Cell Injury, Adaptation and Necrosis
🟢 Lite — Quick Review (1h–1d)
Cell Injury & Necrosis — High-Yield Facts for NEET PG
Causes of Cell Injury:
- Hypoxia (most common cause) — reduced O₂ delivery
- Ischemia — reduced blood flow (vs. hypoxia = low O₂)
- Physical agents — trauma, burns, radiation
- Chemicals — poisons, drugs, alcohol
- Infectious agents — bacteria, viruses, fungi
- Immunologic reactions — autoimmune diseases
- Nutritional deficiencies — protein, vitamin deficiencies
- Genetic defects — enzyme defects, chromosomal abnormalities
Reversible vs Irreversible Injury:
| Feature | Reversible | Irreversible |
|---|---|---|
| Cell swelling | + | + |
| Membrane blebbing | + | +++ |
| Nuclear chromatin | Margination | Pyknosis → Karyorrhexis → Karyolysis |
| Mitochondrial | Swelling | Dense bodies, calcium accumulation |
| ATP | ↓ | Markedly ↓ |
Key Point: Cell death is irreversible when calcium shifts from ER/mitochondria into cytoplasm and lysosomal enzyme activation occurs.
🟡 Standard — Regular Study (2d–2mo)
Cell Adaptation — Types:
Atrophy: Decrease in cell size due to ↓ in function/workload
- Causes: disuse, denervation, loss of hormonal stimulation, poor nutrition, aging
- Example: Small testes in Kallmann syndrome (↓ GnRH)
Hypertrophy: Increase in cell size due to ↑ workload/functional demand
- Examples: Left ventricular hypertrophy (HTN, aortic stenosis), skeletal muscle hypertrophy (exercise)
Hyperplasia: Increase in cell number due to ↑ workload/hormonal stimulation
- Examples: Thyroid hyperplasia (Graves’ disease), endometrial hyperplasia (estrogen excess), prostatic hyperplasia (BPH)
Metaplasia: Replacement of one differentiated cell type with another
- Most common: Squamous metaplasia of respiratory epithelium (smoking) → ciliated columnar → stratified squamous
- Reversible upon removal of stimulus
- Precursor to dysplasia and carcinoma
Dysplasia: Abnormal cell growth with loss of uniformity, architectural orientation, and nuclear features
- Pre-malignant condition (not a true neoplasm)
- Example: Cervical intraepithelial neoplasia (CIN)
Intracellular Accumulations (Four Types):
-
Fatty change (Steatosis): Accumulation of triglycerides
- Causes: Alcohol (most common), diabetes, obesity, malnutrition, toxins (CCl₄)
- Liver most affected → “fatty liver”
- Zone 3 hepatocytes most vulnerable
-
Cholesterol/Atherosclerosis: Foam cells in intima of arteries
-
Proteins: Russell bodies (immunoglobulin in plasma cells), Mallory bodies (keratin intermediate filaments in alcoholic liver disease)
-
Pigments: Lipofuscin (“wear and tear” pigment — aging), hemosiderin (iron overload), melanin
Glycogen: Seen in diabetes mellitus (renal tubular cells), hepatocytes
Necrosis — Types:
| Type | Mechanism | Features | Examples |
|---|---|---|---|
| Coagulative | Denaturation of proteins | Cell outlines preserved, nuclei lost | MI, most organs (except brain) |
| Liquefactive | Enzymatic digestion | Liquid consistency, pseudopustules | Brain abscess, Staphylococcus |
| Caseous | No enzymatic digestion | Cheesy, granular; no cell outlines | Tuberculosis |
| Fat necrosis | Lipase action | Chalky white (saponification) | Acute pancreatitis, breast tissue trauma |
| Fibrinoid | Immune complex deposition | Pink “fibrin-like” material | Vasculitis, rheumatic fever |
