Cell Injury, Death and Adaptations (Apoptosis, Necrosis, Free Radicals) MCQs

Pathology · 123 free questions with answers & explanations.

1. During reperfusion injury after myocardial ischemia, which mechanism is primarily responsible for cardiomyocyte death that was not irreversibly injured during the ischemic phase itself?
2. A pathologist examines autopsy tissue from a patient who died of rabies encephalitis. Cytoplasmic eosinophilic inclusions are noted in hippocampal neurons. These inclusions represent accumulation of which material?
3. Which form of programmed cell death is characterized by cell membrane rupture, release of intracellular contents triggering inflammation, and gasdermin D pore formation — differing fundamentally from classical caspase-3-mediated apoptosis?
4. A renal transplant patient on long-term calcineurin inhibitor therapy develops vacuolar changes in proximal tubular cells without necrosis, progressive tubulointerstitial fibrosis, and arteriolar hyalinosis. This pattern of injury is best classified as:
5. Ferroptosis is a recently characterized form of regulated cell death distinct from apoptosis and necroptosis. It is specifically driven by:
6. In ischemia-reperfusion injury, the paradoxical worsening upon restoration of blood flow is primarily attributable to which mechanism?
7. Autophagy is a cellular process wherein cytoplasmic components are sequestered in double-membrane vesicles (autophagosomes) and delivered to lysosomes. In the context of cell injury, autophagy primarily serves as:
8. Liquefactive necrosis, rather than coagulative necrosis, characteristically occurs in brain infarcts primarily because:
9. A researcher studies ferroptosis — a non-apoptotic regulated cell death. Which combination of biochemical features is SPECIFIC to ferroptosis and distinguishes it from apoptosis and necroptosis?
10. A 55-year-old diabetic man undergoes coronary angioplasty for an acute STEMI. Following reperfusion of the ischemic myocardium, pathology shows focal hypercontraction bands, mitochondrial swelling, and calcium overload in previously ischemic myocytes despite restoration of flow. This is best described as:
11. In acetaminophen (paracetamol) hepatotoxicity, the toxic metabolite NAPQI causes hepatocyte death by which primary mechanism?
12. Pyroptosis is a form of programmed inflammatory cell death that differs from apoptosis. Which molecular mechanism is the DEFINING feature of pyroptosis?
13. Mitophagy is the selective autophagy of damaged mitochondria. In the context of cell injury, which protein complex acts as the primary sensor that tags damaged mitochondria for mitophagic degradation?
14. During reperfusion injury after ischemia, the rapid restoration of pH from acidic conditions triggers massive cell death. Which molecular event specifically occurs at the moment of pH normalization?
15. Pyroptosis is a form of programmed cell death distinct from apoptosis and necrosis. Which of the following best describes the molecular mechanism of gasdermin-D mediated pyroptosis?
16. During the execution phase of intrinsic apoptosis, BAX and BAK oligomerize in the mitochondrial outer membrane to form pores. This leads to release of cytochrome c into the cytoplasm where it binds APAF-1 and procaspase-9 to form the:
17. Ferroptosis is a newly characterized form of regulated cell death. Which of the following best describes the key molecular mechanism distinguishing ferroptosis from other forms of cell death?
18. A patient with acetaminophen overdose develops centrilobular hepatic necrosis. The key mechanism of hepatocyte injury is best described as:
19. During reperfusion injury following myocardial ischemia, which mechanism BEST explains the paradoxical exacerbation of cell death upon restoration of blood flow?
20. A pathologist notes 'coagulative necrosis' in infarcted kidney tissue. The cell outlines are preserved for days despite cell death. This is explained by which mechanism that is ABSENT in the CNS (explaining why brain infarcts show liquefactive necrosis)?
21. In ferroptosis (a recently characterized form of regulated cell death), cell death is driven primarily by which mechanism?
22. In ischemia-reperfusion injury, the paradoxical worsening of cell death upon restoration of blood flow is primarily attributed to which mechanism?
