Mechanisms of Disease & Therapeutics
Integrated Exam 2026 Edition Questions
with Answers and Detailed Rationales
1.
A 58-year-old man with a 40-pack-year smoking history
develops progressive dyspnea and chronic productive cough.
Pulmonary function testing shows a reduced FEV₁/FVC ratio
with minimal reversibility after bronchodilator administration.
Which pathological mechanism best explains his condition?
A. Destruction of alveolar septa caused by α₁-antitrypsin
deficiency
B. Reversible bronchial smooth muscle contraction
C. Chronic airway inflammation with mucus hypersecretion
and airway remodeling
D. Increased pulmonary surfactant production
Answer: C. Chronic airway inflammation with mucus
hypersecretion and airway remodeling
Rationale: Chronic obstructive pulmonary disease, particularly
chronic bronchitis, involves persistent airway inflammation,
,mucus gland enlargement, goblet-cell hyperplasia, and airway
remodeling that produce largely irreversible airflow limitation.
2.
A patient with septic shock develops hypotension, elevated
lactate, and progressive renal dysfunction despite adequate
oxygen saturation. Which mechanism most directly contributes
to cellular injury in this setting?
A. Increased mitochondrial ATP production
B. Impaired tissue perfusion causing cellular hypoxia and
mitochondrial dysfunction
C. Increased oxidative phosphorylation
D. Reduced anaerobic metabolism
Answer: B. Impaired tissue perfusion causing cellular hypoxia
and mitochondrial dysfunction
Rationale: Septic shock causes profound circulatory and
microvascular abnormalities that impair tissue oxygen delivery
and utilization. Cellular ATP depletion promotes membrane
dysfunction, acidosis, and organ injury.
3.
,A 24-year-old woman develops urticaria, wheezing, and
hypotension minutes after receiving intravenous penicillin.
Which immunologic mechanism is primarily responsible?
A. IgG-mediated cytotoxicity
B. Immune-complex deposition
C. T-cell-mediated delayed hypersensitivity
D. IgE-mediated mast-cell degranulation
Answer: D. IgE-mediated mast-cell degranulation
Rationale: Type I hypersensitivity occurs when allergen-specific
IgE bound to mast cells is cross-linked, triggering rapid release
of histamine, leukotrienes, and other mediators responsible for
anaphylaxis.
4.
A patient with rheumatoid arthritis is started on methotrexate.
Which mechanism accounts for its therapeutic effect in this
disease?
A. Direct inhibition of cyclooxygenase-2
B. Blockade of histamine H₁ receptors
C. Suppression of lymphocyte proliferation and inflammatory
mediator production
D. Stimulation of neutrophil migration
, Answer: C. Suppression of lymphocyte proliferation and
inflammatory mediator production
Rationale: Methotrexate, at low doses used for rheumatoid
arthritis, has immunomodulatory and anti-inflammatory
effects, including increased extracellular adenosine and
suppression of immune-cell activity.
5.
A 67-year-old woman develops sudden right-sided weakness
and aphasia. Imaging reveals an infarct in the left middle
cerebral artery territory. Which mechanism causes neuronal
injury during cerebral ischemia?
A. Reduced glutamate release
B. Increased ATP synthesis
C. Excitotoxicity caused by excessive glutamate and
intracellular calcium accumulation
D. Inhibition of free-radical formation
Answer: C. Excitotoxicity caused by excessive glutamate and
intracellular calcium accumulation
Rationale: Ischemic ATP depletion causes neuronal
depolarization and excessive glutamate release. NMDA receptor
activation allows calcium influx, activating destructive enzymes
and promoting oxidative and mitochondrial injury.
Integrated Exam 2026 Edition Questions
with Answers and Detailed Rationales
1.
A 58-year-old man with a 40-pack-year smoking history
develops progressive dyspnea and chronic productive cough.
Pulmonary function testing shows a reduced FEV₁/FVC ratio
with minimal reversibility after bronchodilator administration.
Which pathological mechanism best explains his condition?
A. Destruction of alveolar septa caused by α₁-antitrypsin
deficiency
B. Reversible bronchial smooth muscle contraction
C. Chronic airway inflammation with mucus hypersecretion
and airway remodeling
D. Increased pulmonary surfactant production
Answer: C. Chronic airway inflammation with mucus
hypersecretion and airway remodeling
Rationale: Chronic obstructive pulmonary disease, particularly
chronic bronchitis, involves persistent airway inflammation,
,mucus gland enlargement, goblet-cell hyperplasia, and airway
remodeling that produce largely irreversible airflow limitation.
2.
A patient with septic shock develops hypotension, elevated
lactate, and progressive renal dysfunction despite adequate
oxygen saturation. Which mechanism most directly contributes
to cellular injury in this setting?
A. Increased mitochondrial ATP production
B. Impaired tissue perfusion causing cellular hypoxia and
mitochondrial dysfunction
C. Increased oxidative phosphorylation
D. Reduced anaerobic metabolism
Answer: B. Impaired tissue perfusion causing cellular hypoxia
and mitochondrial dysfunction
Rationale: Septic shock causes profound circulatory and
microvascular abnormalities that impair tissue oxygen delivery
and utilization. Cellular ATP depletion promotes membrane
dysfunction, acidosis, and organ injury.
3.
,A 24-year-old woman develops urticaria, wheezing, and
hypotension minutes after receiving intravenous penicillin.
Which immunologic mechanism is primarily responsible?
A. IgG-mediated cytotoxicity
B. Immune-complex deposition
C. T-cell-mediated delayed hypersensitivity
D. IgE-mediated mast-cell degranulation
Answer: D. IgE-mediated mast-cell degranulation
Rationale: Type I hypersensitivity occurs when allergen-specific
IgE bound to mast cells is cross-linked, triggering rapid release
of histamine, leukotrienes, and other mediators responsible for
anaphylaxis.
4.
A patient with rheumatoid arthritis is started on methotrexate.
Which mechanism accounts for its therapeutic effect in this
disease?
A. Direct inhibition of cyclooxygenase-2
B. Blockade of histamine H₁ receptors
C. Suppression of lymphocyte proliferation and inflammatory
mediator production
D. Stimulation of neutrophil migration
, Answer: C. Suppression of lymphocyte proliferation and
inflammatory mediator production
Rationale: Methotrexate, at low doses used for rheumatoid
arthritis, has immunomodulatory and anti-inflammatory
effects, including increased extracellular adenosine and
suppression of immune-cell activity.
5.
A 67-year-old woman develops sudden right-sided weakness
and aphasia. Imaging reveals an infarct in the left middle
cerebral artery territory. Which mechanism causes neuronal
injury during cerebral ischemia?
A. Reduced glutamate release
B. Increased ATP synthesis
C. Excitotoxicity caused by excessive glutamate and
intracellular calcium accumulation
D. Inhibition of free-radical formation
Answer: C. Excitotoxicity caused by excessive glutamate and
intracellular calcium accumulation
Rationale: Ischemic ATP depletion causes neuronal
depolarization and excessive glutamate release. NMDA receptor
activation allows calcium influx, activating destructive enzymes
and promoting oxidative and mitochondrial injury.
