NUR 631 ADVANCED PHYSIOLOGY AND
PATHOPHYSIOLOGY
FINAL EXAM PREPARATION
200 Exam Questions with Correct Answers and Rationales
GCU NUR 631 Test Bank 2 | 2026-2027
Grand Canyon University | Comprehensive Cumulative Review
Section 1: Cellular Adaptation, Injury, and Neoplasia
Q1: A 72-year-old patient with unilateral hip osteoarthritis has noticeable muscle wasting
in the affected leg compared to the contralateral limb. Which type of cellular adaptation
best describes this finding?
A. Physiologic hypertrophy
B. Pathologic atrophy secondary to reduced workload [CORRECT]
C. Metaplastic transformation
D. Hyperplastic response
Correct Answer: B
Rationale: The muscle wasting in the limb with reduced use is pathologic atrophy caused by decreased mechanical
workload. Atrophy results from decreased protein synthesis and increased protein degradation through the
ubiquitin-proteasome pathway. Physiologic hypertrophy involves an increase in cell size, not a decrease, and would
not explain wasting. Metaplasia and hyperplasia represent different adaptive responses involving cell type
conversion and increased cell number, respectively.
Q2: A 68-year-old woman presents with sudden-onset right-sided weakness. CT
angiography confirms complete occlusion of the left middle cerebral artery. Over the
following weeks, neurons in the affected territory undergo significant reduction in size.
The primary mechanism driving this atrophy is:
A. Activation of proto-oncogenes within the ischemic penumbra
B. Decreased blood supply leading to reduced oxygen and nutrient delivery [CORRECT]
C. Autoimmune-mediated destruction of neuronal cell membranes
D. Accumulation of lipofuscin pigment within the cytoplasm
Correct Answer: B
Rationale: Atrophy from decreased blood supply (ischemia) is a well-characterized pathologic process in which
chronic or acute reduction in perfusion deprives cells of oxygen and nutrients needed for protein synthesis.
Proto-oncogene activation drives proliferation, not atrophy. Autoimmune destruction would cause necrosis or
apoptosis rather than atrophy. Lipofuscin accumulation is a secondary hallmark of aging, not the primary driver of
ischemic atrophy.
Q3: A 55-year-old man with a history of polio at age 8 exhibits significant wasting of the
left lower extremity despite normal arterial perfusion. EMG confirms denervation. Which
pathophysiologic mechanism best explains the atrophy?
A. Disuse atrophy from reduced mechanical loading of the limb
B. Endocrine-mediated catabolism from chronic cortisol elevation
C. Loss of trophic signaling from motor neurons leading to decreased protein synthesis
[CORRECT]
, D. Ischemic injury from obliterative arterial disease in the affected limb
Correct Answer: C
Rationale: Denervation atrophy occurs when motor neuron loss eliminates trophic signals (nerve growth factor,
acetylcholine-stimulated activity) that normally maintain muscle fiber protein synthesis and sarcomere integrity.
Disuse atrophy is driven by mechanical unloading rather than loss of neural input. Endocrine-mediated catabolism is
systemic and would not be limited to one extremity. Ischemic atrophy is ruled out by normal arterial perfusion.
Q4: A 45-year-old male bodybuilder has a resting heart rate of 48 bpm and ECG voltage
criteria for left ventricular hypertrophy. Echocardiography reveals symmetrically
thickened left ventricle with normal cavity size and preserved diastolic function. This is
best classified as:
A. Pathologic hypertrophy with myocyte disarray
B. Physiologic hypertrophy from increased mechanical demand [CORRECT]
C. Concentric hypertrophy from pressure overload
D. Eccentric hypertrophy from volume overload
Correct Answer: B
Rationale: Physiologic hypertrophy occurs in response to increased mechanical demand (exercise) and involves
proportional sarcomere growth preserving normal cardiac architecture and function. Pathologic hypertrophy from
hypertension causes abnormal RAAS signaling leading to fibrosis, myocyte disarray, and diastolic dysfunction.
Concentric hypertrophy is the pressure-overload pattern from HTN with different signaling. Eccentric hypertrophy
involves chamber dilation with wall thinning.
