NSG 533 Advanced Pathophysiology
Exam 2 – Practice Questions with
Complete Solutions, updated and
comprehensive 2025 material
Exam 2 Overview
his graduate-level exam features 100 PhD-caliber multiple-choice questions mirroring
T
Chamberlain’s rigor. Spanning cellular injury/adaptation, inflammation/immunity,
acid-base/electrolyte imbalances, fluid/hemodynamics, and genetic/neoplastic processes, it
integrates cardiovascular, pulmonary, renal, endocrine, and neurologic disorders. Each question
presents a precise clinical stem, four distractors, the bolded correct answer, and a 2–4 sentence
rationale detailing core pathophysiologic mechanisms (e.g., signal transduction, receptor
dynamics, genomic regulation). Designed for advanced clinical reasoning, it prepares learners
to synthesize complex disease cascades and therapeutic targets across systems.
uestion 1
Q
In a patient with chronic hypoxic pulmonary vasoconstriction leading to cor pulmonale, which
cellular adaptation predominates in right ventricular cardiomyocytes?
A. Hyperplasia of sarcoplasmic reticulum
B. Hypertrophy with increased myofibril synthesis
C. Metaplasia to squamous epithelium
D. Dysplasia with nuclear pleomorphism
B. Hypertrophy with increased myofibril synthesis
ight ventricular cardiomyocytes undergo physiologic hypertrophy in response to pressure
R
overload from pulmonary hypertension. Increased sarcomere assembly and myofibril protein
synthesis (via mTOR pathway activation) compensate for wall stress per the Law of Laplace.
Hyperplasia is not possible in terminally differentiated cardiomyocytes; metaplasia and dysplasia
are pathologic and unrelated to pressure adaptation.
uestion 2
Q
A 58-year-old male with alcoholic cirrhosis presents with refractory ascites. Biopsy reveals
hepatocyte ballooning with Mallory-Denk bodies. The primary mechanism of cellular injury is:
A. ATP depletion from impaired oxidative phosphorylation
B. Ubiquitin-proteasome dysfunction with intermediate filament aggregation
,C. Plasma membrane blebbing from Na+/K+ ATPase failure
D. Mitochondrial permeability transition pore opening
B. Ubiquitin-proteasome dysfunction with intermediate filament aggregation
allory-Denk bodies represent keratin 8/18 aggregates due to impaired ubiquitination and
M
chaperone dysfunction in alcoholic hyaline degeneration. While ATP depletion and mitochondrial
injury occur, the hallmark lesion reflects cytoskeletal protein misfolding and failed clearance, not
primary membrane or pore pathology.
uestion 3
Q
During acute tubular necrosis, proximal tubule cells exhibit loss of brush border and apical
blebbing. This reversible injury is mediated by:
A. Caspase-3 activation and DNA fragmentation
B. Actin cytoskeleton disruption via Rho kinase inhibition
C. Lysosomal rupture with cathepsin release
D. Endoplasmic reticulum stress and PERK phosphorylation
B. Actin cytoskeleton disruption via Rho kinase inhibition
Ischemia-induced ATP depletion inactivates Rho GTPases, disrupting actin polymerization and
microvillus integrity. Blebbing results from cortical actin detachment, allowing submembranous
cytoplasm protrusion. Caspase activation marks irreversible apoptosis; lysosomal and ER stress
occur later.
uestion 4
Q
A patient with squamous cell carcinoma of the lung develops hypercalcemia. Paraneoplastic
PTHrP secretion primarily causes bone resorption via:
A. Direct osteoclast maturation through RANKL induction on osteoblasts
B. Osteoblast apoptosis with secondary osteoclast activation
C. Inhibition of osteoprotegerin (OPG) transcription
D. Upregulation of carbonic anhydrase in osteoclasts
A. Direct osteoclast maturation through RANKL induction on osteoblasts
THrP binds PTH1R on osteoblasts, increasing RANKL expression and decreasing OPG,
P
promoting RANK-RANKL signaling and osteoclastogenesis. This receptor-mediated pathway
drives lytic bone lesions; direct effects on osteoclasts are minimal.
uestion 5
Q
In diabetic ketoacidosis, the compensatory respiratory alkalosis is driven by:
A. Carotid body detection of decreased pH stimulating hyperventilation
B. Central chemoreceptor stimulation by elevated PaCO2
, C. JGA renin release secondary to hypovolemia
D. Pulmonary stretch receptor activation from lung expansion
A. Carotid body detection of decreased pH stimulating hyperventilation
etabolic acidosis from ketoacids lowers plasma pH, sensed by peripheral chemoreceptors
M
(carotid > aortic), triggering medullary respiratory center activation and Kussmaul respirations.
