NSG 5140 Advanced Pathophysiology Final Exam Review 2025 |
200 Practice Questions & Answers with Rationales South
College. — 290 Questions
Section 1: Cellular Adaptation and Injury (Questions 1-30)
1 A hepatocyte exposed to chronic low-grade oxidative stress upregulates the expression of several genes. Which
of the following adaptive mechanisms is most likely responsible for the increased synthesis of glutathione
S-transferase and superoxide dismutase?
A) Hypertrophy
B) Hyperplasia
C) Atrophy
D) Metaplasia
Answer: A
Rationale: Correct: Hypertrophy involves increased cell size due to upregulated synthesis of cellular proteins,
including antioxidant enzymes, in response to increased workload or stress. Hyperplasia is increased cell number;
atrophy is decreased cell size; metaplasia is a change in cell type. The question specifically describes increased
synthesis of specific proteins, which is characteristic of hypertrophy.
2 In a myocardial infarction, which of the following sequences best describes the progression from reversible to
irreversible injury?
A) ATP depletion !’ sodium pump failure !’ cellular swelling !’ calcium influx !’ mitochondrial permeability
transition
B) Calcium influx !’ ATP depletion !’ membrane blebbing !’ nuclear pyknosis !’ apoptosis
C) Reactive oxygen species generation !’ lipid peroxidation !’ membrane damage !’ ATP depletion !’ karyolysis
D) Mitochondrial swelling !’ cytochrome c release !’ caspase activation !’ DNA fragmentation !’ cellular
shrinkage
Answer: A
Rationale: Correct: In ischemic injury, ATP depletion first impairs sodium-potassium pump, causing cellular
swelling. Continued ischemia leads to calcium influx and mitochondrial permeability transition, marking
irreversible injury. Option B describes apoptosis but not typical infarction sequence. Option C skips early ATP
depletion. Option D is apoptosis.
3 Which of the following is the most reliable histologic indicator of irreversible cell injury?
A) Cellular swelling and blebbing
B) Nuclear pyknosis, karyorrhexis, and karyolysis
C) Lipid accumulation in the cytoplasm
D) Increased eosinophilia of the cytoplasm
Answer: B
Rationale: Correct: Irreversible injury is characterized by nuclear changes: pyknosis (condensation), karyorrhexis
(fragmentation), and karyolysis (dissolution). Cellular swelling and blebbing (A) can be reversible. Lipid
accumulation (C) is a reversible change. Increased eosinophilia (D) is due to loss of basophilia from RNA
degradation but can occur in reversible injury; nuclear changes are definitive.
,4 A researcher treats cultured neurons with a calcium ionophore to induce injury. Which downstream event is
most directly responsible for the activation of caspases in this model?
A) Activation of phospholipases
B) Cytochrome c release from mitochondria
C) Activation of endonucleases
D) Increased intracellular reactive oxygen species
Answer: B
Rationale: Correct: Elevated cytosolic calcium triggers mitochondrial permeability transition, leading to cytochrome
c release, which binds Apaf-1 and activates caspase-9 (intrinsic apoptosis pathway). Phospholipases (A) cause
membrane damage but not direct caspase activation. Endonucleases (C) cause DNA fragmentation downstream of
caspases. ROS (D) can induce permeability transition but calcium directly causes it.
5 In chronic gastritis caused by Helicobacter pylori infection, the gastric epithelium undergoes transformation
from gastric-type to intestinal-type epithelium. This adaptation is termed:
A) Dysplasia
B) Anaplasia
C) Metaplasia
D) Aplasia
Answer: C
Rationale: Correct: Metaplasia is the reversible replacement of one differentiated cell type with another, often in
response to chronic irritation. Dysplasia (A) is disordered growth, often preneoplastic. Anaplasia (B) is loss of
differentiation in cancer. Aplasia (D) is failure of organ development. The change from gastric to intestinal
epithelium is classic intestinal metaplasia.
6 A patient with severe sepsis develops acute kidney injury. Renal biopsy shows tubular epithelial cells with
swollen mitochondria and rupture of lysosomal membranes. Which mechanism of cell death is most likely
predominant?
A) Apoptosis
B) Necrosis
C) Autophagy
D) Necroptosis
Answer: B
Rationale: Correct: Necrosis is characterized by mitochondrial swelling and lysosomal rupture, leading to cell lysis
and inflammation. Apoptosis (A) shows cell shrinkage and intact organelles. Autophagy (C) involves lysosomal
degradation of cellular components without rupture. Necroptosis (D) is a regulated form of necrosis but the
description of lysosomal rupture is classic for accidental necrosis in sepsis.
