PATHOPHYSIOLOGY OF DISEASE: AN
INTRODUCTION TO CLINICAL MEDICINE
8TH EDITION
AUTHOR(S)GARY D. HAMMER; STEPHEN J.
MCPHEE
Q1
Reference: Ch. 1 — Introduction — Cellular adaptation:
hypertrophy vs. hyperplasia
Stem: A 62-year-old woman with longstanding hypertension
develops concentric left ventricular hypertrophy evident on
echocardiography. Biopsy shows increased cardiomyocyte size
without mitotic figures. Which pathophysiologic mechanism
best explains the myocardial change?
A. Persistent activation of growth factor receptors leading to
increased cell proliferation.
B. Increased mechanical load causing upregulation of
sarcomeric proteins and cell size.
,C. Chronic ischemia causing myocyte apoptosis and subsequent
fibrous replacement.
D. Hormone-dependent hyperplasia mediated by circulating
trophic hormones.
Correct answer: B
Rationale — Correct (B): Pressure overload from hypertension
increases mechanical stress on cardiomyocytes, triggering
intracellular signaling (e.g., stretch-sensitive pathways) that
upregulates sarcomere synthesis and cell size → hypertrophy.
This matches the biopsy finding of larger myocytes without
mitoses. Concepts in Chapter 1 link increased functional
demand and hypertrophic growth via intracellular protein
synthesis.
Rationales — Incorrect:
A. Describes hyperplasia (proliferation) via growth factor
pathways; cardiomyocytes in adults enlarge rather than
proliferate.
C. Chronic ischemia leads to cell death and fibrosis, not isolated
increase in myocyte size.
D. Hormone-driven hyperplasia occurs in hormone-responsive
tissues (e.g., endometrium); not the primary mechanism for
pressure-induced cardiac change.
Teaching point: Pressure overload causes hypertrophy by
increasing cell protein synthesis, not cell number.
,Citation: Hammer, G. D., & McPhee, S. J. (2025).
Pathophysiology of Disease: An Introduction to Clinical Medicine
(8th ed.). Chapter 1.
Q2
Reference: Ch. 1 — Introduction — Reversible versus
irreversible cell injury
Stem: A 45-year-old man had a brief episode of hypotension
during surgery; post-op liver enzymes are transiently elevated
and liver ultrasound is normal. Which cellular event most likely
characterized his hepatic injury?
A. Rapid loss of membrane phospholipids with nuclear
pyknosis.
B. Mitochondrial swelling with preserved nuclear chromatin.
C. Extensive DNA fragmentation and inflammatory infiltration.
D. Influx of neutrophils causing protease-mediated necrosis.
Correct answer: B
Rationale — Correct (B): Brief hypoperfusion typically causes
reversible ischemic injury manifested by reversible
mitochondrial swelling, loss of ATP-dependent functions, and
preserved nuclear chromatin. Chapter 1 emphasizes
mitochondrial dysfunction and swelling as early reversible
changes after sublethal ischemia.
, Rationales — Incorrect:
A. Loss of membrane phospholipids and nuclear pyknosis
indicate irreversible injury/necrosis.
C. DNA fragmentation with inflammation suggests irreversible
cell death and subsequent necrosis/apoptosis progression.
D. Neutrophil influx is a secondary inflammatory response to
necrosis; not the primary immediate reversible change.
Teaching point: Early, reversible ischemia features
mitochondrial swelling and reversible loss of function without
nuclear breakdown.
Citation: Hammer, G. D., & McPhee, S. J. (2025).
Pathophysiology of Disease (8th ed.). Chapter 1.
Q3
Reference: Ch. 1 — Introduction — Mechanisms of cell injury:
hypoxia vs. toxins
Stem: A 28-year-old woman presents after an intentional
ingestion of a household herbicide. She is hypotensive with
lactic acidosis and elevated serum aminotransferases. Which
mechanism most plausibly links this exposure to hepatocellular
necrosis?
A. Direct DNA alkylation causing p53-mediated apoptosis.
B. Uncoupling of oxidative phosphorylation causing ATP
depletion and necrosis.
