PATHOLOGY MCQs: CELL INJURY, DEATH, AND ADAPTATIONS | MCQ Quiz | OmpathStudy Kenya

Question 1

Which of the following best describes the relationship between etiology and pathogenesis?

Accepted Answer

Etiology identifies the initiating cause, while pathogenesis explains the sequence of events leading to disease — Etiology refers to the cause of disease (genetic or environmental factors), while pathogenesis describes the molecular, biochemical, and cellular events that follow the etiologic agent and lead to the development of disease manifestations.

Question 2

A 45-year-old patient presents with chest pain. After 30 minutes of ischemia, the cardiomyocytes show cellular swelling and fat accumulation but maintain intact cell membranes. What stage of cell injury is this?

Accepted Answer

Reversible injury — The key features indicating reversible injury are cellular swelling, fatty change, and intact cell membranes. These changes can be corrected if the damaging stimulus (ischemia) is removed. Irreversible injury would show mitochondrial damage with dense deposits and plasma membrane rupture.

Question 3

Which of the following represents the earliest morphologic manifestation of almost all forms of cell injury?

Accepted Answer

Cellular swelling — Cellular swelling is the earliest visible sign of cell injury, resulting from failure of the ATP-dependent Na+-K+ pump, leading to sodium and water accumulation inside the cell. This occurs before any nuclear changes or membrane disruption.

Question 4

A researcher observes cells under electron microscopy 2 hours after ischemic injury. Which finding would indicate the point of no return (irreversibility)?

Accepted Answer

Severe mitochondrial swelling with large amorphous densities — Two phenomena consistently characterize irreversibility: inability to reverse mitochondrial dysfunction and profound membrane disturbances. Severe mitochondrial damage with amorphous densities (calcium and protein precipitates) indicates irreversible injury, while the other options can occur in reversible injury. ## SECTION 2: CAUSES AND MECHANISMS OF CELL INJURY

Question 5

Which cause of hypoxia differs from ischemia in that it allows anaerobic glycolysis to continue?

Accepted Answer

Carbon monoxide poisoning — Carbon monoxide poisoning causes hypoxia by reducing oxygen-carrying capacity of blood, but blood flow continues, allowing delivery of glucose for anaerobic glycolysis. In ischemia (b, c, d), blood flow is reduced, compromising delivery of substrates for glycolysis, making ischemia more injurious than hypoxia alone.

Question 6

A patient with tuberculosis shows areas of lung tissue with a friable, white, "cheese-like" appearance. What type of necrosis is this?

Accepted Answer

Caseous necrosis — Caseous necrosis is characteristic of tuberculous infection, appearing grossly as friable, white, cheese-like material. Microscopically, it shows structureless collection of fragmented cells and granular debris enclosed within a granulomatous inflammatory border.

Question 7

Why does ischemic injury to the brain result in liquefactive necrosis rather than coagulative necrosis seen in other organs?

Accepted Answer

Hypoxic death of CNS cells manifests as liquefactive necrosis for unknown reasons — For unknown reasons, hypoxic death of cells within the central nervous system often manifests as liquefactive necrosis, which is an exception to the general rule that ischemia causes coagulative necrosis in most organs.

Question 8

A patient with acute pancreatitis develops chalky-white areas in the peritoneal cavity. What is the mechanism of this pathologic finding?

Accepted Answer

Release of pancreatic lipases causing fat necrosis with saponification — In acute pancreatitis, pancreatic enzymes leak and liquefy fat cell membranes, releasing triglycerides. Pancreatic lipases split these into fatty acids, which combine with calcium to produce grossly visible chalky-white areas (fat saponification), characteristic of fat necrosis.

Question 9

Which nuclear change in necrosis is characterized by nuclear shrinkage and increased basophilia?

Accepted Answer

Pyknosis — Pyknosis is characterized by nuclear shrinkage and increased basophilia due to chromatin condensation into a dense, shrunken basophilic mass. Karyolysis is fading of chromatin, and karyorrhexis is fragmentation of the pyknotic nucleus. ## SECTION 3: NECROSIS VS APOPTOSIS

Question 10

Which feature distinguishes necrosis from apoptosis?