7 Which of the following best explains why cardiac myocytes undergo hypertrophy rather than hyperplasia in
response to increased workload?
A) Cardiac myocytes are terminally differentiated and cannot divide.
B) Hypertrophy requires less energy than hyperplasia.
C) Hyperplasia would lead to arrhythmias.
D) Cardiac myocytes have a high capacity for DNA synthesis.
Answer: A
Rationale: Correct: Cardiac myocytes exit the cell cycle after birth and are terminally differentiated, so they cannot
undergo hyperplasia (increase in cell number). They adapt to increased workload by hypertrophy (increase in cell
size). Option B is incorrect because hypertrophy involves substantial protein synthesis. Option C is speculative.
,Option D is false; cardiac myocytes have limited DNA synthesis.
8 A biopsy from a liver with nonalcoholic steatohepatitis shows hepatocytes containing large cytoplasmic lipid
vacuoles that displace the nucleus to the periphery. This finding is best described as:
A) Hydropic change
B) Glycogen infiltration
C) Steatosis
D) Amyloidosis
Answer: C
Rationale: Correct: Steatosis (fatty change) is the abnormal accumulation of triglycerides in hepatocytes, seen as
clear vacuoles that push the nucleus aside. Hydropic change (A) is due to water accumulation from ATP depletion.
Glycogen infiltration (B) appears as pale, granular cytoplasm. Amyloidosis (D) involves extracellular protein
deposits. In steatohepatitis, lipid vacuoles are characteristic.
9 In a cell undergoing apoptosis, which of the following events occurs earliest?
A) Externalization of phosphatidylserine
B) Activation of executioner caspases
C) Formation of apoptotic bodies
D) DNA fragmentation into 180-200 bp pieces
Answer: A
Rationale: Correct: Externalization of phosphatidylserine from the inner to the outer leaflet of the plasma membrane
is an early event in apoptosis, serving as an 'eat-me' signal for phagocytes. Activation of executioner caspases (B)
occurs after initiator caspases are activated, but phosphatidylserine exposure can occur before caspase activation in
some pathways. Apoptotic bodies (C) and DNA fragmentation (D) are later events.
10 A 55-year-old woman with chronic kidney disease develops secondary hyperparathyroidism. Parathyroid gland
biopsy shows an increase in the number of chief cells. This adaptive response is termed:
A) Hypertrophy
B) Hyperplasia
C) Metaplasia
D) Dysplasia
Answer: B
Rationale: Correct: Hyperplasia is an increase in cell number, often in response to hormonal stimulation. In
secondary hyperparathyroidism, chronic hypocalcemia stimulates parathyroid hormone secretion and proliferation
of chief cells. Hypertrophy (A) would involve increased cell size. Metaplasia (C) is a change in cell type. Dysplasia
(D) is disordered growth with potential for neoplasia.
11 A patient with chronic gastroesophageal reflux disease exhibits columnar epithelium in the distal esophagus on
biopsy. Which cellular adaptation is primarily responsible for this change, and what is the most significant
long-term risk associated with it?
A) Metaplasia; increased risk of adenocarcinoma
B) Dysplasia; increased risk of squamous cell carcinoma
C) Hyperplasia; increased risk of adenocarcinoma
D) Atrophy; increased risk of Barrett's esophagus
Answer: A
Rationale: Metaplasia is the reversible replacement of one differentiated cell type with another, often in response to
chronic irritation. In Barrett's esophagus, the normal squamous epithelium is replaced by columnar epithelium,
, which increases the risk of adenocarcinoma. Dysplasia involves abnormal cell growth but is not the initial
adaptation. Hyperplasia is an increase in cell number, not a change in cell type. Atrophy is a decrease in cell size.
12 In a cell exposed to sustained hypoxia, which molecular adaptation primarily occurs to enhance oxygen
delivery, and what transcription factor mediates this response?
A) Increased glycolysis; mediated by HIF-1±
B) Increased mitochondrial biogenesis; mediated by PGC-1±
C) Increased hemoglobin synthesis; mediated by EPO
D) Increased angiogenesis; mediated by VEGF
Answer: A
Rationale: Hypoxia-inducible factor 1± (HIF-1±) stabilizes under low oxygen and upregulates genes that promote
glycolysis (e.g., GLUT1, lactate dehydrogenase) to maintain ATP production. While EPO and VEGF are also HIF
targets, the most immediate adaptation is increased glycolysis. PGC-1± is involved in mitochondrial biogenesis,
which is not the primary acute response to hypoxia.
