, COMSAE COMprEhEnSivE ExAMinAtiOn | nAtiOnAl BOArd Of OStEOpAthiC
MEdiCAl ExAMinErS (nBOME) | ACAdEMiC YEAr 2026/2027 | COMprEhEnSivE
OStEOpAthiC MEdiCAl ExAMinAtiOn | 176 vErifiEd QuEStiOnS And COrrECt
AnSwEr rAtiOnAlES | | vErifiEd BY ExpErtS .
INTRODUCTION
This document contains exactly 176 original Medical-Level questions organized across four
core domains: Domain 1: Foundational Biomedical Sciences (44 questions) ; Domain 2:
Osteopathic Principles and Practice (44 questions) ; Domain 3: Clinical Problem Solving
and Patient Management (44 questions) ; and Domain 4: Health Maintenance and
Preventive Medicine (44 questions) . The content integrates biomedical mechanisms,
osteopathic diagnosis and treatment, clinical decision-making, patient safety, and evidence-
based prevention for the Comprehensive Licensing Examination aligned to Academic
Year 2026/2027.
DOMAIN 1: FOUNDATIONAL BIOMEDICAL SCIENCES (44 QUESTIONS)
Question 1
A reversible inhibitor competes with substrate for an enzyme's active site. Which kinetic change
is expected?
A. The apparent Km increases while Vmax remains unchanged.
B. The apparent Km decreases while Vmax increases.
C. Vmax decreases while Km remains unchanged.
D. Both Km and Vmax decrease to zero.
COrrECt AnSwEr: A ✓
rAtiOnAlE: More substrate can overcome competitive inhibition, so the original maximal
velocity remains attainable. A higher substrate concentration is needed to reach half-maximal
velocity, increasing the apparent Km.
Question 2
A patient with metabolic acidosis has a bicarbonate concentration of 12 mEq/L and an arterial
carbon dioxide pressure of 40 mm Hg. Which interpretation is most accurate?
A. Respiratory compensation is appropriate.
B. A concurrent respiratory alkalosis is present.
C. A concurrent respiratory acidosis is present.
D. The values show isolated metabolic alkalosis.
,COrrECt AnSwEr: C ✓
rAtiOnAlE: Winter's relationship predicts a carbon dioxide pressure near 26 mm Hg, with a
small expected range, when bicarbonate is 12. A measured value of 40 is too high for
compensation and indicates added respiratory acidosis.
Question 3
A woman has a pathogenic mitochondrial DNA variant with high heteroplasmy. Which
inheritance pattern is expected?
A. The variant follows a strict autosomal recessive pattern.
B. All of her children may inherit the variant, but clinical severity can differ.
C. Only her sons can inherit the variant.
D. An affected father transmits the variant to every daughter.
COrrECt AnSwEr: B ✓
rAtiOnAlE: Mitochondria in the embryo are derived predominantly from the oocyte, producing
maternal transmission. Heteroplasmy and replicative segregation cause variable organ
involvement and severity among offspring.
Question 4
Successive generations of a family develop a neurologic disorder at younger ages with
increasing severity. Which genetic mechanism best explains this pattern?
A. Random X chromosome inactivation alone
B. Loss of all mitochondrial DNA
C. Balanced reciprocal translocation without gene disruption
D. Expansion of a trinucleotide repeat
COrrECt AnSwEr: D ✓
rAtiOnAlE: Unstable repeat expansion during gametogenesis can increase repeat length in
later generations. The larger expansion often produces earlier onset or greater severity, a
pattern called anticipation.
Question 5
Which of the following is a characteristic of type II hypersensitivity reactions?
A. Mediated by IgE and mast cells
B. Involves antibody-mediated cell destruction
C. Involves immune complex deposition
D. Mediated by T lymphocytes
COrrECt AnSwEr: B ✓
, rAtiOnAlE: Type II hypersensitivity involves antibodies (IgG or IgM) directed against cell
surface antigens, leading to cell destruction via complement activation or antibody-dependent
cellular cytotoxicity (ADCC). Type I (A) is IgE-mediated; Type III (C) involves immune
complexes; Type IV (D) is T-cell mediated.
Question 6
A patient with a deficiency of glucose-6-phosphate dehydrogenase (G6PD) is exposed to
oxidizing drugs. Which pathophysiological consequence is most likely?
A. Methemoglobinemia
B. Hemolytic anemia
C. Thrombocytosis
D. Leukocytosis
COrrECt AnSwEr: B ✓
rAtiOnAlE: G6PD deficiency impairs the hexose monophosphate shunt, reducing glutathione
production. Without adequate glutathione, red blood cells are susceptible to oxidative damage,
leading to hemolytic anemia.
Question 7
Which of the following is the primary mechanism of action of loop diuretics?
A. Inhibition of carbonic anhydrase
B. Inhibition of the Na+/K+/2Cl– cotransporter in the thick ascending limb
C. Inhibition of the Na+/Cl– cotransporter in the distal convoluted tubule
D. Aldosterone antagonism
COrrECt AnSwEr: B ✓
rAtiOnAlE: Loop diuretics (e.g., furosemide) inhibit the Na+/K+/2Cl– cotransporter in the
thick ascending limb of the loop of Henle, reducing sodium, chloride, and water reabsorption.
Question 8
A 45-year-old patient presents with fatigue, weight gain, cold intolerance, and constipation.
Laboratory studies reveal elevated TSH and low free T4. Which is the most likely diagnosis?
