2026 EDITION COMSAE Phase 1 Form 114
Practice Exam Questions Answers and
Verified Rationales
Question 1 — Physiology
A 24-year-old man develops severe diarrhoea after returning
from a camping trip. Laboratory studies show a serum
sodium concentration of 138 mEq/L and a serum osmolality
of 290 mOsm/kg. His urine osmolality is 600 mOsm/kg.
Which of the following best explains the mechanism
responsible for maintaining his serum osmolality despite
significant fluid loss?
A. Increased secretion of atrial natriuretic peptide
B. Decreased secretion of antidiuretic hormone
C. Increased renal sodium excretion
D. Increased antidiuretic hormone secretion
Answer: D. Increased antidiuretic hormone secretion
Rationale: Volume depletion stimulates antidiuretic hormone
(ADH) release, which increases water reabsorption through
aquaporin-2 channels in the collecting ducts. Although ADH is
primarily regulated by plasma osmolality, significant
hypovolaemia can strongly stimulate its secretion even when
osmolality is normal. This conserves water and helps preserve
circulating volume.
,Question 2 — Biochemistry
A child presents with recurrent fasting hypoglycaemia, lactic
acidosis, hyperuricaemia, and hepatomegaly. Laboratory
evaluation reveals impaired conversion of glucose-6-
phosphate to free glucose. Which enzyme is most likely
deficient?
A. Lysosomal acid α-glucosidase
B. Muscle glycogen phosphorylase
C. Glucose-6-phosphatase
D. Branching enzyme
Answer: C. Glucose-6-phosphatase
Rationale: Glucose-6-phosphatase deficiency causes von
Gierke disease (glycogen storage disease type I). The liver
cannot convert glucose-6-phosphate to free glucose, resulting
in severe fasting hypoglycaemia, lactic acidosis,
hyperuricaemia, and hepatomegaly. The inability to release
glucose also increases reliance on alternative metabolic
pathways.
Question 3 — Microbiology
A 67-year-old man with chronic obstructive pulmonary
disease develops fever, productive cough, and lobar
pneumonia. Sputum Gram stain reveals gram-positive lancet-
shaped diplococci. The organism is α-haemolytic and
,optochin sensitive. Which virulence factor most directly
inhibits phagocytosis?
A. Protein A
B. M protein
C. Lipopolysaccharide
D. Polysaccharide capsule
Answer: D. Polysaccharide capsule
Rationale: Streptococcus pneumoniae is an encapsulated,
gram-positive, lancet-shaped diplococcus that causes
community-acquired pneumonia. Its polysaccharide capsule
inhibits phagocytosis and is a major virulence factor. The
capsule is also the basis for the organism's conjugate and
polysaccharide vaccines.
Question 4 — Pharmacology
A patient with hypertension is started on lisinopril. Two
weeks later, he develops persistent dry cough. His serum
potassium concentration has increased slightly. Which
mechanism best explains these findings?
A. Increased aldosterone secretion
B. Increased sympathetic activity
C. Decreased bradykinin degradation
D. Increased renin inhibition
Answer: C. Decreased bradykinin degradation
Rationale: ACE inhibitors reduce conversion of angiotensin I to
angiotensin II and decrease degradation of bradykinin.
, Accumulation of bradykinin can cause a persistent dry cough
and, rarely, angioedema. Reduced aldosterone secretion also
promotes potassium retention, explaining mild
hyperkalaemia.
Question 5 — Pathology
A 58-year-old smoker presents with haemoptysis and weight
loss. Imaging reveals a central hilar lung mass. Biopsy
demonstrates malignant cells producing keratin pearls. Which
molecular abnormality is most likely involved in the
pathogenesis of this tumour?
A. BCR-ABL translocation
B. APC mutation
C. TP53 mutation
D. RET activation
Answer: C. TP53 mutation
Rationale: Keratin pearls indicate squamous cell carcinoma of
the lung, which is strongly associated with cigarette smoking
and commonly arises centrally near the bronchi. TP53
mutations are frequent in smoking-related lung cancers and
impair the cell-cycle checkpoint and DNA-damage response.
