A 67-year-old man with long-standing hypertension presents with progressive renal dysfunction. Renal biopsy shows hyaline arteriolosclerosis affecting afferent and efferent arterioles, along with global glomerulosclerosis in multiple glomeruli. Which mechanism best explains the vascular changes?
A. Immune-complex deposition
B. Leakage of plasma proteins into vessel wall
C. Hyperplastic smooth muscle growth due to severe malignant hypertension
D. Direct endothelial damage from neutrophils
E. Fibrinoid necrosis due to immune vasculitis
Correct Answer: B
Explanation: Hyaline arteriolosclerosis results from chronic hemodynamic stress causing plasma proteins to leak into vessel walls. Seen in long-standing hypertension and diabetes.
A patient with chronic alcohol use develops hepatomegaly. Liver biopsy reveals macrovesicular fatty change. Which cellular mechanism primarily contributed?
A. Increased β-oxidation
B. Decreased apoprotein synthesis
C. Excessive lysosomal autophagy
D. Mitochondrial hyperplasia
E. Activation of Kupffer cells
Correct Answer: B
Explanation: Alcohol impairs apoprotein synthesis → impaired export of triglycerides → fatty liver.
A pathologist notes dystrophic calcification in an atherosclerotic plaque. Which serum calcium profile is expected?
A. High calcium, high phosphate
B. High calcium, normal phosphate
C. Normal calcium, normal phosphate
D. Low calcium, high phosphate
E. Very low calcium only
Correct Answer: C
Explanation: Dystrophic calcification occurs in necrotic tissue regardless of serum calcium/phosphate levels.
A 54-year-old smoker develops chronic bronchitis. The bronchi show increased goblet cells and submucosal gland hypertrophy. Which mediator is mainly responsible for driving this epithelial change?
A. IL-1
B. TGF-β
C. IFN-γ
D. TNF-α
E. PDGF
Correct Answer: B
Explanation: TGF-β promotes fibrosis and epithelial–mesenchymal transition contributing to airway remodeling in chronic irritation.
A 28-year-old male presents with lymphadenopathy and fever. Node biopsy shows paracortical hyperplasia with abundant interdigitating dendritic cells. Which stimulus most likely triggered this pattern?
A. Chronic bacterial infection
B. Viral infection
C. Parasitic infestation
D. Metastatic tumor
E. Hypersensitivity to drugs
Correct Answer: B
Explanation: Viral infections (e.g., EBV) cause T-cell–mediated paracortical hyperplasia.
A mutation in a proto-oncogene enhances transcriptional activity leading to uncontrolled proliferation. Which gene is most consistent?
A. RB
B. TP53
C. BCL-2
D. MYC
E. APC
Correct Answer: D
Explanation: MYC is a transcription factor proto-oncogene; gain-of-function promotes cell growth.
A patient exposed to chronic UV light develops skin damage mediated by pyrimidine dimer formation. Failure of which repair mechanism causes progression to carcinoma?
A. Base excision repair
B. Mismatch repair
C. Nucleotide excision repair
D. Homologous recombination
E. Nonhomologous end-joining
Correct Answer: C
Explanation: NER removes UV-induced thymine dimers; defective in xeroderma pigmentosum.
A 24-year-old woman presents with persistent fatigue and pallor. Bone marrow shows normocellular marrow with markedly low reticulocyte count. Peripheral smear shows schistocytes. LDH is elevated, haptoglobin low. What is the fundamental cause?
A. Intrinsic membrane defect
B. Increased extravascular hemolysis in spleen
C. Microangiopathic hemolysis
D. Hemoglobin polymerization
E. Autoantibody-mediated RBC destruction
Correct Answer: C
Explanation: Schistocytes + low haptoglobin + elevated LDH indicate microangiopathic hemolytic anemia due to RBC shear injury.
A biopsy shows caseous necrosis surrounded by epithelioid histiocytes and giant cells. Which T-cell subset orchestrates this response?
A. Th1
B. Th2
C. Th17
D. Treg
E. CD8 cytotoxic cells
Correct Answer: A
Explanation: Th1 cells release IFN-γ → macrophage activation → granuloma.
A 76-year-old man suffers an MI. 4 days later, myocardium shows neutrophil infiltration and coagulative necrosis. Which component of necrosis remains intact early on?
