NR507 Advanced Pathophysiology Midterm Bundle
2025/2026 - Weeks 1-4 Reviews with Complete
Solutions & Grade A Guarantee
[Week 1 Focus] 1. A 58-year-old woman with 35-year history of GERD undergoes
endoscopy revealing salmon-pink mucosa above the gastroesophageal junction. Biopsy
shows intestinal-type goblet cells interspersed with gastric cardia epithelium. Which
intracellular signaling pathway best explains this phenotypic switch?
A) Persistent NF-κB activation → pro-inflammatory cytokines → mesenchymal stem cell
recruitment
B) Bile acid–induced CDX2 promoter demethylation → lineage reprogramming of
gastric stem cells
C) Telomerase mutation → clonal proliferation of mutated gastric foveolar cells
D) Autophagy inhibition → accumulation of reactive oxygen species → necrosis
Answer: B
Rationale: Chronic bile and acid exposure methylates/demethylates key promoters,
especially CDX2, driving intestinal metaplasia (a classic adaptive response to chronic
irritation). This represents true phenotypic plasticity of resident gastric stem cells, not
mutagenic proliferation (C) or generic inflammation (A). D implies lethal injury,
inconsistent with viable, reprogrammed epithelium.
[Week 2 Focus] 2. A 68-kg ICU patient on mechanical ventilation receives large-volume
saline boluses for septic shock. ABG: pH 7.28, PaCO₂ 28 mmHg, HCO₃⁻ 18 mEq/L;
serum Na 148 mEq/L, K 3.2 mEq/L, Cl 118 mEq/L. Which pathophysiologic mechanism
best explains the acid-base disorder?
,A) Hyperchloremic-induced renal bicarbonate wasting via chloride-sensing macula
densa
B) Lactic acidosis overwhelming hepatic buffering capacity
C) Respiratory acidosis from hypoventilation
D) Ketoacidosis due to insulin deficiency
Answer: A
Rationale: Supra-physiological chloride delivery to the macula densa suppresses renin
and increases distal HCO₃⁻ loss, producing a dilution-related metabolic acidosis with a
normal anion gap (ΔAG ≈ 0). Low PaCO₂ is compensatory hyperventilation, not primary
respiratory acidosis (C). Lactate (B) and ketones (D) would widen the anion gap—absent
here.
[Week 3 Focus] 3. A 64-year-old man with hypertension awakens with left hemiparesis.
CT shows right lentiform hyperdensity; CTA reveals a 4-mm ruptured lenticulostriate
branch. Within 3 h his serum glutamate level is three-fold normal. Which sequence best
links glutamate to impending neuronal death?
A) Glutamate → NMDA over-activation → Ca²⁺ influx → mitochondrial pore formation →
apoptotic cascades
B) Glutamate → GABA receptor blockade → Na⁺ influx → osmotic lysis
C) Glutamate → AMPA desensitization → K⁺ efflux → membrane hyperpolarization
D) Glutamate → nicotinic receptor phosphorylation → increased acetylcholine release
Answer: A
Rationale: Excitotoxicity is driven by high extracellular glutamate activating NMDA
receptors, flooding neurons with Ca²⁺ that opens mitochondrial permeability-transition
,pores, releasing cytochrome-c and activating caspases. Option B incorrectly assigns
GABA blockade; C implies protection via hyperpolarization; D introduces an irrelevant
cholinergic mechanism.
[Week 4 Focus] 4. A 55-year-old woman with chronic HTN presents with acute
pulmonary edema; echo: LVEF 30 %, concentric wall thickness 1.4 cm, small cavity,
doppler E/A 2.1, septal e′ 4 cm/s. Which cellular remodeling process most directly
produces her diastolic dysfunction?
A) Sarcomeric addition in series → eccentric hypertrophy
B) Increased collagen cross-linking and reduced MMP activity → impaired relaxation
C) β-MHC isoform re-expression → decreased velocity of contraction
D) Neutrophil extracellular traps → micro-vascular occlusion
Answer: B
Rationale: Pressure overload stimulates parallel sarcomere addition (concentric
hypertrophy) and fibroblast activation, depositing stiffer type-I collagen while MMP
activity falls. Cross-link accumulation increases passive stiffness, slowing relaxation
and raising filling pressures. A describes volume-overload eccentric pattern; C affects
systolic velocity, not relaxation; D is inflammatory but not the dominant stiffness
mechanism.
