CELL DEATH

Swelling, denaturation and coagulationSwelling, denaturation and coagulation of proteins Breakdown of cellular organellesBreakdown of cellular organelles Cell ruptureCell rupture Common type of necrosis after exogenous stimuli.

NECROSIS The sum of the morphologic changes that follow cell death in living tissue that follow cell death in living tissue and organ: and organ: Denaturation of proteins. Enzymatic digestion of organelles and cytosol.

Enzymatic digestion by lysosomal enzymes of the dead cells themselves.Enzymatic digestion by lysosomal enzymes of the dead cells themselves. AUTOLYSIS AUTOLYSIS HETEROLYSIS Digestion by lysosomal enzymes of immigrant leukocytes.Digestion by lysosomal enzymes of immigrant leukocytes.

Three pattern of nuclear changes Karyolysis (DNase activity) Pyknosis (DNA condensation) Karyorrhexis (fragmentation of pyknotic nucleus) of pyknotic nucleus)

Morphologic appearance of necrosis Increased eosinophilia:Increased eosinophilia: Loss of RNA in the cytoplasm Loss of RNA in the cytoplasm Increased binding of eosin to denatured Increased binding of eosin to denatured cytoplasmic protein cytoplasmic protein More glassy homogeneous appearanceMore glassy homogeneous appearance Loss of glycogen particles Loss of glycogen particles Vacuolated and moth-eaten cytoplasmVacuolated and moth-eaten cytoplasm Calcification of necrotic cellsCalcification of necrotic cells

TYPES OF CELL DEATH necrosis necrosis Coagulation necrosis Coagulation necrosis Caseous necrosis Caseous necrosis Gangrene Gangrene Liquefaction necrosis( fat necrosis) Liquefaction necrosis( fat necrosis) Fibrinoid necrosis Fibrinoid necrosis ApoptosisApoptosis

Coagulation necrosis Denatures of both structural and enzymatic proteins by injury or the enzymatic proteins by injury or the subsequent increasing intracellular subsequent increasing intracellular acidosis. acidosis.

Caseous necrosis A subtype of coagulation necrosis White and cheesy Tuberculosis Completely obliterated tissue architecture architecture

Gangrene A subtype of coagulation necrosis Dry gangrene Wet gangrene Gas gangrene

Liquefactive necrosis Bacterial or fungal infections Central nervous system Amebiasis

Fat necrosis Traumatic Activated pancreatic lipases

Fibrinoid degeneration Deeply eosinophilic Collagen diseases Necrotic vasculitis Malignant hypertension

APOPTOSIS (Programmed cell death) Programmed destruction of cells duringProgrammed destruction of cells during embryogenesis. embryogenesis. Hormone dependent involution of tissuesHormone dependent involution of tissues in the adult. in the adult. Cell deletion in proliferating cell popula-Cell deletion in proliferating cell popula- tions (intestinal crypt epithelium), tions (intestinal crypt epithelium), tumors, and lymphoid organs. tumors, and lymphoid organs.

Pathologic atrophy in parenchymal Pathologic atrophy in parenchymal organs after duct obstruction. organs after duct obstruction. Cell death by cytotoxic T cells. Cell death by cytotoxic T cells. Cell injury in certain viral diseases. Cell injury in certain viral diseases. Cell death produced by a variety of Cell death produced by a variety of injurious stimuli given in low doses injurious stimuli given in low doses (e.g. mild thermal injury). (e.g. mild thermal injury).

MORPHOLOGICAL FEATURES OF APOPTOSIS Cell shrinkageCell shrinkage Chromatin condensation and fragmentation.Chromatin condensation and fragmentation. Formation of cytoplasmic blebs and apoptoticFormation of cytoplasmic blebs and apoptotic bodies. bodies. Phagocytosis of apoptotic bodies by adjacentPhagocytosis of apoptotic bodies by adjacent healthy cells or macrophages. healthy cells or macrophages. Lack of inflammation.Lack of inflammation.

