2026/2027
NBME CBSE (USMLE Step 1
Medical Exam) Comprehensive
Review and Practice Questions Study
Guide 2026/2027 Edition
Question 1: Lesch-Nyhan Syndrome Biochemistry
A 6-year-old boy presents with intellectual disability, self-mutilation behavior, and
gouty arthritis. Genetic testing reveals HGPRT deficiency. Which pair of nitrogenous
bases is primarily affected in the salvage pathway?
A. Adenine and thymine
B. Guanine and hypoxanthine
C. Cytosine and uracil
D. Guanine and uric acid
E. Xanthine and thymine
Correct Answer: B. Guanine and hypoxanthine
Rationale:
Lesch-Nyhan syndrome is caused by deficiency of hypoxanthine-guanine
phosphoribosyltransferase (HGPRT), an enzyme essential for purine salvage. HGPRT
normally recycles guanine and hypoxanthine into GMP and IMP respectively. Its
deficiency leads to excessive uric acid production and neurological dysfunction. Other
options are incorrect because thymine and cytosine are pyrimidines, uric acid is a
breakdown product rather than a salvaged base, and xanthine is downstream in
degradation rather than salvage.
Question 2: Compartment Syndrome and AKI
A 42-year-old man with a tibial fracture develops severe leg pain, paresthesia, and
dark brown urine. Urinalysis is positive for blood but no RBCs are seen. What is the
most likely cause of his acute kidney injury?
A. Glomerulonephritis
B. Acute tubular necrosis
C. Nephrotic syndrome
D. Interstitial nephritis
E. Renal artery embolism
Correct Answer: B. Acute tubular necrosis
,2026/2027
Rationale:
Rhabdomyolysis from compartment syndrome releases myoglobin, which is
nephrotoxic and causes acute tubular necrosis (ATN). The urinalysis shows “blood”
positivity without RBCs due to myoglobin. Other options involve immune, vascular,
or glomerular mechanisms not consistent with muscle breakdown.
Question 3: Constrictive Pericarditis vs
Cirrhosis
A patient with ascites is being evaluated. Which finding strongly suggests constrictive
pericarditis rather than cirrhosis?
A. Hypoalbuminemia
B. Esophageal varices
C. Elevated jugular venous pressure
D. Splenomegaly
E. Abdominal distension
Correct Answer: C. Elevated jugular venous pressure
Rationale:
Constrictive pericarditis causes impaired ventricular filling leading to systemic
venous congestion and elevated JVP. Cirrhosis causes ascites through portal
hypertension but does not elevate JVP. The remaining options are common in hepatic
disease.
Question 4: Epidermolysis Bullosa Mechanism
A newborn presents with fragile skin and blister formation due to defective anchoring
fibrils. Which structure is primarily affected?
A. Desmosomes
B. Hemidesmosomes
C. Tight junctions
D. Gap junctions
E. Basal keratinocyte nuclei
Correct Answer: B. Hemidesmosomes
Rationale:
Anchoring fibrils composed of type VII collagen stabilize hemidesmosomes, which
attach epidermis to dermis. Defects cause epidermolysis bullosa with blister formation.
Desmosomes are involved in pemphigus vulgaris, not anchoring to basement
membrane.
,2026/2027
Question 5: Jejunum vs Ileum Anatomy
A contrast study shows a segment of small intestine with prominent plicae circulares
and a “feathery” appearance. What is the primary reason?
A. Increased lymphoid tissue
B. Increased villi destruction
C. Greater mucosal surface area
D. Reduced muscularis thickness
E. Reduced blood supply
Correct Answer: C. Greater mucosal surface area
Rationale:
The jejunum has prominent plicae circulares that increase mucosal surface area and
produce a feathery radiographic appearance. The ileum has fewer folds and more
lymphoid tissue (Peyer patches). The difference is structural, not vascular or
destructive.
Question 6: Autoimmune Hemolytic Anemia
A patient with chronic lymphocytic leukemia develops anemia, jaundice, and
spherocytes on smear. What is the most likely mechanism?