Question 6 — Neuroanatomy
A 72-year-old woman suddenly develops weakness of the
right face, arm, and leg. She has expressive aphasia and
Practice Exam Questions Answers and
Verified Rationales
Question 1 — Physiology
A 24-year-old man develops severe diarrhoea after returning
from a camping trip. Laboratory studies show a serum
sodium concentration of 138 mEq/L and a serum osmolality
of 290 mOsm/kg. His urine osmolality is 600 mOsm/kg.
Which of the following best explains the mechanism
responsible for maintaining his serum osmolality despite
significant fluid loss?
A. Increased secretion of atrial natriuretic peptide
B. Decreased secretion of antidiuretic hormone
C. Increased renal sodium excretion
D. Increased antidiuretic hormone secretion
Answer: D. Increased antidiuretic hormone secretion
Rationale: Volume depletion stimulates antidiuretic hormone
(ADH) release, which increases water reabsorption through
aquaporin-2 channels in the collecting ducts. Although ADH is
primarily regulated by plasma osmolality, significant
hypovolaemia can strongly stimulate its secretion even when
osmolality is normal. This conserves water and helps preserve
circulating volume.
,Question 2 — Biochemistry
A child presents with recurrent fasting hypoglycaemia, lactic
acidosis, hyperuricaemia, and hepatomegaly. Laboratory
evaluation reveals impaired conversion of glucose-6-
phosphate to free glucose. Which enzyme is most likely
deficient?
A. Lysosomal acid α-glucosidase
B. Muscle glycogen phosphorylase
C. Glucose-6-phosphatase
D. Branching enzyme
Answer: C. Glucose-6-phosphatase
Rationale: Glucose-6-phosphatase deficiency causes von
Gierke disease (glycogen storage disease type I). The liver
cannot convert glucose-6-phosphate to free glucose, resulting
in severe fasting hypoglycaemia, lactic acidosis,
hyperuricaemia, and hepatomegaly. The inability to release
glucose also increases reliance on alternative metabolic
pathways.
Question 3 — Microbiology
A 67-year-old man with chronic obstructive pulmonary
disease develops fever, productive cough, and lobar
pneumonia. Sputum Gram stain reveals gram-positive lancet-
shaped diplococci. The organism is α-haemolytic and
,optochin sensitive. Which virulence factor most directly
inhibits phagocytosis?
A. Protein A
B. M protein
C. Lipopolysaccharide
D. Polysaccharide capsule
Answer: D. Polysaccharide capsule
Rationale: Streptococcus pneumoniae is an encapsulated,
gram-positive, lancet-shaped diplococcus that causes
community-acquired pneumonia. Its polysaccharide capsule
inhibits phagocytosis and is a major virulence factor. The
capsule is also the basis for the organism's conjugate and
polysaccharide vaccines.
Question 4 — Pharmacology
A patient with hypertension is started on lisinopril. Two
weeks later, he develops persistent dry cough. His serum
potassium concentration has increased slightly. Which
mechanism best explains these findings?
A. Increased aldosterone secretion
B. Increased sympathetic activity
C. Decreased bradykinin degradation
D. Increased renin inhibition
Answer: C. Decreased bradykinin degradation
Rationale: ACE inhibitors reduce conversion of angiotensin I to
angiotensin II and decrease degradation of bradykinin.
, Accumulation of bradykinin can cause a persistent dry cough
and, rarely, angioedema. Reduced aldosterone secretion also
promotes potassium retention, explaining mild
hyperkalaemia.
Question 5 — Pathology
A 58-year-old smoker presents with haemoptysis and weight
loss. Imaging reveals a central hilar lung mass. Biopsy
demonstrates malignant cells producing keratin pearls. Which
molecular abnormality is most likely involved in the
pathogenesis of this tumour?
A. BCR-ABL translocation
B. APC mutation
C. TP53 mutation
D. RET activation
Answer: C. TP53 mutation
Rationale: Keratin pearls indicate squamous cell carcinoma of
the lung, which is strongly associated with cigarette smoking
and commonly arises centrally near the bronchi. TP53
mutations are frequent in smoking-related lung cancers and
impair the cell-cycle checkpoint and DNA-damage response.
Question 6 — Neuroanatomy
A 72-year-old woman suddenly develops weakness of the
right face, arm, and leg. She has expressive aphasia and
