PATHOPHYSIOLOGY OF DISEASE: AN
INTRODUCTION TO CLINICAL MEDICINE
8TH EDITION
AUTHOR(S)GARY D. HAMMER; STEPHEN J.
MCPHEE
TEST BANK
1
Reference
Ch. 1 — Principles: Homeostasis, Stress, and Adaptation
Clinical stem
A 58-year-old man with long-standing hypertension develops
concentric left ventricular hypertrophy and later reports
exertional dyspnea. Laboratory tests show preserved systolic
function but progressive diastolic dysfunction. Which
mechanism most plausibly explains the transition from
compensated hypertrophy to symptomatic diastolic heart
failure?
,A. Progressive loss of cardiomyocytes from necrosis leading to
reduced contractile mass
B. Maladaptive extracellular matrix remodeling with increased
interstitial fibrosis reducing ventricular compliance
C. Persistent neurohormonal blockade causing decreased
myocardial contractility
D. Developmental metaplasia replacing myocardium with
fibrocartilage
Correct answer
B
Rationale — Correct (B)
Pressure overload induces cardiomyocyte hypertrophy as an
adaptive response, but chronic stress promotes extracellular
matrix deposition and interstitial fibrosis. Fibrosis increases
ventricular stiffness, impairs diastolic filling, and explains
preserved systolic function with symptomatic diastolic
dysfunction. This mechanism is described in the chapter’s
discussion of adaptation and maladaptive remodeling.
Rationales — Incorrect
A. Necrosis with loss of contractile mass more commonly leads
to systolic dysfunction rather than isolated diastolic failure.
C. Neurohormonal blockade (e.g., therapeutic) would not
explain progression to dysfunction; persistent neurohormonal
activation—not blockade—contributes to maladaptation.
D. Metaplasia to fibrocartilage is not a recognized cardiac
,response to pressure overload and is mechanistically
implausible.
Teaching point
Chronic pressure overload → hypertrophy → interstitial fibrosis
→ reduced compliance (diastolic dysfunction).
Citation
Hammer, G. D., & McPhee, S. J. (2019). Pathophysiology of
Disease (8th ed.). Chapter 1.
2
Reference
Ch. 1 — Cellular Injury: Mechanisms and Outcomes
Clinical stem
A 35-year-old woman presents after an overdose of
acetaminophen with elevated AST/ALT, rising prothrombin time,
and hepatic encephalopathy. Which cellular mechanism
primarily explains centrilobular hepatic necrosis in
acetaminophen toxicity?
A. Mitochondrial oxidative phosphorylation uncoupling due to
direct alcohol-derived lipid peroxidation
B. Formation of a reactive metabolite causing glutathione
depletion and covalent protein binding with oxidative injury
C. Immune-complex deposition in hepatic sinusoids triggering
complement-mediated cytolysis
D. Ischemic hypoperfusion from systemic hypotension only
, Correct answer
B
Rationale — Correct (B)
Acetaminophen is metabolized to a reactive intermediate
(NAPQI) that depletes glutathione and binds cellular proteins,
producing oxidative stress and mitochondrial dysfunction
leading to hepatocellular necrosis—classically centrilobular.
Chapter 1 outlines chemical injury via reactive metabolites and
antioxidant depletion as central mechanisms.
Rationales — Incorrect
A. Lipid peroxidation is a mechanism of oxidative injury but the
stem specifies acetaminophen; alcohol-related pathways are
different.
C. Immune-complex deposition is not the primary mechanism in
acetaminophen-induced hepatotoxicity.
D. Systemic hypotension can cause ischemic injury but the
pattern and lab findings here point to toxin-mediated
centrilobular necrosis.
Teaching point
Reactive metabolite (NAPQI) → glutathione depletion →
covalent binding → hepatocyte necrosis.
Citation
Hammer, G. D., & McPhee, S. J. (2019). Pathophysiology of
Disease (8th ed.). Chapter 1.