A. Iron deficiency
B. Warm IgG-mediated hemolysis
C. Vitamin B12 deficiency
D. Microangiopathic hemolysis
E. Bone marrow failure
Correct Answer: B. Warm IgG-mediated hemolysis
Rationale:
CLL is associated with warm autoimmune hemolytic anemia where IgG antibodies
coat RBCs leading to splenic destruction and spherocyte formation. Other options do
not explain immune-mediated hemolysis or spherocytes.
Question 7: Mannitol and ADH Response
After infusion of mannitol, what physiological response is expected?
A. Increased osmolality and increased ADH
B. Decreased osmolality and decreased ADH
C. Increased osmolality and decreased ADH
D. No change in osmolality
E. Increased urine glucose
, 2026/2027
Correct Answer: A. Increased osmolality and increased ADH
Rationale:
Mannitol increases plasma osmolality, stimulating hypothalamic osmoreceptors and
increasing ADH secretion. ADH promotes water reabsorption to restore osmotic
balance. Other options contradict normal osmotic physiology.
Question 8: Mitral Regurgitation After MI
A patient develops acute systolic murmur after myocardial infarction. What is the
most likely cause?
A. Aortic stenosis
B. Mitral stenosis
C. Papillary muscle rupture
D. Atrial septal defect
E. Ventricular septal hypertrophy
Correct Answer: C. Papillary muscle rupture
Rationale:
Post-MI ischemia can rupture papillary muscles or chordae tendineae, causing acute
mitral regurgitation. This leads to systolic murmur and pulmonary edema. Other
valvular or septal lesions do not present acutely after MI in this pattern.
Question 9: Hepatitis A Transmission
A patient develops jaundice after eating raw oysters. Which pathogen is most likely?
A. Hepatitis B virus
B. Hepatitis C virus
C. Hepatitis A virus
D. Epstein-Barr virus
E. Cytomegalovirus
Correct Answer: C. Hepatitis A virus
Rationale:
Hepatitis A is transmitted via fecal-oral route, commonly through contaminated food
such as shellfish. It causes acute hepatitis but does not become chronic. Other
hepatitis viruses are blood-borne rather than food-borne.
Question 10: ADHD Treatment Mechanism
NBME CBSE (USMLE Step 1
Medical Exam) Comprehensive
Review and Practice Questions Study
Guide 2026/2027 Edition
Question 1: Lesch-Nyhan Syndrome Biochemistry
A 6-year-old boy presents with intellectual disability, self-mutilation behavior, and
gouty arthritis. Genetic testing reveals HGPRT deficiency. Which pair of nitrogenous
bases is primarily affected in the salvage pathway?
A. Adenine and thymine
B. Guanine and hypoxanthine
C. Cytosine and uracil
D. Guanine and uric acid
E. Xanthine and thymine
Correct Answer: B. Guanine and hypoxanthine
Rationale:
Lesch-Nyhan syndrome is caused by deficiency of hypoxanthine-guanine
phosphoribosyltransferase (HGPRT), an enzyme essential for purine salvage. HGPRT
normally recycles guanine and hypoxanthine into GMP and IMP respectively. Its
deficiency leads to excessive uric acid production and neurological dysfunction. Other
options are incorrect because thymine and cytosine are pyrimidines, uric acid is a
breakdown product rather than a salvaged base, and xanthine is downstream in
degradation rather than salvage.
Question 2: Compartment Syndrome and AKI
A 42-year-old man with a tibial fracture develops severe leg pain, paresthesia, and
dark brown urine. Urinalysis is positive for blood but no RBCs are seen. What is the
most likely cause of his acute kidney injury?
A. Glomerulonephritis
B. Acute tubular necrosis
C. Nephrotic syndrome
D. Interstitial nephritis
E. Renal artery embolism
Correct Answer: B. Acute tubular necrosis
,2026/2027
Rationale:
Rhabdomyolysis from compartment syndrome releases myoglobin, which is
nephrotoxic and causes acute tubular necrosis (ATN). The urinalysis shows “blood”
positivity without RBCs due to myoglobin. Other options involve immune, vascular,
or glomerular mechanisms not consistent with muscle breakdown.
Question 3: Constrictive Pericarditis vs
Cirrhosis
A patient with ascites is being evaluated. Which finding strongly suggests constrictive
pericarditis rather than cirrhosis?