Accepted Answer

Necrosis involves cell swelling while apoptosis involves cell shrinkage — Necrosis is characterized by cell swelling due to membrane damage and loss of osmotic regulation, while apoptosis involves cell shrinkage with intact membranes. DNA fragmentation occurs in both, but caspase activation is specific to apoptosis, not necrosis.

Question 11

Why doesn't apoptosis elicit an inflammatory response?

Accepted Answer

Dead cells are rapidly phagocytosed before membrane rupture and content leakage — In apoptosis, the plasma membrane remains intact and apoptotic bodies are rapidly phagocytosed by macrophages before contents leak out. This prevents release of cellular contents that would trigger inflammation, unlike necrosis where membrane rupture releases DAMPs.

Question 12

A pathologist observes cells with intensely eosinophilic cytoplasm, dense chromatin masses at the nuclear periphery, and membrane-bound fragments without adjacent inflammation. What process is occurring?

Accepted Answer

Apoptosis — The key features of apoptosis are present: cell shrinkage (dense eosinophilic cytoplasm), chromatin condensation at the nuclear membrane periphery, formation of apoptotic bodies (membrane-bound fragments), and absence of inflammation.

Question 13

What is the primary reason that cardiac troponins can be detected in blood 2 hours after myocardial infarction?

Accepted Answer

Release through damaged plasma membranes during necrosis — Necrosis involves loss of membrane integrity, leading to leakage of intracellular proteins into the circulation. Cardiac-specific troponins leak out through damaged plasma membranes and serve as biomarkers for myocardial necrosis, detectable well before histologic changes appear.

Question 14

Which statement about DAMPs (damage-associated molecular patterns) is correct?

Accepted Answer

They include ATP, uric acid, and molecules normally confined within healthy cells — DAMPs are normal intracellular molecules (ATP from mitochondria, uric acid from DNA breakdown) that are released during necrosis when membranes rupture. They are recognized by receptors on macrophages and trigger inflammation and phagocytosis. ## SECTION 4: APOPTOSIS MECHANISMS

Question 15

Which BCL2 family protein is pro-apoptotic and forms channels in the mitochondrial membrane?

Accepted Answer

BAX and BAK — BAX and BAK are pro-apoptotic proteins with BH1-3 domains that oligomerize and form channels in the outer mitochondrial membrane, allowing cytochrome c leakage. BCL2 and BCL-XL are anti-apoptotic, while BID is a BH3-only sensor protein.

Question 16

A researcher studying apoptosis blocks the function of APAF-1. Which step of apoptosis will be directly affected?

Accepted Answer

Formation of the apoptosome and activation of caspase-9 — APAF-1 (apoptosis-activating factor-1) binds to cytochrome c released from mitochondria to form the apoptosome, which then activates caspase-9. Blocking APAF-1 prevents apoptosome formation and subsequent caspase activation, but doesn't affect upstream events like cytochrome c release.

Question 17

Which mechanism initiates the extrinsic pathway of apoptosis?

Accepted Answer

Engagement of death receptors like Fas — The extrinsic pathway is initiated by death receptor engagement (Fas, TNFR1) by their ligands. This recruits FADD and activates caspase-8. The intrinsic pathway is triggered by DNA damage, growth factor withdrawal, or mitochondrial damage.

Question 18

What is the function of BH3-only proteins in apoptosis?

Accepted Answer

They act as sensors of cellular stress and activate BAX/BAK — BH3-only proteins (BAD, BIM, BID, Puma, Noxa) are regulated apoptosis initiators that sense cellular stress and damage. When upregulated, they directly activate BAX/BAK to permeabilize mitochondrial membranes and can also neutralize anti-apoptotic BCL2 proteins.

Question 19

During apoptosis, what signal promotes phagocytosis of apoptotic cells?

Accepted Answer

Externalization of phosphatidylserine on the outer membrane leaflet — In healthy cells, phosphatidylserine is on the inner leaflet of the plasma membrane. During apoptosis, it flips to the outer surface, where it serves as an "eat me" signal recognized by macrophage receptors, promoting efferocytosis without inflammation.

Question 20

Which cellular process is impaired in patients with chronic granulomatous disease?