A. DNA
B. Cell membrane
C. Tissue architecture
D. Nucleus
E. Mitochondria
Correct Answer: C
Explanation: Coagulative necrosis preserves tissue architecture despite loss of nuclei and cytoplasmic detail.
Which molecule is an executioner caspase central to apoptosis?
A. Caspase-1
B. Caspase-2
C. Caspase-3
D. Caspase-11
E. Caspase-14
Correct Answer: C
Explanation: Caspase-3 is a key executioner caspase activating DNA fragmentation and cytoskeleton breakdown.
A tumor with poorly differentiated cells lacking keratinization most likely shows loss of which feature?
A. Polarity
B. Anaplasia
C. Pleomorphism
D. Dysplasia
E. Hyperplasia
Correct Answer: B
Explanation: Anaplasia refers to complete loss of differentiation and normal morphology.
A 58-year-old diabetic patient has a chronic foot ulcer with foul-smelling discharge. Histology shows liquefactive necrosis and numerous neutrophils. What enzyme class predominantly mediates this?
A. Lysosomal hydrolases
B. Caspases
C. Glutathione peroxidases
D. Catalases
E. Topoisomerases
Correct Answer: A
Explanation: Liquefactive necrosis occurs via hydrolytic enzymes released by neutrophils.
Accumulation of lipofuscin granules in the myocardium is most associated with:
A. Severe hypoxia
B. Apoptosis
C. Wear-and-tear aging
D. Alcoholic damage
E. Glycogen storage
Correct Answer: C
Explanation: Lipofuscin is a sign of aging due to lipid peroxidation.
Which molecule acts as the main anti-apoptotic regulator preventing cytochrome c release?
A. Bax
B. Bak
C. Bim
D. Bcl-2
E. Apaf-1
Correct Answer: D
Explanation: Bcl-2 stabilizes mitochondrial membrane preventing apoptosis.
A 38-year-old man with chronic kidney disease presents with metastatic calcification involving gastric mucosa and lungs. Which biochemical abnormality is expected?
A. Normal phosphate, low calcium
B. Low phosphate, low calcium
C. High phosphate, high calcium
D. High calcium, normal phosphate
E. High phosphate, normal calcium
Correct Answer: C
Explanation: CKD → hyperphosphatemia + secondary hyperparathyroidism leading to hypercalcemia → metastatic calcification.
A tumor suppressor gene requires both alleles to be inactivated for malignancy. What concept does this illustrate?
A. Dominant-negative effect
B. Haploinsufficiency
C. Two-hit hypothesis
D. Gene amplification
E. Epigenetic methylation
Correct Answer: C
Explanation: Tumor suppressors (e.g., RB) follow two-hit mechanism.
A patient takes an agent that increases free radical formation. Which enzyme neutralizes superoxide specifically?
A. Catalase
B. Glutathione reductase
C. Superoxide dismutase
D. Myeloperoxidase
E. Peroxiredoxin
Correct Answer: C
Explanation: SOD converts superoxide → hydrogen peroxide.
A newborn presents with hydrops fetalis. Autopsy reveals extramedullary hematopoiesis and severe hemolysis. What type of immune reaction is responsible?
A. Type I
B. Type II
C. Type III
D. Type IV
E. Type V
Correct Answer: B
Explanation: Hemolytic disease of newborn = antibody-mediated RBC destruction → type II hypersensitivity.
A necrotic area from pancreatitis shows chalky white deposits. What is the mechanism?
A. Coagulative necrosis
B. Enzymatic fat necrosis
C. Caseous necrosis
D. Gangrenous necrosis
E. Fibrinoid necrosis
Correct Answer: B
Explanation: Pancreatic lipases digest fat → combine with calcium → fat necrosis.
A 48-year-old woman develops a benign breast mass composed of variable-sized ducts and fibrous stroma. Cells show no atypia. What best characterizes this lesion?
A. Dysplasia
B. Metaplasia
C. Hyperplasia
D. Desmoplasia
E. Anaplasia
Correct Answer: C
Explanation: Hyperplasia increases cell number without atypia; common in hormonal stimulation.
A free radical initiator causes lipid peroxidation. What structural component of the cell is most vulnerable?
A. Lysosomal membrane
B. Nuclear envelope
C. Mitochondrial DNA
D. Plasma membrane phospholipids
E. Peroxisomes
Correct Answer: D
Explanation: Lipid peroxidation primarily damages polyunsaturated fatty acids in membranes.
