PREPARED BY P.DHARANI PRASAD II YEAR B.PHARM II SEM SUB:PATHOPHYSIOLOGY

Transcription

1 CELL INJURY UNIT I PREPARED BY P.DHARANI PRASAD II YEAR B.PHARM II SEM SUB:PATHOPHYSIOLOGY

2 DETECTION OF CELLULAR CHANGES AFTER INJURY BY: LIGHT MICROSCOPY OR GROSS EXAMINATION DETECT CHANGES HOURS TO DAYS AFTER INJURY HISTOCHEMICAL OR ULTRASTRUCTURAL TECHNIQUES DETECT CHANGES MINUTES TO HOURS AFTER INJURY

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4 Patterns of Acute Cell Injury Reversible Injury Cellular swelling: Ultrastructural changes plasma membrane blebbing, blunting and distortion of microvilli mitochondrial swelling, phospholipid-rich amorphous densities dilation of endoplasmic reticulum with detachment of ribosomes and dissociation of polysomes disaggregation of granular and fibrillar elements on nucleus

5 Patterns of Acute Cell Injury Reversible Injury 2. Fatty change: Vacuolation of cells due to accumulation of lipid droplets Results due to disturbance of ribosomal function The liver is commonly affected Occurs in hypoxic injury, toxic (alcohol), metabolic (diabetes mellitus) Moderate fatty changes are reversible, but sever changes may not be

6 Patterns of Acute Cell Injury Irreversible injury: Cell death It is suggested that cell membrane is the central factor in the pathogenesis of irreversible cell injury Also due to: sever mitochondrial dysfunction lysosomal rupture Two patterns of cell death: Necrosis Apoptosis

7 Patterns of Acute Cell Injury Irreversible injury: Cell death 1. Necrosis: Definition: sequence of morphologic changes that follow cell death in living tissue The morphologic appearance of necrosis is due to: Enzymatic digestion of cell: Autolysis: hydrolytic enzymes are derived from the dead cells themselves Heterolysis: hydrolytic enzymes are derived from invading inflammatory cells Denaturation of proteins

8 Patterns of Acute Cell Injury Microscopic appearance of Necrotic dead cells: Cytoplasmic changes eosinophilia (pink) increased due to eosin binding to denatured proteins Decreased basophilia (blue) mainly imparted by RNA Glassy homogenous cytoplasm due to loss of glycogen Clacification may occur late Nuclear changes due to break down of DNA Karyolysis: decrease basophilia of chromatin Pyknosis: nuclear shrinkage and increased basophilia Karyorrhexis: fragmentation of pyknotic nucleus

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10 Kidney, necrosis of tubular cells

11 Patterns of Acute Cell Injury Specific Morphologic Patterns of Necrosis Coagulative necrosis Liquefactive necrosis Gangrenous necrosis Caseous necrosis Fat necrosis Others (fibrinoid necrosis)

12 Specific Morphologic Patterns of Necrosis 1. Coagulative Necrosis: Preservation of the structural outline of the dead (coagulated) cell for days The most common form of necrosis (particularly in myocardium, liver, kidney) characteristic of hypoxic cell death in all tissues except in the brain Myocardial infarction is a very good example Mechanism: denaturation of proteins and enzymes blocking cellular proteolysis preserve cell outline

13 Specific Morphologic Patterns of Necrosis Morphology of Coagulative Necrosis: Gross: pale color, normal firm texture at the beginning become soft later due to digestion by macrophages (may lead to rupture of infarcted myocardium) Microscopic: first few hours no abnormalities later progressive loss of nuclear staining, with preservation of cell boundaries finally damaged cells are removed by macrophages (the presence of necrotic tissue usually evokes inflammatory response followed by repair)

14 Fate of Necrosis Most of necrotic tissue is removed by leukocyte (Phagocytosis) combined with extracellular enzyme digestion If necrotic tissue is not eliminated it attracts Ca ++ salts dystrophic calcification

15 Patterns of Acute Cell Injury Apoptosis (a falling away from) Definition: Programmed cell death It is an active (energy-dependant) programmed single cell death to delete the unwanted or defective cells It has an important role in physiological processes and pathological conditions

16 Apoptosis Physiological processes: during embryogenesis (implantation, organogenesis, developmental involution, separation of digits in limb development) hormone -dependent involution (endometrium during menstruation, lactating breast after weaning) cell deletion in proliferating populations intestinal crypt epithelium deletion of autoreactive T cells in thymus (failure might result in autoimmunity) Pathological conditions: pathologic atrophy-prostate after castration (hormone -dependent involution) Cell death in tumors Cell death induced by cytotoxic drugs and ionizing radiation Councilman s bodies due to viral hepatitis

17 Apoptosis Morphology: Involves single cells or small clusters Cells shrink rapidly, retain intact plasma membrane Formation of cytoplasmic buds Fragmentation into apoptotic bodies Apoptotic bodies phagocytosed or rapidly degraded No inflammatory response Entire process from 5 to 30 minutes

18 Apoptosis

19 Necrosis Vs Apoptosis Necrosis Grp of cells or part of tissue passive process Always pathologic Mechanism is ATP depletion, mb damage Histology: coagulation. liquefaction inflammation Apoptosis: Single cell death in living tissue Active process Physiologic or pathologic Endonucleases Apoptotic bodies No inflammation