, Question 1
A patient with chronic kidney disease has an arterial blood gas showing pH
7.32, PaCO2 30 mmHg, and HCO3- 15 mEq/L. What is the primary acid-base
disorder?
A. Metabolic acidosis with respiratory compensation
B. Respiratory alkalosis with metabolic compensation
C. Mixed metabolic acidosis and respiratory alkalosis
D. Metabolic alkalosis with respiratory compensation
Correct Answer: A - Metabolic acidosis with respiratory
compensation
RATIONALE
The low pH indicates acidosis; the low HCO3- suggests a metabolic
origin. The low PaCO2 reflects respiratory compensation
(hyperventilation), consistent with Winter's formula. Without
compensation, PaCO2 would be higher, so this is not a mixed
disorder.
Question 2
Which molecular defect best explains the premature atherosclerosis seen in
familial hypercholesterolemia?
A. Defective LDL receptor leading to reduced hepatic clearance of LDL
B. Overproduction of apolipoprotein B-100
C. Increased lipoprotein lipase activity
D. Deficiency of cholesteryl ester transfer protein
Correct Answer: A - Defective LDL receptor leading to reduced
hepatic clearance of LDL
Page 2
, RATIONALE
Familial hypercholesterolemia is most commonly caused by mutations
in the LDLR gene, impairing receptor-mediated endocytosis of LDL
and causing markedly elevated LDL-C. Overproduction of apoB-100
occurs in familial combined hyperlipidemia, while increased LPL
activity would lower triglycerides. CETP deficiency leads to high
HDL, not premature atherosclerosis.
Question 3
In a patient with septic shock, which pathophysiologic mechanism primarily
accounts for the hypotension refractory to fluid resuscitation?
A. Inducible nitric oxide synthase-mediated vasodilation
B. Increased systemic vascular resistance
C. Cardiogenic depression due to myocardial infarction
D. Hypovolemia from third-spacing
Correct Answer: A - Inducible nitric oxide synthase-mediated
vasodilation
RATIONALE
Septic shock involves endotoxin-induced upregulation of iNOS,
producing excessive nitric oxide that causes profound vasodilation and
vasopressor-resistant hypotension. Increased SVR is opposite to the
vasodilation seen. Cardiogenic and hypovolemic components may
coexist but are not the primary mechanism of refractory hypotension.
Question 4
Which statement best describes the role of tumor suppressor gene inactivation
in the two-hit hypothesis of retinoblastoma?
A. Both alleles of RB1 must be inactivated for tumor formation.
B. A single hit in RB1 is sufficient for tumorigenesis.
C. RB1 inactivation leads to increased apoptosis.
D. RB1 mutations are always inherited.
Page 3
, Correct Answer: A - Both alleles of RB1 must be inactivated for
tumor formation.
RATIONALE
Knudson's two-hit hypothesis states that both alleles of a tumor
suppressor gene like RB1 must be inactivated (e.g., mutation plus loss
of heterozygosity) for cancer to develop. A single hit is insufficient
because the remaining wild-type allele can still function. RB1
mutations can be sporadic or inherited, and loss of RB1 leads to
uncontrolled cell cycle progression, not increased apoptosis.
Question 5
A patient with heart failure has elevated BNP. Which mechanism best explains
BNP's natriuretic effect?
A. Inhibition of ENaC in the collecting duct
B. Vasoconstriction of afferent arterioles
C. Stimulation of aldosterone release
D. Activation of the renin-angiotensin system
Correct Answer: A - Inhibition of ENaC in the collecting duct
RATIONALE
BNP binds to natriuretic peptide receptor A, increasing cGMP and
inhibiting ENaC in the collecting duct, promoting natriuresis. It also
dilates afferent arterioles and inhibits renin and aldosterone, opposing
the RAAS. Options B, C, and D describe effects opposite to BNP's
actions.
Question 6
Which pathophysiologic process is most directly responsible for the
development of diabetic nephropathy?
A. Hyperglycemia-induced advanced glycation end-products and
mesangial expansion
B. Autoimmune destruction of podocytes
Page 4
A patient with chronic kidney disease has an arterial blood gas showing pH
7.32, PaCO2 30 mmHg, and HCO3- 15 mEq/L. What is the primary acid-base
disorder?
A. Metabolic acidosis with respiratory compensation
B. Respiratory alkalosis with metabolic compensation
C. Mixed metabolic acidosis and respiratory alkalosis
D. Metabolic alkalosis with respiratory compensation
Correct Answer: A - Metabolic acidosis with respiratory
compensation
RATIONALE
The low pH indicates acidosis; the low HCO3- suggests a metabolic
origin. The low PaCO2 reflects respiratory compensation
(hyperventilation), consistent with Winter's formula. Without
compensation, PaCO2 would be higher, so this is not a mixed
disorder.
Question 2
Which molecular defect best explains the premature atherosclerosis seen in
familial hypercholesterolemia?
A. Defective LDL receptor leading to reduced hepatic clearance of LDL
B. Overproduction of apolipoprotein B-100
C. Increased lipoprotein lipase activity
D. Deficiency of cholesteryl ester transfer protein
Correct Answer: A - Defective LDL receptor leading to reduced
hepatic clearance of LDL
Page 2
, RATIONALE
Familial hypercholesterolemia is most commonly caused by mutations
in the LDLR gene, impairing receptor-mediated endocytosis of LDL
and causing markedly elevated LDL-C. Overproduction of apoB-100
occurs in familial combined hyperlipidemia, while increased LPL
activity would lower triglycerides. CETP deficiency leads to high
HDL, not premature atherosclerosis.
Question 3
In a patient with septic shock, which pathophysiologic mechanism primarily
accounts for the hypotension refractory to fluid resuscitation?
A. Inducible nitric oxide synthase-mediated vasodilation
B. Increased systemic vascular resistance
C. Cardiogenic depression due to myocardial infarction
D. Hypovolemia from third-spacing
Correct Answer: A - Inducible nitric oxide synthase-mediated
vasodilation
RATIONALE
Septic shock involves endotoxin-induced upregulation of iNOS,
producing excessive nitric oxide that causes profound vasodilation and
vasopressor-resistant hypotension. Increased SVR is opposite to the
vasodilation seen. Cardiogenic and hypovolemic components may
coexist but are not the primary mechanism of refractory hypotension.
Question 4
Which statement best describes the role of tumor suppressor gene inactivation
in the two-hit hypothesis of retinoblastoma?
A. Both alleles of RB1 must be inactivated for tumor formation.
B. A single hit in RB1 is sufficient for tumorigenesis.
C. RB1 inactivation leads to increased apoptosis.
D. RB1 mutations are always inherited.
Page 3
, Correct Answer: A - Both alleles of RB1 must be inactivated for
tumor formation.
RATIONALE
Knudson's two-hit hypothesis states that both alleles of a tumor
suppressor gene like RB1 must be inactivated (e.g., mutation plus loss
of heterozygosity) for cancer to develop. A single hit is insufficient
because the remaining wild-type allele can still function. RB1
mutations can be sporadic or inherited, and loss of RB1 leads to
uncontrolled cell cycle progression, not increased apoptosis.
Question 5
A patient with heart failure has elevated BNP. Which mechanism best explains
BNP's natriuretic effect?
A. Inhibition of ENaC in the collecting duct
B. Vasoconstriction of afferent arterioles
C. Stimulation of aldosterone release
D. Activation of the renin-angiotensin system
Correct Answer: A - Inhibition of ENaC in the collecting duct
RATIONALE
BNP binds to natriuretic peptide receptor A, increasing cGMP and
inhibiting ENaC in the collecting duct, promoting natriuresis. It also
dilates afferent arterioles and inhibits renin and aldosterone, opposing
the RAAS. Options B, C, and D describe effects opposite to BNP's
actions.
Question 6
Which pathophysiologic process is most directly responsible for the
development of diabetic nephropathy?
A. Hyperglycemia-induced advanced glycation end-products and
mesangial expansion
B. Autoimmune destruction of podocytes
Page 4
