COMSAE PHASE 1 FORM 114 Actual EXAM - AND
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1. A researcher investigates a signaling pathway where a ligand binds to a receptor tyrosine kinase
(RTK), leading to activation of Ras. Which of the following mutations would most likely result in
constitutive activation of the MAP kinase cascade independent of ligand binding?
A. A point mutation in the RTK that abolishes its kinase activity
B. A deletion of the SH2 domain of Grb2
C. A gain-of-function mutation in Ras that impairs GTP hydrolysis
D. Overexpression of a phosphatase that dephosphorylates MEK
Answer: C
Rationale: Ras is a small GTPase that cycles between active GTP-bound and inactive GDP-bound states.
Mutations that impair GTP hydrolysis (e.g., at codon 12 or 61) lock Ras in the active form, constitutively
activating the MAP kinase cascade. Option A would prevent signaling; B would disrupt adaptor
function; D would inhibit the cascade.
2. In a study of cardiac contractility, a drug is found to increase the force of contraction without
changing heart rate. The drug also prolongs the action potential duration. Which of the following
mechanisms is most consistent with these effects?
A. Blockade of L-type calcium channels
B. Activation of ATP-sensitive potassium channels
C. Inhibition of the Na+/Ca2+ exchanger
D. Inhibition of phosphodiesterase 3 in ventricular myocytes
Answer: D
Rationale: Inhibition of phosphodiesterase 3 (PDE3) increases cAMP, leading to enhanced Ca2+ influx
and increased contractility (positive inotropy). PDE3 inhibition also prolongs action potential duration
by slowing repolarization. Option A would decrease contractility; B would shorten APD; C would
increase contractility but not prolong APD.
Page 1
,3. A 35-year-old individual with a history of recurrent sinopulmonary infections and autoimmune
manifestations has a defective complement pathway. Laboratory findings show low C3 levels but
normal C4 levels. Which of the following deficiencies is most likely?
A. C1 esterase inhibitor deficiency
B. C2 deficiency
C. Factor D deficiency
D. C3 nephritic factor
Answer: C
Rationale: Factor D is essential for the alternative pathway of complement activation. Deficiency leads to
impaired opsonization and increased susceptibility to infections. Low C3 with normal C4 indicates
alternative pathway consumption. C1 esterase inhibitor deficiency causes angioedema with normal C3;
C2 deficiency is rare and typically presents with lupus-like symptoms; C3 nephritic factor stabilizes C3
convertase, causing low C3 but normal C4.
4. A 60-year-old individual presents with progressive dysphagia and weight loss. Endoscopy
reveals a mid-esophageal lesion. Biopsy shows nests of malignant cells with intercellular bridges
and individual cell keratinization. Which of the following is the most likely diagnosis?
A. Adenocarcinoma of the esophagus
B. Squamous cell carcinoma of the esophagus
C. Small cell carcinoma of the esophagus
D. Leiomyosarcoma of the esophagus
Answer: B
Rationale: Squamous cell carcinoma of the esophagus is associated with smoking and alcohol, and
histologically shows intercellular bridges and keratin pearls. Adenocarcinoma is more common in the
distal esophagus and associated with Barrett's esophagus. Small cell carcinoma is rare and shows
neuroendocrine features. Leiomyosarcoma arises from smooth muscle and shows spindle cells.
5. A patient with type 2 diabetes mellitus is started on a new medication. After one month,
laboratory tests show a decrease in HbA1c from 8.5% to 7.2%, but also a 2.5 kg weight loss and a
serum creatinine increase from 0.9 to 1.4 mg/dL. Which medication is most likely responsible?
A. Metformin
B. Empagliflozin
C. Pioglitazone
D. Glipizide
Answer: B
Rationale: Empagliflozin, an SGLT2 inhibitor, causes glucosuria leading to improved glycemic control
and weight loss. It can cause acute kidney injury, especially in volume-depleted patients. Metformin
rarely causes weight loss and is not associated with AKI in this context. Pioglitazone causes weight gain.
Glipizide may cause weight gain and hypoglycemia.
Page 2
,6. A 45-year-old individual with no known history presents with sudden severe headache and neck
stiffness. A CT scan shows subarachnoid hemorrhage. Cerebral angiography reveals a saccular
aneurysm at the junction of the anterior communicating artery and the anterior cerebral artery.
Which of the following is the most likely underlying defect in the vessel wall?
