1|Page
NSG 5140 | MIDTERM EXAM ADVANCED
PATHOPHYSIOLOGY 2026 ALL QUESTIONS AND
CORRECT DETAILED ANSWERS WITH
RATIONALES ALREADY A GRADED WITH
EXPERT FEEDBACK |HIGHLY RECOMMENDED
|NEW AND REVISED
1. A 58-year-old patient with chronic hypertension develops left
ventricular wall thickening. Which mechanism best explains this
adaptive response?
A) Increased myocyte number due to cell division
B) Increased myocyte size due to increased workload
C) Replacement of cardiac cells with fibrous tissue
D) Transformation of cardiac cells into smooth muscle
Rationale: Cardiac myocytes are terminally differentiated cells that
respond to increased workload (pressure overload) through
hypertrophy—an increase in cell size—not hyperplasia (increased cell
number).
2. During ischemic injury, the loss of ATP most directly leads to which
cellular event?
A) Increased oxidative phosphorylation
B) Failure of the sodium-potassium pump
C) Increased protein synthesis
D) Mitochondrial membrane stabilization
Rationale: ATP depletion causes failure of the Na⁺/K⁺ ATPase pump,
leading to intracellular sodium accumulation, water influx, cellular
swelling, and eventual cell death if ischemia persists.
3. A pathologist examines a biopsy from the bronchial epithelium of a
chronic smoker. The normal pseudostratified ciliated columnar
,2|Page
epithelium is replaced by stratified squamous epithelium. Which
molecular event is most likely initiating this change?
A) Increased expression of anti-apoptotic Bcl-2 in basal cells
B) Reprogramming of stem cells due to chronic irritation and
altered transcription factor signaling
C) Somatic mutation in the p53 gene leading to loss of cell cycle control
D) Epigenetic silencing of E-cadherin promoting epithelial-
mesenchymal transition
Rationale: Metaplasia—the replacement of one differentiated cell type
by another—results from reprogramming of tissue-resident stem cells
in response to chronic stress, often involving changes in transcription
factors such as Sox2 and p63.
4. A researcher studying pressure overload in cardiac myocytes observes
that sustained mechanical stretch leads to increased protein synthesis and
cell enlargement without cell division. Which intracellular signaling
pathway is most directly responsible for this adaptive response?
A) Activation of the PI3K/Akt/mTOR pathway leading to increased
translation
B) Induction of p53-mediated cell cycle arrest and senescence
C) Upregulation of caspases and initiation of apoptosis
D) Activation of the unfolded protein response (UPR) due to ER stress
Rationale: Cardiac myocytes respond to increased workload by
undergoing hypertrophy, which is driven by the PI3K/Akt/mTOR
pathway that enhances protein synthesis. p53 activation promotes
apoptosis or senescence, not hypertrophy.
5. A patient with prolonged ischemia due to renal artery stenosis has
proximal tubular epithelial cells exhibiting swelling of mitochondria and
dilation of the endoplasmic reticulum on electron microscopy. Which
phase of cell injury does this morphology represent?
A) Irreversible injury; massive calcium influx into mitochondria
B) Reversible injury; depletion of ATP leading to failure of ion
,3|Page
pumps
C) Necroptosis; activation of receptor-interacting protein kinases
D) Apoptosis; cytochrome c release from mitochondria
Rationale: Mitochondrial swelling and ER dilation are characteristic
of reversible cell injury, caused by ATP depletion and failure of ion
pumps. These changes are reversible if oxygen supply is restored.
6. A 45-year-old patient with a family history of breast cancer is found
to have a mutation in the BRCA1 gene. This gene is classified as which
type of gene?
A) Oncogene
B) Tumor suppressor gene
C) Proto-oncogene
D) DNA repair gene
Rationale: BRCA1 is a tumor suppressor gene that normally functions
to repair DNA damage. Loss-of-function mutations increase the risk of
breast and ovarian cancers by allowing accumulation of genetic
mutations.
7. A patient with chronic obstructive pulmonary disease (COPD)
develops cor pulmonale. Which pathophysiological mechanism is most
responsible for this complication?
A) Left ventricular failure
B) Pulmonary hypertension secondary to hypoxic vasoconstriction
C) Systemic hypertension
D) Myocardial infarction
Rationale: Cor pulmonale is right ventricular hypertrophy and failure
caused by pulmonary hypertension. In COPD, chronic hypoxia leads
to pulmonary vasoconstriction, increasing right ventricular afterload.