A. Hypoalbuminemia
B. Esophageal varices
C. Elevated jugular venous pressure
D. Splenomegaly
E. Abdominal distension
Correct Answer: C. Elevated jugular venous pressure
Rationale:
Constrictive pericarditis causes impaired ventricular filling leading to systemic
venous congestion and elevated JVP. Cirrhosis causes ascites through portal
hypertension but does not elevate JVP. The remaining options are common in hepatic
disease.
Question 4: Epidermolysis Bullosa Mechanism
A newborn presents with fragile skin and blister formation due to defective anchoring
fibrils. Which structure is primarily affected?
A. Desmosomes
B. Hemidesmosomes
C. Tight junctions
D. Gap junctions
E. Basal keratinocyte nuclei
Correct Answer: B. Hemidesmosomes
Rationale:
Anchoring fibrils composed of type VII collagen stabilize hemidesmosomes, which
attach epidermis to dermis. Defects cause epidermolysis bullosa with blister formation.
Desmosomes are involved in pemphigus vulgaris, not anchoring to basement
membrane.
,2026/2027
Question 5: Jejunum vs Ileum Anatomy
A contrast study shows a segment of small intestine with prominent plicae circulares
and a “feathery” appearance. What is the primary reason?
A. Increased lymphoid tissue
B. Increased villi destruction
C. Greater mucosal surface area
D. Reduced muscularis thickness
E. Reduced blood supply
Correct Answer: C. Greater mucosal surface area
Rationale:
The jejunum has prominent plicae circulares that increase mucosal surface area and
produce a feathery radiographic appearance. The ileum has fewer folds and more
lymphoid tissue (Peyer patches). The difference is structural, not vascular or
destructive.
Question 6: Autoimmune Hemolytic Anemia
A patient with chronic lymphocytic leukemia develops anemia, jaundice, and
spherocytes on smear. What is the most likely mechanism?
A. Iron deficiency
B. Warm IgG-mediated hemolysis
C. Vitamin B12 deficiency
D. Microangiopathic hemolysis
E. Bone marrow failure
Correct Answer: B. Warm IgG-mediated hemolysis
Rationale:
CLL is associated with warm autoimmune hemolytic anemia where IgG antibodies
coat RBCs leading to splenic destruction and spherocyte formation. Other options do
not explain immune-mediated hemolysis or spherocytes.
Question 7: Mannitol and ADH Response
After infusion of mannitol, what physiological response is expected?
A. Increased osmolality and increased ADH
B. Decreased osmolality and decreased ADH
C. Increased osmolality and decreased ADH
D. No change in osmolality
E. Increased urine glucose
, 2026/2027
Correct Answer: A. Increased osmolality and increased ADH
Rationale:
Mannitol increases plasma osmolality, stimulating hypothalamic osmoreceptors and
increasing ADH secretion. ADH promotes water reabsorption to restore osmotic
balance. Other options contradict normal osmotic physiology.
Question 8: Mitral Regurgitation After MI
A patient develops acute systolic murmur after myocardial infarction. What is the
most likely cause?
A. Aortic stenosis
B. Mitral stenosis
C. Papillary muscle rupture
D. Atrial septal defect
E. Ventricular septal hypertrophy
Correct Answer: C. Papillary muscle rupture
Rationale:
Post-MI ischemia can rupture papillary muscles or chordae tendineae, causing acute
mitral regurgitation. This leads to systolic murmur and pulmonary edema. Other
valvular or septal lesions do not present acutely after MI in this pattern.
Question 9: Hepatitis A Transmission
A patient develops jaundice after eating raw oysters. Which pathogen is most likely?
A. Hepatitis B virus
B. Hepatitis C virus
C. Hepatitis A virus
D. Epstein-Barr virus
E. Cytomegalovirus
Correct Answer: C. Hepatitis A virus
Rationale:
Hepatitis A is transmitted via fecal-oral route, commonly through contaminated food
such as shellfish. It causes acute hepatitis but does not become chronic. Other
hepatitis viruses are blood-borne rather than food-borne.
Question 10: ADHD Treatment Mechanism