13 A researcher treats cultured hepatocytes with a proteasome inhibitor. Which cellular adaptation is most likely to
be impaired, and why?
A) Atrophy; because proteasomes degrade damaged organelles
B) Hypertrophy; because proteasomes are needed for protein synthesis
C) Hyperplasia; because proteasomes regulate cell cycle proteins
D) Metaplasia; because proteasomes control transcription factors
Answer: C
Rationale: Hyperplasia, an increase in cell number, requires cell division, which is tightly regulated by cyclins and
cyclin-dependent kinase inhibitors that are degraded by proteasomes. Inhibiting proteasomes would impair the
turnover of these regulatory proteins, thereby affecting cell cycle progression. Atrophy is mediated by autophagy,
not primarily by proteasomes. Hypertrophy involves increased protein synthesis, not proteasomal degradation.
Metaplasia involves changes in gene expression, but proteasome inhibition does not directly block it.
14 Which of the following best explains why cardiac myocytes undergo hypertrophy rather than hyperplasia in
response to increased workload?
A) Cardiac myocytes are terminally differentiated and cannot re-enter the cell cycle
B) Hypertrophy requires less energy than hyperplasia in cardiac tissue
C) Cardiac myocytes lack growth factor receptors necessary for hyperplasia
D) Hyperplasia would lead to arrhythmias due to disorganized cell division
Answer: A
Rationale: Cardiac myocytes are post-mitotic and cannot undergo cell division, so they increase their size
(hypertrophy) rather than number. This is a fundamental principle of cellular adaptation in permanent tissues.
While energy considerations and growth factor receptors may play roles, the primary reason is the inability to
divide. Arrhythmias are not the reason but a potential consequence of hypertrophy.
15 In a cell undergoing reversible injury due to ischemia, which event is the earliest indicator of cellular swelling?
A) Loss of ATP leading to failure of the Na+/K+ pump
B) Detachment of ribosomes from the rough endoplasmic reticulum
C) Formation of blebs on the plasma membrane
D) Swelling of mitochondria due to increased permeability
Answer: A
Rationale: Ischemia reduces ATP production, impairing the Na+/K+ ATPase pump, leading to sodium and water
200 Practice Questions & Answers with Rationales South
College. — 290 Questions
Section 1: Cellular Adaptation and Injury (Questions 1-30)
1 A hepatocyte exposed to chronic low-grade oxidative stress upregulates the expression of several genes. Which
of the following adaptive mechanisms is most likely responsible for the increased synthesis of glutathione
S-transferase and superoxide dismutase?
A) Hypertrophy
B) Hyperplasia
C) Atrophy
D) Metaplasia
Answer: A
Rationale: Correct: Hypertrophy involves increased cell size due to upregulated synthesis of cellular proteins,
including antioxidant enzymes, in response to increased workload or stress. Hyperplasia is increased cell number;
atrophy is decreased cell size; metaplasia is a change in cell type. The question specifically describes increased
synthesis of specific proteins, which is characteristic of hypertrophy.
2 In a myocardial infarction, which of the following sequences best describes the progression from reversible to
irreversible injury?
A) ATP depletion !’ sodium pump failure !’ cellular swelling !’ calcium influx !’ mitochondrial permeability
transition
B) Calcium influx !’ ATP depletion !’ membrane blebbing !’ nuclear pyknosis !’ apoptosis
C) Reactive oxygen species generation !’ lipid peroxidation !’ membrane damage !’ ATP depletion !’ karyolysis
D) Mitochondrial swelling !’ cytochrome c release !’ caspase activation !’ DNA fragmentation !’ cellular
shrinkage
Answer: A
Rationale: Correct: In ischemic injury, ATP depletion first impairs sodium-potassium pump, causing cellular
swelling. Continued ischemia leads to calcium influx and mitochondrial permeability transition, marking
irreversible injury. Option B describes apoptosis but not typical infarction sequence. Option C skips early ATP
depletion. Option D is apoptosis.
3 Which of the following is the most reliable histologic indicator of irreversible cell injury?
A) Cellular swelling and blebbing
B) Nuclear pyknosis, karyorrhexis, and karyolysis
C) Lipid accumulation in the cytoplasm
D) Increased eosinophilia of the cytoplasm
Answer: B
Rationale: Correct: Irreversible injury is characterized by nuclear changes: pyknosis (condensation), karyorrhexis
(fragmentation), and karyolysis (dissolution). Cellular swelling and blebbing (A) can be reversible. Lipid
accumulation (C) is a reversible change. Increased eosinophilia (D) is due to loss of basophilia from RNA
degradation but can occur in reversible injury; nuclear changes are definitive.
