CELLULAR RESPONSE

TO STRESS & TOXIC
INSULTS: ADAPTATION,
INJURY & DEATH
Dr. NI PUTU SRIWIDYANI, Sp.PA

TOPICS







Adaptation
Causes of cell injury
Morphologic alteration in cell injury
Mechanisms of cell injury
Apoptosis
Intracellular accumulation
Pathologic calcification
Cellular aging

OVERVIEW

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number. phenotype. metabolic activity or function of cells in response to changes in their environment     Hypertrophy Atrophy Hyperplasia Metaplasia .Adaptation of Cellular Growth & Differentiation  Reversible changes in size.

Hypertrophy    Increase in size of cells Due to the synthesis of more structural component of cells Physiologic or pathologic .

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Hyperplasia    Increase in the number of cells in organ or tissue Dividing cells Physiologic hyperplasia    Hormonal hyperplasia Compensatory hyperplasia Pathologic hyperplasia   Endometrial hyperplasia Prostate hyperplasia .

Atrophy   Reduced size of an organ or tissue resulting from a decrease cell size & number Physiologic atrophy    Embryonic structure Post partum Pathologic atrophy   Local Generalized .

 Causes of atrophy       Decreased workload (disuse atrophy) Denervation atrophy Diminished blood suply Inadequate nutrition Loss of endocrine stimulation Pressure .

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Metaplasia   One differentiated cell type (epithelial or mesenchymal) is replaced by another cell type Epithelial metaplasia    Squamous metaplasia Columnar metaplasia Conective tissue metaplasia  Myositis ossificans .

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CELL INJURY .

Causes of cell injury






Oxygen deprivation
Physical agents
Chemical agents & drugs
Infectious agents
Immunologic reactions
Genetic derangements
Nutritional imbalances

Morphologic Alteration in Cell
Injury

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NECROSIS   Result of denaturation of intracellular proteins & enzymatic digestion Morphology:   Increased eosinophilia Nuclear changes: karyolysis. pyknosis. karyorhexis .

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 Patterns of tissue necrosis       Coagulative necrosis Liquefactive necrosis Caseous necrosis Fat necrosis Gangrenous necrosis Fibrinoid necrosis .

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Mechanisms of Cell Injury       Depletion to DNA & Protein of ATP Mitochondrial damage Influx of calcium & loss of calcium homeostasis Accumulation of oxygen-derived free radicals (Oxidative stress) Defect in membrane permeability Damage .

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APOPTOSIS    A pathway of cell death that is induced by a tightly regulated suicide program Activate enzyme Apoptotic bodies “Falling off” .

 Apoptosis in Physiologic Situations      During embryogenesis Involution of hormone-dependent tissue Cell loss in proliferating cell populations Elimination of potentially harmful self-reactive lymphocytes Death of neutrophil and lymphocyte at the end of immune response .

 Apoptosis in Pathologic Condtions     DNA damage Accumulation of misfolded protein Certain infection Pathologic atrophy in parenchymal organs after duct obstruction .

Morphology Changes in Apoptosis  Morphology     Cell shrinkage Chromatin condensation Apoptotic bodies Phagocytosis by macrophages .

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Mechanisms of Apoptosis   Intrinsic (mitochondrial) pathway Extrinsic (death receptor-initiated) pathway .

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INTRACELLULAR DEPOSITIONS      Mechanisms Lipid  Fatty change  Cholesterol (atherosclerosis) Protein  In kidney tubules  Ig in plasma cells Glycogen  Glycogen storage disease Pigment    Carbon Lipofuchsin Iron .

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PATHOLOGIC CALCIFICATION   Dystrophic calcification Metastatic calcification .

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CELLULAR AGING  Result of progresive decline in cellular function & viability caused by genetic abnormalities & the accumulation of cellular & mollecular damage due to exogenous exposure .