CELL INJURY AND CELL ADAPTATIONS - pathology-1 notes - Bsc. Nursing 3rd semester

CELL INJURY AND CELL ADAPTATIONS - pathology-1 notes - Bsc. Nursing 3rd semester

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  PATHOLOGY – I (ForB.Sc. Nursing 3rd Semester) CELL INJURY Etiology and Pathogenesis of Reversible and Irreversible Cell Injury Definition of Cell Injury Cell injury occurs when a cell is unable to maintain normal structure and function due to harmful stimuli or stress. If the damage is mild and temporary, the cell recovers (reversible injury). If the damage is severe and permanent, the cell dies (irreversible injury). Etiology (Causes) of Cell Injury The causes of cell injury are: 1. Hypoxia and Ischemia • Hypoxia = deficiency of oxygen. • Ischemia = reduced blood supply to tissues. Causes: • Anemia • Heart failure • Shock • Respiratory diseases 2. Physical Agents Includes: • Trauma or injury • Heat and cold • Radiation • Electric shock • Pressure changes These directly damage cells and tissues. 3. Chemical Agents and Drugs Examples: • Acids and alkalis • Poisons • Alcohol • Tobacco • Certain medicines • Environmental pollutants These interfere with normal cellular metabolism.
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  4. Infectious Agents •Bacteria • Viruses • Fungi • Parasites They destroy cells either directly or through toxins. 5. Immunological Reactions Abnormal immune reactions may injure cells: • Allergy • Autoimmune diseases • Chronic inflammation 6. Genetic Defects Inherited abnormalities may lead to: • Enzyme deficiencies • Metabolic disorders • Structural defects Example: • Sickle cell anemia 7. Nutritional Imbalance • Protein deficiency • Vitamin deficiency • Obesity • Starvation These affect normal cell growth and function. 8. Aging With aging: • Cellular repair decreases • Metabolism slows • Cells become more vulnerable to injury Types of Cell Injury 1. Reversible Cell Injury 2. Irreversible Cell Injury
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  Pathogenesis of CellInjury Pathogenesis means the mechanism by which cell injury develops. The main steps are: Exposure to injurious agent ↓ Cellular stress and biochemical changes ↓ Structural and functional abnormalities ↓ Adaptation, reversible injury, or irreversible injury 1. Reversible Cell Injury Definition A mild or temporary injury in which the cell can recover completely after removal of the harmful stimulus. Causes • Mild hypoxia • Early infection • Temporary ischemia • Mild chemical injury Pathogenesis of Reversible Cell Injury Decrease in ATP Production ↓ Failure of Sodium-Potassium Pump ↓ Cellular Swelling ↓ Anaerobic Glycolysis Increases ↓ Ribosome Detachment Morphological Changes in Reversible Injury • Organ becomes swollen and pale • Cell swelling • Fatty change • Vacuolation • Blebbing of plasma membrane
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  Outcome If the causeis removed: • Cell returns to normal structure and function. 2. Irreversible Cell Injury Definition A severe injury in which the cell cannot recover and ultimately dies. Cell death occurs by: • Necrosis • Apoptosis Causes • Severe ischemia • Persistent hypoxia • Severe infections • Toxic chemicals • Extensive trauma Pathogenesis of Irreversible Cell Injury Severe ATP Depletion ↓ Mitochondrial Damage ↓ Massive Calcium Influx ↓ Membrane Damage ↓ Lysosomal Rupture ↓ Nuclear Changes Morphological Changes in Irreversible Injury • Severe membrane damage • Cell rupture • Mitochondrial swelling • Nuclear disappearance • Inflammation around dead cells
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  Differences Between Reversibleand Irreversible Cell Injury Feature Reversible Injury Irreversible Injury Severity Mild Severe Recovery Possible Not possible ATP depletion Mild Severe Membrane damage Mild Permanent Nuclear changes Absent Present Cell fate Survival Cell death Necrosis Definition Necrosis is the pathological death of cells or tissues in a living body due to irreversible injury. It is usually associated with inflammation and enzymatic digestion of cells. Etiology (Causes) of Necrosis 1. Ischemia and Hypoxia • Most common cause • Reduced blood supply leads to oxygen deprivation Examples: • Myocardial infarction • Gangrene 2. Physical Agents • Trauma • Burns • Frostbite • Radiation • Electric shock These directly damage tissues. 3. Chemical Agents and Drugs Examples: • Strong acids and alkalis • Heavy metals • Poisons • Alcohol • Toxic drugs They destroy cell membranes and enzymes.
