, CHAPTER LIST
Chapter 1: Cell Adaptation, Injury, Death, and Aging
Chapter 2: Inflammation and Repair
Chapter 3: Immunopathology
Chapter 4: Neoplasia
Chapter 5: Developmental and Genetic Diseases
Chapter 6: Infectious and Parasitic Diseases
Chapter 7: The Amyloidoses
Chapter 8: Blood Vessels and Hemodynamic Disorders
Chapter 9: Heart
Chapter 10: The Respiratory System
Chapter 11: The Gastrointestinal Tract
Chapter 12: The Liver and Biliary System
Chapter 13: The Exocrine Pancreas
Chapter 14: The Kidney
Chapter 15: The Lower Urinary Tract and Male Reproductive System
Chapter 16: The Female Reproductive Tract
Chapter 17: The Breast
Chapter 18: Hematopathology
Chapter 19: Endocrine System, Diabetes, and Nutritional Diseases
Chapter 20: The Skin
Chapter 21: The Head and Neck
Chapter 22: Bones, Joints, and Soft Tissue
Chapter 23: Skeletal Muscle
Chapter 24: The Central Nervous System and Eye
Chapter 25: Traumatic and Environmental Injury
,Chapter 1: Cell Adaptation, Injury, Death, and
Aging
Context: Cellular responses to stress (hypertrophy, hyperplasia, atrophy,
metaplasia), reversible/irreversible injury, apoptosis vs necrosis, and aging
mechanisms.
Why it matters: Foundation for understanding disease mechanisms from
molecule → cell → tissue → clinical picture.
1) A patient with long-standing hypertension develops concentric
left ventricular thickening with increased cardiomyocyte size but
no increase in cell number. Which molecular program best
explains this adaptation?
A. Increased cyclin-dependent kinase activity driving G1→S progression
B. Activation of growth factor signaling with increased gene transcription for
contractile proteins
C. Telomerase activation causing prolonged replicative capacity
D. Loss of E-cadherin with epithelial–mesenchymal transition
Answer: B
Rationale: Cardiomyocytes are terminally differentiated, so pressure overload
triggers hypertrophy, not hyperplasia. Hypertrophy occurs via
mechanosensor and growth factor pathways (e.g., PI3K/AKT, MAPK) that
increase transcription/translation of contractile proteins and fetal gene
programs, enlarging cell size. Cyclins (A) are more relevant to proliferative
hyperplasia. Telomerase (C) relates to replicative lifespan/aging and some
cancers. EMT (D) is a differentiation program relevant to fibrosis and tumor
invasion, not classic cardiomyocyte hypertrophy.
Key words: hypertrophy, pressure overload, PI3K/AKT, MAPK, fetal gene
program
2) A smoker’s bronchial epithelium shows replacement of
pseudostratified ciliated columnar cells with stratified squamous
epithelium. The most important consequence of this change is:
A. Increased risk of viral entry due to increased ACE2 expression
B. Decreased mucus clearance, predisposing to infection
C. Immediate progression to invasive carcinoma
D. Reduced susceptibility to oxidative injury
,Answer: B
Rationale: This is squamous metaplasia, an adaptive, reversible substitution
of one differentiated cell type for another better suited to stress. The tradeoff is
loss of specialized function—here, ciliary clearance, increasing infection risk.
Metaplasia can increase malignancy risk over time, but it does not
“immediately” become invasive cancer (C). ACE2 (A) is unrelated to the core
mechanism here. Oxidative injury susceptibility (D) is not the key clinical
consequence.
Key words: metaplasia, squamous metaplasia, smoking, loss of cilia, infection
risk
3) A liver biopsy shows enlarged hepatocytes with abundant
smooth endoplasmic reticulum after prolonged exposure to a drug
metabolized by cytochrome P450. This change best represents:
A. Atrophy due to decreased protein synthesis
B. Hypertrophy due to increased synthetic capacity
C. Hyperplasia due to increased mitotic activity
D. Necrosis due to mitochondrial permeability transition
Answer: B
Rationale: Induction of smooth ER reflects adaptive hypertrophy to increase
detoxification capacity (CYP450 induction). This is a reversible adaptation.
