ANATOMICAL CHART COMPANY ATLAS
OF PATHOPHYSIOLOGY
4TH EDITION
• AUTHOR(S)JULIE STEWART
TEST BANK
Reference: Part I — Cells, Homeostasis, and Disease — Cellular
Hypoxia and ATP Depletion
Stem: A 68-year-old man with long-standing peripheral arterial
disease arrives with a painful, pale lower leg after a night of
severe leg cramping. Pulse is weak in the affected foot; capillary
refill is delayed. Cellular ATP production is most likely impaired
by which primary pathophysiologic mechanism?
A. Inhibition of Na⁺/K⁺-ATPase from ATP depletion
B. Excessive mitochondrial biogenesis increasing oxygen
,demand
C. Increased membrane cholesterol stiffening ion channels
D. Overactivation of lysosomal hydrolases due to alkalosis
Correct answer: A
Rationale — Correct (A): Ischemia leads to decreased oxidative
phosphorylation and ATP depletion, causing failure of the
Na⁺/K⁺-ATPase pump. Pump failure allows intracellular Na⁺ and
water accumulation, producing cellular swelling and impaired
membrane potentials consistent with ischemic hypoxic injury.
Rationale — Incorrect (B): Mitochondrial biogenesis is not an
acute response to ischemia; it would not increase ATP during
hypoxia and is not the immediate mechanism of ATP depletion.
Rationale — Incorrect (C): Membrane cholesterol changes
affect fluidity chronically but do not explain acute ATP loss
causing ion pump failure.
Rationale — Incorrect (D): Lysosomal hydrolase activation
occurs with lysosomal rupture (acidic environment), not from
alkalosis, and is a downstream effect, not the primary cause of
ATP depletion.
Teaching point: ATP depletion → Na⁺/K⁺ pump failure → cellular
swelling; hallmark of acute hypoxic injury.
Citation: Stewart, J. (4th ed.). Anatomical Chart Company Atlas
of Pathophysiology. Part I.
2)
,Reference: Part I — Cells, Homeostasis, and Disease —
Reperfusion Injury & Free Radicals
Stem: A 55-year-old woman undergoes successful
thrombectomy for acute myocardial infarction. Several hours
later she develops worsening myocardial dysfunction from
oxidative damage. Which mechanism best explains reperfusion
injury?
A. Sudden restoration of oxygen generates reactive oxygen
species (ROS) that damage membranes and mitochondria
B. Reoxygenation causes intracellular alkalosis activating DNA
repair enzymes that digest myocardium
C. Reperfusion directly hyperpolarizes cell membranes
preventing Ca²⁺ influx
D. Oxygen restores ATP immediately, preventing further injury
and causing no cellular damage
Correct answer: A
Rationale — Correct (A): Reperfusion of ischemic tissue
reintroduces oxygen leading to abrupt ROS formation
(superoxide, hydroxyl radical). ROS damage lipids, proteins, and
mitochondrial membranes, exacerbate Ca²⁺ influx, and promote
cell death—classic ischemia-reperfusion injury.
Rationale — Incorrect (B): Intracellular alkalosis and DNA repair
activation are not primary drivers of reperfusion myocardial
damage; ROS-mediated lipid and protein oxidation are.
Rationale — Incorrect (C): Reperfusion does not hyperpolarize
membranes to prevent Ca²⁺ influx; instead, cell membrane and
mitochondrial damage permit uncontrolled Ca²⁺ entry.
, Rationale — Incorrect (D): ATP restoration is incomplete and
delayed; reperfusion paradoxically causes additional oxidative
injury.
Teaching point: Reperfusion → burst of ROS → oxidative
membrane/mitochondrial damage and worsening cell death.
Citation: Stewart, J. (4th ed.). Anatomical Chart Company Atlas
of Pathophysiology. Part I.
3)
Reference: Part I — Cells, Homeostasis, and Disease — Free
Radical Injury & Antioxidant Defenses
Stem: A 40-year-old patient with chronic acetaminophen
overdose shows hepatic necrosis. Which intracellular defense
failure most directly contributes to hepatocyte susceptibility to
free radical injury?
