1. Necrosis Apoptosis

2. Different Types of Cell Death TermDefinition Necrosis Antemortem pathologic cell death Apoptosis Antemortem programmed cell death AutolysisPostmortem cell death

3. Necrosis Spectrum of morphologic changes that follow cell death in living tissue Increased eosinophilia Myelin figures Nuclear changes

4. Increased eosinophilia binding of eosin to denatured proteins causes increased cytoplasmic eosinophilia  more pink loss of DNA, RNA causes decreased basophilia  less blue

5. Myelin figures Dead cells are replaced by large whorled phospholipid masses

6. Nuclear Changes Karyolysis : the basophilia of chromatin fades due to breakdown of DNA Pyknosis : Nuclear shrinkage and increased basophilia Karyorrhexis : fragmentation of the nucleus

10. Patterns of Necrosis In Tissues Coagulative necrosis : the outline of the dead cells are maintained and the tissue is somewhat firm. Example: myocardial infarction.

17. Patterns of Necrosis In Tissues Liquefactive necrosis : the dead cells undergo disintegration and affected tissue is liquefied. Examples: focus of bacterial infections, cerebral infarction.

24. Patterns of Necrosis In Tissues. Caseous necrosis : a form of coagulative necrosis (cheese-like). Example: tuberculosis lesions.

29. Patterns of Necrosis In Tissues Fat necrosis : enzymatic digestion of fat. Example: necrosis of fat by pancreatic enzymes.

33. Patterns of Necrosis In Tissues Gangrenous necrosis : Necrosis (secondary to ischemia) usually with superimposed infection. Dry gangrene Wet gangrene Example: necrosis of distal limbs, usually foot and toes in diabetes.

38. APOPTOSIS A pathway of cell death that helps to eliminate unwanted cells by an internally programmed series of events effected by dedicated gene products.

39. Physiologic situations During development for removal of excess cells during Programmed destruction of cells during embryogenesis To maintain cell population in tissues with high turnover of cells, such as skin, bowels. Hormone-dependent involution - Endometrium, ovary, breasts etc. To eliminate immune cells after cytokine depletion, and autoreactive T-cells in developing thymus.

41. Pathological conditions During development for removal of excess cells during To eliminate cells with DNA damage by radiation, cytotoxic agents etc. To remove damaged cells by virus Cell death in tumors.

42. Normal cell proliferation is important for growth and development replacement of destroyed cells Cell death is important for programmed death of cells not needed after a certain point in development removal of potentially dangerous damaged cells

43. Morphological changes shrinkage of cell volume and shape chromatin condensation, DNA fragmentation, and peripheral clumping (most characteristic feature of apoptosis) formation of surface blebs fragmentation into apoptotic bodies phagocytosis of apoptotic bodies by macrophages

49. Biochemical features Protein cleavage : caspases DNA breakdown : oligonucleosomes in multiples of 180 – 200 base pairs Phagocytic recognition : phosphatidylserine, thrombospondin

51. SEQUENTIAL EVENTS IN APOPTOTIC CELL DEATH Apoptosis may be triggered by: cytotoxic T cells receptor-ligand interactions on the cell membrane withdrawal of growth factors or hormones injury (radiation, toxins, free radicals)

56. NECROSISAPOPTOSIS STIMULI irreversible ischemia / hypoxiacytotoxic T cells receptor-ligand interactions withdrawal of growth factors or hormones, injury (radiation, toxins, free radicals) MORPHOLOGY cell swelling random nuclear fragments inflammation cell shrinkage specific DNA fragmentation no inflammation TISSUE REACTIONS enzymatic degradation denaturation of proteins shrinkage of cell volume and shape chromatin condensation surface blebs apoptotic bodies