NR507 Advanced Pathophysiology Midterm Exam
Bundle 2025/2026 - 100% Correct Complete
Solutions & Verified Answers
1. A 55-year-old male with T2DM and proteinuria presents with sudden-onset
dyspnea and chest pain. CXR shows pulmonary infiltrates and pleural effusion.
Urinalysis reveals oval fat bodies. Which pathophysiologic mechanism best
explains the pulmonary findings?
A) Increased alveolar-capillary membrane permeability from advanced glycation
end-products
B) Microvascular albumin leakage due to glomerular basement membrane
thickening
C) Osmotic pulmonary edema from severe hypoalbuminemia
D) Capillary-alveolar barrier disruption by immune-complex deposition
Answer: C
Rationale: Heavy proteinuria → serum albumin <2 g/dL → decreased plasma
oncotic pressure → transudative pleural effusion and pulmonary edema; not
primary membrane injury or immune complexes.
2. A 38-year-old woman with longstanding SLE develops progressive dyspnea and
bibasilar crackles. HRCT shows ground-glass opacities and reticular changes.
Autoantibodies to Smith antigen are positive. Which cellular process is the
primary driver of the lung injury?
A) Type II pneumocyte hyperplasia with surfactant overproduction
B) Immune-complex-mediated activation of the classical complement pathway
C) Neutrophil extracellular trap (NET) formation causing endothelial injury
D) CD8+ T-cell cytotoxicity against alveolar basement membrane
Answer: B
Rationale: Anti-Smith immune complexes deposit in alveolar capillaries →
classical complement activation (C3a, C5a) → chemotaxis and tissue damage;
NETs are more common in vasculitides, not primary lupus pneumonitis.
3. A 30-year-old with untreated HIV (CD4 180) presents with fever, dry cough, and
hypoxemia. BAL reveals pink “foam” and PAS-positive material. Which defect
underlies the alveolar injury?
A) Impaired surfactant phospholipid recycling by dysfunctional alveolar
, macrophages
B) Type I pneumocyte apoptosis via gp120-mediated fusion
C) Surfactant protein B gene mutation leading to absent lamellar bodies
D) Alveolar-capillary membrane thickening from amyloid deposition
Answer: A
Rationale: HIV-associated PAP is due to GM-CSF autoantibodies → alveolar
macrophage dysfunction → impaired surfactant clearance → PAS-positive
proteinaceous material; not viral fusion or genetic defect.
4. A 28-year-old with cystic fibrosis (ΔF508/ΔF508) presents with recurrent
hemoptysis and digital clubbing. CT shows dilated, thick-walled bronchi. Which
molecular abnormality is the primary contributor to the bronchiectatic process?
A) Defective chloride secretion → dehydrated airway surface liquid → impaired
mucociliary clearance
B) Excessive sodium absorption → airway wall edema → lumen narrowing
C) Mucin hypersecretion via EGFR over-activation
D) Neutrophil elastase gene polymorphism causing uncontrolled proteolysis
Answer: A
Rationale: ΔF508 → misfolded CFTR → absent chloride secretion and excessive
ENaC-mediated sodium absorption → dehydrated mucus → ciliary stasis and
chronic infection → bronchiectasis; proteolysis is secondary.
5. A 60-year-old former smoker presents with progressive exertional dyspnea and
barrel chest. PFTs: FEV₁/FVC 0.55, DLCO reduced. Chest CT shows upper-lobe
predominant centrilobular emphysema. Which protease-antiprotease imbalance
is central to the emphysematous process?
A) Elastase-α1-antitrypsin
B) MMP-9-TIMP-1
C) Cathepsin G-C1-inhibitor
D) Neutrophil elastase-SLPI
Answer: A
Rationale: Cigarette smoke recruits neutrophils → releases elastase; in α1-AT deficiency
(or functional impairment) elastase destroys alveolar walls → emphysema; other pairs
are less central.
6. A 35-year-old with anti-MDA5 positive dermatomyositis develops acute hypoxic
respiratory failure. HRCT shows diffuse ground-glass and traction
bronchiectasis. Which immune pathway is the primary driver?
, A) Complement C5b-9 membrane attack complex on alveolar cells
B) Type I interferon hyper-stimulation of alveolar macrophages
C) IL-17-mediated neutrophilic recruitment
D) IgG4-related fibroblast proliferation
Answer: B
Rationale: Anti-MDA5 → sustained type I IFN signaling → macrophage activation and
cytokine storm → rapidly progressive interstitial lung disease; complement and IL-17
are less dominant.
7. A 50-year-old with idiopathic pulmonary fibrosis presents with acute desaturation
and new ground-glass opacities superimposed on fibrotic changes. BAL shows
>20 % eosinophils. Which pathophysiologic process is most likely?
A) Acute exacerbation due to alveolar epithelial cell apoptosis and fibrin
deposition
B) Cryptogenic organizing pneumonia with intraluminal granulation tissue
C) Drug-induced pneumonitis with T-cell mediated eosinophilic infiltration
D) Diffuse alveolar hemorrhage from capillaritis
Answer: A
Rationale: AE-IPF involves repeated micro-injury to type II pneumocytes → apoptosis,
fibrin exudation, and fibroblast foci; eosinophils can be present but are not the driver.
