Cell Injury & Cellular Adaptations – Ultra-Short Revision Notes
Cell Injury & Cellular Adaptations
Ultra-Short Revision Notes · NEET PG | INI-CET | FMGE
High-yield conceptsMechanismsExam one-linersCalcification
Dystrophic = damaged tissue; metastatic = normal tissue + mineral imbalance.
Dystrophic = damaged tissue; metastatic = normal tissue + mineral imbalance.
Autophagy
Cellular recycling through lysosomal degradation.
Cellular recycling through lysosomal degradation.
ROS injury
Lipid peroxidation, protein oxidation, DNA damage.
Lipid peroxidation, protein oxidation, DNA damage.
Cellular aging
Telomere attrition, DNA damage, oxidative stress, stem-cell exhaustion.
Telomere attrition, DNA damage, oxidative stress, stem-cell exhaustion.
Ferroptosis
Iron-dependent cell death driven by lipid peroxidation.
Iron-dependent cell death driven by lipid peroxidation.
Practice bank
100 original MCQs with answer explanations.
100 original MCQs with answer explanations.
11. Pathological Calcification
Abnormal deposition of calcium salts in tissues.
Dystrophic calcification
- Occurs in dead or damaged tissues.
- Serum calcium is generally normal.
- Examples: atherosclerotic plaques, damaged heart valves, caseous TB lesions, fat necrosis and psammoma bodies.
Psammoma bodies: concentric laminated calcifications; seen in papillary thyroid carcinoma, serous papillary ovarian carcinoma, meningioma and mesothelioma.
Metastatic calcification
- Occurs in otherwise normal tissues due to disturbed calcium-phosphate metabolism.
- Causes: hyperparathyroidism, bone destruction, vitamin D-related disorders and chronic renal failure with secondary hyperparathyroidism.
- Sites: kidneys (nephrocalcinosis), lungs, gastric mucosa, systemic arteries and pulmonary veins.
| Feature | Dystrophic | Metastatic |
|---|---|---|
| Tissue | Damaged / necrotic | Usually normal |
| Serum calcium | Usually normal | Often increased or mineral balance disturbed |
| Examples | Atherosclerosis, damaged valves | Hyperparathyroidism, renal failure |
Calcium stains
- Von Kossa: black; detects phosphate/carbonate anions associated with calcium salts, not calcium directly.
- Alizarin Red S: orange-red.
12. Autophagy
Cellular process in which damaged organelles and cellular components are degraded by lysosomes.
| Type | Mechanism / key fact |
|---|---|
| Macroautophagy | Double-membrane autophagosome → fusion with lysosome → autolysosome. |
| Microautophagy | Direct lysosomal membrane invagination / engulfment. |
| Chaperone-mediated autophagy (CMA) | HSC70 recognizes KFERQ motif; LAMP-2A mediates lysosomal uptake. |
- Mitophagy: selective removal of damaged mitochondria; PINK1-Parkin pathway.
- Beclin-1: autophagy initiation.
- LC3: autophagosome membrane marker.
- mTOR: inhibits autophagy.
- AMPK: promotes autophagy.
Starvation → mTOR inhibition / AMPK activation → increased autophagy
13. Free Radical Injury
Reactive oxygen species (ROS) are reactive molecules capable of damaging cellular components.
Superoxide
O₂•−
O₂•−
Hydrogen peroxide
H₂O₂ (ROS, not a free radical)
H₂O₂ (ROS, not a free radical)
Hydroxyl radical
•OH; highly reactive
•OH; highly reactive
Sources: mitochondrial electron transport chain, inflammation, radiation, chemical agents and reperfusion injury.
Mechanisms of injury
- Lipid peroxidation → membrane damage.
- Protein oxidation → enzyme dysfunction.
- DNA damage → mutations and cell death.
| Antioxidant | Function |
|---|---|
| SOD | Superoxide → H₂O₂ + O₂ |
| Catalase | H₂O₂ → H₂O + O₂ |
| Glutathione peroxidase | Removes H₂O₂ and lipid peroxides using glutathione |
| Vitamin E | Lipid-soluble membrane antioxidant |
| Vitamin C | Water-soluble antioxidant |
| Vitamin A | Has antioxidant properties |
2 O₂•− + 2 H⁺ —SOD→ H₂O₂ + O₂
2 H₂O₂ —Catalase→ 2 H₂O + O₂
2 H₂O₂ —Catalase→ 2 H₂O + O₂
Fenton reaction: Fe²⁺ + H₂O₂ → Fe³⁺ + OH⁻ + •OH. It generates the highly reactive hydroxyl radical.
