PATHOPHYSIOLOGY OF DISEASE: AN
INTRODUCTION TO CLINICAL MEDICINE
8TH EDITION
AUTHOR(S)GARY D. HAMMER; STEPHEN J.
MCPHEE
1
Reference
Ch. 1 — Introduction — Homeostasis, Stress, and Disease
Clinical stem (2–4 sentences)
A 62-year-old man presents with progressive fatigue, mild
orthostatic dizziness, and decreased exercise tolerance over 3
months. Vital signs show a resting tachycardia; labs reveal a
persistently elevated resting cortisol and fasting glucose near
the upper limit of normal. Which pathophysiologic process best
explains his decreased physiologic reserve and emergence of
symptomatic dysfunction under minor stressors?
,Options
A. Failure of negative feedback in a homeostatic axis leading to
allostatic overload
B. Primary loss of organ mass (irreversible loss of functional
parenchyma)
C. Acute cellular injury with necrosis and release of intracellular
enzymes
D. Adaptive metaplasia that increases tissue resilience
Correct answer
A
Rationales
Correct (A): Chronic elevation of stress hormones (eg, cortisol)
reflects dysregulated homeostasis and produces allostatic load
— cumulative physiologic burden that reduces reserve and
predisposes to symptomatic dysfunction under relatively minor
additional stress. This mechanism links systemic biochemical
changes to reduced adaptability described in the Introduction.
Incorrect (B): Loss of organ mass produces decreased function
but the vignette emphasizes systemic hormonal dysregulation
and gradual loss of reserve rather than primary parenchymal
destruction.
Incorrect (C): Acute necrotic injury is abrupt and associated
with inflammatory markers and enzyme release, not a chronic
hypercortisolemic picture.
Incorrect (D): Metaplasia is an adaptive cellular phenotype
change; it may alter resilience locally but does not explain
,systemic hormonal elevation and generalized decreased
reserve.
Teaching point
Allostatic overload (failed homeostasis) reduces physiologic
reserve and causes systemic vulnerability.
Citation
Hammer, G. D., & McPhee, S. J. (2025). Pathophysiology of
Disease (8th ed.). Chapter 1.
2
Reference
Ch. 1 — Introduction — Cellular Adaptation: Atrophy,
Hypertrophy, Hyperplasia, Metaplasia
Clinical stem (2–4 sentences)
A 55-year-old female smoker develops persistent cough and
hemoptysis. Bronchoscopy shows squamous epithelium
replacing normal pseudostratified ciliated columnar epithelium
in bronchial mucosa. Which mechanistic statement best
explains how this epithelial change modifies subsequent
disease risk?
Options
A. Metaplasia reflects reprogramming of stem/progenitor cells
to a more stress-resistant phenotype but increases malignant
transformation risk.
B. Hypertrophy of epithelial cells increases mucociliary
, clearance and protects against infection.
C. Atrophy of the bronchial epithelium reduces oxygen
consumption and prevents neoplasia.
D. Hyperplasia of mucus-secreting cells eliminates carcinogenic
risk by diluting toxins.
Correct answer
A
Rationales
Correct (A): Metaplasia is a stress-induced, reversible
reprogramming of progenitor cells toward a phenotype better
able to withstand chronic insult (e.g., squamous for tobacco
exposure). This increased proliferative activity and genomic
stress raises the risk of dysplasia and neoplasia, a concept
emphasized in Chapter 1’s discussion of adaptation versus
maladaptation.
Incorrect (B): Hypertrophy is enlargement of existing cells, not
the observed epithelial replacement; hypertrophy of airway
epithelium would not logically increase mucociliary clearance.
Incorrect (C): Atrophy implies reduced size/function but does
not account for the active replacement by squamous cells; it
does not prevent neoplasia.
Incorrect (D): Hyperplasia of mucus cells may increase mucus
but does not eliminate carcinogen risk; increased proliferation
can itself predispose to dysregulation.