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  4. Infectious Agents •Bacteria • Viruses • Fungi • Parasites Microorganisms and their toxins cause tissue destruction. 5. Immunological Injury Abnormal immune reactions may damage tissues: • Autoimmune diseases • Hypersensitivity reactions 6. Enzymatic Destruction Digestive enzymes may destroy tissues. Example: • Pancreatitis causing fat necrosis Pathogenesis of Necrosis Necrosis develops through a sequence of irreversible cellular changes. Severe Cell Injury ↓ Loss of Membrane Integrity ↓ Calcium Influx ↓ Lysosomal Enzyme Release ↓ Nuclear Changes ↓ Inflammatory Reaction Morphological Features of Necrosis Cytoplasmic Changes • Increased eosinophilia • Glassy appearance • Vacuolation
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  Nuclear Changes • Pyknosis •Karyorrhexis • Karyolysis Tissue Changes • Loss of tissue architecture • Cell fragmentation • Inflammation Types of Necrosis 1. Coagulative Necrosis Definition Type of necrosis where tissue architecture is preserved for some days. Cause • Ischemia or infarction Common Sites • Heart • Kidney • Spleen Features • Firm tissue • Cells appear ghost-like • Protein denaturation predominates 2. Liquefactive Necrosis Definition Necrotic tissue becomes soft and liquid due to enzymatic digestion. Causes • Bacterial infections • Fungal infections • Brain infarction Features • Formation of pus • Tissue liquefaction 3. Caseous Necrosis Definition Soft, cheese-like necrosis commonly seen in tuberculosis. Cause • Tuberculosis • Some fungal infections
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  Features • White cheesyappearance • Combination of coagulative and liquefactive necrosis Microscopy • Granuloma formation • Loss of tissue architecture 4. Fat Necrosis Definition Necrosis of fatty tissue caused by lipase enzyme action. Causes • Acute pancreatitis • Trauma to fat tissue Features • Chalky white deposits • Fat saponification 5. Fibrinoid Necrosis Definition Necrosis involving blood vessel walls with deposition of immune complexes. Causes • Vasculitis • Hypertension • Autoimmune diseases Features • Bright pink fibrin-like appearance under microscope 6. Gangrenous Necrosis Definition Necrosis of limbs or tissues due to severe ischemia. Types Dry Gangrene • Due to ischemia • Tissue becomes dry and black Wet Gangrene • Bacterial infection added • Tissue becomes swollen and foul-smelling Gas Gangrene • Caused by Clostridium bacteria • Gas bubbles present in tissues
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  Differences Between Necrosisand Apoptosis Feature Necrosis Apoptosis Nature Pathological Physiological/pathological Cell size Swelling Shrinkage Membrane Ruptured Intact Inflammation Present Absent Cell contents Leak out Remain enclosed Area affected Group of cells Single cells Outcome of Necrosis • Inflammation • Healing by fibrosis • Calcification • Scar formation • Organ dysfunction Gangrene Definition Gangrene is a type of tissue necrosis that occurs due to loss of blood supply, often associated with bacterial infection. The affected tissue becomes dead, discolored, and may become infected. Etiology (Causes) of Gangrene 1. Ischemia (Loss of Blood Supply) Most common cause. Occurs due to: • Atherosclerosis • Diabetes mellitus • Thrombosis • Embolism • Peripheral vascular disease Result: • Oxygen deprivation leading to tissue death 2. Infection Certain bacteria invade dead tissues and worsen tissue destruction. Common organism: • Clostridium perfringens (gas gangrene)
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  3. Trauma andInjury • Crush injuries • Burns • Frostbite • Severe wounds These damage blood vessels and reduce circulation. 4. Diabetes Mellitus Diabetes causes: • Poor blood circulation • Neuropathy • Increased risk of infection Commonly affects feet. 5. Smoking Smoking damages blood vessels and reduces blood flow. 6. Immunocompromised Conditions Patients with weak immunity are more prone to infections leading to gangrene. Pathogenesis of Gangrene Gangrene develops through the following steps: Reduced Blood Supply ↓ Cell Injury and Necrosis ↓ Bacterial Infection ↓ Inflammation and Tissue Breakdown ↓ Spread of Tissue Death Types of Gangrene 1. Dry Gangrene Definition Gangrene caused mainly by ischemia without infection. Causes • Peripheral arterial disease • Diabetes • Atherosclerosis
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  Common Sites • Toes •Feet • Fingers Features • Tissue becomes dry, shriveled, and black • Clear line of demarcation present • Slow progression • Coagulative necrosis • Minimal bacterial infection 2. Wet Gangrene Definition Gangrene associated with severe bacterial infection and tissue liquefaction. Causes • Sudden loss of blood supply • Intestinal obstruction • Severe infections Common Sites • Intestine • Mouth • Lungs • Limbs Gross Features • Tissue swollen and soft • Foul-smelling • Black or greenish color • No clear demarcation • Liquefactive necrosis • Numerous bacteria and inflammatory cells 3. Gas Gangrene Definition A rapidly spreading gangrene caused by gas-forming bacteria. Causative Organism • Clostridium perfringens Causes • Deep contaminated wounds • Surgical wounds • Trauma