8. A 45-year-old with systemic sclerosis presents with progressive dyspnea and
elevated JVP. Echo shows RV dilatation and TR velocity 4 m/s. Which vascular
change underlies the pulmonary pressure elevation?
A) Concentric intimal fibrosis and medial hypertrophy of small pulmonary
arteries
B) Plexiform arteriopathy with angioproliferative lesions
C) Recurrent thrombo-emboli organized in major pulmonary vessels
D) Alveolar hypoxia-induced vasoconstriction only
Answer: A
, Rationale: Scleroderma-associated PAH shows concentric intimal fibrosis and medial
hypertrophy → increased PVR; plexiform lesions are seen in idiopathic PAH, not
CTD-PAH.
9. A 28-year-old with acute asthma exacerbation receives high-dose albuterol and
develops sinus tachycardia at 150 bpm and a widened QRS. Which adrenergic
mechanism explains the ECG change?
A) β2-mediated vasodilation causing reflex sympathetic surge
B) β1 stimulation increasing phase-0 depolarization velocity in His-Purkinje fibers
C) β2-mediated hypokalemia enhancing digitalis-like effect
D) Direct β2 agonism on ventricular myocyte calcium channels
Answer: B
Rationale: High-dose albuterol loses β2 selectivity → β1 activation → faster conduction
and possible bundle-branch block pattern; hypokalemia does not widen QRS.
10. A 28-year-old with cystic fibrosis post-lung transplant develops obliterative
bronchiolitis. Which immunologic process is the primary driver?
A) Donor-specific anti-HLA antibodies activating complement and endothelial
injury
B) CD4+ Th17 cells secreting IL-17 → neutrophilic inflammation in airway lumen
C) Cytotoxic CD8+ T-cells targeting mismatched MHC on bronchial epithelium
D) NK cell antibody-dependent cellular cytotoxicity against airway cells
Answer: C
Rationale: Chronic rejection in lung transplant is dominated by cytotoxic T-lymphocytes
recognizing donor MHC on bronchial epithelium → epithelial apoptosis → obliterative
bronchiolitis; antibodies play lesser role.
11. A 55-year-old with HFpEF and morbid obesity presents with dyspnea on exertion
and bilateral leg edema. BNP is elevated. Which myocardial change is most
characteristic of HFpEF in this patient?
A) Concentric left-ventricular hypertrophy with reduced compliance
B) Eccentric LV dilatation with ↓contractility
Bundle 2025/2026 - 100% Correct Complete
Solutions & Verified Answers
1. A 55-year-old male with T2DM and proteinuria presents with sudden-onset
dyspnea and chest pain. CXR shows pulmonary infiltrates and pleural effusion.
Urinalysis reveals oval fat bodies. Which pathophysiologic mechanism best
explains the pulmonary findings?
A) Increased alveolar-capillary membrane permeability from advanced glycation
end-products
B) Microvascular albumin leakage due to glomerular basement membrane
thickening
C) Osmotic pulmonary edema from severe hypoalbuminemia
D) Capillary-alveolar barrier disruption by immune-complex deposition
Answer: C
Rationale: Heavy proteinuria → serum albumin <2 g/dL → decreased plasma
oncotic pressure → transudative pleural effusion and pulmonary edema; not
primary membrane injury or immune complexes.
2. A 38-year-old woman with longstanding SLE develops progressive dyspnea and
bibasilar crackles. HRCT shows ground-glass opacities and reticular changes.
Autoantibodies to Smith antigen are positive. Which cellular process is the
primary driver of the lung injury?
A) Type II pneumocyte hyperplasia with surfactant overproduction
B) Immune-complex-mediated activation of the classical complement pathway
C) Neutrophil extracellular trap (NET) formation causing endothelial injury
D) CD8+ T-cell cytotoxicity against alveolar basement membrane
Answer: B
Rationale: Anti-Smith immune complexes deposit in alveolar capillaries →
classical complement activation (C3a, C5a) → chemotaxis and tissue damage;
NETs are more common in vasculitides, not primary lupus pneumonitis.
3. A 30-year-old with untreated HIV (CD4 180) presents with fever, dry cough, and
hypoxemia. BAL reveals pink “foam” and PAS-positive material. Which defect
underlies the alveolar injury?
A) Impaired surfactant phospholipid recycling by dysfunctional alveolar
, macrophages
B) Type I pneumocyte apoptosis via gp120-mediated fusion
C) Surfactant protein B gene mutation leading to absent lamellar bodies
D) Alveolar-capillary membrane thickening from amyloid deposition
Answer: A
Rationale: HIV-associated PAP is due to GM-CSF autoantibodies → alveolar
macrophage dysfunction → impaired surfactant clearance → PAS-positive
proteinaceous material; not viral fusion or genetic defect.
4. A 28-year-old with cystic fibrosis (ΔF508/ΔF508) presents with recurrent
hemoptysis and digital clubbing. CT shows dilated, thick-walled bronchi. Which
molecular abnormality is the primary contributor to the bronchiectatic process?