Necrosis Apoptosis Necrosis Apoptosis Stimuli Hypoxia Physical Toxins Pathological Toxins Pathological Histology Cell swelling Single cell Coagulation N Chromatin Coagulation N Chromatin Disruption of condensation Disruption of condensation organelles Apoptotic bodies organelles Apoptotic bodies DNA Random Internucleosomal breakdown Diffuse

Necrosis Apoptosis Necrosis Apoptosis Mechanism ATP depletion Gene activation Membrane Endonuclease Membrane Endonuclease injury injury Free radicals Free radicals Tissue Inflammation No inflammation reaction Phagocytosis of reaction Phagocytosis of apoptotic bodies apoptotic bodies

Fig 1-18

Biochemical features of apoptosis 1.PROTEIN CLEAVAGE: Caspases (cysteine protease) Caspases (cysteine protease) Nuclear scaffold Nuclear scaffold Cytoskeletal protein Cytoskeletal protein 2.PROTEIN CROSS-LINKING: Transglutaminase Transglutaminase Cytoplasmic protein  shrunken shalls Cytoplasmic protein  shrunken shalls  apoptotic bodies  apoptotic bodies Biochemical features of apoptosis Biochemical features of apoptosis

3. DNA breakdown: kb pieces Ca2+, Mg2+ dependent endonucleases Ca2+, Mg2+ dependent endonucleases DNA oligonucleosomes DNA oligonucleosomes DNA ladders (also seen in necrosis) DNA ladders (also seen in necrosis) 4. PHAGOCYTIC RECOGNITION Receptors on macrophages for the Receptors on macrophages for the surface components surface components (phosphatidylserine, thrombospondin) (phosphatidylserine, thrombospondin) on apoptotic bodies. on apoptotic bodies.

Fig 1-19

Apoptosis-associated genesApoptosis-associated genes bcl-2, c-myc, p53 bcl-2, c-myc, p53

Fig 1-20

AbsorptionAbsorption Discharge: Erosion UlcerDischarge: Erosion Ulcer Sinus Fistula Cavitation Sinus Fistula Cavitation OrganizationOrganization EncapsulationEncapsulation CalcificationCalcification Fates of necrosis

Regeneration: Completely regeneration Fibrous repair Chapter Three Repair Repair Section A

Labile cellsLabile cells Stable cellsStable cells Permanent cellsPermanent cells Regeneration capacity

1. Cell-cell interaction Conditioned medium Conditioned medium Contact inhibition Contact inhibition 2. Extracellular matrix Laminin:  Epithelia Laminin:  Epithelia  Fibroblasts  Fibroblasts Fibronectin :  Epithelia Fibronectin :  Epithelia  Fibroblasts  Fibroblasts 3. Growth factors Factors influencing regeneration

GROWTH FACTORS EGF, TGF-A, PDGF, aFGF, bFGF, IGF-1, IGF-2, VEGF, HGF, MG-CSF, M-CSF, G-CSF, ERYTHROPOITIN, ILs, TNF, IFN, NGF.

Section B Fibrous Repair Granulation tissues: Newly formed capillariesNewly formed capillaries FibroblastsFibroblasts Inflammatory cellsInflammatory cells

Granulation tissues Fibrous repair Fibrous repair Organization Organization Wound healing Wound healing

Fig 4-14

Fig 4-15

Healing by first intentionHealing by first intention Healing by second intentionHealing by second intention Healing under scabHealing under scab Wound healing

Fig 4-18

Fig 4-19

Systemic factors influencing wound healing: NutritionNutrition Metabolic statusMetabolic status Circulatory statusCirculatory status HormonesHormones

InfectionInfection Mechanical factorsMechanical factors Foreign bodiesForeign bodies Size, location and types of woundSize, location and types of wound Local factors influencing wound healing:

Liquefactive necrosis Bacterial or fungal infections Central nervous system Amebiasis

Fat necrosis Traumatic Activated pancreatic lipases