,4 A researcher treats cultured neurons with a calcium ionophore to induce injury. Which downstream event is
most directly responsible for the activation of caspases in this model?
A) Activation of phospholipases
B) Cytochrome c release from mitochondria
C) Activation of endonucleases
D) Increased intracellular reactive oxygen species
Answer: B
Rationale: Correct: Elevated cytosolic calcium triggers mitochondrial permeability transition, leading to cytochrome
c release, which binds Apaf-1 and activates caspase-9 (intrinsic apoptosis pathway). Phospholipases (A) cause
membrane damage but not direct caspase activation. Endonucleases (C) cause DNA fragmentation downstream of
caspases. ROS (D) can induce permeability transition but calcium directly causes it.
5 In chronic gastritis caused by Helicobacter pylori infection, the gastric epithelium undergoes transformation
from gastric-type to intestinal-type epithelium. This adaptation is termed:
A) Dysplasia
B) Anaplasia
C) Metaplasia
D) Aplasia
Answer: C
Rationale: Correct: Metaplasia is the reversible replacement of one differentiated cell type with another, often in
response to chronic irritation. Dysplasia (A) is disordered growth, often preneoplastic. Anaplasia (B) is loss of
differentiation in cancer. Aplasia (D) is failure of organ development. The change from gastric to intestinal
epithelium is classic intestinal metaplasia.
6 A patient with severe sepsis develops acute kidney injury. Renal biopsy shows tubular epithelial cells with
swollen mitochondria and rupture of lysosomal membranes. Which mechanism of cell death is most likely
predominant?
A) Apoptosis
B) Necrosis
C) Autophagy
D) Necroptosis
Answer: B
Rationale: Correct: Necrosis is characterized by mitochondrial swelling and lysosomal rupture, leading to cell lysis
and inflammation. Apoptosis (A) shows cell shrinkage and intact organelles. Autophagy (C) involves lysosomal
degradation of cellular components without rupture. Necroptosis (D) is a regulated form of necrosis but the
description of lysosomal rupture is classic for accidental necrosis in sepsis.
7 Which of the following best explains why cardiac myocytes undergo hypertrophy rather than hyperplasia in
response to increased workload?
A) Cardiac myocytes are terminally differentiated and cannot divide.
B) Hypertrophy requires less energy than hyperplasia.
C) Hyperplasia would lead to arrhythmias.
D) Cardiac myocytes have a high capacity for DNA synthesis.
Answer: A
Rationale: Correct: Cardiac myocytes exit the cell cycle after birth and are terminally differentiated, so they cannot
undergo hyperplasia (increase in cell number). They adapt to increased workload by hypertrophy (increase in cell
size). Option B is incorrect because hypertrophy involves substantial protein synthesis. Option C is speculative.
,Option D is false; cardiac myocytes have limited DNA synthesis.
8 A biopsy from a liver with nonalcoholic steatohepatitis shows hepatocytes containing large cytoplasmic lipid
vacuoles that displace the nucleus to the periphery. This finding is best described as:
A) Hydropic change
B) Glycogen infiltration
C) Steatosis
D) Amyloidosis
Answer: C
Rationale: Correct: Steatosis (fatty change) is the abnormal accumulation of triglycerides in hepatocytes, seen as
clear vacuoles that push the nucleus aside. Hydropic change (A) is due to water accumulation from ATP depletion.
Glycogen infiltration (B) appears as pale, granular cytoplasm. Amyloidosis (D) involves extracellular protein
deposits. In steatohepatitis, lipid vacuoles are characteristic.
9 In a cell undergoing apoptosis, which of the following events occurs earliest?
A) Externalization of phosphatidylserine
B) Activation of executioner caspases
C) Formation of apoptotic bodies
D) DNA fragmentation into 180-200 bp pieces
Answer: A
Rationale: Correct: Externalization of phosphatidylserine from the inner to the outer leaflet of the plasma membrane
is an early event in apoptosis, serving as an 'eat-me' signal for phagocytes. Activation of executioner caspases (B)
occurs after initiator caspases are activated, but phosphatidylserine exposure can occur before caspase activation in
some pathways. Apoptotic bodies (C) and DNA fragmentation (D) are later events.