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  Pathogenesis Bacteria produce: • Exotoxins •Gas in tissues This causes: • Muscle destruction • Toxin absorption • Severe toxemia Features • Swelling • Severe pain • Crepitus (crackling sound due to gas) • Foul-smelling discharge • Muscle necrosis • Gas bubbles • Numerous bacteria Clinical Features of Gangrene • Pain • Swelling • Discoloration • Loss of sensation • Foul smell • Fever (in infected gangrene) Complications of Gangrene • Septicemia • Shock • Organ failure • Amputation • Death
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  CELLULAR ADAPTATIONS Definition Cellular adaptationrefers to reversible structural and functional changes in cells in response to physiological or pathological stress. These changes help the cell survive under altered conditions. Types of Cellular Adaptations 1. Atrophy 2. Hypertrophy 3. Hyperplasia 4. Metaplasia 5. Dysplasia 6. Apoptosis 1. Atrophy Definition Atrophy is a decrease in the size of cells, resulting in reduction in the size of an organ or tissue. Causes (Etiology) • Aging • Loss of hormonal stimulation • Disuse • Loss of nerve supply • Reduced blood supply • Malnutrition • Pressure Pathogenesis Reduced workload / nutrition / blood supply ↓ Decreased metabolic activity ↓ Decreased protein synthesis + Increased protein degradation ↓ Autophagy of organelles ↓ Cell shrinkage ↓ Atrophy
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  Morphological Features • Organbecomes small and shrunken • Cells contain fewer organelles • Increased autophagic vacuoles 2. Hypertrophy Definition Hypertrophy is an increase in the size of cells resulting in enlargement of an organ. Causes • Enlargement of skeletal muscles in exercise • Uterine enlargement during pregnancy • Hypertension causing enlargement of heart Pathogenesis Increased workload / hormonal stimulation ↓ Activation of signaling pathways ↓ Increased gene expression ↓ Increased protein synthesis ↓ Increase in cell size and organelles ↓ Hypertrophy Morphological Features • Organ becomes enlarged • Cells show increased cytoplasm and organelles • Increased cell size • Enlarged nucleus
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  3. Hyperplasia Definition Hyperplasia isan increase in the number of cells resulting in enlargement of tissue or organ. Types Physiological Hyperplasia • Hormonal hyperplasia • Compensatory hyperplasia Pathological Hyperplasia • Excess hormonal stimulation • Viral infections Pathogenesis Hormonal / growth factor stimulation ↓ Activation of cell cycle ↓ DNA synthesis and mitosis ↓ Increase in number of cells ↓ Enlargement of tissue or organ ↓ Hyperplasia Morphological Features • Enlarged organ • Increased number of normal cells • Increased mitotic figures • Preserved tissue architecture Difference Between Hypertrophy and Hyperplasia Feature Hypertrophy Hyperplasia Change Increase in cell size Increase in cell number Mechanism Increased protein synthesis Increased cell division Occurs in Permanent cells Labile/stable cells
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  4. Metaplasia Definition Metaplasia isa reversible change in which one adult cell type is replaced by another adult cell type. Causes • Chronic irritation • Smoking • Vitamin A deficiency • Chronic inflammation Pathogenesis Chronic irritation / inflammation ↓ Repeated cellular injury ↓ Stem cell reprogramming ↓ Replacement of one mature cell type by another ↓ Metaplasia ↓ Persistent stress may lead to dysplasia Types Epithelial Metaplasia • Columnar to squamous • Squamous to columnar Mesenchymal Metaplasia • Bone or cartilage formation in soft tissue Features ▪ Replacement of one mature cell type by another ▪ Altered epithelial appearance ▪ Loss of normal tissue characteristics
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  5. Dysplasia Definition Dysplasia isabnormal growth and maturation of cells with loss of cellular uniformity and architectural orientation. Causes • Chronic irritation • Persistent infection • Precancerous changes Common Sites • Cervix • Respiratory tract Pathogenesis Chronic irritation / infection ↓ Repeated cellular injury ↓ DNA damage and mutations ↓ Abnormal cell proliferation ↓ Loss of maturation and organization ↓ Dysplasia ↓ Possible progression to carcinoma Morphological Features • Pleomorphism • Hyperchromatic nuclei • Increased mitosis • Loss of arrangement • Increased nuclear-cytoplasmic ratio
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  6. Apoptosis Definition Apoptosis isprogrammed cell death in which cells die in a controlled manner without causing inflammation. Causes • Embryonic development • Hormone-dependent tissue involution • Elimination of damaged cells • DNA damage • Viral infections • Atrophy after duct obstruction Pathogenesis of Apoptosis Two major pathways: 1. Intrinsic (Mitochondrial) Pathway • Triggered by DNA damage • Cytochrome c released from mitochondria • Activation of caspases DNA damage / Growth factor withdrawal / Oxidative stress ↓ Mitochondrial damage ↓ Cytochrome c release ↓ Apoptosome formation ↓ Caspase-9 activation ↓ Executioner caspases (3, 6, 7) ↓ Apoptosis
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  2. Extrinsic (DeathReceptor) Pathway • Triggered by Fas ligand/TNF receptors • Activation of caspases Fas ligand / TNF ↓ Death receptor activation ↓ Caspase-8 activation ↓ Executioner caspases (3, 6, 7) ↓ Apoptosis Morphological Features • Cell shrinkage • Chromatin condensation • Formation of apoptotic bodies • No inflammation