PATHOPHYSIOLOGY OF DISEASE: AN
INTRODUCTION TO CLINICAL MEDICINE
8TH EDITION
AUTHOR(S)GARY D. HAMMER; STEPHEN J.
MCPHEE
TEST BANK
1
Reference
Ch. 1 — Fundamental Concepts — Homeostasis and Allostasis
Clinical stem (2–4 sentences)
A 62-year-old man with poorly controlled type 2 diabetes
presents with fatigue, mild orthostatic hypotension, and
recurrent infections. Vital signs show low-grade fever.
Laboratory testing reveals persistent hyperglycemia and an
elevated HbA1c. Which concept best explains why diverse organ
systems are now failing to maintain stable internal conditions?
,Options
A. Loss of negative feedback leading to failure of homeostasis.
B. Ineffective allostatic load causing cumulative physiologic
wear and tear.
C. Failure of feed-forward mechanisms increasing anticipatory
responses.
D. Primary maladaptive genetic set point causing fixed
homeostatic thresholds.
Correct answer
B
Rationales
Correct (B): Chronic metabolic stress in diabetes exemplifies
increased allostatic load — cumulative physiologic burden from
repeated adaptive responses (e.g., hyperglycemia,
inflammation) that eventually impairs multiple systems,
explaining fatigue, autonomic dysfunction, and infection
susceptibility. This links repeated adaptive physiology to
multisystem decline as described in Chapter 1.
Incorrect (A): While loss of negative feedback can destabilize a
variable acutely, the patient’s multisystem, chronic
deterioration is better explained by cumulative allostatic load
rather than a single failed negative feedback loop.
Incorrect (C): Feed-forward mechanisms are anticipatory and
may be beneficial; they do not primarily account for chronic
organ wear seen here.
Incorrect (D): A fixed genetic set point would not explain
,progressive, stress-related systemic deterioration due to
environmental/metabolic burden.
Teaching point
Allostatic load: chronic adaptive responses cause cumulative
organ dysfunction.
Citation
Hammer, G. D., & McPhee, S. J. (2025). Pathophysiology of
Disease (8th ed.). Chapter 1.
2
Reference
Ch. 1 — Cellular Injury — Reversible versus Irreversible Injury
Clinical stem
A 45-year-old woman arrives after a lightning strike. She had a
brief period of unconsciousness; on arrival she is awake but has
myalgias and dark urine. CK is markedly elevated; urinalysis
shows myoglobinuria. Which cellular process best explains
acute rhabdomyolysis leading to myoglobin release?
Options
A. Reversible cell swelling due to ATP depletion and Na⁺/K⁺
pump failure.
B. Irreversible loss of plasma membrane integrity from severe
ATP depletion and calcium influx.
C. Increased autophagic vacuolization protecting myocytes from
necrosis.
, D. Apoptosis via caspase activation causing orderly myocyte
removal.
Correct answer
B
Rationales
Correct (B): Severe ATP depletion from electroporation and
direct membrane injury permits uncontrolled Ca²⁺ influx,
activates proteases and phospholipases, and causes loss of
membrane integrity — hallmarks of irreversible injury and
necrosis leading to myoglobin release. Chapter 1 links
membrane disruption and calcium overload to irreversible cell
death.
Incorrect (A): Reversible swelling occurs earlier with Na⁺/K⁺
pump failure but does not explain frank myoglobinuria and
massive CK elevation which indicate necrosis.
Incorrect (C): Autophagy is generally protective and would not
account for acute necrosis with release of intracellular contents.
Incorrect (D): Apoptosis is energy-dependent and
compartmentalized without leakage of intracellular enzymes;
myoglobinuria indicates necrosis, not apoptosis.
Teaching point
Loss of membrane integrity and calcium overload produce
irreversible necrosis and myoglobin release.
Citation
Hammer, G. D., & McPhee, S. J. (2025). 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 — Fundamental Concepts — Homeostasis and Allostasis
Clinical stem (2–4 sentences)
A 62-year-old man with poorly controlled type 2 diabetes
presents with fatigue, mild orthostatic hypotension, and
recurrent infections. Vital signs show low-grade fever.
Laboratory testing reveals persistent hyperglycemia and an
elevated HbA1c. Which concept best explains why diverse organ
systems are now failing to maintain stable internal conditions?
,Options
A. Loss of negative feedback leading to failure of homeostasis.
B. Ineffective allostatic load causing cumulative physiologic
wear and tear.
C. Failure of feed-forward mechanisms increasing anticipatory
responses.
D. Primary maladaptive genetic set point causing fixed
homeostatic thresholds.
Correct answer
B
Rationales
Correct (B): Chronic metabolic stress in diabetes exemplifies
increased allostatic load — cumulative physiologic burden from
repeated adaptive responses (e.g., hyperglycemia,
inflammation) that eventually impairs multiple systems,
explaining fatigue, autonomic dysfunction, and infection
susceptibility. This links repeated adaptive physiology to
multisystem decline as described in Chapter 1.
Incorrect (A): While loss of negative feedback can destabilize a
variable acutely, the patient’s multisystem, chronic
deterioration is better explained by cumulative allostatic load
rather than a single failed negative feedback loop.
Incorrect (C): Feed-forward mechanisms are anticipatory and
may be beneficial; they do not primarily account for chronic
organ wear seen here.
Incorrect (D): A fixed genetic set point would not explain
,progressive, stress-related systemic deterioration due to
environmental/metabolic burden.
Teaching point
Allostatic load: chronic adaptive responses cause cumulative
organ dysfunction.
Citation
Hammer, G. D., & McPhee, S. J. (2025). Pathophysiology of
Disease (8th ed.). Chapter 1.
2
Reference
Ch. 1 — Cellular Injury — Reversible versus Irreversible Injury
Clinical stem
A 45-year-old woman arrives after a lightning strike. She had a
brief period of unconsciousness; on arrival she is awake but has
myalgias and dark urine. CK is markedly elevated; urinalysis
shows myoglobinuria. Which cellular process best explains
acute rhabdomyolysis leading to myoglobin release?
Options
A. Reversible cell swelling due to ATP depletion and Na⁺/K⁺
pump failure.
B. Irreversible loss of plasma membrane integrity from severe
ATP depletion and calcium influx.
C. Increased autophagic vacuolization protecting myocytes from
necrosis.
, D. Apoptosis via caspase activation causing orderly myocyte
removal.
Correct answer
B
Rationales
Correct (B): Severe ATP depletion from electroporation and
direct membrane injury permits uncontrolled Ca²⁺ influx,
activates proteases and phospholipases, and causes loss of
membrane integrity — hallmarks of irreversible injury and
necrosis leading to myoglobin release. Chapter 1 links
membrane disruption and calcium overload to irreversible cell
death.
Incorrect (A): Reversible swelling occurs earlier with Na⁺/K⁺
pump failure but does not explain frank myoglobinuria and
massive CK elevation which indicate necrosis.
Incorrect (C): Autophagy is generally protective and would not
account for acute necrosis with release of intracellular contents.
Incorrect (D): Apoptosis is energy-dependent and
compartmentalized without leakage of intracellular enzymes;
myoglobinuria indicates necrosis, not apoptosis.
Teaching point
Loss of membrane integrity and calcium overload produce
irreversible necrosis and myoglobin release.
Citation
Hammer, G. D., & McPhee, S. J. (2025). Pathophysiology of
Disease (8th ed.). Chapter 1.
