⚡ Causes of cellular injury
- Hypoxia — most common cause; ATP depletion via impaired oxidative phosphorylation.
- Ischemia (reduced arterial flow / venous outflow): atherosclerosis, thrombus, embolism.
- Cardiopulmonary failure & reduced O₂‑carrying capacity (anemia, CO poisoning).
- Pathogens — direct cytolysis, toxin production, or host inflammatory response.
- Immunologic dysfunction — hypersensitivity reactions, autoimmune attack.
- Genetic abnormalities — e.g., lysosomal storage disorders → toxic accumulations.
- Chemical injury — drugs, poisons (CN⁻, As, Hg), pollutants, alcohol, tobacco.
- Physical injury — trauma, burns, radiation, extreme temperatures, pressure.
- Nutritional imbalance
- Marasmus: total caloric deficit → muscle wasting.
- Kwashiorkor: protein deficit → edema, ascites.
- Excess: obesity, atherosclerosis.
- Vitamin deficits: A (night blindness, metaplasia), C (scurvy), D (rickets/osteomalacia), K (bleeding), B₁₂ (megaloblastic anemia, neuropathy), folate (neural tube defects), niacin (pellagra: diarrhoea, dermatitis, dementia).
- Vitamin K deficiency risk: prematurity, fat malabsorption (cystic fibrosis, celiac).
⚙️ Key mechanisms & targets
- Free radical injury — superoxide, hydroxyl radical, H₂O₂. Damage lipids, proteins, DNA.
- ATP depletion — disrupts Na⁺/K⁺ & Ca²⁺ pumps; ↑ anaerobic glycolysis → ↓ pH.
- Membrane damage — complement attack, loss of ion gradients, influx of Ca²⁺.
- Mitochondrial dysfunction — ↓ ATP, MPT pore formation, release of cytochrome c (apoptosis).
- Calcium overload — activates proteases, ATPases, phospholipases, endonucleases.
Superoxide→SOD→H₂O₂→catalase/GPx→H₂O
- Protective: vitamins A, C, E; superoxide dismutase; glutathione peroxidase; catalase.
🔄 Reversible → irreversible injury
reversible
- ↓ ATP → ↓ Na⁺ pump → cellular swelling (hydropic).
- Anaerobic glycolysis → glycogen depletion, lactic acid, ↓ pH.
- Ribosome detachment → ↓ protein synthesis.
- Membrane blebs, myelin figures.
irreversible
- Severe membrane damage → massive Ca²⁺ influx, enzyme leakage.
- Mitochondrial swelling + dense bodies; oxidative phosphorylation fails.
- Lysosomal rupture → autolysis.
- Nuclear changes: pyknosis, karyorrhexis, karyolysis.
- Loss of membrane integrity → serum markers: troponin (heart), AST/ALT (liver), amylase/lipase (pancreas), ALP/GGT (hepatobiliary).
🔥 Necrosis — patterns with inflammation
| type | features | common sites |
|---|---|---|
| Coagulative | protein denaturation; cell outline preserved, nucleus lost | heart, liver, kidney (not brain) |
| Liquefactive | hydrolytic enzymes → autolysis/heterolysis; pus (suppuration) | abscess, brain infarct, pancreas |
| Caseous | soft, cheese‑like; coagulation + liquefaction | granulomas (TB, fungi) |
| Fat | lipases → fatty acids + Ca²⁺ → chalky white (saponification) | acute pancreatitis |
| Fibrinoid | eosinophilic, homogeneous; immune / hypertensive injury | vessels (type II/III hypersensitivity) |
| Gangrenous | gross term; dry (coagulative) vs wet (liquefactive) | limbs, GI, gallbladder, testes |
- Necrotic debris may undergo dystrophic calcification.
🌀 Apoptosis — no inflammation
- Morphology: cell shrinkage, pyknosis, karyorrhexis, membrane blebbing → apoptotic bodies (phagocytosed).
- Stimuli: DNA damage (radiation), hormone/growth factor withdrawal (progesterone drop → endometrial apoptosis), Fas‑mediated death signals.
- Regulators: bcl‑2 (anti‑apoptotic, inhibits cytochrome c release); p53 (pro‑apoptotic when DNA repair fails).
- Execution: caspase cascade (cysteine‑aspartic proteases) → digest nuclear/cytoskeletal proteins.
- Physiologic examples: embryogenesis, thymic selection, menstrual cycle.
- Pathologic examples: viral hepatitis (Councilman bodies), graft‑vs‑host disease, cystic fibrosis.
- Syndactyly: failure of apoptosis in interdigital spaces.
- GVHD: donor T‑cells attack host → apoptosis in skin, mucosa, liver, GI.
📈 Cellular adaptation
- Atrophy — ↓ size/function. Causes: disuse, ischemia, denervation, malnutrition, aging. Lipofuscin granules, autophagosomes.
- Hypertrophy — ↑ size (protein synthesis). Physiologic: weightlifting, puberty, gravid uterus. Pathologic: cardiac hypertrophy in hypertension.
- Hyperplasia — ↑ cell number. Physiologic: compensatory (hepatectomy), hormonal (breast), lymphoid. Pathologic: endometrial, prostatic.
- Metaplasia — reversible change to another cell type. Example: bronchial squamous metaplasia (smoking), Barrett esophagus (columnar in esophagus). Mediated by stem cell differentiation.
- High‑altitude hypoxia → RBC hyperplasia (secondary polycythemia).
🧪 Accumulations & serum markers
- Lipids: triglycerides (fatty liver), cholesterol (atherosclerosis), complex lipids (sphingolipidoses).
- Proteins: Russell bodies (multiple myeloma), proximal tubule protein droplets.
- Glycogen: storage diseases (enzyme defects).
- Hyaline: pink/glassy (H&E). Examples: arteriolosclerosis, amyloid, hyaline membrane.
- Calcium
- Dystrophic: necrotic tissue (fat necrosis, psammoma bodies, atherosclerotic plaques).
- Metastatic: hypercalcemia (hyperparathyroidism, renal failure, sarcoidosis, vitamin D excess) → stomach, kidneys, lungs, vessels.
- Pigments: anthracotic (carbon), lipofuscin (wear‑and‑tear), melanin, hemosiderin (Prussian blue+), bilirubin (kernicterus).
| marker | injury |
|---|---|
| Troponin, CK‑MB, LDH | myocardial |
| AST, ALT | hepatic |
| Amylase, lipase | pancreatic |
| ALP, GGT | hepatobiliary |