23. A pathologist observes cells with hyperchromatic shrunken nuclei, condensed cytoplasm, and cytoplasmic membrane-bound vesicles being phagocytosed by neighboring cells without inflammation. This pattern of cell death involves which molecular executor?
24. A patient with Wilson disease accumulates copper in hepatocytes leading to mitochondrial injury and oxidative stress. The primary mechanism of copper-induced free radical generation is:
25. Ferroptosis is a recently characterized form of regulated cell death. Which best describes its mechanism?
26. Pathologic calcification in dystrophic calcification occurs in dead or dying tissue despite normal serum calcium and phosphate. The initiating event at the cellular level is:
27. A researcher discovers that a novel drug induces gasdermin D (GSDMD) pore formation in macrophages after inflammasome activation, releasing IL-1beta and IL-18 along with cellular contents. This form of cell death is best classified as:
28. In ischemia-reperfusion injury, xanthine oxidase contributes to burst reactive oxygen species production during reoxygenation. The critical step converting xanthine dehydrogenase to xanthine oxidase during ischemia involves:
29. Electron microscopy of a cardiomyocyte undergoing early reversible ischemic injury shows amorphous densities in the mitochondrial matrix. What is the biochemical significance of these densities?
30. Ferroptosis is a recently characterized regulated cell death modality. Which of the following best describes the central biochemical mechanism of ferroptosis?
31. In ischemia-reperfusion injury, the burst of reactive oxygen species upon reperfusion is primarily generated by which mechanism?
32. During reperfusion injury following myocardial ischemia, mitochondria play a central role in the amplification of cell death. The mitochondrial permeability transition pore (MPTP) opens during reperfusion. Which molecular event specifically triggers MPTP opening during reperfusion but NOT during ischemia alone?
33. Ferroptosis has been recognized as a distinct form of regulated cell death distinct from apoptosis, necroptosis, and necrosis. Which set of biochemical features correctly distinguishes ferroptosis from classical intrinsic apoptosis?
34. A 60-year-old man with long-standing diabetes develops an area of dry gangrene in the foot. Histological sections of the ischemic tissue show preservation of cell outlines, nuclear pyknosis, and loss of cytoplasmic basophilia, without neutrophilic infiltration. Which statement correctly explains why coagulative necrosis (compared to liquefactive necrosis) lacks early neutrophilic infiltration in ischemic tissue?
35. During reperfusion injury following myocardial ischaemia, massive superoxide generation occurs from multiple sources. The enzyme responsible for the BURST of superoxide from neutrophils recruited to infarcted myocardium is:
36. Ferroptosis is a recently characterised form of regulated cell death distinct from apoptosis and necroptosis. Which of the following best defines the mechanism of ferroptosis?
37. Hepatocytes show ballooning degeneration and Mallory-Denk bodies (MDB) in a patient with alcoholic hepatitis. Which cytoskeletal proteins are the major constituents of MDB and what is the mechanism of their abnormal aggregation?
38. A cell undergoes regulated necrosis triggered by TNF-alpha binding when caspases are inhibited. This pathway activates RIPK3 which phosphorylates MLKL. What is the mechanism by which phospho-MLKL causes cell death?
39. A patient with ischemia-reperfusion injury to the kidney shows massive tubular cell death on reperfusion despite having had only modest injury during ischemia itself. Which iron-dependent mechanism of cell death, distinct from apoptosis and classical necrosis, is now recognised as a key driver of this injury?
40. A cell shows the following ultrastructural features: electron-dense mitochondria with amorphous densities, membrane blebbing, nuclear condensation, and intact plasma membrane. Which type of cell death is most consistent with these findings at early stages?
41. Ferroptosis is a recently characterized form of regulated cell death distinct from apoptosis and necroptosis. Which of the following BEST characterizes the mechanism and morphology of ferroptosis?
42. Ischemia-reperfusion injury paradoxically causes more cellular damage than sustained ischemia alone. Which sequence of events BEST explains why reperfusion augments injury?