A. Hyperthyroidism
B. Hypothyroidism
C. Cushing's syndrome
D. Addison's disease
COrrECt AnSwEr: B ✓
MEdiCAl ExAMinErS (nBOME) | ACAdEMiC YEAr 2026/2027 | COMprEhEnSivE
OStEOpAthiC MEdiCAl ExAMinAtiOn | 176 vErifiEd QuEStiOnS And COrrECt
AnSwEr rAtiOnAlES | | vErifiEd BY ExpErtS .
INTRODUCTION
This document contains exactly 176 original Medical-Level questions organized across four
core domains: Domain 1: Foundational Biomedical Sciences (44 questions) ; Domain 2:
Osteopathic Principles and Practice (44 questions) ; Domain 3: Clinical Problem Solving
and Patient Management (44 questions) ; and Domain 4: Health Maintenance and
Preventive Medicine (44 questions) . The content integrates biomedical mechanisms,
osteopathic diagnosis and treatment, clinical decision-making, patient safety, and evidence-
based prevention for the Comprehensive Licensing Examination aligned to Academic
Year 2026/2027.
DOMAIN 1: FOUNDATIONAL BIOMEDICAL SCIENCES (44 QUESTIONS)
Question 1
A reversible inhibitor competes with substrate for an enzyme's active site. Which kinetic change
is expected?
A. The apparent Km increases while Vmax remains unchanged.
B. The apparent Km decreases while Vmax increases.
C. Vmax decreases while Km remains unchanged.
D. Both Km and Vmax decrease to zero.
COrrECt AnSwEr: A ✓
rAtiOnAlE: More substrate can overcome competitive inhibition, so the original maximal
velocity remains attainable. A higher substrate concentration is needed to reach half-maximal
velocity, increasing the apparent Km.
Question 2
A patient with metabolic acidosis has a bicarbonate concentration of 12 mEq/L and an arterial
carbon dioxide pressure of 40 mm Hg. Which interpretation is most accurate?
A. Respiratory compensation is appropriate.
B. A concurrent respiratory alkalosis is present.
C. A concurrent respiratory acidosis is present.
D. The values show isolated metabolic alkalosis.
,COrrECt AnSwEr: C ✓
rAtiOnAlE: Winter's relationship predicts a carbon dioxide pressure near 26 mm Hg, with a
small expected range, when bicarbonate is 12. A measured value of 40 is too high for
compensation and indicates added respiratory acidosis.
Question 3
A woman has a pathogenic mitochondrial DNA variant with high heteroplasmy. Which
inheritance pattern is expected?
A. The variant follows a strict autosomal recessive pattern.
B. All of her children may inherit the variant, but clinical severity can differ.
C. Only her sons can inherit the variant.
D. An affected father transmits the variant to every daughter.
COrrECt AnSwEr: B ✓
rAtiOnAlE: Mitochondria in the embryo are derived predominantly from the oocyte, producing
maternal transmission. Heteroplasmy and replicative segregation cause variable organ
involvement and severity among offspring.
Question 4
Successive generations of a family develop a neurologic disorder at younger ages with
increasing severity. Which genetic mechanism best explains this pattern?
A. Random X chromosome inactivation alone
B. Loss of all mitochondrial DNA
C. Balanced reciprocal translocation without gene disruption
D. Expansion of a trinucleotide repeat
COrrECt AnSwEr: D ✓
rAtiOnAlE: Unstable repeat expansion during gametogenesis can increase repeat length in
later generations. The larger expansion often produces earlier onset or greater severity, a
pattern called anticipation.
Question 5
Which of the following is a characteristic of type II hypersensitivity reactions?
A. Mediated by IgE and mast cells
B. Involves antibody-mediated cell destruction
C. Involves immune complex deposition
D. Mediated by T lymphocytes
COrrECt AnSwEr: B ✓
, rAtiOnAlE: Type II hypersensitivity involves antibodies (IgG or IgM) directed against cell
surface antigens, leading to cell destruction via complement activation or antibody-dependent
cellular cytotoxicity (ADCC). Type I (A) is IgE-mediated; Type III (C) involves immune
complexes; Type IV (D) is T-cell mediated.
Question 6
A patient with a deficiency of glucose-6-phosphate dehydrogenase (G6PD) is exposed to
oxidizing drugs. Which pathophysiological consequence is most likely?
A. Methemoglobinemia
B. Hemolytic anemia
C. Thrombocytosis
D. Leukocytosis
COrrECt AnSwEr: B ✓
rAtiOnAlE: G6PD deficiency impairs the hexose monophosphate shunt, reducing glutathione
production. Without adequate glutathione, red blood cells are susceptible to oxidative damage,
leading to hemolytic anemia.
Question 7
Which of the following is the primary mechanism of action of loop diuretics?
A. Inhibition of carbonic anhydrase
B. Inhibition of the Na+/K+/2Cl– cotransporter in the thick ascending limb
C. Inhibition of the Na+/Cl– cotransporter in the distal convoluted tubule
D. Aldosterone antagonism
COrrECt AnSwEr: B ✓
rAtiOnAlE: Loop diuretics (e.g., furosemide) inhibit the Na+/K+/2Cl– cotransporter in the
thick ascending limb of the loop of Henle, reducing sodium, chloride, and water reabsorption.
Question 8
A 45-year-old patient presents with fatigue, weight gain, cold intolerance, and constipation.
Laboratory studies reveal elevated TSH and low free T4. Which is the most likely diagnosis?
A. Hyperthyroidism
B. Hypothyroidism
C. Cushing's syndrome
D. Addison's disease
COrrECt AnSwEr: B ✓