Hyperplasia (C) implies increased cell number. Necrosis (D) and atrophy (A) do
not match the described organelle expansion and functional upregulation.
Key words: smooth ER, CYP450 induction, drug metabolism, hypertrophy,
adaptive response
4) A renal tubular epithelial cell subjected to mild ischemia
develops cellular swelling and membrane blebs but remains viable.
The most likely immediate mechanism is:
A. Increased ATP leading to Na⁺/K⁺ ATPase hyperactivity
B. Decreased ATP causing failure of ion pumps and osmotic swelling
C. Caspase activation causing DNA laddering
D. Lysosomal rupture causing enzymatic autodigestion
Answer: B
Rationale: Mild ischemia → ↓ oxidative phosphorylation → ↓ ATP. Failure of
Na⁺/K⁺ ATPase leads to Na⁺ and water influx → cell swelling (hydropic
change) and membrane blebbing—classic reversible injury. Caspases (C) are
,apoptosis. Lysosomal rupture (D) is more consistent with necrosis/irreversible
injury.
Key words: reversible injury, ATP depletion, Na⁺/K⁺ pump failure, hydropic
change, ischemia
5) Which morphologic finding most strongly indicates irreversible
cell injury?
A. Fatty change in hepatocytes
B. Ribosomal detachment from rough ER
C. Amorphous densities in mitochondria with membrane rupture
D. Cellular swelling with intact plasma membrane
Answer: C
Rationale: Irreversible injury correlates with severe mitochondrial
dysfunction and membrane damage. Mitochondrial amorphous densities and
membrane rupture point to irreversible injury/necrosis. Fatty change (A),
ribosomal detachment (B), and swelling (D) are classically reversible.
Key words: irreversible injury, mitochondrial damage, membrane rupture,
necrosis markers
6) A patient with acute pancreatitis shows areas of chalky white
deposits in peripancreatic fat. The primary mechanism is:
A. Protein denaturation leading to coagulative necrosis
B. Enzymatic fat necrosis with calcium soap formation
C. Caspase-mediated apoptosis of adipocytes
D. Liquefactive necrosis due to bacterial infection
Answer: B
Rationale: Pancreatic lipases digest triglycerides in fat → free fatty acids bind
calcium → saponification causing chalky deposits. Coagulative necrosis (A)
fits ischemic solid organs. Apoptosis (C) is not the dominant pattern here.
Liquefactive necrosis (D) is typical in brain infarcts and abscesses.
Key words: fat necrosis, pancreatitis, lipase, saponification, calcium soaps
7) A tissue specimen shows preserved architecture with
eosinophilic “ghost” cells and loss of nuclei after infarction in the
kidney. This pattern is:
,A. Coagulative necrosis
B. Liquefactive necrosis
C. Caseous necrosis
D. Fibrinoid necrosis
Answer: A
Rationale: Coagulative necrosis preserves tissue architecture early after
ischemia in most solid organs (except brain). Liquefactive (B) is for brain
infarcts/abscesses. Caseous (C) is typical of TB granulomas. Fibrinoid (D)
occurs in immune-mediated vascular injury.
Key words: infarct, coagulative necrosis, ghost cells, ischemia, preserved
architecture
8) A cell receives a signal through the intrinsic apoptosis
pathway. Which event is most upstream and specific to this
pathway?
A. Binding of Fas ligand to Fas receptor
B. Release of cytochrome c from mitochondria
C. Massive influx of calcium through ruptured membranes
D. Activation of neutrophil myeloperoxidase
Answer: B
Rationale: Intrinsic apoptosis is triggered by internal stress (DNA damage,
growth factor withdrawal, ER stress) leading to mitochondrial outer
membrane permeabilization and cytochrome c release, activating caspase-
9. Fas–FasL (A) is extrinsic. Calcium influx via ruptured membranes (C)
suggests necrosis. MPO (D) is inflammation-related.