43. During ischemia-reperfusion injury, which enzyme system is responsible for generating the burst of reactive oxygen species (ROS) that occurs specifically at reperfusion rather than during ischemia?
44. Pyroptosis, a form of programmed inflammatory cell death, is mechanistically distinguished from classical apoptosis by:
45. Ferroptosis, a non-apoptotic regulated cell death mechanism relevant to degenerative diseases and cancer cell death, is fundamentally driven by:
46. During reperfusion of ischemic myocardium, a burst of reactive oxygen species (ROS) is generated. The enzyme primarily responsible for this reperfusion-associated superoxide burst in cardiomyocytes, distinct from mitochondrial sources, is:
47. Necroptosis is a regulated form of necrotic cell death. Which molecular platform mediates this process?
48. A 45-year-old woman develops hepatocellular injury after acetaminophen overdose. Liver biopsy shows centrilobular necrosis with loss of nuclear detail and cytoplasmic swelling. The predominant cell death mechanism here is:
49. Ferroptosis is a regulated form of non-apoptotic cell death characterized by iron-dependent lipid peroxidation. Which enzyme normally prevents ferroptosis by reducing lipid hydroperoxides in biological membranes?
50. Pyroptosis is a pro-inflammatory form of programmed cell death executed by gasdermin family proteins. Which caspase is responsible for canonical inflammasome-activated pyroptosis in macrophages infected with intracellular bacteria?
51. In reperfusion injury following myocardial ischemia, the 'oxygen paradox' involves rapid reintroduction of oxygen to ischemic mitochondria. Which event during the first minutes of reperfusion is most responsible for cardiomyocyte death that was not yet irreversible during ischemia?
52. During ischemia-reperfusion injury, the burst of ROS on reoxygenation is primarily generated by:
53. Which form of cell death is characterized by membrane rupture, cellular swelling, and release of DAMPs (danger-associated molecular patterns) that trigger inflammation?
54. A cell undergoes pyroptosis. The molecular executor cleaving gasdermin D to form plasma membrane pores is:
55. A hepatocyte undergoing apoptosis is found to have cytochrome c released from mitochondria into the cytosol. Which downstream event is DIRECTLY triggered by cytosolic cytochrome c?
56. A patient receives an accidental overdose of acetaminophen. Hepatocytes in zone 3 (centrilobular) show coagulative necrosis. What is the primary mechanism of cell death in acetaminophen toxicity?
57. Metaplasia of the urothelium to squamous epithelium in the urinary bladder most commonly indicates which underlying etiology in endemic regions?
58. Reperfusion of ischaemic myocardium paradoxically causes additional cardiomyocyte death. Which of the following molecular events is the PRIMARY driver of reperfusion injury?
59. A 45-year-old man with alcoholic liver disease shows hepatocyte ballooning on biopsy with cytoplasmic accumulation of irregular eosinophilic material (Mallory-Denk bodies). This material consists primarily of which components?
60. In the intrinsic (mitochondrial) pathway of apoptosis, which event is the CRITICAL initiating step that commits the cell to death?
61. Reperfusion injury after myocardial infarction causes additional cell death largely through which primary mechanism?
62. Which form of cell death is characterized by cell swelling, membrane rupture, release of intracellular contents, and an inflammatory response — distinguishing it from programmed cell death?
63. Lipofuscin accumulates in aging or atrophic cells. It is BEST described as:
64. During myocardial ischaemia, the earliest ultrastructural change detectable within 15-30 minutes of onset is:
65. A patient with chronic pressure overload develops cardiac hypertrophy. This is an example of which type of cellular adaptation?
66. Ferroptosis is a distinct form of regulated cell death characterised by:
67. During ischemia-reperfusion injury, which enzyme activated by calcium influx converts xanthine dehydrogenase (XDH) to xanthine oxidase (XO), producing superoxide?