A. Defect in the tunica adventitia leading to media thinning
B. Absence of the internal elastic lamina and media
C. Cystic medial necrosis
D. Atherosclerotic plaque erosion
Answer: B
Rationale: Saccular (berry) aneurysms occur at arterial bifurcations and are characterized by a defect in
the internal elastic lamina and a thinning or absence of the media. Option A is incorrect because the
adventitia is usually intact. Cystic medial necrosis is seen in aortic dissections. Atherosclerotic plaques
are associated with fusiform aneurysms.
7. A researcher is studying the effect of a new drug on neurotransmitter levels. The drug is found
to inhibit the vesicular monoamine transporter 2 (VMAT2). Which of the following is the most
likely effect on synaptic transmission?
A. Increased cytosolic concentrations of monoamines in the presynaptic terminal
B. Increased release of monoamines into the synaptic cleft
C. Decreased synthesis of monoamines
D. Increased reuptake of monoamines from the synaptic cleft
Answer: A
Rationale: VMAT2 packages monoamines into synaptic vesicles. Inhibition leads to accumulation of
monoamines in the cytosol, where they can be degraded by MAO. This reduces vesicular release, not
increase. Synthesis is not directly affected; reuptake is mediated by transporters on the plasma
membrane, not VMAT.
8. In a population-based study, the incidence of a disease is 100 per 100,000 person-years. A new
screening test has a sensitivity of 90% and a specificity of 95%. The prevalence of the disease in the
screened population is 1%. What is the positive predictive value (PPV) of this test?
A. 15.4%
B. 18.2%
C. 85.7%
D. 90.0%
Answer: A
Rationale: With prevalence 1%, in 1000 people, 10 have disease. True positives = 10*0.9=9; false
negatives=1. Non-diseased=990; false positives=990*0.05=49.5. PPV =
TP/(TP+FP)=9/(9+49.5)=9/58.515.4%. Option B would correspond to a different calculation; C and D
are too high.
Page 3
, 9. A 28-year-old individual with a history of intravenous drug use presents with fever, weight loss,
and a heart murmur. Blood cultures grow Streptococcus viridans. Echocardiography reveals a
vegetation on the mitral valve. Which of the following is the most likely complication if left
untreated?
A. Myocardial infarction due to coronary artery embolization
B. Glomerulonephritis due to immune complex deposition
C. Brain abscess due to septic emboli
D. Pulmonary embolism from right-sided vegetation
Answer: B
Rationale: Infective endocarditis, especially with Streptococcus viridans, can lead to immune
complex-mediated glomerulonephritis (e.g., membranoproliferative GN). Myocardial infarction is rare;
brain abscess is more common with Staphylococcus aureus. Pulmonary embolism occurs with
right-sided endocarditis, but mitral valve is left-sided.
10. A 50-year-old individual with chronic alcoholism is brought to the emergency department with
confusion and ataxia. Laboratory findings show elevated serum osmolality and a high anion gap
metabolic acidosis. Urine microscopy reveals calcium oxalate crystals. Which of the following is the
most likely cause?
A. Methanol ingestion
B. Ethylene glycol ingestion
C. Isopropyl alcohol ingestion
D. Salicylate poisoning
Answer: B
Rationale: Ethylene glycol metabolism produces oxalic acid, which precipitates as calcium oxalate
crystals in urine, causing acute kidney injury. It also leads to high anion gap metabolic acidosis and
elevated osmolality. Methanol causes formic acid accumulation and retinal toxicity; isopropyl alcohol
produces ketosis without acidosis; salicylate causes mixed acid-base disorder.
11. A 45-year-old patient with a history of type 2 diabetes and hypertension presents with acute
onset of severe right flank pain radiating to the groin, associated with nausea and hematuria. CT
reveals a 5 mm calculus at the ureterovesical junction with moderate hydronephrosis. Urinalysis
shows pH 6.5, specific gravity 1.020, and no crystals. Serum calcium, uric acid, and oxalate are
normal. Which of the following is the most likely composition of the stone?
A. Calcium oxalate monohydrate
B. Struvite
C. Uric acid
D. Calcium phosphate
Answer: D
Rationale: Calcium phosphate stones are associated with distal renal tubular acidosis (RTA) or
hyperparathyroidism. Normal serum calcium and pH >5.5 suggest incomplete distal RTA. Struvite
stones require urease-producing bacteria and alkaline urine. Uric acid stones occur with acidic urine
(pH <5.5) and hyperuricosuria. Calcium oxalate stones are common but less likely given normal oxalate
and calcium.
