PATHOPHYSIOLOGY OF DISEASE: AN
INTRODUCTION TO CLINICAL MEDICINE
8TH EDITION
AUTHOR(S)GARY D. HAMMER; STEPHEN J.
MCPHEE
TEST BANK
1)
Reference
Ch. 1 — Introduction — Homeostasis, Adaptation, and Stress
Responses
Clinical stem
A 58-year-old man with long-standing poorly controlled type 2
diabetes reports progressive numbness in his feet and
orthostatic lightheadedness. Exam shows diminished ankle
reflexes and resting tachycardia; orthostatic vitals reveal a 25
mmHg drop in systolic pressure on standing. Which
,pathophysiologic explanation best links his chronic metabolic
state to these autonomic and peripheral nerve findings?
A. Persistent hyperglycemia causes nonenzymatic glycation and
osmotic neuronal swelling, producing focal demyelination.
B. Chronic hyperglycemia promotes microvascular ischemia and
accumulation of advanced glycation end products (AGEs),
leading to distal axonal degeneration and autonomic
neuropathy.
C. Recurrent hypoglycemia causes selective loss of large
myelinated fibers with preservation of small unmyelinated C
fibers, producing autonomic dysfunction.
D. Autoimmune targeting of schwann cells after long-term
hyperglycemia results in segmental demyelination and rapid
conduction block.
Correct answer
B
Rationales
Correct (B): Chapter 1 frames disease as disordered physiology
where chronic metabolic stress (hyperglycemia) causes
microvascular endothelial injury and nonenzymatic glycation
(AGEs) that impair perfusion and axonal transport. These
mechanisms preferentially produce distal, length-dependent
axonal degeneration affecting both peripheral sensory fibers
and small autonomic fibers, explaining distal numbness and
orthostatic hypotension. (Hammer & McPhee, Ch.1).
AccessMedicine
,Incorrect (A): Enzymatic/nonenzymatic glycation and osmotic
effects are implicated in neuropathy, but osmotic neuronal
swelling is a less central mechanism than microvascular
ischemia and AGE-mediated dysfunction; focal demyelination is
not the primary pattern in diabetic distal symmetric
polyneuropathy.
Incorrect (C): Recurrent hypoglycemia causes neuronal
dysfunction but does not explain the chronic progressive
length-dependent neuropathy pattern or AGE/microvascular
changes seen with chronic hyperglycemia.
Incorrect (D): Autoimmune schwann cell targeting produces
inflammatory demyelinating neuropathies (e.g., CIDP); diabetic
neuropathy is largely metabolic and ischemic with axonal
degeneration rather than primary immune demyelination.
Teaching point
Chronic hyperglycemia → microvascular ischemia and AGEs →
length-dependent axonal degeneration and autonomic
neuropathy.
Citation
Hammer, G. D., & McPhee, S. J. (2025). Pathophysiology of
Disease (8th ed.). Chapter 1. AccessMedicine
2)
, Reference
Ch. 1 — Introduction — Cellular Injury and Reversible vs
Irreversible Damage
Clinical stem
A 45-year-old woman presents with acute onset severe
abdominal pain after a hypotensive episode during surgery.
Serum lactate is markedly elevated. CT shows patchy
hypoattenuation of bowel consistent with ischemia. On biopsy,
mucosal cells show mitochondrial swelling and clumping of
nuclear chromatin but intact plasma membranes. Which
statement best characterizes the cellular injury stage and its
reversibility?
A. Mitochondrial swelling with intact membranes indicates
irreversible injury and immediate cell necrosis.
B. Nuclear chromatin clumping with preserved membranes
implies reversible injury that may recover if perfusion is
restored.
C. Elevated lactate indicates irreversible damage because
anaerobic glycolysis has overwhelmed the cell.
D. Loss of membrane integrity is required before mitochondrial
changes occur; therefore cells are already necrotic.
