NR 507 Advanced Pathophysiology
NR 507
Advanced Pathophysiology
Midterm Exam— 2026/2027
Question 1
A 58-year-old with long-standing hypertension develops left ventricular wall thickening on
echocardiogram, with preserved ejection fraction. Which cellular adaptation best explains this finding?
A. Hypertrophy of cardiac myocytes
B. Hyperplasia of cardiac myocytes
C. Metaplasia of cardiac myocytes
D. Dysplasia of cardiac myocytes
Correct Answer: A. Hypertrophy of cardiac myocytes
Rationale: Cardiac myocytes are terminally differentiated and cannot undergo mitotic division, so the adaptive
response to chronic pressure overload is an increase in cell size (hypertrophy) rather than cell number
(hyperplasia). Hyperplasia is reserved for tissues with mitotically active cells such as epithelium or liver.
Question 2
Chronic acid reflux causes the normal stratified squamous epithelium of the distal esophagus to be
replaced by columnar epithelium resembling intestinal mucosa. This process is best classified as:
A. Hyperplasia
B. Metaplasia
C. Dysplasia
D. Atrophy
Correct Answer: B. Metaplasia
Rationale: Metaplasia is the reversible replacement of one differentiated cell type by another better suited to
withstand chronic irritation. Barrett esophagus is the classic example, and it is a risk factor for dysplastic
progression rather than dysplasia itself.
1
, NR 507 Advanced Pathophysiology
Question 3
A skeletal muscle group is immobilized in a cast for eight weeks. On removal, the muscle is visibly
smaller. The primary mechanism underlying this change is:
A. Increased protein synthesis
B. Decreased cell number via apoptosis only
C. Decreased organelle and protein content per cell
D. Replacement of muscle fibers with fibrous tissue
Correct Answer: C. Decreased organelle and protein content per cell
Rationale: Disuse atrophy results from a shift in the balance between protein synthesis and degradation, with
increased autophagy and ubiquitin-proteasome-mediated breakdown of organelles and contractile proteins,
shrinking individual cell size. This differs from fibrosis, which involves collagen replacement rather than cell
shrinkage.
Question 4
During a myocardial infarction, ATP depletion leads to failure of the Na+/K+-ATPase pump. Which
downstream event occurs first in the sequence of reversible cell injury?
A. Mitochondrial permeability transition pore opening
B. Nuclear pyknosis and karyorrhexis
C. Activation of caspase-mediated apoptosis
D. Cellular and organelle swelling from sodium and water influx
Correct Answer: D. Cellular and organelle swelling from sodium and water influx
Rationale: Loss of ATP-dependent ion pumping allows sodium and water to enter the cell, producing early,
reversible hydropic swelling of the cell and endoplasmic reticulum. Mitochondrial pore opening and nuclear
changes occur later and mark the transition to irreversible injury.
Question 5
A pathology report describes hepatocytes with intensely eosinophilic, shrunken cytoplasm, chromatin
condensation, and fragmentation into membrane-bound bodies, without surrounding inflammation. This
describes:
A. Apoptosis
B. Coagulative necrosis
C. Liquefactive necrosis
D. Caseous necrosis
Correct Answer: A. Apoptosis
Rationale: Apoptosis is programmed, energy-dependent cell death characterized by cell shrinkage, chromatin
condensation, and formation of apoptotic bodies that are phagocytosed without eliciting an inflammatory
response. Necrosis, by contrast, provokes inflammation and cell swelling or lysis.
2
, NR 507 Advanced Pathophysiology
Question 6
An area of the brain undergoes an ischemic stroke. Weeks later, imaging shows a fluid-filled cystic cavity
where the infarct occurred. This pattern of tissue death is termed:
A. Caseous necrosis
B. Liquefactive necrosis
C. Fat necrosis
D. Fibrinoid necrosis
Correct Answer: B. Liquefactive necrosis
Rationale: The brain has minimal structural stroma and abundant hydrolytic enzymes released from dying
cells, so infarcted neural tissue is digested and liquefied rather than retaining its architecture, leaving a cystic
cavity. Coagulative necrosis, seen in most other organs, instead preserves tissue outline for days.