68. Which type of cell death is characterised by mitochondrial outer membrane permeabilisation (MOMP) releasing cytochrome c, activating caspase-9 via the apoptosome?
69. A cell under ER stress activates the unfolded protein response (UPR). Which branch of the UPR, if unresolved, triggers CHOP-mediated transcriptional activation of pro-apoptotic genes?
70. Reperfusion injury after myocardial ischemia is primarily mediated by which of the following mechanisms?
71. In the intrinsic (mitochondrial) pathway of apoptosis, cytochrome c released from mitochondria activates caspase-9 by forming a complex with which scaffold protein?
72. Which type of necrosis is characteristically seen in solid organs infected by Mycobacterium tuberculosis?
73. Reperfusion injury after myocardial ischemia is primarily mediated by:
74. In the intrinsic (mitochondrial) pathway of apoptosis, cytochrome c released from mitochondria activates caspase-9 by forming a complex with:
75. Pyroptosis, a recently characterised form of programmed cell death prominent in macrophages during bacterial infection, differs from classical apoptosis in that it:
76. In ischemia-reperfusion injury, the burst of reactive oxygen species during reperfusion causes greater damage than ischemia alone. The most important source of this ROS burst in cardiomyocytes at the moment of reperfusion is:
77. Pyknosis, karyorrhexis, and karyolysis are sequential nuclear changes seen in necrosis. The enzyme primarily responsible for karyolysis is:
78. A patient receiving long-term phenobarbital therapy has liver biopsy showing smooth endoplasmic reticulum (SER) hypertrophy. This represents which type of cellular adaptation?
79. Autophagy is upregulated in nutrient-starved cells. The key kinase that is INHIBITED during starvation to permit autophagy initiation is:
80. In the intrinsic (mitochondrial) pathway of apoptosis, cytochrome c release from mitochondria is triggered by pro-apoptotic BAX and BAK. The anti-apoptotic protein that normally prevents cytochrome c release by binding BAX is:
81. Fatty change (steatosis) of the liver in alcoholism is reversible. The predominant mechanism of lipid accumulation in hepatocytes with chronic alcohol use is:
82. During reperfusion injury after myocardial ischemia, excessive calcium entry into mitochondria opens which channel, triggering loss of inner mitochondrial membrane potential and cell death?
83. Liquefactive necrosis is the predominant pattern of necrosis in ischemic brain infarction because:
84. In the intrinsic (mitochondrial) pathway of apoptosis, which protein directly inhibits the release of cytochrome c by maintaining outer mitochondrial membrane integrity?
85. Which of the following distinguishes apoptosis from necrosis at the ultrastructural level?
86. In ischemia-reperfusion injury, which mechanism is primarily responsible for the paradoxical increase in cell death upon restoration of blood flow?
87. A 45-year-old chronic alcoholic develops a fatty liver (hepatic steatosis). Which is the earliest and most reversible change occurring in hepatocytes in this condition?
88. Metaplasia is best defined as:
89. Councilman bodies (acidophilic globules) seen in viral hepatitis represent:
90. In the intrinsic (mitochondrial) pathway of apoptosis, cytochrome c release from mitochondria is promoted by which pro-apoptotic BCL2 family member acting as a 'BH3-only' sensor?
91. Dystrophic calcification differs from metastatic calcification in that dystrophic calcification occurs:
92. Reperfusion injury after ischemia is mediated primarily by which mechanism?
93. In ischemic cell injury, which change represents the POINT OF IRREVERSIBILITY?
94. Which statement BEST distinguishes necroptosis from classical apoptosis?
95. The 'chain reaction' of lipid peroxidation is initiated by which free radical and propagated by which species?
96. Ferroptosis is a recently described form of regulated cell death. Which of the following best characterizes the molecular mechanism of ferroptosis?
97. A liver biopsy from an alcoholic patient shows swollen hepatocytes with cytoplasmic eosinophilic inclusions composed of aggregated intermediate filaments. These inclusions are called:
98. During ischemia-reperfusion injury, the xanthine oxidase pathway generates reactive oxygen species. Which substrate is most directly oxidized by xanthine oxidase to generate superoxide?