Q5: A 58-year-old man with 15 years of poorly controlled hypertension (BP 170/100
mmHg) presents with dyspnea on exertion. Echocardiography reveals left ventricular
wall thickness of 16 mm (normal <11 mm) with a small left ventricular cavity. The
primary driver of this adaptation is:
A. Increased stroke volume causing chamber dilation and wall thinning
B. Pressure overload activating RAAS and mechanical stress pathways [CORRECT]
C. Estrogen-mediated stimulation of myocardial cell proliferation
D. Viral myocarditis triggering compensatory myocyte enlargement
Correct Answer: B
Rationale: Chronic pressure overload from hypertension activates mechanical stress sensors (integrins,
stretch-activated channels) and neurohormonal pathways (RAAS, endothelin-1) stimulating cardiomyocyte
hypertrophy through PI3K/Akt and MAPK signaling, producing concentric hypertrophy. Increased stroke volume
causes eccentric, not concentric, hypertrophy. Estrogen does not drive cardiac hypertrophy. Viral myocarditis causes
dilated cardiomyopathy.
Q6: A 34-year-old woman undergoes partial hepatectomy for a benign liver adenoma.
Follow-up imaging at 6 months shows the liver has returned to its original volume. The
cellular mechanism responsible is:
A. Pathologic hyperplasia driven by estrogen receptor overexpression
B. Physiologic hyperplasia mediated by hepatocyte growth factor (HGF) and EGF
[CORRECT]
C. Hypertrophy of remaining hepatocytes without cell division
D. Metaplasia of bile duct epithelium to functional hepatocytes
Correct Answer: B
Rationale: Liver regeneration after partial hepatectomy is a classic example of physiologic hyperplasia where
growth factors (HGF, EGF, TGF-alpha) and cytokines (TNF-alpha, IL-6) stimulate remaining hepatocytes to re-enter
the cell cycle. Pathologic hyperplasia from estrogen occurs in endometrial tissue. Hypertrophy alone would not
restore liver mass. Metaplasia involves conversion between cell types, not compensatory proliferation.
Q7: A 52-year-old obese woman with anovulatory cycles and unopposed estrogen
therapy has irregular vaginal bleeding. Endometrial biopsy reveals glandular
,proliferation with crowding and mild architectural complexity but no cytologic atypia.
This is best classified as:
A. Physiologic hyperplasia of the endometrium
B. Pathologic endometrial hyperplasia without atypia [CORRECT]
C. Endometrial metaplasia
D. Well-differentiated endometrial adenocarcinoma
Correct Answer: B
Rationale: Pathologic endometrial hyperplasia without atypia results from chronic unopposed estrogenic
stimulation (obesity, anovulation, exogenous estrogen) driving glandular proliferation beyond the normal physiologic
response. Physiologic hyperplasia occurs cyclically and is self-limited. Metaplasia involves a change in cell type, not
increased cell number. Adenocarcinoma requires cytologic atypia and stromal invasion, which are absent.
Q8: A 48-year-old man with a 20-year history of chronic GERD undergoes upper
endoscopy revealing salmon-colored mucosa extending 4 cm above the
gastroesophageal junction. Biopsy confirms columnar epithelium with intestinal-type
goblet cells replacing normal stratified squamous epithelium. This adaptation is:
A. Squamous dysplasia with high-grade cytologic atypia
B. Intestinal metaplasia (Barrett esophagus) from chronic acid exposure [CORRECT]
C. Hyperplastic transformation of esophageal submucosal glands
D. Malignant degeneration to esophageal adenocarcinoma
Correct Answer: B
Rationale: Barrett esophagus is a classic example of metaplasia where chronic reflux causes stratified squamous
epithelium to be replaced by intestinal-type columnar epithelium with goblet cells. This provides better acid
resistance but predisposes to dysplasia and adenocarcinoma. Squamous dysplasia involves atypical changes within
squamous epithelium, not replacement by a different cell type. Malignant degeneration requires cytologic atypia and
invasion.
Q9: A 60-year-old man with a 40-pack-year smoking history has a bronchial biopsy
showing replacement of normal ciliated columnar epithelium by stratified squamous
epithelium in the large airways. The advanced practice nurse recognizes that this
adaptation:
A. Represents an irreversible malignant transformation
B. Is a protective response to chronic irritation that increases risk of squamous cell
carcinoma [CORRECT]
C. Indicates hypersensitivity pneumonitis from organic dust exposure
D. Is caused by aspiration of gastric contents into the bronchial tree
Correct Answer: B
Rationale: Squamous metaplasia in the respiratory tract is a reversible adaptive response to chronic cigarette
smoke irritation, replacing columnar with more resistant stratified squamous epithelium. While not malignant itself,
it creates a favorable environment for genetic damage and progression to dysplasia and squamous cell carcinoma.