Key words: intrinsic apoptosis, cytochrome c, caspase-9, mitochondrial
permeabilization, BAX/BAK
9) A tumor suppressor pathway detects severe DNA damage and
induces apoptosis. Which protein is most directly involved in
deciding this outcome?
A. BCL-2
B. p53
C. EGFR
D. NF-κB
, Answer: B
Rationale: p53 responds to DNA damage by halting the cell cycle (via p21)
and, if damage is irreparable, promoting apoptosis (e.g., upregulating BAX,
PUMA). BCL-2 (A) is anti-apoptotic but is not the central “damage sensor.”
EGFR (C) is proliferative signaling. NF-κB (D) often promotes
survival/inflammation.
Key words: p53, DNA damage response, apoptosis decision, cell cycle arrest,
BAX/PUMA
10) A patient has chronic venous congestion with brown
discoloration of lung tissue. Microscopy shows macrophages filled
with golden-brown granules. These granules are:
A. Lipofuscin from lipid peroxidation
B. Hemosiderin from iron storage after hemorrhage
C. Melanin from melanocyte activation
D. Amyloid from misfolded protein deposition
Answer: B
Rationale: Chronic congestion causes micro-hemorrhage; macrophages
phagocytose RBCs and store iron as hemosiderin (“heart failure cells” in
lungs). Lipofuscin (A) is wear-and-tear pigment in aging cells. Melanin (C) is
unrelated. Amyloid (D) is extracellular and has distinct staining behavior.
Key words: hemosiderin, chronic congestion, heart failure cells, iron,
macrophages
11) A neuron exposed to prolonged hypoxia undergoes rapid
enzymatic digestion of dead cells, leading to softening of tissue.
This necrosis is best classified as:
A. Coagulative
B. Liquefactive
C. Fat
D. Caseous
Answer: B
Rationale: Brain infarcts characteristically produce liquefactive necrosis due
to high lipid content and enzymatic digestion. Coagulative necrosis is typical
elsewhere.
Key words: brain infarct, liquefactive necrosis, enzymatic digestion, softening
Chapter 1: Cell Adaptation, Injury, Death, and Aging
Chapter 2: Inflammation and Repair
Chapter 3: Immunopathology
Chapter 4: Neoplasia
Chapter 5: Developmental and Genetic Diseases
Chapter 6: Infectious and Parasitic Diseases
Chapter 7: The Amyloidoses
Chapter 8: Blood Vessels and Hemodynamic Disorders
Chapter 9: Heart
Chapter 10: The Respiratory System
Chapter 11: The Gastrointestinal Tract
Chapter 12: The Liver and Biliary System
Chapter 13: The Exocrine Pancreas
Chapter 14: The Kidney
Chapter 15: The Lower Urinary Tract and Male Reproductive System
Chapter 16: The Female Reproductive Tract
Chapter 17: The Breast
Chapter 18: Hematopathology
Chapter 19: Endocrine System, Diabetes, and Nutritional Diseases
Chapter 20: The Skin
Chapter 21: The Head and Neck
Chapter 22: Bones, Joints, and Soft Tissue
Chapter 23: Skeletal Muscle
Chapter 24: The Central Nervous System and Eye
Chapter 25: Traumatic and Environmental Injury
,Chapter 1: Cell Adaptation, Injury, Death, and
Aging
Context: Cellular responses to stress (hypertrophy, hyperplasia, atrophy,
metaplasia), reversible/irreversible injury, apoptosis vs necrosis, and aging
mechanisms.
Why it matters: Foundation for understanding disease mechanisms from
molecule → cell → tissue → clinical picture.
1) A patient with long-standing hypertension develops concentric
left ventricular thickening with increased cardiomyocyte size but
no increase in cell number. Which molecular program best
explains this adaptation?