| Gangrenous | Coagulative + putrefaction | Black/Green discoloration | Dry gangrene (limbs), wet (gas gangrene) |
Apoptosis vs Necrosis:
| Feature | Apoptosis | Necrosis |
|---|---|---|
| Nature | Programmed, physiological | Uncontrolled, pathological |
| Cell size | Shrinks | Swells |
| Nucleus | Fragmentation (karyorrhexis) | Liquefies (karyolysis) |
| Inflammation | None | Prominent |
| Energy | ATP required | No ATP needed |
| Example | Embryogenesis, T-cell selection | MI, trauma, infection |
Caspases — executioner enzymes of apoptosis
- Intrinsic pathway: Mitochondrial (cytochrome c release)
- Extrinsic pathway: Death receptors (Fas, TNF)
Apoptosis = “Cell Suicide” | Necrosis = “Cell Murder”
🔴 Extended — Deep Study (3mo+)
Free Radical Injury (Oxidative Stress):
- Reactive Oxygen Species (ROS): O₂⁻ (superoxide), H₂O₂, OH• (hydroxyl radical)
- Reactive Nitrogen Species (RNS): NO, ONOO⁻ (peroxynitrite)
- Sources: Mitochondria (normal metabolism), xenobiotics, radiation, inflammation
- Defense mechanisms: SOD (superoxide dismutase), glutathione, catalase, vitamin E/C
- Damage: Lipid peroxidation → membrane damage, protein oxidation, DNA damage
Ischemia-Reperfusion Injury:
- Paradoxical worsening after restoration of blood flow
- Mechanisms: ROS generation, complement activation, neutrophil infiltration
- Clinical: Seen in MI treatment (thrombolysis/PCI), stroke, organ transplantation
Chemical/Toxin Injury:
- CCl₄ → Trichloromethyl free radical → lipid peroxidation → fatty liver → cirrhosis
- Cyanide: Blocks cytochrome oxidase → histotoxic hypoxia
- Carbon monoxide: Binds Hb → ↓ O₂ carrying capacity
- Methanol → Formaldehyde → optic nerve damage, CNS depression
Mechanisms of Cell Death:
- ATP depletion — reversible → irreversible
- Mitochondrial dysfunction — MPT pore opening → cytochrome c release
- Calcium influx — activates degradative enzymes (phospholipases, proteases, endonucleases)
- Membrane damage — phospholipid degradation
- DNA damage — activation of poly-ADP-ribose polymerase (PARP)
Necrosis Cascade:
Ischemia → ATP depletion → Na⁺/K⁺ ATPase failure → Cell swelling → Membrane blebbing → Calcium influx → Enzyme activation → Nuclear changes (pyknosis → karyorrhexis → karyolysis) → Cell dissolution
Gangrene:
- Dry gangrene: Coagulative necrosis + desiccation; occurs in arteries (not veins); common in DM, atherosclerosis
- Wet gangrene: Superimposed infection on coagulative necrosis; more rapid; foul odor
- Gas gangrene: Clostridium perfringens infection; crepitus on palpation; emergency
Key NEET-PG Clinical Pearls:
- Methanol poisoning → optic atrophy, CNS damage; treat with ethanol (competitive substrate for alcohol dehydrogenase)
- CCl₄ → centrilobular necrosis; classic teaching point for free radical injury
- Fat necrosis of breast → calcifications on mammography (post-traumatic)
- Russell bodies = stacked immunoglobulin in ER of plasma cells (chronic inflammation, plasma cell neoplasms)
- Mallory-Denk bodies = aggregates of keratin filaments in alcoholic hepatitis
- Neurodegeneration = excitotoxicity (glutamate → ↑ intracellular Ca²⁺ → oxidative stress)
Aging and Cell Injury:
- Telomere shortening → replicative senescence
- Accumulation of lipofuscin (“brown atrophy” of heart)
- Mitochondrial DNA mutations (ROS damage)
- Protein misfolding → ER stress → unfolded protein response
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