PATHOPHYSIOLOGY OF DISEASE: AN
INTRODUCTION TO CLINICAL MEDICINE
8TH EDITION
AUTHOR(S)GARY D. HAMMER; STEPHEN J.
MCPHEE
TEST BANK
Ch. 1 — Introduction — Homeostatic Failure and
Compensatory Injury
Clinical stem: A 68-year-old man with longstanding
hypertension presents with progressive dyspnea and lower-
extremity edema. Echocardiography shows concentric LV
hypertrophy and preserved ejection fraction. Laboratory studies
reveal mild elevation of B-type natriuretic peptide. Which
pathophysiologic process most plausibly links chronic pressure
overload to the progressive symptoms?
,A. Apoptosis of cardiomyocytes secondary to chronic oxidative
stress, leading to ventricular dilation
B. Adaptive cardiomyocyte hypertrophy increasing wall
thickness but eventually causing diastolic dysfunction
C. Replacement fibrosis from acute ischemic necrosis producing
regional systolic dysfunction
D. Myocyte hyperplasia increasing chamber size and impairing
contractility
Correct answer: B
Rationale — Correct (B): Chronic pressure overload drives
cardiomyocyte hypertrophy as an adaptive response to
normalize wall stress; increased myocyte size enlarges wall
thickness (concentric hypertrophy) but raises myocardial
stiffness and impairs diastolic filling, producing heart failure
with preserved ejection fraction. Hammer & McPhee describe
adaptive hypertrophy as a compensatory cellular response to
chronic biomechanical stress that can become maladaptive.
Rationale — Incorrect:
A — Apoptosis may occur from oxidative stress but apoptosis
primarily reduces cell number rather than producing concentric
hypertrophy and preserved EF; it more often contributes to
progressive loss of contractile units.
C — Replacement fibrosis following acute ischemic necrosis
causes regional systolic dysfunction (reduced EF) rather than
concentric hypertrophy with diastolic impairment.
D — Mature cardiomyocytes do not undergo hyperplasia in
,adults; increased mass occurs via hypertrophy, not cell
proliferation.
Teaching point: Chronic pressure overload → cardiomyocyte
hypertrophy → increased stiffness → diastolic dysfunction.
Citation: Hammer, G. D., & McPhee, S. J. (2025).
Pathophysiology of Disease (8th ed.). Chapter 1.
Ch. 1 — Introduction — Reversible versus Irreversible Cell
Injury
Clinical stem: A 45-year-old woman arrives after several hours
of severe limb compression from a motor vehicle accident. On
exam the muscle is swollen, tense, and has diminished distal
pulses. Laboratory tests show rising serum creatine kinase and
early lactate accumulation in venous blood from the limb.
Which cellular event best distinguishes reversible from
irreversible ischemic injury in this context?
A. Depletion of cellular ATP with failure of Na⁺/K⁺ ATPase
causing cellular swelling
B. Loss of mitochondrial membrane potential with formation of
the mitochondrial permeability transition pore (MPTP) and
rupture of lysosomal membranes
C. Increased glycolysis with lactic acidosis and accumulation of
intracellular glycogen
D. Activation of heat-shock proteins facilitating protein refolding
and cell recovery
, Correct answer: B
Rationale — Correct (B): Irreversible ischemic injury is marked
by profound mitochondrial dysfunction including loss of
membrane potential and opening of the MPTP, leading to
failure of oxidative phosphorylation, release of pro-apoptotic
factors, and eventual membrane rupture; lysosomal rupture
with enzymatic digestion further ensures irreversible necrosis.
Hammer & McPhee highlight MPTP opening as a key event
demarcating irreversible injury.
Rationale — Incorrect:
A — ATP depletion and Na⁺/K⁺ pump failure produce reversible
cellular swelling if oxygen is restored in time; they are early,
potentially reversible events.
C — Increased glycolysis and lactic acid accumulation are
adaptive metabolic changes in hypoxia and do not by
themselves define irreversibility.
D — Heat-shock proteins are protective chaperones that
promote recovery, not markers of irreversible injury.
Teaching point: Mitochondrial permeability transition pore
opening marks the transition to irreversible cell death.
Citation: Hammer, G. D., & McPhee, S. J. (2025).
Pathophysiology of Disease (8th ed.). Chapter 1.