Accepted Answer

Generation of superoxide by leukocytes — Chronic granulomatous disease results from defects in NADPH oxidase, which is required for the respiratory burst that generates superoxide (O2•−) in leukocytes. This impairs their ability to kill phagocytosed microbes, leading to recurrent infections. ## SECTION 5: OTHER MECHANISMS OF CELL DEATH

Question 21

What distinguishes necroptosis from classical necrosis?

Accepted Answer

Necroptosis is a regulated process involving specific signaling pathways — Necroptosis is "programmed necrosis" - it resembles necrosis morphologically but is triggered by defined signaling pathways (RIPK1/RIPK3/MLKL). It is caspase-independent, unlike apoptosis. Classical necrosis is passive cell death from severe injury.

Question 22

A patient with viral infection shows cell death accompanied by IL-1 release and fever. Which mechanism is most likely?

Accepted Answer

Pyroptosis — Pyroptosis is characterized by caspase-1 activation (by the inflammasome in response to microbial products), which cleaves pro-IL-1 to active IL-1 (causing fever - "pyro"). The caspases also cause cell death with inflammatory response, unlike classical apoptosis.

Question 23

Which protein must be phosphorylated by RIPK3 to execute necroptosis?

Accepted Answer

MLKL — In necroptosis, RIPK3 phosphorylates MLKL (mixed lineage kinase domain-like protein), which then oligomerizes and translocates to the plasma membrane, causing membrane disruption characteristic of necrotic cell death.

Question 24

Ferroptosis is characterized by which primary mechanism?

Accepted Answer

Unchecked lipid peroxidation of cellular membranes — Ferroptosis occurs when iron or ROS overwhelm glutathione-dependent antioxidant defenses, causing unchecked lipid peroxidation of membranes. This disrupts membrane function and leads to cell death. It's iron-dependent (hence "ferro") and can be prevented by reducing iron levels. ## SECTION 6: AUTOPHAGY

Question 25

What is the primary function of autophagy in starved cells?

Accepted Answer

Recycle cellular components to generate metabolites and energy — Autophagy is a survival mechanism where cells digest their own contents (organelles, proteins) and recycle the products for energy and metabolite production. In starvation, cells "cannibalize" themselves to survive until nutrients become available again.

Question 26

Which cellular structure is believed to be the primary source of the autophagosome isolation membrane?

Accepted Answer

Endoplasmic reticulum — The isolation membrane (phagophore) that forms the autophagosome is believed to be primarily derived from the ER, though other membrane sources like plasma membrane and mitochondria may contribute.

Question 27

PE-lipidated LC3 is a marker for which cellular process?

Accepted Answer

Autophagy — LC3 (microtubule-associated protein light chain 3) becomes covalently linked to phosphatidylethanolamine (PE) during autophagy. PE-lipidated LC3 increases during autophagy and is a useful marker for identifying cells undergoing this process.

Question 28

Which disease has been linked to single nucleotide polymorphisms in the autophagy gene ATG16L1?

Accepted Answer

Crohn disease — Genome-wide association studies have linked both Crohn disease and ulcerative colitis (inflammatory bowel diseases) to SNPs in ATG16L1, an autophagy-related gene. The mechanism by which these polymorphisms promote intestinal inflammation is not fully understood.

Question 29

What happens when autophagy is inadequate to cope with cellular stress?

Accepted Answer

The cell may undergo cell death — While autophagy is typically a survival mechanism, if it is inadequate to cope with the stressor, it can trigger cell death. Autophagic vacuolization often precedes or accompanies cell death, though whether autophagy causes death or is simply a response to the lethal stress is debated. ## SECTION 7: MECHANISMS OF CELL INJURY - MITOCHONDRIA AND ATP

Question 30

Which change best indicates that a cell has progressed from reversible to irreversible injury?

Accepted Answer

Opening of the mitochondrial permeability transition pore — Two phenomena consistently characterize irreversibility: inability to reverse mitochondrial dysfunction and profound membrane disturbances. Opening of the mitochondrial permeability transition pore leads to loss of membrane potential, irreversible failure of ATP generation, and progression to necrosis.

Question 31

In ATP-depleted cells, which metabolic pathway attempts to maintain energy production?