10 A 55-year-old woman with chronic kidney disease develops secondary hyperparathyroidism. Parathyroid gland
biopsy shows an increase in the number of chief cells. This adaptive response is termed:
A) Hypertrophy
B) Hyperplasia
C) Metaplasia
D) Dysplasia
Answer: B
Rationale: Correct: Hyperplasia is an increase in cell number, often in response to hormonal stimulation. In
secondary hyperparathyroidism, chronic hypocalcemia stimulates parathyroid hormone secretion and proliferation
of chief cells. Hypertrophy (A) would involve increased cell size. Metaplasia (C) is a change in cell type. Dysplasia
(D) is disordered growth with potential for neoplasia.
11 A patient with chronic gastroesophageal reflux disease exhibits columnar epithelium in the distal esophagus on
biopsy. Which cellular adaptation is primarily responsible for this change, and what is the most significant
long-term risk associated with it?
A) Metaplasia; increased risk of adenocarcinoma
B) Dysplasia; increased risk of squamous cell carcinoma
C) Hyperplasia; increased risk of adenocarcinoma
D) Atrophy; increased risk of Barrett's esophagus
Answer: A
Rationale: Metaplasia is the reversible replacement of one differentiated cell type with another, often in response to
chronic irritation. In Barrett's esophagus, the normal squamous epithelium is replaced by columnar epithelium,
, which increases the risk of adenocarcinoma. Dysplasia involves abnormal cell growth but is not the initial
adaptation. Hyperplasia is an increase in cell number, not a change in cell type. Atrophy is a decrease in cell size.
12 In a cell exposed to sustained hypoxia, which molecular adaptation primarily occurs to enhance oxygen
delivery, and what transcription factor mediates this response?
A) Increased glycolysis; mediated by HIF-1±
B) Increased mitochondrial biogenesis; mediated by PGC-1±
C) Increased hemoglobin synthesis; mediated by EPO
D) Increased angiogenesis; mediated by VEGF
Answer: A
Rationale: Hypoxia-inducible factor 1± (HIF-1±) stabilizes under low oxygen and upregulates genes that promote
glycolysis (e.g., GLUT1, lactate dehydrogenase) to maintain ATP production. While EPO and VEGF are also HIF
targets, the most immediate adaptation is increased glycolysis. PGC-1± is involved in mitochondrial biogenesis,
which is not the primary acute response to hypoxia.
13 A researcher treats cultured hepatocytes with a proteasome inhibitor. Which cellular adaptation is most likely to
be impaired, and why?
A) Atrophy; because proteasomes degrade damaged organelles
B) Hypertrophy; because proteasomes are needed for protein synthesis
C) Hyperplasia; because proteasomes regulate cell cycle proteins
D) Metaplasia; because proteasomes control transcription factors
Answer: C
Rationale: Hyperplasia, an increase in cell number, requires cell division, which is tightly regulated by cyclins and
cyclin-dependent kinase inhibitors that are degraded by proteasomes. Inhibiting proteasomes would impair the
turnover of these regulatory proteins, thereby affecting cell cycle progression. Atrophy is mediated by autophagy,
not primarily by proteasomes. Hypertrophy involves increased protein synthesis, not proteasomal degradation.
Metaplasia involves changes in gene expression, but proteasome inhibition does not directly block it.
14 Which of the following best explains why cardiac myocytes undergo hypertrophy rather than hyperplasia in
response to increased workload?
A) Cardiac myocytes are terminally differentiated and cannot re-enter the cell cycle
B) Hypertrophy requires less energy than hyperplasia in cardiac tissue
C) Cardiac myocytes lack growth factor receptors necessary for hyperplasia
D) Hyperplasia would lead to arrhythmias due to disorganized cell division
Answer: A
Rationale: Cardiac myocytes are post-mitotic and cannot undergo cell division, so they increase their size
(hypertrophy) rather than number. This is a fundamental principle of cellular adaptation in permanent tissues.
While energy considerations and growth factor receptors may play roles, the primary reason is the inability to
divide. Arrhythmias are not the reason but a potential consequence of hypertrophy.
15 In a cell undergoing reversible injury due to ischemia, which event is the earliest indicator of cellular swelling?
A) Loss of ATP leading to failure of the Na+/K+ pump
B) Detachment of ribosomes from the rough endoplasmic reticulum
C) Formation of blebs on the plasma membrane
D) Swelling of mitochondria due to increased permeability
Answer: A
Rationale: Ischemia reduces ATP production, impairing the Na+/K+ ATPase pump, leading to sodium and water