8. A 32-year-old woman presents with fatigue, weight gain, and cold
intolerance. Laboratory studies reveal elevated TSH and low free T4
levels. Which pathophysiological process is most likely occurring?
A) Hashimoto thyroiditis with autoimmune destruction of thyroid
, 4|Page
follicles
B) Graves disease with TSH receptor antibodies
C) Pituitary adenoma with TSH hypersecretion
D) Euthyroid sick syndrome
Rationale: Elevated TSH with low free T4 indicates primary
hypothyroidism. Hashimoto thyroiditis is the most common cause,
characterized by autoimmune destruction of thyroid follicles and
lymphocytic infiltration.
9. The sodium-potassium pump moves which ions in which direction?
A) 2 Na⁺ out and 3 K⁺ into the cell
B) 3 Na⁺ out and 2 K⁺ into the cell
C) 3 Na⁺ in and 2 K⁺ out of the cell
D) 2 Na⁺ in and 3 K⁺ out of the cell
Rationale: The sodium-potassium pump moves 3 Na⁺ ions out of the
cell and 2 K⁺ ions into the cell, creating an electrochemical gradient
essential for membrane potential.
10. A 67-year-old man with a history of atherosclerosis presents with
sudden-onset severe chest pain radiating to his left arm. ECG reveals
ST-segment elevation. Which pathophysiological event most likely
precipitated this condition?
A) Coronary artery vasospasm
B) Rupture of an atherosclerotic plaque with thrombus formation
C) Embolism from a left ventricular thrombus
D) Spontaneous coronary artery dissection
Rationale: Acute myocardial infarction with ST-segment elevation is
most commonly caused by rupture of an unstable atherosclerotic
plaque, leading to platelet aggregation, thrombus formation, and
complete coronary artery occlusion.
11. A 24-year-old woman is diagnosed with systemic lupus
erythematosus (SLE). Which type of hypersensitivity reaction is
primarily responsible for the tissue damage in this autoimmune disease?
NSG 5140 | MIDTERM EXAM ADVANCED
PATHOPHYSIOLOGY 2026 ALL QUESTIONS AND
CORRECT DETAILED ANSWERS WITH
RATIONALES ALREADY A GRADED WITH
EXPERT FEEDBACK |HIGHLY RECOMMENDED
|NEW AND REVISED
1. A 58-year-old patient with chronic hypertension develops left
ventricular wall thickening. Which mechanism best explains this
adaptive response?
A) Increased myocyte number due to cell division
B) Increased myocyte size due to increased workload
C) Replacement of cardiac cells with fibrous tissue
D) Transformation of cardiac cells into smooth muscle
Rationale: Cardiac myocytes are terminally differentiated cells that
respond to increased workload (pressure overload) through
hypertrophy—an increase in cell size—not hyperplasia (increased cell
number).
2. During ischemic injury, the loss of ATP most directly leads to which
cellular event?
A) Increased oxidative phosphorylation
B) Failure of the sodium-potassium pump
C) Increased protein synthesis
D) Mitochondrial membrane stabilization
Rationale: ATP depletion causes failure of the Na⁺/K⁺ ATPase pump,
leading to intracellular sodium accumulation, water influx, cellular
swelling, and eventual cell death if ischemia persists.
3. A pathologist examines a biopsy from the bronchial epithelium of a
chronic smoker. The normal pseudostratified ciliated columnar
,2|Page
epithelium is replaced by stratified squamous epithelium. Which
molecular event is most likely initiating this change?
A) Increased expression of anti-apoptotic Bcl-2 in basal cells
B) Reprogramming of stem cells due to chronic irritation and
altered transcription factor signaling
C) Somatic mutation in the p53 gene leading to loss of cell cycle control
D) Epigenetic silencing of E-cadherin promoting epithelial-
mesenchymal transition
Rationale: Metaplasia—the replacement of one differentiated cell type
by another—results from reprogramming of tissue-resident stem cells
in response to chronic stress, often involving changes in transcription
factors such as Sox2 and p63.