Page 4
ANSWERS | VERIFIED AND WELL DETAILED
ANSWERS | PLUS RATIONALES | GUARANTEED
PASS | LATEST EXAM UPDATE | STUVIA
VERIFIED | EXAM PREP | STUDY GUIDE |
PRACTICE TEST
1. A researcher investigates a signaling pathway where a ligand binds to a receptor tyrosine kinase
(RTK), leading to activation of Ras. Which of the following mutations would most likely result in
constitutive activation of the MAP kinase cascade independent of ligand binding?
A. A point mutation in the RTK that abolishes its kinase activity
B. A deletion of the SH2 domain of Grb2
C. A gain-of-function mutation in Ras that impairs GTP hydrolysis
D. Overexpression of a phosphatase that dephosphorylates MEK
Answer: C
Rationale: Ras is a small GTPase that cycles between active GTP-bound and inactive GDP-bound states.
Mutations that impair GTP hydrolysis (e.g., at codon 12 or 61) lock Ras in the active form, constitutively
activating the MAP kinase cascade. Option A would prevent signaling; B would disrupt adaptor
function; D would inhibit the cascade.
2. In a study of cardiac contractility, a drug is found to increase the force of contraction without
changing heart rate. The drug also prolongs the action potential duration. Which of the following
mechanisms is most consistent with these effects?
A. Blockade of L-type calcium channels
B. Activation of ATP-sensitive potassium channels
C. Inhibition of the Na+/Ca2+ exchanger
D. Inhibition of phosphodiesterase 3 in ventricular myocytes
Answer: D
Rationale: Inhibition of phosphodiesterase 3 (PDE3) increases cAMP, leading to enhanced Ca2+ influx
and increased contractility (positive inotropy). PDE3 inhibition also prolongs action potential duration
by slowing repolarization. Option A would decrease contractility; B would shorten APD; C would
increase contractility but not prolong APD.
Page 1
,3. A 35-year-old individual with a history of recurrent sinopulmonary infections and autoimmune
manifestations has a defective complement pathway. Laboratory findings show low C3 levels but
normal C4 levels. Which of the following deficiencies is most likely?
A. C1 esterase inhibitor deficiency
B. C2 deficiency
C. Factor D deficiency
D. C3 nephritic factor
Answer: C
Rationale: Factor D is essential for the alternative pathway of complement activation. Deficiency leads to
impaired opsonization and increased susceptibility to infections. Low C3 with normal C4 indicates
alternative pathway consumption. C1 esterase inhibitor deficiency causes angioedema with normal C3;
C2 deficiency is rare and typically presents with lupus-like symptoms; C3 nephritic factor stabilizes C3
convertase, causing low C3 but normal C4.
4. A 60-year-old individual presents with progressive dysphagia and weight loss. Endoscopy
reveals a mid-esophageal lesion. Biopsy shows nests of malignant cells with intercellular bridges
and individual cell keratinization. Which of the following is the most likely diagnosis?
A. Adenocarcinoma of the esophagus
B. Squamous cell carcinoma of the esophagus
C. Small cell carcinoma of the esophagus
D. Leiomyosarcoma of the esophagus
Answer: B
Rationale: Squamous cell carcinoma of the esophagus is associated with smoking and alcohol, and
histologically shows intercellular bridges and keratin pearls. Adenocarcinoma is more common in the
distal esophagus and associated with Barrett's esophagus. Small cell carcinoma is rare and shows
neuroendocrine features. Leiomyosarcoma arises from smooth muscle and shows spindle cells.
5. A patient with type 2 diabetes mellitus is started on a new medication. After one month,
laboratory tests show a decrease in HbA1c from 8.5% to 7.2%, but also a 2.5 kg weight loss and a
serum creatinine increase from 0.9 to 1.4 mg/dL. Which medication is most likely responsible?
A. Metformin
B. Empagliflozin
C. Pioglitazone
D. Glipizide
Answer: B
Rationale: Empagliflozin, an SGLT2 inhibitor, causes glucosuria leading to improved glycemic control
and weight loss. It can cause acute kidney injury, especially in volume-depleted patients. Metformin
rarely causes weight loss and is not associated with AKI in this context. Pioglitazone causes weight gain.
Glipizide may cause weight gain and hypoglycemia.
Page 2
,6. A 45-year-old individual with no known history presents with sudden severe headache and neck
stiffness. A CT scan shows subarachnoid hemorrhage. Cerebral angiography reveals a saccular
aneurysm at the junction of the anterior communicating artery and the anterior cerebral artery.
Which of the following is the most likely underlying defect in the vessel wall?