[Week 1 → 4 Integration] 5. A 42-year-old smoker exhibits elevated plasma
homocysteine. Endothelial ROS generated by homocysteine oxidize LDL, provoking
macrophage ingestion and foam-cell formation. Which co-existing Week-1 mediator
amplifies endothelial E-selectin expression to accelerate Week-4 atherogenesis?
A) IL-1β-induced NF-κB nuclear translocation
B) TGF-β–Smad2/3 fibrotic signaling
C) Autophagic LC3-II conversion
, D) Telomere shortening–p53 activation
Answer: A
Rationale: IL-1β (acute-phase cytokine from Week 1) potently activates NF-κB,
up-regulating endothelial adhesion molecules (E-selectin, VCAM-1) requisite for
monocyte recruitment into nascent plaque. TGF-β (B) is anti-inflammatory; C & D are not
immediate adhesion-molecule drivers.
[Week 2 Focus] 6. A post-craniotomy patient develops SIADH; serum Na drops from 138
to 122 mEq/L in 24 h. Which neuro-cellular consequence of rapid hyponatremia best
explains the observed confusion and potential for seizures?
A) Water efflux from neurons → cellular dehydration → membrane depolarization
B) Water influx → astrocyte swelling → decreased extracellular glutamate uptake →
excitotoxicity
C) Increased Na-K-ATPase activity → Na⁺ extrusion → hyperpolarization block
D) Osmotic demyelination via oligodendrocyte apoptosis
Answer: B
Rationale: Rapid fall in serum Na lowers extracellular tonicity, driving water into
astrocytes. Swollen astrocytes up-regulate AQP-4 but transiently reduce glutamate
re-uptake, raising synaptic glutamate and lowering seizure threshold. Option A
describes hypernatremia; C is compensatory but insufficient; D (ODS) occurs with overly
rapid correction, not with acute hyponatremia itself.
[Week 3 Focus] 7. A 72-year-old man with early Alzheimer’s shows disproportionate
impairment in olfactory identification on psych testing. Which early-stage
neuropathologic distribution best accounts for this deficit?
A) Accumulation of tau neurofibrillary tangles in entorhinal cortex → hippocampal
disconnection
2025/2026 - Weeks 1-4 Reviews with Complete
Solutions & Grade A Guarantee
[Week 1 Focus] 1. A 58-year-old woman with 35-year history of GERD undergoes
endoscopy revealing salmon-pink mucosa above the gastroesophageal junction. Biopsy
shows intestinal-type goblet cells interspersed with gastric cardia epithelium. Which
intracellular signaling pathway best explains this phenotypic switch?
A) Persistent NF-κB activation → pro-inflammatory cytokines → mesenchymal stem cell
recruitment
B) Bile acid–induced CDX2 promoter demethylation → lineage reprogramming of
gastric stem cells
C) Telomerase mutation → clonal proliferation of mutated gastric foveolar cells
D) Autophagy inhibition → accumulation of reactive oxygen species → necrosis
Answer: B
Rationale: Chronic bile and acid exposure methylates/demethylates key promoters,
especially CDX2, driving intestinal metaplasia (a classic adaptive response to chronic
irritation). This represents true phenotypic plasticity of resident gastric stem cells, not
mutagenic proliferation (C) or generic inflammation (A). D implies lethal injury,
inconsistent with viable, reprogrammed epithelium.
[Week 2 Focus] 2. A 68-kg ICU patient on mechanical ventilation receives large-volume
saline boluses for septic shock. ABG: pH 7.28, PaCO₂ 28 mmHg, HCO₃⁻ 18 mEq/L;
serum Na 148 mEq/L, K 3.2 mEq/L, Cl 118 mEq/L. Which pathophysiologic mechanism
best explains the acid-base disorder?
,A) Hyperchloremic-induced renal bicarbonate wasting via chloride-sensing macula
densa
B) Lactic acidosis overwhelming hepatic buffering capacity
C) Respiratory acidosis from hypoventilation
D) Ketoacidosis due to insulin deficiency
Answer: A
Rationale: Supra-physiological chloride delivery to the macula densa suppresses renin
and increases distal HCO₃⁻ loss, producing a dilution-related metabolic acidosis with a
normal anion gap (ΔAG ≈ 0). Low PaCO₂ is compensatory hyperventilation, not primary
respiratory acidosis (C). Lactate (B) and ketones (D) would widen the anion gap—absent
here.