A. Increased cyclin-dependent kinase activity driving G1→S progression
B. Activation of growth factor signaling with increased gene transcription for
contractile proteins
C. Telomerase activation causing prolonged replicative capacity
D. Loss of E-cadherin with epithelial–mesenchymal transition
Answer: B
Rationale: Cardiomyocytes are terminally differentiated, so pressure overload
triggers hypertrophy, not hyperplasia. Hypertrophy occurs via
mechanosensor and growth factor pathways (e.g., PI3K/AKT, MAPK) that
increase transcription/translation of contractile proteins and fetal gene
programs, enlarging cell size. Cyclins (A) are more relevant to proliferative
hyperplasia. Telomerase (C) relates to replicative lifespan/aging and some
cancers. EMT (D) is a differentiation program relevant to fibrosis and tumor
invasion, not classic cardiomyocyte hypertrophy.
Key words: hypertrophy, pressure overload, PI3K/AKT, MAPK, fetal gene
program
2) A smoker’s bronchial epithelium shows replacement of
pseudostratified ciliated columnar cells with stratified squamous
epithelium. The most important consequence of this change is:
A. Increased risk of viral entry due to increased ACE2 expression
B. Decreased mucus clearance, predisposing to infection
C. Immediate progression to invasive carcinoma
D. Reduced susceptibility to oxidative injury
,Answer: B
Rationale: This is squamous metaplasia, an adaptive, reversible substitution
of one differentiated cell type for another better suited to stress. The tradeoff is
loss of specialized function—here, ciliary clearance, increasing infection risk.
Metaplasia can increase malignancy risk over time, but it does not
“immediately” become invasive cancer (C). ACE2 (A) is unrelated to the core
mechanism here. Oxidative injury susceptibility (D) is not the key clinical
consequence.
Key words: metaplasia, squamous metaplasia, smoking, loss of cilia, infection
risk
3) A liver biopsy shows enlarged hepatocytes with abundant
smooth endoplasmic reticulum after prolonged exposure to a drug
metabolized by cytochrome P450. This change best represents:
A. Atrophy due to decreased protein synthesis
B. Hypertrophy due to increased synthetic capacity
C. Hyperplasia due to increased mitotic activity
D. Necrosis due to mitochondrial permeability transition
Answer: B
Rationale: Induction of smooth ER reflects adaptive hypertrophy to increase
detoxification capacity (CYP450 induction). This is a reversible adaptation.
Hyperplasia (C) implies increased cell number. Necrosis (D) and atrophy (A) do
not match the described organelle expansion and functional upregulation.
Key words: smooth ER, CYP450 induction, drug metabolism, hypertrophy,
adaptive response
4) A renal tubular epithelial cell subjected to mild ischemia
develops cellular swelling and membrane blebs but remains viable.
The most likely immediate mechanism is:
A. Increased ATP leading to Na⁺/K⁺ ATPase hyperactivity
B. Decreased ATP causing failure of ion pumps and osmotic swelling
C. Caspase activation causing DNA laddering
D. Lysosomal rupture causing enzymatic autodigestion
Answer: B
Rationale: Mild ischemia → ↓ oxidative phosphorylation → ↓ ATP. Failure of
Na⁺/K⁺ ATPase leads to Na⁺ and water influx → cell swelling (hydropic
change) and membrane blebbing—classic reversible injury. Caspases (C) are
,apoptosis. Lysosomal rupture (D) is more consistent with necrosis/irreversible
injury.
Key words: reversible injury, ATP depletion, Na⁺/K⁺ pump failure, hydropic
change, ischemia
5) Which morphologic finding most strongly indicates irreversible
cell injury?
A. Fatty change in hepatocytes
B. Ribosomal detachment from rough ER
C. Amorphous densities in mitochondria with membrane rupture
D. Cellular swelling with intact plasma membrane
Answer: C
Rationale: Irreversible injury correlates with severe mitochondrial
dysfunction and membrane damage. Mitochondrial amorphous densities and
membrane rupture point to irreversible injury/necrosis. Fatty change (A),
ribosomal detachment (B), and swelling (D) are classically reversible.