A. Defect in the tunica adventitia leading to media thinning
B. Absence of the internal elastic lamina and media
C. Cystic medial necrosis
D. Atherosclerotic plaque erosion
Answer: B
Rationale: Saccular (berry) aneurysms occur at arterial bifurcations and are characterized by a defect in
the internal elastic lamina and a thinning or absence of the media. Option A is incorrect because the
adventitia is usually intact. Cystic medial necrosis is seen in aortic dissections. Atherosclerotic plaques
are associated with fusiform aneurysms.
7. A researcher is studying the effect of a new drug on neurotransmitter levels. The drug is found
to inhibit the vesicular monoamine transporter 2 (VMAT2). Which of the following is the most
likely effect on synaptic transmission?
A. Increased cytosolic concentrations of monoamines in the presynaptic terminal
B. Increased release of monoamines into the synaptic cleft
C. Decreased synthesis of monoamines
D. Increased reuptake of monoamines from the synaptic cleft
Answer: A
Rationale: VMAT2 packages monoamines into synaptic vesicles. Inhibition leads to accumulation of
monoamines in the cytosol, where they can be degraded by MAO. This reduces vesicular release, not
increase. Synthesis is not directly affected; reuptake is mediated by transporters on the plasma
membrane, not VMAT.
8. In a population-based study, the incidence of a disease is 100 per 100,000 person-years. A new
screening test has a sensitivity of 90% and a specificity of 95%. The prevalence of the disease in the
screened population is 1%. What is the positive predictive value (PPV) of this test?
A. 15.4%
B. 18.2%
C. 85.7%
D. 90.0%
Answer: A
Rationale: With prevalence 1%, in 1000 people, 10 have disease. True positives = 10*0.9=9; false
negatives=1. Non-diseased=990; false positives=990*0.05=49.5. PPV =
TP/(TP+FP)=9/(9+49.5)=9/58.515.4%. Option B would correspond to a different calculation; C and D
are too high.
Page 3
, 9. A 28-year-old individual with a history of intravenous drug use presents with fever, weight loss,
and a heart murmur. Blood cultures grow Streptococcus viridans. Echocardiography reveals a
vegetation on the mitral valve. Which of the following is the most likely complication if left
untreated?
A. Myocardial infarction due to coronary artery embolization
B. Glomerulonephritis due to immune complex deposition
C. Brain abscess due to septic emboli
D. Pulmonary embolism from right-sided vegetation
Answer: B
Rationale: Infective endocarditis, especially with Streptococcus viridans, can lead to immune
complex-mediated glomerulonephritis (e.g., membranoproliferative GN). Myocardial infarction is rare;
brain abscess is more common with Staphylococcus aureus. Pulmonary embolism occurs with
right-sided endocarditis, but mitral valve is left-sided.
10. A 50-year-old individual with chronic alcoholism is brought to the emergency department with
confusion and ataxia. Laboratory findings show elevated serum osmolality and a high anion gap
metabolic acidosis. Urine microscopy reveals calcium oxalate crystals. Which of the following is the
most likely cause?
A. Methanol ingestion
B. Ethylene glycol ingestion
C. Isopropyl alcohol ingestion
D. Salicylate poisoning
Answer: B
Rationale: Ethylene glycol metabolism produces oxalic acid, which precipitates as calcium oxalate
crystals in urine, causing acute kidney injury. It also leads to high anion gap metabolic acidosis and
elevated osmolality. Methanol causes formic acid accumulation and retinal toxicity; isopropyl alcohol
produces ketosis without acidosis; salicylate causes mixed acid-base disorder.
11. A 45-year-old patient with a history of type 2 diabetes and hypertension presents with acute
onset of severe right flank pain radiating to the groin, associated with nausea and hematuria. CT
reveals a 5 mm calculus at the ureterovesical junction with moderate hydronephrosis. Urinalysis
shows pH 6.5, specific gravity 1.020, and no crystals. Serum calcium, uric acid, and oxalate are
normal. Which of the following is the most likely composition of the stone?
A. Calcium oxalate monohydrate
B. Struvite
C. Uric acid
D. Calcium phosphate
Answer: D
Rationale: Calcium phosphate stones are associated with distal renal tubular acidosis (RTA) or
hyperparathyroidism. Normal serum calcium and pH >5.5 suggest incomplete distal RTA. Struvite
stones require urease-producing bacteria and alkaline urine. Uric acid stones occur with acidic urine
(pH <5.5) and hyperuricosuria. Calcium oxalate stones are common but less likely given normal oxalate
and calcium.
Page 4