A 70-year-old man with abdominal aortic aneurysm has localized elastic fiber fragmentation. What contributed most to this degeneration?
A. Excessive TGF-β
B. Decreased metalloproteinase activity
C. Increased metalloproteinase activity
D. Hyperplastic smooth muscle cells
E. Immune complex deposition
Correct Answer: C
Explanation: MMP overactivity causes elastic tissue breakdown in aneurysm formation.
A patient with chronic inflammation develops amyloid deposits in kidneys. Congo red stain is positive. What secondary event leads to organ damage?
A. Cytotoxic T-cell infiltration
B. Compression of adjacent parenchyma
C. Activation of eosinophils
D. Nuclear fragmentation
E. Fibrinoid necrosis
Correct Answer: B
Explanation: Amyloid causes extracellular deposition → compresses tissue → organ dysfunction.
Which intracellular change represents reversible cellular injury?
A. Nuclear pyknosis
B. Karyorrhexis
C. Karyolysis
D. Plasma membrane rupture
E. Cellular swelling
Correct Answer: E
Explanation: Swelling due to loss of ionic homeostasis = reversible injury. Nuclear changes are irreversible.
A 62-year-old man with chronic liver disease develops peripheral edema. Histology shows decreased plasma protein synthesis. Which mechanism primarily drives the edema?
A. Increased oncotic pressure
B. Increased hydrostatic pressure
C. Lymphatic obstruction
D. Reduced plasma albumin
E. Sodium loss
Correct Answer: D
Explanation: Low albumin decreases oncotic pressure → fluid shifts into interstitium.
A patient with chronic granulomatous inflammation shows presence of multinucleated giant cells. These cells form due to fusion of activated macrophages under the influence of:
A. IL-10
B. IL-4
C. IFN-γ
D. TNF-α
E. IL-6
Correct Answer: C
Explanation: IFN-γ (from Th1 cells) activates macrophages → fusion into giant cells.
A tissue exposed to chronic irritation such as smoking shows transformation of bronchial columnar epithelium into stratified squamous epithelium. This represents:
A. Dysplasia
B. Metaplasia
C. Hyperplasia
D. Aplasia
E. Neoplasia
Correct Answer: B
Explanation: Reversible change where one mature cell type is replaced by another more protective type.
A 51-year-old man with uncontrolled diabetes develops thickened basement membranes in capillaries. This occurs due to:
A. Hyaline arteriolosclerosis
B. Nonenzymatic glycation
C. Increased VEGF
D. Immune complex deposition
E. Endothelial apoptosis
Correct Answer: B
Explanation: Chronic hyperglycemia → nonenzymatic glycation → basement membrane thickening (diabetic microangiopathy).
A carcass shows putrefaction and tissue liquefaction from bacterial enzymatic digestion. This process represents:
A. Apoptosis
B. Liquefactive necrosis
C. Coagulative necrosis
D. Gangrenous necrosis
E. Fat necrosis
Correct Answer: B
Explanation: Liquefaction from hydrolytic enzymes produced by bacteria.
A patient with chronic steroid therapy shows decreased lymphoid tissue size. The mechanism is:
A. Enhanced neutrophil activity
B. Induced apoptosis of lymphocytes
C. Increased macrophage proliferation
D. Increased T-cell maturation
E. Increased B-cell mitosis
Correct Answer: B
Explanation: Glucocorticoids trigger apoptosis of lymphocytes → lymphoid involution.
A 25-year-old male develops severe chest pain after trauma. Microscopy shows hypereosinophilic fibers lacking nuclei. What is the earliest sign of irreversible injury?
A. Cell swelling
B. Plasma membrane blebbing
C. Loss of RNA
D. Mitochondrial membrane damage
E. Nuclear chromatin clumping
Correct Answer: D
Explanation: Mitochondrial membrane damage → inability to generate ATP = irreversible.
A gene mutation causes inability to induce p21 protein. This affects regulation of:
A. G2/M checkpoint
B. G1/S checkpoint
C. Mitotic spindle assembly
D. Cyclin D destruction
E. Cyclin A synthesis
Correct Answer: B
Explanation: p21 inhibits CDK-cyclin complexes → controls G1/S checkpoint (p53-dependent).