Key words: irreversible injury, mitochondrial damage, membrane rupture,
necrosis markers
6) A patient with acute pancreatitis shows areas of chalky white
deposits in peripancreatic fat. The primary mechanism is:
A. Protein denaturation leading to coagulative necrosis
B. Enzymatic fat necrosis with calcium soap formation
C. Caspase-mediated apoptosis of adipocytes
D. Liquefactive necrosis due to bacterial infection
Answer: B
Rationale: Pancreatic lipases digest triglycerides in fat → free fatty acids bind
calcium → saponification causing chalky deposits. Coagulative necrosis (A)
fits ischemic solid organs. Apoptosis (C) is not the dominant pattern here.
Liquefactive necrosis (D) is typical in brain infarcts and abscesses.
Key words: fat necrosis, pancreatitis, lipase, saponification, calcium soaps
7) A tissue specimen shows preserved architecture with
eosinophilic “ghost” cells and loss of nuclei after infarction in the
kidney. This pattern is:
,A. Coagulative necrosis
B. Liquefactive necrosis
C. Caseous necrosis
D. Fibrinoid necrosis
Answer: A
Rationale: Coagulative necrosis preserves tissue architecture early after
ischemia in most solid organs (except brain). Liquefactive (B) is for brain
infarcts/abscesses. Caseous (C) is typical of TB granulomas. Fibrinoid (D)
occurs in immune-mediated vascular injury.
Key words: infarct, coagulative necrosis, ghost cells, ischemia, preserved
architecture
8) A cell receives a signal through the intrinsic apoptosis
pathway. Which event is most upstream and specific to this
pathway?
A. Binding of Fas ligand to Fas receptor
B. Release of cytochrome c from mitochondria
C. Massive influx of calcium through ruptured membranes
D. Activation of neutrophil myeloperoxidase
Answer: B
Rationale: Intrinsic apoptosis is triggered by internal stress (DNA damage,
growth factor withdrawal, ER stress) leading to mitochondrial outer
membrane permeabilization and cytochrome c release, activating caspase-
9. Fas–FasL (A) is extrinsic. Calcium influx via ruptured membranes (C)
suggests necrosis. MPO (D) is inflammation-related.
Key words: intrinsic apoptosis, cytochrome c, caspase-9, mitochondrial
permeabilization, BAX/BAK
9) A tumor suppressor pathway detects severe DNA damage and
induces apoptosis. Which protein is most directly involved in
deciding this outcome?
A. BCL-2
B. p53
C. EGFR
D. NF-κB
, Answer: B
Rationale: p53 responds to DNA damage by halting the cell cycle (via p21)
and, if damage is irreparable, promoting apoptosis (e.g., upregulating BAX,
PUMA). BCL-2 (A) is anti-apoptotic but is not the central “damage sensor.”
EGFR (C) is proliferative signaling. NF-κB (D) often promotes
survival/inflammation.
Key words: p53, DNA damage response, apoptosis decision, cell cycle arrest,
BAX/PUMA
10) A patient has chronic venous congestion with brown
discoloration of lung tissue. Microscopy shows macrophages filled
with golden-brown granules. These granules are:
A. Lipofuscin from lipid peroxidation
B. Hemosiderin from iron storage after hemorrhage
C. Melanin from melanocyte activation
D. Amyloid from misfolded protein deposition
Answer: B
Rationale: Chronic congestion causes micro-hemorrhage; macrophages
phagocytose RBCs and store iron as hemosiderin (“heart failure cells” in
lungs). Lipofuscin (A) is wear-and-tear pigment in aging cells. Melanin (C) is
unrelated. Amyloid (D) is extracellular and has distinct staining behavior.
Key words: hemosiderin, chronic congestion, heart failure cells, iron,
macrophages
11) A neuron exposed to prolonged hypoxia undergoes rapid
enzymatic digestion of dead cells, leading to softening of tissue.
This necrosis is best classified as:
A. Coagulative
B. Liquefactive
C. Fat
D. Caseous
Answer: B
Rationale: Brain infarcts characteristically produce liquefactive necrosis due
to high lipid content and enzymatic digestion. Coagulative necrosis is typical
elsewhere.
Key words: brain infarct, liquefactive necrosis, enzymatic digestion, softening