Hypersensitivity pneumonitis involves interstitial inflammation, not epithelial metaplasia. Aspiration causes
bronchiolitis or lipoid pneumonia.
Q10: A 28-year-old woman has an abnormal Pap smear. Colposcopic cervical biopsy
shows disordered epithelial maturation with nuclear enlargement, hyperchromasia, and
mitotic figures extending into the upper third of the epithelium. No stromal invasion is
identified. These findings are most consistent with:
A. Low-grade cervical intraepithelial neoplasia (CIN 1)
B. High-grade cervical dysplasia (CIN 3 / carcinoma in situ) [CORRECT]
C. Invasive squamous cell carcinoma of the cervix
D. Metaplastic transformation of the cervical transformation zone
Correct Answer: B
, Rationale: High-grade cervical dysplasia (CIN 3) is characterized by disordered maturation with atypical cells
involving the full thickness or upper two-thirds of the epithelium, with nuclear pleomorphism, hyperchromasia, and
mitotic figures in superficial layers. Absence of stromal invasion distinguishes dysplasia from invasive carcinoma.
Low-grade CIN 1 involves only the lower third. Metaplasia involves cell type change without the cytologic atypia
described.
Q11: A 65-year-old man with Barrett esophagus has surveillance biopsy showing glands
with architectural irregularity, nuclear stratification, and loss of polarity. The abnormal
cells remain confined within the basement membrane. This finding represents:
A. An irreversible malignant neoplasm requiring immediate esophagectomy
B. A preinvasive lesion (dysplasia) with significant risk for progression to adenocarcinoma
[CORRECT]
C. A reversible inflammatory change that will resolve with PPI therapy alone
D. Metaplastic transformation that does not require further surveillance
Correct Answer: B
Rationale: Dysplasia is a preinvasive neoplastic transformation with cytologic and architectural atypia confined
above the basement membrane. In Barrett esophagus, dysplasia significantly increases the risk of progression to
invasive adenocarcinoma, requiring close surveillance. It is not yet invasive malignancy as the basement membrane
is intact. PPI therapy does not reverse established dysplasia.
Q12: Which of the following best distinguishes apoptosis from necrosis at the cellular
level?
A. Apoptosis requires ATP and activates caspases; necrosis is a passive,
energy-independent process [CORRECT]
B. Necrosis is a programmed process regulated by Bcl-2; apoptosis is always pathologic
C. Both apoptosis and necrosis produce identical inflammatory responses in surrounding tissue
D. Apoptosis causes cellular swelling and organelle disruption; necrosis causes cell shrinkage
Correct Answer: A
Rationale: Apoptosis is an active, ATP-dependent, genetically programmed cell death mediated by caspase
activation producing cell shrinkage, chromatin condensation, and apoptotic bodies without inflammation. Necrosis is
a passive, energy-independent process causing cell swelling, membrane rupture, and robust inflammation. The Bcl-2
family regulates apoptosis, not necrosis. The inflammatory responses are fundamentally different between the two
processes.
Q13: A 70-year-old woman with rheumatoid arthritis has been taking methotrexate for 10
years. Labs show pancytopenia, and bone marrow biopsy reveals increased apoptotic
cells. The mechanism of methotrexate-induced apoptosis is:
A. Inhibition of dihydrofolate reductase leading to DNA synthesis disruption and intrinsic
apoptotic pathway activation [CORRECT]
B. Direct activation of TNF receptors on hematopoietic stem cells
C. Complement-mediated lysis of erythroid precursors in the marrow space
D. Iron overload causing free radical generation and necrotic cell death
Correct Answer: A
Rationale: Methotrexate inhibits dihydrofolate reductase, depleting tetrahydrofolate and disrupting purine and
pyrimidine synthesis, leading to DNA damage that triggers the intrinsic apoptotic pathway through p53 activation
and cytochrome c release. TNF receptor activation is a different apoptotic mechanism not primary to methotrexate.
Complement causes necrosis-type injury. Iron overload is unrelated to methotrexate toxicity.