A 40-year-old farmer with chronic silicosis develops persistent hilar lymphadenopathy with fibrosis. Which mechanism enhances fibroblast activity?
A. IL-2
B. IFN-β
C. TGF-β
D. IL-8
E. TNF-β
Correct Answer: C
Explanation: TGF-β is the key growth factor promoting fibroblast proliferation and collagen deposition.
A benign tumor of smooth muscle cells is termed:
A. Fibroma
B. Leiomyoma
C. Adenoma
D. Sarcoma
E. Carcinoma
Correct Answer: B
Explanation: Leiomyoma = benign tumor of smooth muscle.
A child with recurrent infections has impaired neutrophil oxidative burst. Granulomas form repeatedly. This defect is due to deficiency of:
A. NADPH oxidase
B. Myeloperoxidase
C. Catalase
D. Peroxidase
E. Lactic dehydrogenase
Correct Answer: A
Explanation: NADPH oxidase deficiency → CGD → recurrent infections + granulomas.
A 69-year-old man has an ulcerated colon tumor that invades through muscularis propria. Cells show large nuclei, high mitotic rate. What feature indicates malignancy?
A. Increased cell size
B. Pleomorphism
C. Increased cell number
D. Fibrosis
E. Loss of polarity
Correct Answer: B
Explanation: Pleomorphism = hallmark of anaplasia and malignancy.
A lymph node with acute inflammation shows neutrophilic infiltration. The primary mediator attracting neutrophils is:
A. IL-10
B. TGF-β
C. IL-8
D. IL-4
E. C3b
Correct Answer: C
Explanation: IL-8 is a strong chemotactic factor for neutrophils.
A patient with severe atherosclerosis has cholesterol clefts in plaques. Which reaction follows rupture?
A. Dystrophic calcification
B. Caseous necrosis
C. Foreign body granuloma
D. Fat necrosis
E. Amyloid deposition
Correct Answer: C
Explanation: Cholesterol crystals → foreign body type giant cell reaction.
A 42-year-old woman with autoimmune thyroid disease develops palpable neck nodes. Cytology shows numerous tingible body macrophages in germinal centers. This finding indicates:
A. High mitotic activity of B cells
B. Caseous necrosis
C. Fibrosis
D. Viral suppression
E. Amyloid accumulation
Correct Answer: A
Explanation: Tingible body macrophages clear apoptotic B cells → active germinal center proliferation.
A patient with severe hypotension develops acute tubular necrosis. Histology shows loss of brush border and epithelial shedding. The main cause is:
A. Free radical accumulation
B. Mitochondrial damage
C. Dysregulated apoptosis
D. Protein misfolding
E. Increased collagen synthesis
Correct Answer: B
Explanation: Ischemia damages mitochondrial membranes → ATP depletion → necrosis.
A carcinoma compresses nearby nerves causing pain. This event is due to:
A. Paraneoplastic effect
B. Direct local invasion
C. Hematogenous spread
D. Lymphatic dissemination
E. Immune-mediated damage
Correct Answer: B
Explanation: Local invasion/compression causes symptoms.
A patient exposed to ionizing radiation develops marrow aplasia. The dominant mechanism of cell death is:
A. Necrosis
B. Coagulation
C. Apoptosis
D. Fibrinoid damage
E. Autophagy
Correct Answer: C
Explanation: DNA damage → p53 activation → apoptosis.
A 60-year-old chronic smoker presents with a high-grade lung tumor. Tumor cells express cytokeratin but lack glandular or squamous differentiation. The tumor is classified as:
A. Metaplasia
B. Carcinoma in situ
C. Anaplastic carcinoma
D. Hamartoma
E. Sarcoma
Correct Answer: C
Explanation: Poorly differentiated epithelial tumor = anaplastic carcinoma.
A kidney biopsy shows fibrinoid necrosis in arteriole walls. This is characteristic of:
A. Diabetes
B. Malignant hypertension
C. Chronic hypoxia
D. Venous obstruction
E. Amyloidosis
Correct Answer: B
Explanation: Malignant hypertension → vessel wall necrosis with fibrin deposition.
A 47-year-old woman with chronic inflammation shows increased ESR. What drives this?
