, Question 1
A cell exposed to prolonged hypoxia exhibits mitochondrial permeability
transition pore opening with cytochrome c release. Which downstream event
most directly commits this cell to irreversible injury?
A. Activation of caspase-9 within the apoptosome
B. ATP depletion below 10% of normal
C. Influx of calcium via reverse-mode Na+/Ca2+ exchanger
D. Ribosomal detachment from the endoplasmic reticulum
Correct Answer: A - Activation of caspase-9 within the
apoptosome
RATIONALE
Cytochrome c release triggers apoptosome formation and caspase-9
activation, which irreversibly commits the cell to apoptosis. ATP
depletion and calcium influx are reversible early events; ribosomal
detachment is a reversible ultrastructural change.
Question 2
In a patient with septic shock, which pattern of cytokine elevation best
distinguishes the hyperinflammatory from the immunosuppressive phase?
A. Persistent TNF- and IL-6 elevation with low IL-10
B. Early IL-10 elevation with subsequent TNF- decline and monocyte
HLA-DR downregulation
C. Sustained IL-1 elevation with normal HLA-DR expression
D. Elevated IL-17 with suppressed IL-10 throughout
Correct Answer: B - Early IL-10 elevation with subsequent TNF-
decline and monocyte HLA-DR downregulation
Page 2
, RATIONALE
The immunosuppressive phase is characterized by IL-10 dominance,
reduced TNF-, and monocyte HLA-DR downregulation, reflecting
immune paralysis. Persistent TNF- and IL-6 indicate ongoing
hyperinflammation; IL-17 patterns suggest autoimmune rather than
septic profiles.
Question 3
A patient with chronic kidney disease has an eGFR of 25 mL/min/1.73m².
Which acid-base disturbance is most likely and what is the primary
compensatory mechanism?
A. Metabolic alkalosis; hypoventilation
B. High anion gap metabolic acidosis; hyperventilation
C. Normal anion gap metabolic acidosis; hyperventilation
D. Respiratory acidosis; renal bicarbonate retention
Correct Answer: C - Normal anion gap metabolic acidosis;
hyperventilation
RATIONALE
CKD causes normal anion gap metabolic acidosis due to impaired
ammonium excretion and bicarbonate loss. Respiratory compensation
via hyperventilation lowers PaCO2; high anion gap acidosis is more
typical of advanced renal failure with retained acids.
Question 4
Which molecular alteration best explains the constitutive activation of the
JAK2-STAT pathway in polycythemia vera?
A. BCR-ABL1 fusion gene
B. JAK2 V617F point mutation
C. CALR frameshift mutation
D. Mpl receptor overexpression
Page 3
A cell exposed to prolonged hypoxia exhibits mitochondrial permeability
transition pore opening with cytochrome c release. Which downstream event
most directly commits this cell to irreversible injury?
A. Activation of caspase-9 within the apoptosome
B. ATP depletion below 10% of normal
C. Influx of calcium via reverse-mode Na+/Ca2+ exchanger
D. Ribosomal detachment from the endoplasmic reticulum
Correct Answer: A - Activation of caspase-9 within the
apoptosome
RATIONALE
Cytochrome c release triggers apoptosome formation and caspase-9
activation, which irreversibly commits the cell to apoptosis. ATP
depletion and calcium influx are reversible early events; ribosomal
detachment is a reversible ultrastructural change.
Question 2
In a patient with septic shock, which pattern of cytokine elevation best
distinguishes the hyperinflammatory from the immunosuppressive phase?
A. Persistent TNF- and IL-6 elevation with low IL-10
B. Early IL-10 elevation with subsequent TNF- decline and monocyte
HLA-DR downregulation
C. Sustained IL-1 elevation with normal HLA-DR expression
D. Elevated IL-17 with suppressed IL-10 throughout
Correct Answer: B - Early IL-10 elevation with subsequent TNF-
decline and monocyte HLA-DR downregulation
Page 2
, RATIONALE
The immunosuppressive phase is characterized by IL-10 dominance,
reduced TNF-, and monocyte HLA-DR downregulation, reflecting
immune paralysis. Persistent TNF- and IL-6 indicate ongoing
hyperinflammation; IL-17 patterns suggest autoimmune rather than
septic profiles.
Question 3
A patient with chronic kidney disease has an eGFR of 25 mL/min/1.73m².
Which acid-base disturbance is most likely and what is the primary
compensatory mechanism?
A. Metabolic alkalosis; hypoventilation
B. High anion gap metabolic acidosis; hyperventilation
C. Normal anion gap metabolic acidosis; hyperventilation
D. Respiratory acidosis; renal bicarbonate retention
Correct Answer: C - Normal anion gap metabolic acidosis;
hyperventilation
RATIONALE
CKD causes normal anion gap metabolic acidosis due to impaired
ammonium excretion and bicarbonate loss. Respiratory compensation
via hyperventilation lowers PaCO2; high anion gap acidosis is more
typical of advanced renal failure with retained acids.
Question 4
Which molecular alteration best explains the constitutive activation of the
JAK2-STAT pathway in polycythemia vera?
A. BCR-ABL1 fusion gene
B. JAK2 V617F point mutation
C. CALR frameshift mutation
D. Mpl receptor overexpression
Page 3