A) Defective chloride secretion → dehydrated airway surface liquid → impaired
mucociliary clearance
B) Excessive sodium absorption → airway wall edema → lumen narrowing
C) Mucin hypersecretion via EGFR over-activation
D) Neutrophil elastase gene polymorphism causing uncontrolled proteolysis
Answer: A
Rationale: ΔF508 → misfolded CFTR → absent chloride secretion and excessive
ENaC-mediated sodium absorption → dehydrated mucus → ciliary stasis and
chronic infection → bronchiectasis; proteolysis is secondary.
5. A 60-year-old former smoker presents with progressive exertional dyspnea and
barrel chest. PFTs: FEV₁/FVC 0.55, DLCO reduced. Chest CT shows upper-lobe
predominant centrilobular emphysema. Which protease-antiprotease imbalance
is central to the emphysematous process?
A) Elastase-α1-antitrypsin
B) MMP-9-TIMP-1
C) Cathepsin G-C1-inhibitor
D) Neutrophil elastase-SLPI
Answer: A
Rationale: Cigarette smoke recruits neutrophils → releases elastase; in α1-AT deficiency
(or functional impairment) elastase destroys alveolar walls → emphysema; other pairs
are less central.
6. A 35-year-old with anti-MDA5 positive dermatomyositis develops acute hypoxic
respiratory failure. HRCT shows diffuse ground-glass and traction
bronchiectasis. Which immune pathway is the primary driver?
, A) Complement C5b-9 membrane attack complex on alveolar cells
B) Type I interferon hyper-stimulation of alveolar macrophages
C) IL-17-mediated neutrophilic recruitment
D) IgG4-related fibroblast proliferation
Answer: B
Rationale: Anti-MDA5 → sustained type I IFN signaling → macrophage activation and
cytokine storm → rapidly progressive interstitial lung disease; complement and IL-17
are less dominant.
7. A 50-year-old with idiopathic pulmonary fibrosis presents with acute desaturation
and new ground-glass opacities superimposed on fibrotic changes. BAL shows
>20 % eosinophils. Which pathophysiologic process is most likely?
A) Acute exacerbation due to alveolar epithelial cell apoptosis and fibrin
deposition
B) Cryptogenic organizing pneumonia with intraluminal granulation tissue
C) Drug-induced pneumonitis with T-cell mediated eosinophilic infiltration
D) Diffuse alveolar hemorrhage from capillaritis
Answer: A
Rationale: AE-IPF involves repeated micro-injury to type II pneumocytes → apoptosis,
fibrin exudation, and fibroblast foci; eosinophils can be present but are not the driver.
8. A 45-year-old with systemic sclerosis presents with progressive dyspnea and
elevated JVP. Echo shows RV dilatation and TR velocity 4 m/s. Which vascular
change underlies the pulmonary pressure elevation?
A) Concentric intimal fibrosis and medial hypertrophy of small pulmonary
arteries
B) Plexiform arteriopathy with angioproliferative lesions
C) Recurrent thrombo-emboli organized in major pulmonary vessels
D) Alveolar hypoxia-induced vasoconstriction only
Answer: A
, Rationale: Scleroderma-associated PAH shows concentric intimal fibrosis and medial
hypertrophy → increased PVR; plexiform lesions are seen in idiopathic PAH, not
CTD-PAH.
9. A 28-year-old with acute asthma exacerbation receives high-dose albuterol and
develops sinus tachycardia at 150 bpm and a widened QRS. Which adrenergic
mechanism explains the ECG change?
A) β2-mediated vasodilation causing reflex sympathetic surge
B) β1 stimulation increasing phase-0 depolarization velocity in His-Purkinje fibers
C) β2-mediated hypokalemia enhancing digitalis-like effect
D) Direct β2 agonism on ventricular myocyte calcium channels
Answer: B
Rationale: High-dose albuterol loses β2 selectivity → β1 activation → faster conduction
and possible bundle-branch block pattern; hypokalemia does not widen QRS.
10. A 28-year-old with cystic fibrosis post-lung transplant develops obliterative
bronchiolitis. Which immunologic process is the primary driver?
A) Donor-specific anti-HLA antibodies activating complement and endothelial
injury
B) CD4+ Th17 cells secreting IL-17 → neutrophilic inflammation in airway lumen
C) Cytotoxic CD8+ T-cells targeting mismatched MHC on bronchial epithelium
D) NK cell antibody-dependent cellular cytotoxicity against airway cells
Answer: C
Rationale: Chronic rejection in lung transplant is dominated by cytotoxic T-lymphocytes
recognizing donor MHC on bronchial epithelium → epithelial apoptosis → obliterative
bronchiolitis; antibodies play lesser role.
11. A 55-year-old with HFpEF and morbid obesity presents with dyspnea on exertion
and bilateral leg edema. BNP is elevated. Which myocardial change is most
characteristic of HFpEF in this patient?
A) Concentric left-ventricular hypertrophy with reduced compliance
B) Eccentric LV dilatation with ↓contractility