A. Increased albumin
B. Increased fibrinogen
C. Increased bilirubin
D. Increased ceruloplasmin
E. Increased transferrin
Correct Answer: B
Explanation: Fibrinogen promotes rouleaux formation → increased ESR.
Loss of E-cadherin in epithelial tumors promotes:
A. Apoptosis
B. Tissue necrosis
C. Metastasis
D. Inflammation
E. Angiogenesis
Correct Answer: C
Explanation: Loss of adhesion molecules facilitates detachment and invasion.
A patient with chronic renal failure develops anemia. Bone marrow is normocellular, RBC indices normal. The mechanism is deficiency of:
A. Iron
B. EPO
C. Folate
D. B12
E. Hemoglobin A
Correct Answer: B
Explanation: CKD decreases EPO production → normocytic anemia.
A malignant tumor in colon spreads to liver. This spread indicates:
A. Lymphatic dissemination
B. Direct extension
C. Hematogenous spread
D. Transcoelomic spread
E. Perineural invasion
Correct Answer: C
Explanation: Colon → portal vein → liver metastasis.
A cell undergoing apoptosis shows nuclear fragmentation into multiple pieces. This process is termed:
A. Pyknosis
B. Karyolysis
C. Karyorrhexis
D. Chromatin clumping
E. Balloon degeneration
Correct Answer: C
Explanation: Karyorrhexis = fragmentation of nucleus.
A patient receives prolonged oxygen therapy leading to free radical injury. Which molecule neutralizes hydrogen peroxide?
A. Superoxide dismutase
B. Catalase
C. NADPH oxidase
D. Myeloperoxidase
E. Cytochrome oxidase
Correct Answer: B
Explanation: Catalase converts H₂O₂ → H₂O + O₂.
A chronically inflamed tissue begins to show metaplasia with increased keratin formation. This adaptation is driven by:
A. IL-1
B. TGF-β
C. IL-12
D. IFN-γ
E. PDGF
Correct Answer: B
Explanation: TGF-β promotes fibrosis and epithelial remodeling.
A neonate born with hydrocephalus has calcified parietal lesions. Histology shows dystrophic calcification around necrotic glial tissue. Why does calcification occur?
A. High serum calcium
B. Normal calcium, dead tissue
C. Immunologic injury
D. Iron overload
E. Triglyceride accumulation
Correct Answer: B
Explanation: Dystrophic calcification occurs in necrotic tissue despite normal calcium levels.
A lung tumor secretes PTH-related peptide causing hypercalcemia. This represents:
A. Direct invasion
B. Metastasis
C. Paraneoplastic syndrome
D. Apoptosis
E. Coagulative necrosis
Correct Answer: C
Explanation: Hormone-like secretion by tumor cells = paraneoplastic effect.
A patient with chronic liver failure develops gynecomastia. Which mechanism explains this?
A. Increased estrogen clearance
B. Decreased estrogen metabolism
C. Increased testosterone metabolism
D. Fibrosis of mammary tissue
E. Aldosterone accumulation
Correct Answer: B
Explanation: Liver disease decreases estrogen metabolism → feminizing effects.
A tumor with vimentin positivity but negative cytokeratin originates from:
A. Epithelium
B. Blood cells
C. Mesenchyme
D. Nervous tissue
E. Endothelium
Correct Answer: C
Explanation: Vimentin marks mesenchymal origin → sarcomas.
A 40-year-old man with chronic hepatitis develops hepatocellular carcinoma. The underlying change leading to malignancy is:
A. Hyperplasia
B. Dysplasia
C. Hypertrophy
D. Metaplasia
E. Apoptosis
Correct Answer: B
Explanation: Chronic injury → dysplasia → carcinoma sequence.
A macrophage engulfing apoptotic bodies avoids inflammation because apoptotic cells express:
A. Complement
B. IgG
C. Phosphatidylserine
D. Cytokinin receptors
E. Integrins
Correct Answer: C
Explanation: Phosphatidylserine flips to outer membrane → recognized by macrophages → silent clearance.
Chronic lymphoid hyperplasia progresses to lymphoma after genetic instability. Which enzyme defect likely promoted rearrangements?
A. DNA polymerase
B. Telomerase
C. p53
D. RAG
E. Topoisomerase I
Correct Answer: C
Explanation: Loss of p53 → genomic instability → tumor progression.
