INTRODUCTION “All organ injuries start with structural or molecular alterations in cells” concept began by Virchow in 1800's •modern study of disease attempts to understand how cells react to injury, often at the subcellular or molecular level, and how this is manifested in the whole animal.
Classes of Cell Injury Irreversible --> cell death. Types: Necrosis : pathological ( dissolution of dead cells by its own digestive enzymes ) Apoptosis: PROGRAMMED cell death Reversible If stressor removed, and If cell damage mild: cells survive
PROBABLE CAUSES The first is the inability to reverse mitochondrial dysfunction (lack of oxidative phosphorylation and ATP generation ) even after resolution of the original injury. The second is the development of profound disturbances in membrane function.
NECROSIS
NECROSIS DEFINITION : Death of a group of contiguous cells within a living tissue or organ Affect both nucleus and cytoplasm Unregulated cell death with inflammation
Morphological changes DURING NECROSIS Cytoplasmic Nuclear Cytoplasmic changes : Cytoplasmic eosinophilia due to loss of normal basophilia & increased binding of eosin to denaturated proteins (Granular or homogenous glassy) Nuclear changes: Pyknosis : shrinkage-increased staining with haematoxylin Karyorrhexis : fragmentation Karyolysis : total disappearance
COAGULATIVE NECROSIS In: infarcts of kidney, heart, spleen Gross: pale , yellow, opaque, firm Mic.: All cellular details are lost but general architecture of the tissue is preserved Surrounding tissue----acute inflammation Ex: Infarction - heart Infarction - kidney
CASEATION NECROSIS In: Tuberculosis Necrotic tissue is partially liquefied---cheesy material ( caseation ) Mic : Both cellular details & general architecture of dead tissue are lost--- structureless eosinophilic material
FAT NECROSIS Traumatic : in female breast Enzymatic : in acute hemorrhagic pancreatitis Gross: opaque & white fat cells appear cloudy, surrounded by chronic inflammatory cells, histiocytes , foreign body giant cells
Fibrinoid Necrosis Fibrinoid necrosis is a form of necrosis , or tissue death, in which there is accumulation of amorphous, basic, proteinaceous material in the tissue matrix with a staining pattern reminiscent of fibrin.
APOPTOSIS
APOPTOSIS (programmed cell death) Definition: death of individual cells surrounded by viable cells when a cell dies through activation of an internally suicide program It is an active process—energy dependent Does not elicit inflammatory response May be physiologic or pathologic
APOPTOSIS CAUSES PHYSIOLOGIC During embryogenesis e.g. removal of interdigital webs during embryonic development of toes and fingers Hormone-dependent e.g. endometrial cell loss in menstruation PATHOLOGIC Irradiated tissues Cell death induced by cytotoxic T-lymphocytes Viral infections e.g. viral hepatitis Cell death in tumours
Differences between necrosis and apoptosis Necrosis Death of groups of cells A passive process—not energy-dependent Elicits inflammatory response Always pathologic Apoptosis Death of individual cells Active process—energy-dependent Does not elicit inflammatory response May be pathologic or physiologic