4. A researcher studying pressure overload in cardiac myocytes observes
that sustained mechanical stretch leads to increased protein synthesis and
cell enlargement without cell division. Which intracellular signaling
pathway is most directly responsible for this adaptive response?
A) Activation of the PI3K/Akt/mTOR pathway leading to increased
translation
B) Induction of p53-mediated cell cycle arrest and senescence
C) Upregulation of caspases and initiation of apoptosis
D) Activation of the unfolded protein response (UPR) due to ER stress
Rationale: Cardiac myocytes respond to increased workload by
undergoing hypertrophy, which is driven by the PI3K/Akt/mTOR
pathway that enhances protein synthesis. p53 activation promotes
apoptosis or senescence, not hypertrophy.
5. A patient with prolonged ischemia due to renal artery stenosis has
proximal tubular epithelial cells exhibiting swelling of mitochondria and
dilation of the endoplasmic reticulum on electron microscopy. Which
phase of cell injury does this morphology represent?
A) Irreversible injury; massive calcium influx into mitochondria
B) Reversible injury; depletion of ATP leading to failure of ion
,3|Page
pumps
C) Necroptosis; activation of receptor-interacting protein kinases
D) Apoptosis; cytochrome c release from mitochondria
Rationale: Mitochondrial swelling and ER dilation are characteristic
of reversible cell injury, caused by ATP depletion and failure of ion
pumps. These changes are reversible if oxygen supply is restored.
6. A 45-year-old patient with a family history of breast cancer is found
to have a mutation in the BRCA1 gene. This gene is classified as which
type of gene?
A) Oncogene
B) Tumor suppressor gene
C) Proto-oncogene
D) DNA repair gene
Rationale: BRCA1 is a tumor suppressor gene that normally functions
to repair DNA damage. Loss-of-function mutations increase the risk of
breast and ovarian cancers by allowing accumulation of genetic
mutations.
7. A patient with chronic obstructive pulmonary disease (COPD)
develops cor pulmonale. Which pathophysiological mechanism is most
responsible for this complication?
A) Left ventricular failure
B) Pulmonary hypertension secondary to hypoxic vasoconstriction
C) Systemic hypertension
D) Myocardial infarction
Rationale: Cor pulmonale is right ventricular hypertrophy and failure
caused by pulmonary hypertension. In COPD, chronic hypoxia leads
to pulmonary vasoconstriction, increasing right ventricular afterload.
8. A 32-year-old woman presents with fatigue, weight gain, and cold
intolerance. Laboratory studies reveal elevated TSH and low free T4
levels. Which pathophysiological process is most likely occurring?
A) Hashimoto thyroiditis with autoimmune destruction of thyroid
, 4|Page
follicles
B) Graves disease with TSH receptor antibodies
C) Pituitary adenoma with TSH hypersecretion
D) Euthyroid sick syndrome
Rationale: Elevated TSH with low free T4 indicates primary
hypothyroidism. Hashimoto thyroiditis is the most common cause,
characterized by autoimmune destruction of thyroid follicles and
lymphocytic infiltration.
9. The sodium-potassium pump moves which ions in which direction?
A) 2 Na⁺ out and 3 K⁺ into the cell
B) 3 Na⁺ out and 2 K⁺ into the cell
C) 3 Na⁺ in and 2 K⁺ out of the cell
D) 2 Na⁺ in and 3 K⁺ out of the cell
Rationale: The sodium-potassium pump moves 3 Na⁺ ions out of the
cell and 2 K⁺ ions into the cell, creating an electrochemical gradient
essential for membrane potential.
10. A 67-year-old man with a history of atherosclerosis presents with
sudden-onset severe chest pain radiating to his left arm. ECG reveals
ST-segment elevation. Which pathophysiological event most likely
precipitated this condition?
A) Coronary artery vasospasm
B) Rupture of an atherosclerotic plaque with thrombus formation
C) Embolism from a left ventricular thrombus
D) Spontaneous coronary artery dissection
Rationale: Acute myocardial infarction with ST-segment elevation is
most commonly caused by rupture of an unstable atherosclerotic
plaque, leading to platelet aggregation, thrombus formation, and
complete coronary artery occlusion.
11. A 24-year-old woman is diagnosed with systemic lupus
erythematosus (SLE). Which type of hypersensitivity reaction is
primarily responsible for the tissue damage in this autoimmune disease?