A tissue subjected to high oxidative stress increases synthesis of heat-shock proteins. Their major function is:
A. DNA repair
B. Protein folding
C. Mitochondrial replication
D. Lipid catabolism
E. Cytoskeletal synthesis
Correct Answer: B
Explanation: HSPs stabilize and refold damaged proteins.
A diabetic patient suffers gangrene in foot. The tissue becomes black, dry, shrunken. This represents:
A. Liquefactive necrosis
B. Fat necrosis
C. Wet gangrene
D. Dry gangrene
E. Apoptosis
Correct Answer: D
Explanation: Dry gangrene = mummified necrosis from vascular obstruction.
Atherosclerotic plaque formation begins with:
A. Smooth muscle hyperplasia
B. Endothelial injury
C. Thrombosis
D. Hematoma
E. Lipid crystallization
Correct Answer: B
Explanation: Endothelial injury allows LDL entry → inflammatory response.
A patient with multiple myeloma shows amyloid light-chain deposition in kidneys. These fibrils are composed of:
A. Beta-pleated sheets
B. Alpha helices
C. Random coils
D. Collagen bundles
E. Elastin
Correct Answer: A
Explanation: Amyloid proteins aggregate in β-pleated sheet configuration.
A tumor shows increased angiogenesis via VEGF. This occurs due to activation of:
A. p21
B. HIF-1
C. BRCA1
D. Rb
E. Bax
Correct Answer: B
Explanation: Hypoxia → HIF-1 → VEGF → angiogenesis.
A 77-year-old man develops confusion with headache. MRI shows diffuse cerebral atrophy. Accumulated pigment with golden-brown granules is seen histologically. This pigment is:
A. Melanin
B. Bilirubin
C. Lipofuscin
D. Iron
E. Hemosiderin
Correct Answer: C
Explanation: Lipofuscin = wear-and-tear pigment.
A patient with chronic hypoxia shows increased erythropoiesis. This represents:
A. Pathologic hyperplasia
B. Physiologic hyperplasia
C. Metaplasia
D. Atrophy
E. Dysplasia
Correct Answer: B
Explanation: Hypoxia → EPO → physiologic hyperplasia of erythroid precursors.
A patient develops cirrhosis with nodules of regenerating hepatocytes separated by fibrous bands. What mediator drives fibrosis?
A. IL-5
B. IL-2
C. TGF-β
D. GM-CSF
E. TNF-γ
Correct Answer: C
Explanation: TGF-β is the major fibrogenic cytokine.
A colon polyp forms a mushroom-like mass but remains confined to mucosa. This lesion is classified as:
A. Sessile carcinoma
B. Pedunculated adenoma
C. Hyperplasia
D. Sarcoma
E. Anaplastic mass
Correct Answer: B
Explanation: Pedunculated adenomas form stalk-like projections.
A 32-year-old woman presents with recurrent oral ulcers and fatigue. Labs show iron deficiency anemia due to chronic blood loss from GI lesions. Chronic epithelial damage promotes which adaptation?
A. Steatosis
B. Metaplasia
C. Anaplasia
D. Hypertrophy
E. Hyperplasia
Correct Answer: E
Explanation: Chronic injury → compensatory epithelial hyperplasia.
A patient with severe burns shows elevated potassium due to:
A. ATP depletion
B. Mitochondrial division
C. Loss of nuclear membrane
D. Increased Na/K ATPase activity
E. Increased autophagy
Correct Answer: A
Explanation: ATP depletion disrupts Na/K pump → extracellular K⁺ accumulation.
A mutation causing increased cyclin D activity most directly accelerates:
A. G0 → G1 transition
B. G1 → S transition
C. S → G2 transition
D. G2 → M transition
E. M → G1 transition
Correct Answer: B
Explanation: Cyclin D-CDK4 pushes cells through G1/S checkpoint.
A biopsy of sarcoma shows marked variability in nuclear size and shape. This represents:
A. Metaplasia
B. Pleomorphism
C. Dysplasia
D. Hypertrophy
E. Aplasia
Correct Answer: B
Explanation: Pleomorphism is hallmark of malignant tumors.
A 55-year-old man with longstanding GERD develops columnar epithelium replacing esophageal squamous mucosa. This change increases cancer risk primarily because:
A. It promotes fibrosis
B. It reduces blood flow
C. It destabilizes genome during proliferation
D. It increases mucus production
E. It improves acid secretion
Correct Answer: C
Explanation: Metaplasia under chronic stress predisposes to dysplasia.