Accepted Answer

Glycolysis (anaerobic) — When ATP is depleted (e.g., from ischemia), cells stimulate glycogenolysis and glycolysis to generate ATP anaerobically from glucose. This produces much less ATP than oxidative phosphorylation and leads to lactic acid accumulation, but is the only energy source when oxygen is unavailable.

Question 32

What is the consequence of ATP depletion on the Na+-K+ ATPase pump?

Accepted Answer

Decreased pump activity leading to sodium influx and cell swelling — The Na+-K+ ATPase pump requires ATP to maintain low intracellular sodium. When ATP is depleted, pump activity fails, sodium accumulates inside cells, water follows osmotically, and cells swell. This is one of the earliest manifestations of reversible injury.

Question 33

Which organelle releases cytochrome c into the cytoplasm during the intrinsic apoptosis pathway?

Accepted Answer

Mitochondria — In the intrinsic (mitochondrial) pathway of apoptosis, BAX/BAK form channels in the mitochondrial outer membrane, allowing cytochrome c and other pro-apoptotic proteins to leak from the mitochondrial intermembrane space into the cytoplasm, where cytochrome c initiates caspase activation.

Question 34

Why does lactic acid accumulate in ischemic tissue?

Accepted Answer

Anaerobic glycolysis produces lactate as an end product — During ischemia, cells rely on anaerobic glycolysis for ATP production. This pathway converts glucose to pyruvate, which is then reduced to lactate (lactic acid) instead of entering the citric acid cycle. Accumulation of lactic acid reduces intracellular pH. ## SECTION 8: MEMBRANE DAMAGE AND CALCIUM

Question 35

Which mechanism contributes to membrane damage during cell injury?

Accepted Answer

Calcium-mediated activation of phospholipases — Increased cytosolic Ca2+ activates phospholipases, which degrade membrane phospholipids. This produces detergent-like breakdown products (free fatty acids, lysophospholipids) that further damage membranes, creating a vicious cycle.

Question 36

What is the normal concentration difference of calcium between the cytosol and extracellular fluid?

Accepted Answer

Extracellular Ca2+ is higher (about 10,000-fold) — Cytosolic free Ca2+ is normally maintained at very low concentrations (~0.1 µmol) compared with extracellular levels of 1.3 mmol (about 10,000-fold difference). Most intracellular Ca2+ is sequestered in mitochondria and ER.

Question 37

How does excessive cytosolic calcium lead to cell injury?

Accepted Answer

It opens the mitochondrial permeability transition pore and activates degradative enzymes — Excessive cytosolic Ca2+ causes injury by: 1) accumulating in mitochondria and opening the permeability transition pore (causing ATP depletion), and 2) activating phospholipases (membrane damage), proteases (cytoskeletal/membrane damage), endonucleases (DNA damage), and ATPases (hastening ATP depletion).

Question 38

Myelin figures observed in injured cells are composed of which substance?

Accepted Answer

Phospholipids from damaged membranes — Myelin figures are whorled phospholipid precipitates derived from damaged cellular membranes. They appear in both reversible and irreversible injury and may be phagocytosed or further degraded into fatty acids, which can calcify.

Question 39

Which free radical is considered the most reactive and responsible for most lipid, protein, and DNA damage?

Accepted Answer

Hydroxyl radical (•OH) — The hydroxyl radical (•OH) is the most reactive oxygen-derived free radical and is the principal ROS responsible for damaging lipids (via peroxidation), proteins, and DNA. It can be generated from H2O2 by the Fenton reaction or by ionizing radiation.

Question 40

In the Fenton reaction, which transition metal catalyzes the formation of hydroxyl radicals?

Accepted Answer

Iron — The Fenton reaction is: H2O2 + Fe2+ → Fe3+ + •OH + OH−. Iron (and copper) donate or accept electrons and catalyze free radical formation. Most intracellular iron is in the Fe3+ state and must be reduced to Fe2+ (by superoxide) to participate in this reaction.

Question 41

How do transferrin, ferritin, and ceruloplasmin help prevent free radical damage?