Q14: A 62-year-old man presents with crushing substernal chest pain. Coronary
angiography reveals 100% occlusion of the LAD. Despite reperfusion, he develops a
transmural MI. Histology at 48 hours would most likely show:
A. Liquefactive necrosis with abundant neutrophilic infiltration and pus formation
B. Coagulative necrosis with preserved cellular outlines and loss of nuclear detail
[CORRECT]
PATHOPHYSIOLOGY
FINAL EXAM PREPARATION
200 Exam Questions with Correct Answers and Rationales
GCU NUR 631 Test Bank 2 | 2026-2027
Grand Canyon University | Comprehensive Cumulative Review
Section 1: Cellular Adaptation, Injury, and Neoplasia
Q1: A 72-year-old patient with unilateral hip osteoarthritis has noticeable muscle wasting
in the affected leg compared to the contralateral limb. Which type of cellular adaptation
best describes this finding?
A. Physiologic hypertrophy
B. Pathologic atrophy secondary to reduced workload [CORRECT]
C. Metaplastic transformation
D. Hyperplastic response
Correct Answer: B
Rationale: The muscle wasting in the limb with reduced use is pathologic atrophy caused by decreased mechanical
workload. Atrophy results from decreased protein synthesis and increased protein degradation through the
ubiquitin-proteasome pathway. Physiologic hypertrophy involves an increase in cell size, not a decrease, and would
not explain wasting. Metaplasia and hyperplasia represent different adaptive responses involving cell type
conversion and increased cell number, respectively.
Q2: A 68-year-old woman presents with sudden-onset right-sided weakness. CT
angiography confirms complete occlusion of the left middle cerebral artery. Over the
following weeks, neurons in the affected territory undergo significant reduction in size.
The primary mechanism driving this atrophy is:
A. Activation of proto-oncogenes within the ischemic penumbra
B. Decreased blood supply leading to reduced oxygen and nutrient delivery [CORRECT]
C. Autoimmune-mediated destruction of neuronal cell membranes
D. Accumulation of lipofuscin pigment within the cytoplasm
Correct Answer: B
Rationale: Atrophy from decreased blood supply (ischemia) is a well-characterized pathologic process in which
chronic or acute reduction in perfusion deprives cells of oxygen and nutrients needed for protein synthesis.
Proto-oncogene activation drives proliferation, not atrophy. Autoimmune destruction would cause necrosis or
apoptosis rather than atrophy. Lipofuscin accumulation is a secondary hallmark of aging, not the primary driver of
ischemic atrophy.
Q3: A 55-year-old man with a history of polio at age 8 exhibits significant wasting of the
left lower extremity despite normal arterial perfusion. EMG confirms denervation. Which
pathophysiologic mechanism best explains the atrophy?
A. Disuse atrophy from reduced mechanical loading of the limb
B. Endocrine-mediated catabolism from chronic cortisol elevation
C. Loss of trophic signaling from motor neurons leading to decreased protein synthesis
[CORRECT]
, D. Ischemic injury from obliterative arterial disease in the affected limb
Correct Answer: C
Rationale: Denervation atrophy occurs when motor neuron loss eliminates trophic signals (nerve growth factor,
acetylcholine-stimulated activity) that normally maintain muscle fiber protein synthesis and sarcomere integrity.
Disuse atrophy is driven by mechanical unloading rather than loss of neural input. Endocrine-mediated catabolism is
systemic and would not be limited to one extremity. Ischemic atrophy is ruled out by normal arterial perfusion.
Q4: A 45-year-old male bodybuilder has a resting heart rate of 48 bpm and ECG voltage
criteria for left ventricular hypertrophy. Echocardiography reveals symmetrically
thickened left ventricle with normal cavity size and preserved diastolic function. This is
best classified as:
A. Pathologic hypertrophy with myocyte disarray
B. Physiologic hypertrophy from increased mechanical demand [CORRECT]
C. Concentric hypertrophy from pressure overload
D. Eccentric hypertrophy from volume overload
Correct Answer: B
Rationale: Physiologic hypertrophy occurs in response to increased mechanical demand (exercise) and involves
proportional sarcomere growth preserving normal cardiac architecture and function. Pathologic hypertrophy from
hypertension causes abnormal RAAS signaling leading to fibrosis, myocyte disarray, and diastolic dysfunction.
Concentric hypertrophy is the pressure-overload pattern from HTN with different signaling. Eccentric hypertrophy
involves chamber dilation with wall thinning.
