Irreversible cell injury

1. IRREVERSIBLE CELL INJURY

2. The molecular mechanisms connecting most forms of  cell injury to ultimate cell death have proved elusive, for several reasons.

3. First, there are clearly many ways to injure a cell, not all of them invariably fatal.

4. Second, the numerous macromolecules,  enzymes , and  organelles within the cell are so closely interdependent that it is difficult to distinguish a primary injury from secondary (and not necessarily relevant) ripple effects.

5. Third, the "point of no return," at which irreversible damage has occurred, is still largely undetermined; thus, we have no precise cut-off point to establish cause and effect.

6. Finally, there is probably no single common final pathway by which cells die. It is, therefore, difficult to define the stage beyond which the cell is irretrievably doomed to destruction.

7. Classes of Cell Injury Reversible If stressor removed, and If cell damage mild: cells survive Irreversible --> cell death. Types: Apoptosis: normal (leaves falling) as in menses, aging PROGRAMMED Necrosis : patho -logical ... Autolysis :  after  death of entire organism ( dissolution of dead cells by its own digestive enzymes )

8. 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.

9. NECROSIS

10. 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

11. 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

12. TYPES : NECROSIS Coagulative Liquefactive Caseation Fat

13. 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            COAGULATIVE NECROSIS

14. In: centers of pyogenic abscess amoebiasis infarcts of C.N.S. Necrotic tissue---completely liquified ---turbid fluid----absorbed----space Ex: Brain - infarction  Amoebiasis ---liver  LIQUEFACTIVE NECROSIS

15. In: Tuberculosis Necrotic tissue is partially liquefied---cheesy material ( caseation ) Mic : Both cellular details & general architecture of dead tissue are lost--- structureless eosinophilic material CASEATION NECROSIS

16. 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           FAT NECROSIS

17. APOPTOSIS

18. 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

19. 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

20. 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

21. FAT NECROSIS

22. FATTY CHANGE  Definition : -abnormal accumulation of triglycerides within parenchymal cells Sites: Liver (the most common) Others, heart, kidney,-- Pathogenesis:   Excessive accumulation of triglycerides within the liver may result from defects in any one of the events in the sequence from fatty acid entry to lipoprotein exit

23. FATTY CHANGE CAUSES Congestive heart failure Diabetes mellitus Severe anaemia Ischaemia Septicaemia Poisons malnutrition

24. FATTY CHANGE EFFECTS In all organs, fatty change appears as clear vacuoles within parenchymal cells Due to fat solvents used in paraffin embedding To identify fat, frozen tissue sections are stained with Sudan IV or Oil Red-O---orange-red colour When mild - - - no effects on  cell  function Severe - - - - - -impair   cell  function

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