Accepted Answer

They bind iron and copper, preventing their participation in ROS generation — Free iron and copper catalyze ROS formation (Fenton reaction). Storage and transport proteins (transferrin, ferritin, lactoferrin, ceruloplasmin) bind these metals and minimize their reactivity, preventing them from participating in reactions that generate harmful free radicals.

Question 42

Which pathologic process is NOT typically associated with free radical injury?

Accepted Answer

Hypertrophic cardiomyopathy — Free radical injury is important in ischemia-reperfusion injury, chemical/radiation injury, cellular aging, and microbial killing by phagocytes. Hypertrophic cardiomyopathy is primarily caused by increased workload leading to enhanced protein synthesis, not free radical damage.

Question 43

What is the significance of the GSSG/GSH ratio in cells?

Accepted Answer

It reflects the oxidative state and ability to detoxify ROS — The ratio of oxidized glutathione (GSSG) to reduced glutathione (GSH) reflects the oxidative state of the cell. Glutathione peroxidase uses GSH to break down H2O2 and free radicals, producing GSSG. A high GSSG/GSH ratio indicates oxidative stress and reduced capacity to detoxify ROS.

Question 44

Which mechanism initiates lipid peroxidation in cell membranes?

Accepted Answer

Double bonds in unsaturated fatty acids are attacked by free radicals — Lipid peroxidation is initiated when free radicals (especially •OH) attack double bonds in unsaturated fatty acids of membrane lipids. This produces lipid peroxides, which are unstable and reactive, creating an autocatalytic chain reaction that causes extensive membrane damage. ## SECTION 10: ER STRESS AND PROTEIN MISFOLDING

Question 45

What is the unfolded protein response designed to do?

Accepted Answer

Restore protein homeostasis by increasing chaperones and reducing protein load — The unfolded protein response is activated when misfolded proteins accumulate in the ER. It attempts to restore homeostasis by: 1) increasing chaperone production, 2) enhancing proteasomal degradation, and 3) slowing protein translation. If unsuccessful, it triggers apoptosis.

Question 46

In α1-antitrypsin deficiency, where do the mutant proteins accumulate?

Accepted Answer

In the endoplasmic reticulum of hepatocytes — Mutant α1-antitrypsin misfolds slowly, and partially folded intermediates aggregate in the ER of hepatocytes rather than being secreted. This causes ER stress and liver damage. The absence of the enzyme in circulation leads to emphysema because the enzyme normally protects lungs from protease damage.

Question 47

Russell bodies in plasma cells represent accumulation of which substance?

Accepted Answer

Immunoglobulins in distended endoplasmic reticulum — Russell bodies are large homogeneous eosinophilic inclusions in plasma cells actively synthesizing excessive amounts of immunoglobulins. The ER becomes hugely distended with accumulated secretory proteins, creating these characteristic structures. ## SECTION 11: ISCHEMIA AND REPERFUSION INJURY

Question 48

Which mechanism contributes to reperfusion injury?

Accepted Answer

Generation of reactive oxygen species and calcium overload — Reperfusion injury occurs through several mechanisms: 1) increased ROS generation during reoxygenation by leukocytes and damaged cells, 2) calcium overload from influx through damaged membranes, 3) inflammation from recruited neutrophils, and 4) complement activation. These cause additional cell death beyond the ischemic injury.

Question 49

What is the proposed benefit of hypothermia in ischemic brain injury?

Accepted Answer

It reduces metabolic demands, cell swelling, free radicals, and inflammation — Therapeutic hypothermia (lowering core temperature to ~92°F) reduces metabolic demands of stressed cells, decreases cell swelling, suppresses free radical formation, and inhibits the inflammatory response. All of these contribute to decreased cell and tissue injury in ischemic brain and spinal cord injury.

Question 50

How soon after myocardial ischemia can cardiac troponins be detected in blood?

Accepted Answer

2 hours — Cardiac-specific troponins can be detected in blood as early as 2 hours after myocardial cell necrosis, well before histologic evidence of infarction becomes apparent. They leak through damaged plasma membranes and serve as sensitive and specific biomarkers for myocardial injury.

PATHOLOGY MCQs: CELL INJURY, DEATH, AND ADAPTATIONS | MCQ Quiz | OmpathStudy Kenya

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