INTRODUCTION TO CLINICAL MEDICINE
8TH EDITION
AUTHOR(S)GARY D. HAMMER; STEPHEN J.
MCPHEE
1
Reference
Ch. 1 — Introduction — Homeostasis, Stress, and Disease
Clinical stem (2–4 sentences)
A 62-year-old man presents with progressive fatigue, mild
orthostatic dizziness, and decreased exercise tolerance over 3
months. Vital signs show a resting tachycardia; labs reveal a
persistently elevated resting cortisol and fasting glucose near
the upper limit of normal. Which pathophysiologic process best
explains his decreased physiologic reserve and emergence of
symptomatic dysfunction under minor stressors?
,Options
A. Failure of negative feedback in a homeostatic axis leading to
allostatic overload
B. Primary loss of organ mass (irreversible loss of functional
parenchyma)
C. Acute cellular injury with necrosis and release of intracellular
enzymes
D. Adaptive metaplasia that increases tissue resilience
Correct answer
A
Rationales
Correct (A): Chronic elevation of stress hormones (eg, cortisol)
reflects dysregulated homeostasis and produces allostatic load
— cumulative physiologic burden that reduces reserve and
predisposes to symptomatic dysfunction under relatively minor
additional stress. This mechanism links systemic biochemical
changes to reduced adaptability described in the Introduction.
Incorrect (B): Loss of organ mass produces decreased function
but the vignette emphasizes systemic hormonal dysregulation
and gradual loss of reserve rather than primary parenchymal
destruction.
Incorrect (C): Acute necrotic injury is abrupt and associated
with inflammatory markers and enzyme release, not a chronic
hypercortisolemic picture.
Incorrect (D): Metaplasia is an adaptive cellular phenotype
change; it may alter resilience locally but does not explain
,systemic hormonal elevation and generalized decreased
reserve.
Teaching point
Allostatic overload (failed homeostasis) reduces physiologic
reserve and causes systemic vulnerability.
Citation
Hammer, G. D., & McPhee, S. J. (2025). Pathophysiology of
Disease (8th ed.). Chapter 1.
2
Reference
Ch. 1 — Introduction — Cellular Adaptation: Atrophy,
Hypertrophy, Hyperplasia, Metaplasia
Clinical stem (2–4 sentences)
A 55-year-old female smoker develops persistent cough and
hemoptysis. Bronchoscopy shows squamous epithelium
replacing normal pseudostratified ciliated columnar epithelium
in bronchial mucosa. Which mechanistic statement best
explains how this epithelial change modifies subsequent
disease risk?
Options
A. Metaplasia reflects reprogramming of stem/progenitor cells
to a more stress-resistant phenotype but increases malignant
transformation risk.
B. Hypertrophy of epithelial cells increases mucociliary
, clearance and protects against infection.
C. Atrophy of the bronchial epithelium reduces oxygen
consumption and prevents neoplasia.
D. Hyperplasia of mucus-secreting cells eliminates carcinogenic
risk by diluting toxins.
Correct answer
A
Rationales
Correct (A): Metaplasia is a stress-induced, reversible
reprogramming of progenitor cells toward a phenotype better
able to withstand chronic insult (e.g., squamous for tobacco
exposure). This increased proliferative activity and genomic
stress raises the risk of dysplasia and neoplasia, a concept
emphasized in Chapter 1’s discussion of adaptation versus
maladaptation.
Incorrect (B): Hypertrophy is enlargement of existing cells, not
the observed epithelial replacement; hypertrophy of airway
epithelium would not logically increase mucociliary clearance.
Incorrect (C): Atrophy implies reduced size/function but does
not account for the active replacement by squamous cells; it
does not prevent neoplasia.
Incorrect (D): Hyperplasia of mucus cells may increase mucus
but does not eliminate carcinogen risk; increased proliferation
can itself predispose to dysregulation.