INTRODUCTION TO CLINICAL MEDICINE
8TH EDITION
AUTHOR(S)GARY D. HAMMER; STEPHEN J.
MCPHEE
TEST BANK
1
Reference
Ch. 1 — Principles: Homeostasis, Stress, and Adaptation
Clinical stem
A 58-year-old man with long-standing hypertension develops
concentric left ventricular hypertrophy and later reports
exertional dyspnea. Laboratory tests show preserved systolic
function but progressive diastolic dysfunction. Which
mechanism most plausibly explains the transition from
compensated hypertrophy to symptomatic diastolic heart
failure?
,A. Progressive loss of cardiomyocytes from necrosis leading to
reduced contractile mass
B. Maladaptive extracellular matrix remodeling with increased
interstitial fibrosis reducing ventricular compliance
C. Persistent neurohormonal blockade causing decreased
myocardial contractility
D. Developmental metaplasia replacing myocardium with
fibrocartilage
Correct answer
B
Rationale — Correct (B)
Pressure overload induces cardiomyocyte hypertrophy as an
adaptive response, but chronic stress promotes extracellular
matrix deposition and interstitial fibrosis. Fibrosis increases
ventricular stiffness, impairs diastolic filling, and explains
preserved systolic function with symptomatic diastolic
dysfunction. This mechanism is described in the chapter’s
discussion of adaptation and maladaptive remodeling.
Rationales — Incorrect
A. Necrosis with loss of contractile mass more commonly leads
to systolic dysfunction rather than isolated diastolic failure.
C. Neurohormonal blockade (e.g., therapeutic) would not
explain progression to dysfunction; persistent neurohormonal
activation—not blockade—contributes to maladaptation.
D. Metaplasia to fibrocartilage is not a recognized cardiac
,response to pressure overload and is mechanistically
implausible.
Teaching point
Chronic pressure overload → hypertrophy → interstitial fibrosis
→ reduced compliance (diastolic dysfunction).
Citation
Hammer, G. D., & McPhee, S. J. (2019). Pathophysiology of
Disease (8th ed.). Chapter 1.
2
Reference
Ch. 1 — Cellular Injury: Mechanisms and Outcomes
Clinical stem
A 35-year-old woman presents after an overdose of
acetaminophen with elevated AST/ALT, rising prothrombin time,
and hepatic encephalopathy. Which cellular mechanism
primarily explains centrilobular hepatic necrosis in
acetaminophen toxicity?
A. Mitochondrial oxidative phosphorylation uncoupling due to
direct alcohol-derived lipid peroxidation
B. Formation of a reactive metabolite causing glutathione
depletion and covalent protein binding with oxidative injury
C. Immune-complex deposition in hepatic sinusoids triggering
complement-mediated cytolysis
D. Ischemic hypoperfusion from systemic hypotension only
, Correct answer
B
Rationale — Correct (B)
Acetaminophen is metabolized to a reactive intermediate
(NAPQI) that depletes glutathione and binds cellular proteins,
producing oxidative stress and mitochondrial dysfunction
leading to hepatocellular necrosis—classically centrilobular.
Chapter 1 outlines chemical injury via reactive metabolites and
antioxidant depletion as central mechanisms.
Rationales — Incorrect
A. Lipid peroxidation is a mechanism of oxidative injury but the
stem specifies acetaminophen; alcohol-related pathways are
different.
C. Immune-complex deposition is not the primary mechanism in
acetaminophen-induced hepatotoxicity.
D. Systemic hypotension can cause ischemic injury but the
pattern and lab findings here point to toxin-mediated
centrilobular necrosis.
Teaching point
Reactive metabolite (NAPQI) → glutathione depletion →
covalent binding → hepatocyte necrosis.
Citation
Hammer, G. D., & McPhee, S. J. (2019). Pathophysiology of
Disease (8th ed.). Chapter 1.