Aortic dissection is exacerbated by degradation of collagen and elastin. Which cells produce MMPs contributing to the damage?
A. Neutrophils
B. T-cells
C. Smooth muscle cells
D. Endothelial cells
E. Hepatocytes
Correct Answer: C
Explanation: Vascular smooth muscle cells produce MMPs → degrade ECM.
A patient infected with hepatitis C has ongoing apoptosis in hepatocytes. Cytochrome c released from mitochondria activates:
A. Caspase-1
B. Caspase-3
C. Caspase-11
D. Caspase-14
E. Caspase-8
Correct Answer: B
Explanation: Intrinsic pathway activates caspase-9 → caspase-3.
A tumor releases IL-1 and TNF causing fever and weight loss. These are classified as:
A. Paraneoplastic autoimmune effects
B. Hormonal effects
C. Paraneoplastic cytokine effects
D. Direct invasion effects
E. Lymphatic obstruction
Correct Answer: C
Explanation: Cytokines cause constitutional symptoms.
A patient with heart failure develops nutmeg liver. The pattern is due to:
A. Portal hypertension
B. Passive congestion
C. Increased bile secretion
D. Lymphatic obstruction
E. Viral injury
Correct Answer: B
Explanation: Right-sided HF → congested central veins → nutmeg pattern.
A 40-year-old man presents with severe headache. CSF shows xanthochromia. RBC breakdown in subarachnoid space produces a pigment responsible for yellow color. That pigment is:
A. Melanin
B. Bilirubin
C. Hematoidin
D. Hemosiderin
E. Lipofuscin
Correct Answer: B
Explanation: RBC breakdown → biliverdin → bilirubin → xanthochromia.
A patient with chronic infection has increased acute-phase reactants. What effect does IL-6 mainly produce?
A. Leukocytosis
B. Fever
C. Acute-phase protein synthesis
D. Vasodilation
E. Chemotaxis
Correct Answer: C
Explanation: IL-6 stimulates liver → acute-phase proteins.
A mitochondrial DNA mutation causes lactic acidosis due to defective:
A. Glycolysis
B. TCA cycle enzymes
C. Ribosome function
D. Peroxisomal enzymes
E. Cytoskeletal filaments
Correct Answer: B
Explanation: Mitochondrial defects impair oxidative phosphorylation → lactic acidosis.
A teenager sustains crush injury to leg. Hours later, CK rises markedly due to muscle necrosis. Which structural change confirms irreversible damage?
A. Ribosomal detachment
B. Calcium influx
C. Nuclear fragmentation
D. Cell swelling
E. ER dilation
Correct Answer: C
Explanation: Nuclear fragmentation (karyorrhexis) = irreversible necrosis.
A patient with autoimmune gastritis progresses to gastric carcinoma. Which cellular change is precancerous?
A. Hypertrophy
B. Atrophy
C. Dysplasia
D. Hyperplasia
E. Metaplasia
Correct Answer: C
Explanation: Chronic inflammation → dysplasia → carcinoma.
A child with cystic fibrosis has pancreatic insufficiency due to:
A. Fatty infiltration
B. Fibrosis and atrophy
C. Hyperplasia
D. Metaplasia
E. Lipofuscin accumulation
Correct Answer: B
Explanation: Obstruction → chronic inflammation → fibrosis → atrophy.
A patient receives chemotherapeutic drugs causing DNA cross-linking. Which repair mechanism fixes this?
A. Base excision
B. Mismatch repair
C. Nucleotide excision
D. Homologous recombination
E. Mismatch proofreading
Correct Answer: D
Explanation: Double-strand breaks from cross-linking require homologous recombination.
A neonate with severe jaundice develops kernicterus. Bilirubin deposition occurs mainly in:
A. Cerebellum
B. Liver
C. Basal ganglia
D. Heart
E. Lung
Correct Answer: C
Explanation: Unconjugated bilirubin deposits in basal ganglia → neurologic damage.
Sustained pressure on cardiac muscle leads to:
A. Hyperplasia
B. Hypertrophy
C. Metaplasia
D. Atrophy
E. Dysplasia
Correct Answer: B
Explanation: Permanent cells adapt by hypertrophy, not hyperplasia.