Q5: A 58-year-old man with 15 years of poorly controlled hypertension (BP 170/100
mmHg) presents with dyspnea on exertion. Echocardiography reveals left ventricular
wall thickness of 16 mm (normal <11 mm) with a small left ventricular cavity. The
primary driver of this adaptation is:
A. Increased stroke volume causing chamber dilation and wall thinning
B. Pressure overload activating RAAS and mechanical stress pathways [CORRECT]
C. Estrogen-mediated stimulation of myocardial cell proliferation
D. Viral myocarditis triggering compensatory myocyte enlargement
Correct Answer: B
Rationale: Chronic pressure overload from hypertension activates mechanical stress sensors (integrins,
stretch-activated channels) and neurohormonal pathways (RAAS, endothelin-1) stimulating cardiomyocyte
hypertrophy through PI3K/Akt and MAPK signaling, producing concentric hypertrophy. Increased stroke volume
causes eccentric, not concentric, hypertrophy. Estrogen does not drive cardiac hypertrophy. Viral myocarditis causes
dilated cardiomyopathy.
Q6: A 34-year-old woman undergoes partial hepatectomy for a benign liver adenoma.
Follow-up imaging at 6 months shows the liver has returned to its original volume. The
cellular mechanism responsible is:
A. Pathologic hyperplasia driven by estrogen receptor overexpression
B. Physiologic hyperplasia mediated by hepatocyte growth factor (HGF) and EGF
[CORRECT]
C. Hypertrophy of remaining hepatocytes without cell division
D. Metaplasia of bile duct epithelium to functional hepatocytes
Correct Answer: B
Rationale: Liver regeneration after partial hepatectomy is a classic example of physiologic hyperplasia where
growth factors (HGF, EGF, TGF-alpha) and cytokines (TNF-alpha, IL-6) stimulate remaining hepatocytes to re-enter
the cell cycle. Pathologic hyperplasia from estrogen occurs in endometrial tissue. Hypertrophy alone would not
restore liver mass. Metaplasia involves conversion between cell types, not compensatory proliferation.
Q7: A 52-year-old obese woman with anovulatory cycles and unopposed estrogen
therapy has irregular vaginal bleeding. Endometrial biopsy reveals glandular
,proliferation with crowding and mild architectural complexity but no cytologic atypia.
This is best classified as:
A. Physiologic hyperplasia of the endometrium
B. Pathologic endometrial hyperplasia without atypia [CORRECT]
C. Endometrial metaplasia
D. Well-differentiated endometrial adenocarcinoma
Correct Answer: B
Rationale: Pathologic endometrial hyperplasia without atypia results from chronic unopposed estrogenic
stimulation (obesity, anovulation, exogenous estrogen) driving glandular proliferation beyond the normal physiologic
response. Physiologic hyperplasia occurs cyclically and is self-limited. Metaplasia involves a change in cell type, not
increased cell number. Adenocarcinoma requires cytologic atypia and stromal invasion, which are absent.
Q8: A 48-year-old man with a 20-year history of chronic GERD undergoes upper
endoscopy revealing salmon-colored mucosa extending 4 cm above the
gastroesophageal junction. Biopsy confirms columnar epithelium with intestinal-type
goblet cells replacing normal stratified squamous epithelium. This adaptation is:
A. Squamous dysplasia with high-grade cytologic atypia
B. Intestinal metaplasia (Barrett esophagus) from chronic acid exposure [CORRECT]
C. Hyperplastic transformation of esophageal submucosal glands
D. Malignant degeneration to esophageal adenocarcinoma
Correct Answer: B
Rationale: Barrett esophagus is a classic example of metaplasia where chronic reflux causes stratified squamous
epithelium to be replaced by intestinal-type columnar epithelium with goblet cells. This provides better acid
resistance but predisposes to dysplasia and adenocarcinoma. Squamous dysplasia involves atypical changes within
squamous epithelium, not replacement by a different cell type. Malignant degeneration requires cytologic atypia and
invasion.
Q9: A 60-year-old man with a 40-pack-year smoking history has a bronchial biopsy
showing replacement of normal ciliated columnar epithelium by stratified squamous
epithelium in the large airways. The advanced practice nurse recognizes that this
adaptation:
A. Represents an irreversible malignant transformation
B. Is a protective response to chronic irritation that increases risk of squamous cell
carcinoma [CORRECT]
C. Indicates hypersensitivity pneumonitis from organic dust exposure
D. Is caused by aspiration of gastric contents into the bronchial tree
Correct Answer: B
Rationale: Squamous metaplasia in the respiratory tract is a reversible adaptive response to chronic cigarette
smoke irritation, replacing columnar with more resistant stratified squamous epithelium. While not malignant itself,
it creates a favorable environment for genetic damage and progression to dysplasia and squamous cell carcinoma.