Question 7
Chronic hypoxia causes a cell to accumulate lipid droplets in its cytoplasm rather than undergo cell death.
This reversible intracellular accumulation reflects:
A. Direct DNA damage from hypoxia
B. Lysosomal storage disease
C. Impaired lipid metabolism secondary to disrupted oxidative phosphorylation
D. Excess extracellular matrix deposition
Correct Answer: C. Impaired lipid metabolism secondary to disrupted oxidative phosphorylation
Rationale: Hypoxia impairs mitochondrial fatty acid oxidation, causing triglycerides to accumulate within the
cell as fatty change, a reversible sublethal injury commonly seen in the liver, heart, and kidney. This is distinct
from inherited lysosomal storage disorders, which involve enzyme deficiencies rather than hypoxic injury.
Question 8
Free radical-mediated cell injury causes damage primarily through which mechanism?
A. Direct inhibition of DNA polymerase
B. Activation of the complement cascade
C. Competitive inhibition of the Na+/K+-ATPase
D. Peroxidation of membrane lipids and protein cross-linking
Correct Answer: D. Peroxidation of membrane lipids and protein cross-linking
Rationale: Reactive oxygen species abstract electrons from polyunsaturated fatty acids in membranes, causing
lipid peroxidation that disrupts membrane integrity, and they also cross-link and denature proteins and
damage DNA bases. Antioxidant enzymes such as superoxide dismutase and catalase normally limit this
damage.
3
, NR 507 Advanced Pathophysiology
Question 9
A biopsy from a patient with chronic tuberculosis shows a central area of amorphous, structureless,
cheese-like debris surrounded by granulomatous inflammation. This necrosis pattern is:
A. Caseous
B. Coagulative
C. Fat
D. Gangrenous
Correct Answer: A. Caseous
Rationale: Caseous necrosis combines features of coagulative and liquefactive necrosis and is characteristic
of granulomatous infections such as tuberculosis, where macrophages and lymphocytes wall off the friable,
cheese-like necrotic center. It appears grossly white and crumbly and microscopically amorphous with no
preserved cellular outlines.
Question 10
Sustained elevation of intracellular calcium during cell injury contributes to irreversible damage primarily
by:
A. Stimulating protein synthesis to repair the cell
B. Activating phospholipases, proteases, and endonucleases that degrade cellular components
C. Restoring mitochondrial ATP production
D. Inhibiting apoptotic signaling
Correct Answer: B. Activating phospholipases, proteases, and endonucleases that degrade cellular
components
Rationale: Loss of calcium homeostasis activates a group of degradative enzymes, including phospholipases
that damage membranes, proteases that break down cytoskeletal proteins, and endonucleases that fragment
chromatin, all of which push the cell toward irreversible injury. Elevated cytosolic calcium is considered a
final common pathway in many forms of cell death.
Question 11
A 32-year-old woman reports fatigue and pica (craving ice). Labs show Hgb 9.1 g/dL, MCV 68 fL, and
low ferritin. The most likely underlying mechanism is:
A. Defective globin chain synthesis from a genetic mutation
B. Vitamin B12 malabsorption impairing DNA synthesis
C. Impaired hemoglobin synthesis from insufficient iron for heme production
D. Autoimmune destruction of red cell precursors
Correct Answer: C. Impaired hemoglobin synthesis from insufficient iron for heme production
Rationale: Low ferritin confirms depleted iron stores, and without adequate iron, heme synthesis is limited,
producing small, hemoglobin-poor (microcytic, hypochromic) red cells. Pica, particularly ice craving
(pagophagia), is a classic and relatively specific symptom of iron-deficiency anemia.