Central chemoreceptors respond primarily to CO2/pH changes in CSF, not initial compensation.
uestion 6
Q
A 42-year-old female with Graves’ disease develops thyroid storm. The exaggerated adrenergic
response is due to:
A. Increased β-adrenergic receptor density on cardiomyocytes
B. Enhanced T3-mediated transcription of Na+/K+ ATPase
C. TSH receptor antibody cross-reactivity with cardiac receptors
D. Reduced catecholamine reuptake via NET1 downregulation
B. Enhanced T3-mediated transcription of Na+/K+ ATPase
xcess T3 upregulates sarcolemmal Na+/K+ ATPase and β-adrenergic receptors, amplifying
E
catecholamine sensitivity without increasing circulating levels. This genomic effect heightens
cardiac output and thermogenesis; direct antibody cross-reactivity is not established.
uestion 7
Q
In type 1 hypersensitivity, mast cell degranulation releases histamine that causes vasodilation
via:
A. H1 receptor → Gq → PLC → IP3/DAG
B. H2 receptor → Gs → cAMP → PKA
C. H1 receptor → Gi → decreased cAMP
D. H3 receptor → inhibition of neurotransmitter release
A. H1 receptor → Gq → PLC → IP3/DAG
istamine binds H1 receptors on vascular endothelium, activating phospholipase C, generating
H
IP3 (Ca2+ release) and DAG (PKC activation), leading to nitric oxide synthesis and vasodilation.
H2 mediates gastric acid secretion; H3 is presynaptic inhibitory.
uestion 8
Q
A patient with rheumatoid arthritis on methotrexate develops pancytopenia. Bone marrow biopsy
shows megaloblastic changes. The mechanism is:
A. Dihydrofolate reductase inhibition → impaired thymidylate synthesis
B. DNA polymerase α inhibition → stalled replication forks
C. Ribonucleotide reductase inhibition → depleted dNTP pools
Exam 2 – Practice Questions with
Complete Solutions, updated and
comprehensive 2025 material
Exam 2 Overview
his graduate-level exam features 100 PhD-caliber multiple-choice questions mirroring
T
Chamberlain’s rigor. Spanning cellular injury/adaptation, inflammation/immunity,
acid-base/electrolyte imbalances, fluid/hemodynamics, and genetic/neoplastic processes, it
integrates cardiovascular, pulmonary, renal, endocrine, and neurologic disorders. Each question
presents a precise clinical stem, four distractors, the bolded correct answer, and a 2–4 sentence
rationale detailing core pathophysiologic mechanisms (e.g., signal transduction, receptor
dynamics, genomic regulation). Designed for advanced clinical reasoning, it prepares learners
to synthesize complex disease cascades and therapeutic targets across systems.
uestion 1
Q
In a patient with chronic hypoxic pulmonary vasoconstriction leading to cor pulmonale, which
cellular adaptation predominates in right ventricular cardiomyocytes?
A. Hyperplasia of sarcoplasmic reticulum
B. Hypertrophy with increased myofibril synthesis
C. Metaplasia to squamous epithelium
D. Dysplasia with nuclear pleomorphism
B. Hypertrophy with increased myofibril synthesis
ight ventricular cardiomyocytes undergo physiologic hypertrophy in response to pressure
R
overload from pulmonary hypertension. Increased sarcomere assembly and myofibril protein
synthesis (via mTOR pathway activation) compensate for wall stress per the Law of Laplace.