[Week 3 Focus] 3. A 64-year-old man with hypertension awakens with left hemiparesis.
CT shows right lentiform hyperdensity; CTA reveals a 4-mm ruptured lenticulostriate
branch. Within 3 h his serum glutamate level is three-fold normal. Which sequence best
links glutamate to impending neuronal death?
A) Glutamate → NMDA over-activation → Ca²⁺ influx → mitochondrial pore formation →
apoptotic cascades
B) Glutamate → GABA receptor blockade → Na⁺ influx → osmotic lysis
C) Glutamate → AMPA desensitization → K⁺ efflux → membrane hyperpolarization
D) Glutamate → nicotinic receptor phosphorylation → increased acetylcholine release
Answer: A
Rationale: Excitotoxicity is driven by high extracellular glutamate activating NMDA
receptors, flooding neurons with Ca²⁺ that opens mitochondrial permeability-transition
,pores, releasing cytochrome-c and activating caspases. Option B incorrectly assigns
GABA blockade; C implies protection via hyperpolarization; D introduces an irrelevant
cholinergic mechanism.
[Week 4 Focus] 4. A 55-year-old woman with chronic HTN presents with acute
pulmonary edema; echo: LVEF 30 %, concentric wall thickness 1.4 cm, small cavity,
doppler E/A 2.1, septal e′ 4 cm/s. Which cellular remodeling process most directly
produces her diastolic dysfunction?
A) Sarcomeric addition in series → eccentric hypertrophy
B) Increased collagen cross-linking and reduced MMP activity → impaired relaxation
C) β-MHC isoform re-expression → decreased velocity of contraction
D) Neutrophil extracellular traps → micro-vascular occlusion
Answer: B
Rationale: Pressure overload stimulates parallel sarcomere addition (concentric
hypertrophy) and fibroblast activation, depositing stiffer type-I collagen while MMP
activity falls. Cross-link accumulation increases passive stiffness, slowing relaxation
and raising filling pressures. A describes volume-overload eccentric pattern; C affects
systolic velocity, not relaxation; D is inflammatory but not the dominant stiffness
mechanism.
[Week 1 → 4 Integration] 5. A 42-year-old smoker exhibits elevated plasma
homocysteine. Endothelial ROS generated by homocysteine oxidize LDL, provoking
macrophage ingestion and foam-cell formation. Which co-existing Week-1 mediator
amplifies endothelial E-selectin expression to accelerate Week-4 atherogenesis?
A) IL-1β-induced NF-κB nuclear translocation
B) TGF-β–Smad2/3 fibrotic signaling
C) Autophagic LC3-II conversion
, D) Telomere shortening–p53 activation
Answer: A
Rationale: IL-1β (acute-phase cytokine from Week 1) potently activates NF-κB,
up-regulating endothelial adhesion molecules (E-selectin, VCAM-1) requisite for
monocyte recruitment into nascent plaque. TGF-β (B) is anti-inflammatory; C & D are not
immediate adhesion-molecule drivers.
[Week 2 Focus] 6. A post-craniotomy patient develops SIADH; serum Na drops from 138
to 122 mEq/L in 24 h. Which neuro-cellular consequence of rapid hyponatremia best
explains the observed confusion and potential for seizures?
A) Water efflux from neurons → cellular dehydration → membrane depolarization
B) Water influx → astrocyte swelling → decreased extracellular glutamate uptake →
excitotoxicity
C) Increased Na-K-ATPase activity → Na⁺ extrusion → hyperpolarization block
D) Osmotic demyelination via oligodendrocyte apoptosis
Answer: B
Rationale: Rapid fall in serum Na lowers extracellular tonicity, driving water into
astrocytes. Swollen astrocytes up-regulate AQP-4 but transiently reduce glutamate
re-uptake, raising synaptic glutamate and lowering seizure threshold. Option A
describes hypernatremia; C is compensatory but insufficient; D (ODS) occurs with overly
rapid correction, not with acute hyponatremia itself.
[Week 3 Focus] 7. A 72-year-old man with early Alzheimer’s shows disproportionate
impairment in olfactory identification on psych testing. Which early-stage
neuropathologic distribution best accounts for this deficit?
A) Accumulation of tau neurofibrillary tangles in entorhinal cortex → hippocampal
disconnection