A patient develops systemic amyloidosis. Kidney biopsy shows deposition of amorphous material. Congophilic staining indicates:
A. Calcium
B. Protein misfolding
C. Iron
D. Glycogen
E. Lipids
Correct Answer: B
Explanation: Amyloid = misfolded proteins forming β-pleated sheets.
A malignant tumor shows high mitotic index. This is due to increased activity of:
A. p53
B. p21
C. Cyclin/CDK complexes
D. Rb
E. TGF-β
Correct Answer: C
Explanation: Cyclin/CDK promote cell-cycle progression.
A patient with chronic alcohol abuse develops Mallory bodies. These structures contain:
A. Glycogen
B. Keratin intermediate filaments
C. Collagen
D. Mucin
E. Fatty droplets
Correct Answer: B
Explanation: Hepatocyte injury → keratin filament aggregates (Mallory-Denk bodies).
A patient with viral hepatitis develops Councilman bodies. These represent:
A. Apoptotic hepatocytes
B. Fat necrosis
C. Liquefaction
D. Dysplasia
E. Reversible injury
Correct Answer: A
Explanation: Councilman bodies = apoptotic hepatocytes.
A patient develops thrombosis in a large vein. What factor directly promotes clot formation?
A. High albumin
B. Increased antithrombin
C. Endothelial injury
D. High protein C
E. High plasmin
Correct Answer: C
Explanation: Endothelial damage → exposure of collagen, tissue factor → thrombosis.
A lymphoma spreads along tissue planes, producing multiple enlarged nodes. This indicates:
A. Hematogenous spread
B. Lymphatic dissemination
C. Direct invasion
D. Transcoelomic spread
E. Perineural invasion
Correct Answer: B
Explanation: Lymphoid tumors spread via lymphatic routes.
A 47-year-old man develops ulcerative colitis. Colon shows inflammatory infiltration with crypt abscesses. Ongoing damage predisposes to which?
A. Hyperplasia
B. Dysplasia
C. Metaplasia
D. Hypertrophy
E. Fibromatosis
Correct Answer: B
Explanation: Chronic inflammation increases risk of dysplasia → carcinoma.
A patient with megaloblastic anemia has hypersegmented neutrophils due to:
A. Impaired DNA synthesis
B. Protein accumulation
C. Mitochondrial swelling
D. Loss of adhesion molecules
E. Increased membrane lipids
Correct Answer: A
Explanation: Folate/B12 deficiency → impaired DNA replication → nuclear maturation delay.
A severely hypoxic cell shifts to anaerobic glycolysis. What toxic metabolite accumulates?
A. Uric acid
B. Lactic acid
C. Bilirubin
D. Peroxide
E. Nitric oxide
Correct Answer: B
Explanation: Anaerobic glycolysis → lactic acidosis.
A patient develops a keloid after injury. This abnormality is due to:
A. Excess fibroblast apoptosis
B. Excess collagen deposition
C. Loss of epithelial cells
D. Autoimmune destruction
E. Iron deficiency
Correct Answer: B
Explanation: Keloids = excessive type III collagen.
A 32-year-old man has a renal mass with clear cytoplasm. Cells contain accumulated lipids and glycogen. This tumor is most likely:
A. Wilms tumor
B. Chromophobe carcinoma
C. Clear cell renal carcinoma
D. Transitional carcinoma
E. Oncocytoma
Correct Answer: C
Explanation: Clear cytoplasm = lipid/glycogen-rich → clear cell RCC.
A malignant melanoma metastasizes to brain. This occurs mainly via:
A. Lymphatics
B. Venous channels
C. Direct penetration
D. CSF spread
E. Transcoelomic seeding
Correct Answer: B
Explanation: Hematogenous spread via veins is typical for melanoma.
A patient develops fibrosis in lungs after chronic exposure to dust. Which cells initiate fibrosis?
A. Neutrophils
B. Macrophages
C. B cells
D. Mast cells
E. Plasma cells
Correct Answer: B
Explanation: Macrophages release TGF-β → fibroblast activation.
A patient with iron overload has brown granules in hepatocytes. These are identified as:
A. Lipofuscin
B. Hemosiderin
C. Bilirubin
D. Glycogen
E. Amyloid
Correct Answer: B
Explanation: Hemosiderin = iron-storage pigment, positive with Prussian blue stain.