Correct answer
B
Rationales
Correct (B): Chapter 1 emphasizes that early ischemic injury
produces reversible changes — mitochondrial swelling,
INTRODUCTION TO CLINICAL MEDICINE
8TH EDITION
AUTHOR(S)GARY D. HAMMER; STEPHEN J.
MCPHEE
TEST BANK
1)
Reference
Ch. 1 — Introduction — Homeostasis, Adaptation, and Stress
Responses
Clinical stem
A 58-year-old man with long-standing poorly controlled type 2
diabetes reports progressive numbness in his feet and
orthostatic lightheadedness. Exam shows diminished ankle
reflexes and resting tachycardia; orthostatic vitals reveal a 25
mmHg drop in systolic pressure on standing. Which
,pathophysiologic explanation best links his chronic metabolic
state to these autonomic and peripheral nerve findings?
A. Persistent hyperglycemia causes nonenzymatic glycation and
osmotic neuronal swelling, producing focal demyelination.
B. Chronic hyperglycemia promotes microvascular ischemia and
accumulation of advanced glycation end products (AGEs),
leading to distal axonal degeneration and autonomic
neuropathy.
C. Recurrent hypoglycemia causes selective loss of large
myelinated fibers with preservation of small unmyelinated C
fibers, producing autonomic dysfunction.
D. Autoimmune targeting of schwann cells after long-term
hyperglycemia results in segmental demyelination and rapid
conduction block.
Correct answer
B
Rationales
Correct (B): Chapter 1 frames disease as disordered physiology
where chronic metabolic stress (hyperglycemia) causes
microvascular endothelial injury and nonenzymatic glycation
(AGEs) that impair perfusion and axonal transport. These
mechanisms preferentially produce distal, length-dependent
axonal degeneration affecting both peripheral sensory fibers
and small autonomic fibers, explaining distal numbness and
orthostatic hypotension. (Hammer & McPhee, Ch.1).
AccessMedicine
,Incorrect (A): Enzymatic/nonenzymatic glycation and osmotic
effects are implicated in neuropathy, but osmotic neuronal
swelling is a less central mechanism than microvascular
ischemia and AGE-mediated dysfunction; focal demyelination is
not the primary pattern in diabetic distal symmetric
polyneuropathy.
Incorrect (C): Recurrent hypoglycemia causes neuronal
dysfunction but does not explain the chronic progressive
length-dependent neuropathy pattern or AGE/microvascular
changes seen with chronic hyperglycemia.
Incorrect (D): Autoimmune schwann cell targeting produces
inflammatory demyelinating neuropathies (e.g., CIDP); diabetic
neuropathy is largely metabolic and ischemic with axonal
degeneration rather than primary immune demyelination.
Teaching point
Chronic hyperglycemia → microvascular ischemia and AGEs →
length-dependent axonal degeneration and autonomic
neuropathy.
Citation
Hammer, G. D., & McPhee, S. J. (2025). Pathophysiology of
Disease (8th ed.). Chapter 1. AccessMedicine
2)
, Reference
Ch. 1 — Introduction — Cellular Injury and Reversible vs
Irreversible Damage
Clinical stem
A 45-year-old woman presents with acute onset severe
abdominal pain after a hypotensive episode during surgery.
Serum lactate is markedly elevated. CT shows patchy
hypoattenuation of bowel consistent with ischemia. On biopsy,
mucosal cells show mitochondrial swelling and clumping of
nuclear chromatin but intact plasma membranes. Which
statement best characterizes the cellular injury stage and its
reversibility?
A. Mitochondrial swelling with intact membranes indicates
irreversible injury and immediate cell necrosis.
B. Nuclear chromatin clumping with preserved membranes
implies reversible injury that may recover if perfusion is
restored.
C. Elevated lactate indicates irreversible damage because
anaerobic glycolysis has overwhelmed the cell.
D. Loss of membrane integrity is required before mitochondrial
changes occur; therefore cells are already necrotic.
Correct answer
B
Rationales
Correct (B): Chapter 1 emphasizes that early ischemic injury
produces reversible changes — mitochondrial swelling,