Ischemia-reperfusion injury
- Reintroduction of oxygen after ischemia can generate ROS.
- Additional contributors: calcium overload, inflammatory response and complement activation.
- Reperfusion may cause additional injury beyond the initial ischemic damage.
14. Cellular Aging
- Telomere shortening: repeated cell division shortens telomeres; p53/p21 pathways promote senescence.
- DNA damage: cumulative damage and reduced repair capacity.
- Oxidative stress: ROS-mediated cellular injury.
- Loss of proteostasis: accumulation of misfolded proteins.
- Stem-cell exhaustion: reduced regenerative capacity.
Telomerase adds repetitive DNA sequences to telomeres; active in germ cells and many stem cells and commonly reactivated in cancer cells.
| Syndrome | Defect |
|---|---|
| Werner syndrome | WRN helicase |
| Hutchinson-Gilford progeria | LMNA mutation |
| Ataxia-telangiectasia | ATM mutation |
| Cockayne syndrome | Transcription-coupled DNA repair |
15. Ferroptosis
Regulated iron-dependent cell death caused by excessive lipid peroxidation.
Increased iron + lipid ROS + reduced glutathione / GPX4 activity → lipid membrane damage → ferroptosis
| Molecule | Role |
|---|---|
| Iron | Promotes lipid peroxidation |
| GPX4 | Major inhibitor; detoxifies lipid peroxides |
| Glutathione | Required for GPX4 function |
| SLC7A11 | Cystine uptake via system Xc− |
| ACSL4 | Promotes PUFA incorporation into membrane phospholipids |
Exam one-liners: Erastin inhibits system Xc−; RSL3 inhibits GPX4; Ferrostatin-1 inhibits ferroptosis.
16. High-Yield One-Liners
| Concept | Answer |
|---|---|
| Most common reversible cell injury | Cellular swelling |
| Hydropic change | Na⁺/K⁺ ATPase failure |
| Fatty change commonly occurs in | Liver |
| Nuclear changes in necrosis | Pyknosis → Karyorrhexis → Karyolysis |
| Solid organ infarction | Coagulative necrosis |
| Brain infarction | Liquefactive necrosis |
| TB | Caseous necrosis |
| Acute pancreatitis | Fat necrosis |
| Apoptosis executioner | Caspase-3 |
| Intrinsic / extrinsic initiators | Caspase-9 / Caspase-8 |
| Apoptosome | Cytochrome c + Apaf-1 |
| Anti-apoptotic protein | BCL-2 |
| Pro-apoptotic proteins | BAX, BAK |
| Apoptosis assay | TUNEL |
| Eat-me signal | Phosphatidylserine |
| Necroptosis | RIPK1, RIPK3, MLKL |
| Pyroptosis | Caspase-1, Gasdermin D |
| Brown atrophy | Lipofuscin |
| Iron pigment / stain | Hemosiderin / Prussian blue |
| Melanin stain | Fontana-Masson |
| Glycogen stain | PAS |
| Calcium stains | Von Kossa / Alizarin Red S |
| Autophagy marker | LC3 |
| Mitophagy | PINK1-Parkin |
| Autophagy inhibitor | mTOR |
| Free radical scavenger enzyme | SOD |
| Highly reactive ROS | Hydroxyl radical |
| Progeria gene | LMNA |
17. Last-Minute Differentiation
| Concept | Remember |
|---|---|
| Necrosis vs apoptosis | Membrane rupture / inflammation vs controlled cell death with little inflammation |
| Coagulative vs liquefactive | Architecture preserved vs digested/lost |
| Hypertrophy vs hyperplasia | Cell size vs cell number |
| Metaplasia vs dysplasia | Change in mature cell type vs disordered growth/atypia |
| Dystrophic vs metastatic calcification | Damaged tissue vs usually normal tissue with mineral imbalance |
| Lipofuscin vs hemosiderin | Wear-and-tear pigment vs iron-storage pigment |
| Necroptosis vs pyroptosis | RIPK3/MLKL vs inflammasome/caspase-1/gasdermin D |
| Autophagy vs apoptosis | Cellular component recycling vs programmed cell death |
Revision strategy: Revisit necrosis patterns, caspases, calcification, ROS enzymes, autophagy markers and regulated cell-death pathways. Practice the MCQs after revising each section.