4
NR 507
Advanced Pathophysiology
Midterm Exam— 2026/2027
Question 1
A 58-year-old with long-standing hypertension develops left ventricular wall thickening on
echocardiogram, with preserved ejection fraction. Which cellular adaptation best explains this finding?
A. Hypertrophy of cardiac myocytes
B. Hyperplasia of cardiac myocytes
C. Metaplasia of cardiac myocytes
D. Dysplasia of cardiac myocytes
Correct Answer: A. Hypertrophy of cardiac myocytes
Rationale: Cardiac myocytes are terminally differentiated and cannot undergo mitotic division, so the adaptive
response to chronic pressure overload is an increase in cell size (hypertrophy) rather than cell number
(hyperplasia). Hyperplasia is reserved for tissues with mitotically active cells such as epithelium or liver.
Question 2
Chronic acid reflux causes the normal stratified squamous epithelium of the distal esophagus to be
replaced by columnar epithelium resembling intestinal mucosa. This process is best classified as:
A. Hyperplasia
B. Metaplasia
C. Dysplasia
D. Atrophy
Correct Answer: B. Metaplasia
Rationale: Metaplasia is the reversible replacement of one differentiated cell type by another better suited to
withstand chronic irritation. Barrett esophagus is the classic example, and it is a risk factor for dysplastic
progression rather than dysplasia itself.
1
, NR 507 Advanced Pathophysiology
Question 3
A skeletal muscle group is immobilized in a cast for eight weeks. On removal, the muscle is visibly
smaller. The primary mechanism underlying this change is:
A. Increased protein synthesis
B. Decreased cell number via apoptosis only
C. Decreased organelle and protein content per cell
D. Replacement of muscle fibers with fibrous tissue
Correct Answer: C. Decreased organelle and protein content per cell
Rationale: Disuse atrophy results from a shift in the balance between protein synthesis and degradation, with
increased autophagy and ubiquitin-proteasome-mediated breakdown of organelles and contractile proteins,
shrinking individual cell size. This differs from fibrosis, which involves collagen replacement rather than cell
shrinkage.
Question 4
During a myocardial infarction, ATP depletion leads to failure of the Na+/K+-ATPase pump. Which
downstream event occurs first in the sequence of reversible cell injury?
A. Mitochondrial permeability transition pore opening
B. Nuclear pyknosis and karyorrhexis
C. Activation of caspase-mediated apoptosis
D. Cellular and organelle swelling from sodium and water influx
Correct Answer: D. Cellular and organelle swelling from sodium and water influx
Rationale: Loss of ATP-dependent ion pumping allows sodium and water to enter the cell, producing early,
reversible hydropic swelling of the cell and endoplasmic reticulum. Mitochondrial pore opening and nuclear
changes occur later and mark the transition to irreversible injury.
Question 5
A pathology report describes hepatocytes with intensely eosinophilic, shrunken cytoplasm, chromatin
condensation, and fragmentation into membrane-bound bodies, without surrounding inflammation. This
describes:
A. Apoptosis
B. Coagulative necrosis
C. Liquefactive necrosis
D. Caseous necrosis
Correct Answer: A. Apoptosis
Rationale: Apoptosis is programmed, energy-dependent cell death characterized by cell shrinkage, chromatin
condensation, and formation of apoptotic bodies that are phagocytosed without eliciting an inflammatory
response. Necrosis, by contrast, provokes inflammation and cell swelling or lysis.
2
, NR 507 Advanced Pathophysiology
Question 6
An area of the brain undergoes an ischemic stroke. Weeks later, imaging shows a fluid-filled cystic cavity
where the infarct occurred. This pattern of tissue death is termed:
A. Caseous necrosis
B. Liquefactive necrosis
C. Fat necrosis
D. Fibrinoid necrosis
Correct Answer: B. Liquefactive necrosis
Rationale: The brain has minimal structural stroma and abundant hydrolytic enzymes released from dying
cells, so infarcted neural tissue is digested and liquefied rather than retaining its architecture, leaving a cystic
cavity. Coagulative necrosis, seen in most other organs, instead preserves tissue outline for days.