99. A pathologist notes that infarcted myocardium from 3 days ago shows nuclear pyknosis, karyorrhexis, and karyolysis with preserved cell outlines. This is an example of which type of necrosis?
100. The intrinsic (mitochondrial) pathway of apoptosis is initiated by which key event?
101. Reperfusion injury following restoration of blood flow to ischemic myocardium is primarily mediated by:
102. A pathologist examining a section of infarcted myocardium notes cells with eosinophilic, homogeneous cytoplasm, nuclear karyorrhexis, and preservation of the overall tissue architecture with ghost outlines. This pattern of cell death is called:
103. In the intrinsic (mitochondrial) pathway of apoptosis, cytochrome c released from mitochondria binds to which cytoplasmic adaptor protein to form the apoptosome?
104. Reperfusion injury after myocardial ischemia is predominantly mediated by which mechanism?
105. Which of the following features histologically and biochemically distinguishes apoptosis from necrosis?
106. In carbon tetrachloride (CCl4) hepatotoxicity, the toxic intermediate generated by the cytochrome P450 system that initiates lipid peroxidation is:
107. A 40-year-old man with alcoholic liver disease undergoes liver biopsy. Pathology shows eosinophilic hyaline intracytoplasmic inclusions in hepatocytes. These 'Mallory-Denk bodies' are composed primarily of which proteins?
108. Pyroptosis is a form of programmed cell death distinct from apoptosis and necroptosis. It is triggered by inflammasome activation. Which effector protein of pyroptosis directly executes membrane pore formation?
109. Metaplasia is a reversible adaptive change. Barrett's oesophagus represents columnar metaplasia of squamous epithelium due to acid reflux. Which type of columnar epithelium must be present histologically to define Barrett's oesophagus and carry cancer risk?
110. A cell undergoes apoptosis via the intrinsic (mitochondrial) pathway. The key initiating event is:
111. Coagulative necrosis is characteristically seen in infarcts of all organs EXCEPT the brain. The reason brain infarcts show liquefactive necrosis is:
112. Reperfusion injury following myocardial ischemia is mediated primarily by which mechanism?
113. Cellular adaptation characterized by a decrease in cell size due to reduced protein synthesis and increased autophagy in a starvation state is called:
114. Which of the following is the earliest ultrastructural change identifiable by electron microscopy in reversible cell injury?
115. Ferroptosis is a regulated cell death modality distinct from apoptosis and necrosis. Which molecular hallmark best distinguishes ferroptosis from classical apoptosis?
116. During reperfusion after myocardial ischemia, the most damaging reactive oxygen species generated primarily by xanthine oxidase and NADPH oxidase is:
117. Pyroptosis is a form of programmed cell death distinct from apoptosis. The key executioner protein that forms membrane pores in pyroptosis is:
118. In acetaminophen hepatotoxicity, the toxic metabolite responsible for cell injury is NAPQI (N-acetyl-p-benzoquinone imine). When glutathione stores are depleted, NAPQI causes cell death primarily by:
119. Which adaptation represents a response to increased functional demand rather than cell injury, and is the underlying mechanism for physiological cardiac hypertrophy in athletes?
120. Liquefactive necrosis (as opposed to coagulation necrosis) is the characteristic pattern in brain infarcts. Which feature of the brain tissue BEST explains this susceptibility to liquefactive necrosis?
121. A 2-year-old child with recurrent respiratory infections is found to have immotile bronchial cilia on electron microscopy showing absent dynein arms. This primary ciliary dyskinesia (Kartagener syndrome with situs inversus) is caused by mutation in which structural protein?
122. Ferroptosis is a recently characterized form of regulated cell death distinct from apoptosis and necroptosis. It is defined by:
123. Liquefactive necrosis, unlike coagulative necrosis, is the predominant pattern of necrosis in the brain because: