, Question 1
A cell exposed to prolonged hypoxia shows decreased ATP, increased
anaerobic glycolysis, and failure of the Na+/K+ ATPase. Which subsequent
event most directly commits the cell to irreversible injury?
A. Influx of calcium and activation of phospholipases, proteases, and
endonucleases
B. Cellular swelling due to sodium and water accumulation
C. Ribosomal detachment and decreased protein synthesis
D. Lactate accumulation and intracellular acidosis
Correct Answer: A - Influx of calcium and activation of
phospholipases, proteases, and endonucleases
RATIONALE
Irreversible injury is marked by severe mitochondrial dysfunction,
membrane damage, and calcium influx that activates degradative
enzymes. Swelling, ribosomal detachment, and acidosis are reversible
early changes. Calcium overload is the critical commitment point.
Question 2
Which statement best distinguishes the molecular mechanism of a
gain-of-function mutation in a proto-oncogene from that of a tumor suppressor
gene?
A. Proto-oncogene mutations typically require both alleles to be affected,
whereas tumor suppressor mutations are dominant.
B. Proto-oncogene mutations are usually dominant and require only one
allele, while tumor suppressor mutations typically require biallelic
inactivation.
C. Proto-oncogene mutations always involve chromosomal
translocations, whereas tumor suppressor mutations are point mutations.
D. Proto-oncogene mutations lead to loss of function, whereas tumor
suppressor mutations lead to constitutive activation.
Page 2
, Correct Answer: B - Proto-oncogene mutations are usually
dominant and require only one allele, while tumor suppressor
mutations typically require biallelic inactivation.
RATIONALE
Proto-oncogenes become oncogenes through dominant
gain-of-function alterations (often one allele). Tumor suppressor genes
follow Knudson's two-hit hypothesis, requiring inactivation of both
alleles. The other options misstate the genetics or mechanisms.
Question 3
A patient with sepsis has hypotension refractory to fluids. Which
pathophysiologic mechanism best explains the failure of vasopressors to
restore blood pressure initially?
A. Upregulation of alpha-1 adrenergic receptors
B. Excessive nitric oxide production causing vasoplegia and decreased
vascular tone
C. Increased systemic vascular resistance due to endothelin release
D. Enhanced baroreceptor sensitivity leading to bradycardia
Correct Answer: B - Excessive nitric oxide production causing
vasoplegia and decreased vascular tone
RATIONALE
In septic shock, inflammatory mediators induce inducible nitric oxide
synthase, producing excess NO that causes profound vasodilation and
vasopressor resistance. Other options describe opposite or unrelated
mechanisms.
Question 4
Which laboratory pattern best supports a diagnosis of syndrome of
inappropriate antidiuretic hormone (SIADH) rather than cerebral salt wasting?
A. Serum osmolality <275 mOsm/kg, urine osmolality >100 mOsm/kg,
Page 3
A cell exposed to prolonged hypoxia shows decreased ATP, increased
anaerobic glycolysis, and failure of the Na+/K+ ATPase. Which subsequent
event most directly commits the cell to irreversible injury?
A. Influx of calcium and activation of phospholipases, proteases, and
endonucleases
B. Cellular swelling due to sodium and water accumulation
C. Ribosomal detachment and decreased protein synthesis
D. Lactate accumulation and intracellular acidosis
Correct Answer: A - Influx of calcium and activation of
phospholipases, proteases, and endonucleases
RATIONALE
Irreversible injury is marked by severe mitochondrial dysfunction,
membrane damage, and calcium influx that activates degradative
enzymes. Swelling, ribosomal detachment, and acidosis are reversible
early changes. Calcium overload is the critical commitment point.
Question 2
Which statement best distinguishes the molecular mechanism of a
gain-of-function mutation in a proto-oncogene from that of a tumor suppressor
gene?
A. Proto-oncogene mutations typically require both alleles to be affected,
whereas tumor suppressor mutations are dominant.
B. Proto-oncogene mutations are usually dominant and require only one
allele, while tumor suppressor mutations typically require biallelic
inactivation.
C. Proto-oncogene mutations always involve chromosomal
translocations, whereas tumor suppressor mutations are point mutations.
D. Proto-oncogene mutations lead to loss of function, whereas tumor
suppressor mutations lead to constitutive activation.
Page 2
, Correct Answer: B - Proto-oncogene mutations are usually
dominant and require only one allele, while tumor suppressor
mutations typically require biallelic inactivation.
RATIONALE
Proto-oncogenes become oncogenes through dominant
gain-of-function alterations (often one allele). Tumor suppressor genes
follow Knudson's two-hit hypothesis, requiring inactivation of both
alleles. The other options misstate the genetics or mechanisms.
Question 3
A patient with sepsis has hypotension refractory to fluids. Which
pathophysiologic mechanism best explains the failure of vasopressors to
restore blood pressure initially?
A. Upregulation of alpha-1 adrenergic receptors
B. Excessive nitric oxide production causing vasoplegia and decreased
vascular tone
C. Increased systemic vascular resistance due to endothelin release
D. Enhanced baroreceptor sensitivity leading to bradycardia
Correct Answer: B - Excessive nitric oxide production causing
vasoplegia and decreased vascular tone
RATIONALE
In septic shock, inflammatory mediators induce inducible nitric oxide
synthase, producing excess NO that causes profound vasodilation and
vasopressor resistance. Other options describe opposite or unrelated
mechanisms.
Question 4
Which laboratory pattern best supports a diagnosis of syndrome of
inappropriate antidiuretic hormone (SIADH) rather than cerebral salt wasting?
A. Serum osmolality <275 mOsm/kg, urine osmolality >100 mOsm/kg,
Page 3