Ch. 1 — Introduction — Hypoxia versus Ischemia Mechanisms
INTRODUCTION TO CLINICAL MEDICINE
8TH EDITION
AUTHOR(S)GARY D. HAMMER; STEPHEN J.
MCPHEE
TEST BANK
Ch. 1 — Introduction — Homeostatic Failure and
Compensatory Injury
Clinical stem: A 68-year-old man with longstanding
hypertension presents with progressive dyspnea and lower-
extremity edema. Echocardiography shows concentric LV
hypertrophy and preserved ejection fraction. Laboratory studies
reveal mild elevation of B-type natriuretic peptide. Which
pathophysiologic process most plausibly links chronic pressure
overload to the progressive symptoms?
,A. Apoptosis of cardiomyocytes secondary to chronic oxidative
stress, leading to ventricular dilation
B. Adaptive cardiomyocyte hypertrophy increasing wall
thickness but eventually causing diastolic dysfunction
C. Replacement fibrosis from acute ischemic necrosis producing
regional systolic dysfunction
D. Myocyte hyperplasia increasing chamber size and impairing
contractility
Correct answer: B
Rationale — Correct (B): Chronic pressure overload drives
cardiomyocyte hypertrophy as an adaptive response to
normalize wall stress; increased myocyte size enlarges wall
thickness (concentric hypertrophy) but raises myocardial
stiffness and impairs diastolic filling, producing heart failure
with preserved ejection fraction. Hammer & McPhee describe
adaptive hypertrophy as a compensatory cellular response to
chronic biomechanical stress that can become maladaptive.
Rationale — Incorrect:
A — Apoptosis may occur from oxidative stress but apoptosis
primarily reduces cell number rather than producing concentric
hypertrophy and preserved EF; it more often contributes to
progressive loss of contractile units.
C — Replacement fibrosis following acute ischemic necrosis
causes regional systolic dysfunction (reduced EF) rather than
concentric hypertrophy with diastolic impairment.
D — Mature cardiomyocytes do not undergo hyperplasia in
,adults; increased mass occurs via hypertrophy, not cell
proliferation.
Teaching point: Chronic pressure overload → cardiomyocyte
hypertrophy → increased stiffness → diastolic dysfunction.
Citation: Hammer, G. D., & McPhee, S. J. (2025).
Pathophysiology of Disease (8th ed.). Chapter 1.
Ch. 1 — Introduction — Reversible versus Irreversible Cell
Injury
Clinical stem: A 45-year-old woman arrives after several hours
of severe limb compression from a motor vehicle accident. On
exam the muscle is swollen, tense, and has diminished distal
pulses. Laboratory tests show rising serum creatine kinase and
early lactate accumulation in venous blood from the limb.
Which cellular event best distinguishes reversible from
irreversible ischemic injury in this context?
A. Depletion of cellular ATP with failure of Na⁺/K⁺ ATPase
causing cellular swelling
B. Loss of mitochondrial membrane potential with formation of
the mitochondrial permeability transition pore (MPTP) and
rupture of lysosomal membranes
C. Increased glycolysis with lactic acidosis and accumulation of
intracellular glycogen
D. Activation of heat-shock proteins facilitating protein refolding
and cell recovery
, Correct answer: B
Rationale — Correct (B): Irreversible ischemic injury is marked
by profound mitochondrial dysfunction including loss of
membrane potential and opening of the MPTP, leading to
failure of oxidative phosphorylation, release of pro-apoptotic
factors, and eventual membrane rupture; lysosomal rupture
with enzymatic digestion further ensures irreversible necrosis.
Hammer & McPhee highlight MPTP opening as a key event
demarcating irreversible injury.
Rationale — Incorrect:
A — ATP depletion and Na⁺/K⁺ pump failure produce reversible
cellular swelling if oxygen is restored in time; they are early,
potentially reversible events.
C — Increased glycolysis and lactic acid accumulation are
adaptive metabolic changes in hypoxia and do not by
themselves define irreversibility.
D — Heat-shock proteins are protective chaperones that
promote recovery, not markers of irreversible injury.
Teaching point: Mitochondrial permeability transition pore
opening marks the transition to irreversible cell death.
Citation: Hammer, G. D., & McPhee, S. J. (2025).
Pathophysiology of Disease (8th ed.). Chapter 1.
Ch. 1 — Introduction — Hypoxia versus Ischemia Mechanisms