Hypersensitivity pneumonitis involves interstitial inflammation, not epithelial metaplasia. Aspiration causes
bronchiolitis or lipoid pneumonia.
Q10: A 28-year-old woman has an abnormal Pap smear. Colposcopic cervical biopsy
shows disordered epithelial maturation with nuclear enlargement, hyperchromasia, and
mitotic figures extending into the upper third of the epithelium. No stromal invasion is
identified. These findings are most consistent with:
A. Low-grade cervical intraepithelial neoplasia (CIN 1)
B. High-grade cervical dysplasia (CIN 3 / carcinoma in situ) [CORRECT]
C. Invasive squamous cell carcinoma of the cervix
D. Metaplastic transformation of the cervical transformation zone
Correct Answer: B
, Rationale: High-grade cervical dysplasia (CIN 3) is characterized by disordered maturation with atypical cells
involving the full thickness or upper two-thirds of the epithelium, with nuclear pleomorphism, hyperchromasia, and
mitotic figures in superficial layers. Absence of stromal invasion distinguishes dysplasia from invasive carcinoma.
Low-grade CIN 1 involves only the lower third. Metaplasia involves cell type change without the cytologic atypia
described.
Q11: A 65-year-old man with Barrett esophagus has surveillance biopsy showing glands
with architectural irregularity, nuclear stratification, and loss of polarity. The abnormal
cells remain confined within the basement membrane. This finding represents:
A. An irreversible malignant neoplasm requiring immediate esophagectomy
B. A preinvasive lesion (dysplasia) with significant risk for progression to adenocarcinoma
[CORRECT]
C. A reversible inflammatory change that will resolve with PPI therapy alone
D. Metaplastic transformation that does not require further surveillance
Correct Answer: B
Rationale: Dysplasia is a preinvasive neoplastic transformation with cytologic and architectural atypia confined
above the basement membrane. In Barrett esophagus, dysplasia significantly increases the risk of progression to
invasive adenocarcinoma, requiring close surveillance. It is not yet invasive malignancy as the basement membrane
is intact. PPI therapy does not reverse established dysplasia.
Q12: Which of the following best distinguishes apoptosis from necrosis at the cellular
level?
A. Apoptosis requires ATP and activates caspases; necrosis is a passive,
energy-independent process [CORRECT]
B. Necrosis is a programmed process regulated by Bcl-2; apoptosis is always pathologic
C. Both apoptosis and necrosis produce identical inflammatory responses in surrounding tissue
D. Apoptosis causes cellular swelling and organelle disruption; necrosis causes cell shrinkage
Correct Answer: A
Rationale: Apoptosis is an active, ATP-dependent, genetically programmed cell death mediated by caspase
activation producing cell shrinkage, chromatin condensation, and apoptotic bodies without inflammation. Necrosis is
a passive, energy-independent process causing cell swelling, membrane rupture, and robust inflammation. The Bcl-2
family regulates apoptosis, not necrosis. The inflammatory responses are fundamentally different between the two
processes.
Q13: A 70-year-old woman with rheumatoid arthritis has been taking methotrexate for 10
years. Labs show pancytopenia, and bone marrow biopsy reveals increased apoptotic
cells. The mechanism of methotrexate-induced apoptosis is:
A. Inhibition of dihydrofolate reductase leading to DNA synthesis disruption and intrinsic
apoptotic pathway activation [CORRECT]
B. Direct activation of TNF receptors on hematopoietic stem cells
C. Complement-mediated lysis of erythroid precursors in the marrow space
D. Iron overload causing free radical generation and necrotic cell death
Correct Answer: A
Rationale: Methotrexate inhibits dihydrofolate reductase, depleting tetrahydrofolate and disrupting purine and
pyrimidine synthesis, leading to DNA damage that triggers the intrinsic apoptotic pathway through p53 activation
and cytochrome c release. TNF receptor activation is a different apoptotic mechanism not primary to methotrexate.
Complement causes necrosis-type injury. Iron overload is unrelated to methotrexate toxicity.
Q14: A 62-year-old man presents with crushing substernal chest pain. Coronary
angiography reveals 100% occlusion of the LAD. Despite reperfusion, he develops a
transmural MI. Histology at 48 hours would most likely show:
A. Liquefactive necrosis with abundant neutrophilic infiltration and pus formation
B. Coagulative necrosis with preserved cellular outlines and loss of nuclear detail
[CORRECT]
