocardial infarction. Rupture of the papillary muscle or its attached chordae tendineae causes acute flail mitral leaflet and massive mitral regurgitation. Question 9 A traveler develops acute viral hepatitis (fever, jaundice, elevated ALT/AST) two weeks after consuming raw oysters at a coastal restaurant. Which viral pathogen is the most likely cause? • A. Hepatitis B virus (HBV) • B. Hepatitis A virus (HAV) • C. Hepatitis C virus (HCV) • D. Epstein-Barr virus (EBV) • E. Vibrio vulnificus Correct Answer: B. Hepatitis A virus (HAV) Rationale: Hepatitis A virus (HAV) is a picornavirus transmitted via the fecal-oral route. Consuming contaminated water or raw/undercooked shellfish (such as oysters harvested from sewage-polluted waters) is a classic mode of transmission. HBV and HCV are blood-borne pathogens. Question 10 A 7-year-old child diagnosed with Attention-Deficit/Hyperactivity Disorder (ADHD) is started on first-line pharmacotherapy with methylphenidate. What is the primary mechanism of action of this drug? • A. Potentiation of GABA-mediated chloride conductance • B. Increasing synaptic concentrations of dopamine and norepinephrine • C. Voltage-gated sodium channel blockade D. Selective inhibition of serotonin reuptake (SSRI) E. Competitive central beta-adrenergic blockade Correct Answer: B. Increasing synaptic concentrations of dopamine and norepinephrine Rationale: First-line psychostimulants for ADHD (such as methylphenidate and amphetamines) act by blocking the reuptake and/or stimulating the presynaptic release of dopamine and norepinephrine in the prefrontal cortex, enhancing executive functioning, focus, and impulse control.