Question 7
Chronic hypoxia causes a cell to accumulate lipid droplets in its cytoplasm rather than undergo cell death.
This reversible intracellular accumulation reflects:
A. Direct DNA damage from hypoxia
B. Lysosomal storage disease
C. Impaired lipid metabolism secondary to disrupted oxidative phosphorylation
D. Excess extracellular matrix deposition
Correct Answer: C. Impaired lipid metabolism secondary to disrupted oxidative phosphorylation
Rationale: Hypoxia impairs mitochondrial fatty acid oxidation, causing triglycerides to accumulate within the
cell as fatty change, a reversible sublethal injury commonly seen in the liver, heart, and kidney. This is distinct
from inherited lysosomal storage disorders, which involve enzyme deficiencies rather than hypoxic injury.
Question 8
Free radical-mediated cell injury causes damage primarily through which mechanism?
A. Direct inhibition of DNA polymerase
B. Activation of the complement cascade
C. Competitive inhibition of the Na+/K+-ATPase
D. Peroxidation of membrane lipids and protein cross-linking
Correct Answer: D. Peroxidation of membrane lipids and protein cross-linking
Rationale: Reactive oxygen species abstract electrons from polyunsaturated fatty acids in membranes, causing
lipid peroxidation that disrupts membrane integrity, and they also cross-link and denature proteins and
damage DNA bases. Antioxidant enzymes such as superoxide dismutase and catalase normally limit this
damage.
3
, NR 507 Advanced Pathophysiology
Question 9
A biopsy from a patient with chronic tuberculosis shows a central area of amorphous, structureless,
cheese-like debris surrounded by granulomatous inflammation. This necrosis pattern is:
A. Caseous
B. Coagulative
C. Fat
D. Gangrenous
Correct Answer: A. Caseous
Rationale: Caseous necrosis combines features of coagulative and liquefactive necrosis and is characteristic
of granulomatous infections such as tuberculosis, where macrophages and lymphocytes wall off the friable,
cheese-like necrotic center. It appears grossly white and crumbly and microscopically amorphous with no
preserved cellular outlines.
Question 10
Sustained elevation of intracellular calcium during cell injury contributes to irreversible damage primarily
by:
A. Stimulating protein synthesis to repair the cell
B. Activating phospholipases, proteases, and endonucleases that degrade cellular components
C. Restoring mitochondrial ATP production
D. Inhibiting apoptotic signaling
Correct Answer: B. Activating phospholipases, proteases, and endonucleases that degrade cellular
components
Rationale: Loss of calcium homeostasis activates a group of degradative enzymes, including phospholipases
that damage membranes, proteases that break down cytoskeletal proteins, and endonucleases that fragment
chromatin, all of which push the cell toward irreversible injury. Elevated cytosolic calcium is considered a
final common pathway in many forms of cell death.
Question 11
A 32-year-old woman reports fatigue and pica (craving ice). Labs show Hgb 9.1 g/dL, MCV 68 fL, and
low ferritin. The most likely underlying mechanism is:
A. Defective globin chain synthesis from a genetic mutation
B. Vitamin B12 malabsorption impairing DNA synthesis
C. Impaired hemoglobin synthesis from insufficient iron for heme production
D. Autoimmune destruction of red cell precursors
Correct Answer: C. Impaired hemoglobin synthesis from insufficient iron for heme production
Rationale: Low ferritin confirms depleted iron stores, and without adequate iron, heme synthesis is limited,
producing small, hemoglobin-poor (microcytic, hypochromic) red cells. Pica, particularly ice craving
(pagophagia), is a classic and relatively specific symptom of iron-deficiency anemia.
4