Hyperplasia is not possible in terminally differentiated cardiomyocytes; metaplasia and dysplasia
are pathologic and unrelated to pressure adaptation.
uestion 2
Q
A 58-year-old male with alcoholic cirrhosis presents with refractory ascites. Biopsy reveals
hepatocyte ballooning with Mallory-Denk bodies. The primary mechanism of cellular injury is:
A. ATP depletion from impaired oxidative phosphorylation
B. Ubiquitin-proteasome dysfunction with intermediate filament aggregation
,C. Plasma membrane blebbing from Na+/K+ ATPase failure
D. Mitochondrial permeability transition pore opening
B. Ubiquitin-proteasome dysfunction with intermediate filament aggregation
allory-Denk bodies represent keratin 8/18 aggregates due to impaired ubiquitination and
M
chaperone dysfunction in alcoholic hyaline degeneration. While ATP depletion and mitochondrial
injury occur, the hallmark lesion reflects cytoskeletal protein misfolding and failed clearance, not
primary membrane or pore pathology.
uestion 3
Q
During acute tubular necrosis, proximal tubule cells exhibit loss of brush border and apical
blebbing. This reversible injury is mediated by:
A. Caspase-3 activation and DNA fragmentation
B. Actin cytoskeleton disruption via Rho kinase inhibition
C. Lysosomal rupture with cathepsin release
D. Endoplasmic reticulum stress and PERK phosphorylation
B. Actin cytoskeleton disruption via Rho kinase inhibition
Ischemia-induced ATP depletion inactivates Rho GTPases, disrupting actin polymerization and
microvillus integrity. Blebbing results from cortical actin detachment, allowing submembranous
cytoplasm protrusion. Caspase activation marks irreversible apoptosis; lysosomal and ER stress
occur later.
uestion 4
Q
A patient with squamous cell carcinoma of the lung develops hypercalcemia. Paraneoplastic
PTHrP secretion primarily causes bone resorption via:
A. Direct osteoclast maturation through RANKL induction on osteoblasts
B. Osteoblast apoptosis with secondary osteoclast activation
C. Inhibition of osteoprotegerin (OPG) transcription
D. Upregulation of carbonic anhydrase in osteoclasts
A. Direct osteoclast maturation through RANKL induction on osteoblasts
THrP binds PTH1R on osteoblasts, increasing RANKL expression and decreasing OPG,
P
promoting RANK-RANKL signaling and osteoclastogenesis. This receptor-mediated pathway
drives lytic bone lesions; direct effects on osteoclasts are minimal.
uestion 5
Q
In diabetic ketoacidosis, the compensatory respiratory alkalosis is driven by:
A. Carotid body detection of decreased pH stimulating hyperventilation
B. Central chemoreceptor stimulation by elevated PaCO2
, C. JGA renin release secondary to hypovolemia
D. Pulmonary stretch receptor activation from lung expansion
A. Carotid body detection of decreased pH stimulating hyperventilation
etabolic acidosis from ketoacids lowers plasma pH, sensed by peripheral chemoreceptors
M
(carotid > aortic), triggering medullary respiratory center activation and Kussmaul respirations.
Central chemoreceptors respond primarily to CO2/pH changes in CSF, not initial compensation.
uestion 6
Q
A 42-year-old female with Graves’ disease develops thyroid storm. The exaggerated adrenergic
response is due to:
A. Increased β-adrenergic receptor density on cardiomyocytes
B. Enhanced T3-mediated transcription of Na+/K+ ATPase
C. TSH receptor antibody cross-reactivity with cardiac receptors
D. Reduced catecholamine reuptake via NET1 downregulation
B. Enhanced T3-mediated transcription of Na+/K+ ATPase
xcess T3 upregulates sarcolemmal Na+/K+ ATPase and β-adrenergic receptors, amplifying
E
catecholamine sensitivity without increasing circulating levels. This genomic effect heightens
cardiac output and thermogenesis; direct antibody cross-reactivity is not established.
uestion 7
Q
In type 1 hypersensitivity, mast cell degranulation releases histamine that causes vasodilation
via:
A. H1 receptor → Gq → PLC → IP3/DAG
B. H2 receptor → Gs → cAMP → PKA
C. H1 receptor → Gi → decreased cAMP
D. H3 receptor → inhibition of neurotransmitter release
A. H1 receptor → Gq → PLC → IP3/DAG
istamine binds H1 receptors on vascular endothelium, activating phospholipase C, generating
H
IP3 (Ca2+ release) and DAG (PKC activation), leading to nitric oxide synthesis and vasodilation.
H2 mediates gastric acid secretion; H3 is presynaptic inhibitory.
uestion 8
Q
A patient with rheumatoid arthritis on methotrexate develops pancytopenia. Bone marrow biopsy
shows megaloblastic changes. The mechanism is:
A. Dihydrofolate reductase inhibition → impaired thymidylate synthesis
B. DNA polymerase α inhibition → stalled replication forks
C. Ribonucleotide reductase inhibition → depleted dNTP pools