C. Autoimmune-mediated cytotoxic T lymphocyte attack on
INTRODUCTION TO CLINICAL MEDICINE
8TH EDITION
AUTHOR(S)GARY D. HAMMER; STEPHEN J.
MCPHEE
Q1
Reference: Ch. 1 — Introduction — Cellular adaptation:
hypertrophy vs. hyperplasia
Stem: A 62-year-old woman with longstanding hypertension
develops concentric left ventricular hypertrophy evident on
echocardiography. Biopsy shows increased cardiomyocyte size
without mitotic figures. Which pathophysiologic mechanism
best explains the myocardial change?
A. Persistent activation of growth factor receptors leading to
increased cell proliferation.
B. Increased mechanical load causing upregulation of
sarcomeric proteins and cell size.
,C. Chronic ischemia causing myocyte apoptosis and subsequent
fibrous replacement.
D. Hormone-dependent hyperplasia mediated by circulating
trophic hormones.
Correct answer: B
Rationale — Correct (B): Pressure overload from hypertension
increases mechanical stress on cardiomyocytes, triggering
intracellular signaling (e.g., stretch-sensitive pathways) that
upregulates sarcomere synthesis and cell size → hypertrophy.
This matches the biopsy finding of larger myocytes without
mitoses. Concepts in Chapter 1 link increased functional
demand and hypertrophic growth via intracellular protein
synthesis.
Rationales — Incorrect:
A. Describes hyperplasia (proliferation) via growth factor
pathways; cardiomyocytes in adults enlarge rather than
proliferate.
C. Chronic ischemia leads to cell death and fibrosis, not isolated
increase in myocyte size.
D. Hormone-driven hyperplasia occurs in hormone-responsive
tissues (e.g., endometrium); not the primary mechanism for
pressure-induced cardiac change.
Teaching point: Pressure overload causes hypertrophy by
increasing cell protein synthesis, not cell number.
,Citation: Hammer, G. D., & McPhee, S. J. (2025).
Pathophysiology of Disease: An Introduction to Clinical Medicine
(8th ed.). Chapter 1.
Q2
Reference: Ch. 1 — Introduction — Reversible versus
irreversible cell injury
Stem: A 45-year-old man had a brief episode of hypotension
during surgery; post-op liver enzymes are transiently elevated
and liver ultrasound is normal. Which cellular event most likely
characterized his hepatic injury?
A. Rapid loss of membrane phospholipids with nuclear
pyknosis.
B. Mitochondrial swelling with preserved nuclear chromatin.
C. Extensive DNA fragmentation and inflammatory infiltration.
D. Influx of neutrophils causing protease-mediated necrosis.
Correct answer: B
Rationale — Correct (B): Brief hypoperfusion typically causes
reversible ischemic injury manifested by reversible
mitochondrial swelling, loss of ATP-dependent functions, and
preserved nuclear chromatin. Chapter 1 emphasizes
mitochondrial dysfunction and swelling as early reversible
changes after sublethal ischemia.
, Rationales — Incorrect:
A. Loss of membrane phospholipids and nuclear pyknosis
indicate irreversible injury/necrosis.
C. DNA fragmentation with inflammation suggests irreversible
cell death and subsequent necrosis/apoptosis progression.
D. Neutrophil influx is a secondary inflammatory response to
necrosis; not the primary immediate reversible change.
Teaching point: Early, reversible ischemia features
mitochondrial swelling and reversible loss of function without
nuclear breakdown.
Citation: Hammer, G. D., & McPhee, S. J. (2025).
Pathophysiology of Disease (8th ed.). Chapter 1.
Q3
Reference: Ch. 1 — Introduction — Mechanisms of cell injury:
hypoxia vs. toxins
Stem: A 28-year-old woman presents after an intentional
ingestion of a household herbicide. She is hypotensive with
lactic acidosis and elevated serum aminotransferases. Which
mechanism most plausibly links this exposure to hepatocellular
necrosis?
A. Direct DNA alkylation causing p53-mediated apoptosis.
B. Uncoupling of oxidative phosphorylation causing ATP
depletion and necrosis.
C. Autoimmune-mediated cytotoxic T lymphocyte attack on