A. Glutathione depletion limiting neutralization of reactive
metabolites
B. Increased catalase activity causing hydrogen peroxide
accumulation
C. Heightened superoxide dismutase (SOD) expression
producing more radicals
D. Elevated ceruloplasmin sequestering iron and preventing
lipid peroxidation
Correct answer: A
OF PATHOPHYSIOLOGY
4TH EDITION
• AUTHOR(S)JULIE STEWART
TEST BANK
Reference: Part I — Cells, Homeostasis, and Disease — Cellular
Hypoxia and ATP Depletion
Stem: A 68-year-old man with long-standing peripheral arterial
disease arrives with a painful, pale lower leg after a night of
severe leg cramping. Pulse is weak in the affected foot; capillary
refill is delayed. Cellular ATP production is most likely impaired
by which primary pathophysiologic mechanism?
A. Inhibition of Na⁺/K⁺-ATPase from ATP depletion
B. Excessive mitochondrial biogenesis increasing oxygen
,demand
C. Increased membrane cholesterol stiffening ion channels
D. Overactivation of lysosomal hydrolases due to alkalosis
Correct answer: A
Rationale — Correct (A): Ischemia leads to decreased oxidative
phosphorylation and ATP depletion, causing failure of the
Na⁺/K⁺-ATPase pump. Pump failure allows intracellular Na⁺ and
water accumulation, producing cellular swelling and impaired
membrane potentials consistent with ischemic hypoxic injury.
Rationale — Incorrect (B): Mitochondrial biogenesis is not an
acute response to ischemia; it would not increase ATP during
hypoxia and is not the immediate mechanism of ATP depletion.
Rationale — Incorrect (C): Membrane cholesterol changes
affect fluidity chronically but do not explain acute ATP loss
causing ion pump failure.
Rationale — Incorrect (D): Lysosomal hydrolase activation
occurs with lysosomal rupture (acidic environment), not from
alkalosis, and is a downstream effect, not the primary cause of
ATP depletion.
Teaching point: ATP depletion → Na⁺/K⁺ pump failure → cellular
swelling; hallmark of acute hypoxic injury.
Citation: Stewart, J. (4th ed.). Anatomical Chart Company Atlas
of Pathophysiology. Part I.
2)
,Reference: Part I — Cells, Homeostasis, and Disease —
Reperfusion Injury & Free Radicals
Stem: A 55-year-old woman undergoes successful
thrombectomy for acute myocardial infarction. Several hours
later she develops worsening myocardial dysfunction from
oxidative damage. Which mechanism best explains reperfusion
injury?
A. Sudden restoration of oxygen generates reactive oxygen
species (ROS) that damage membranes and mitochondria
B. Reoxygenation causes intracellular alkalosis activating DNA
repair enzymes that digest myocardium
C. Reperfusion directly hyperpolarizes cell membranes
preventing Ca²⁺ influx
D. Oxygen restores ATP immediately, preventing further injury
and causing no cellular damage
Correct answer: A
Rationale — Correct (A): Reperfusion of ischemic tissue
reintroduces oxygen leading to abrupt ROS formation
(superoxide, hydroxyl radical). ROS damage lipids, proteins, and
mitochondrial membranes, exacerbate Ca²⁺ influx, and promote
cell death—classic ischemia-reperfusion injury.
Rationale — Incorrect (B): Intracellular alkalosis and DNA repair
activation are not primary drivers of reperfusion myocardial
damage; ROS-mediated lipid and protein oxidation are.
Rationale — Incorrect (C): Reperfusion does not hyperpolarize
membranes to prevent Ca²⁺ influx; instead, cell membrane and
mitochondrial damage permit uncontrolled Ca²⁺ entry.
, Rationale — Incorrect (D): ATP restoration is incomplete and
delayed; reperfusion paradoxically causes additional oxidative
injury.
Teaching point: Reperfusion → burst of ROS → oxidative
membrane/mitochondrial damage and worsening cell death.
Citation: Stewart, J. (4th ed.). Anatomical Chart Company Atlas
of Pathophysiology. Part I.
3)
Reference: Part I — Cells, Homeostasis, and Disease — Free
Radical Injury & Antioxidant Defenses
Stem: A 40-year-old patient with chronic acetaminophen
overdose shows hepatic necrosis. Which intracellular defense
failure most directly contributes to hepatocyte susceptibility to
free radical injury?
A. Glutathione depletion limiting neutralization of reactive
metabolites
B. Increased catalase activity causing hydrogen peroxide
accumulation
C. Heightened superoxide dismutase (SOD) expression
producing more radicals
D. Elevated ceruloplasmin sequestering iron and preventing
lipid peroxidation
Correct answer: A
