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Necrosis and apoptosis

  1. Necrosis and Apoptosis Presentor: Dr. Bishal Paudel 1st Year Orthopaedics Resident
  2. Objectives • To define necrosis and apoptosis • To explain morphology and mechanism • To illustrate different types of necrosis • To discuss briefly about the difference between necrosis and apoptosis
  3. Cell injury
  4. Reversible vs Irreversible cell injury
  5. Necrosis • Series of changes that accompany cell death, largely resulting from the degradative action of enzymes on lethally injured cells • characterized by swelling, denaturation and coagulation of proteins, breakdown of cellular organelles and cell rupture • caused by extra-cellular enzymes, liberated from inflammatory cells
  6. NECROSIS: MORPHOLOGY Light microscopy (H & E stains) • Necrotic cells -eosinophilia, glassy homogeneous appearance • Cytoplasm- vacuolated • Myelin figures- whorled phospholipid masses • Calcified dead cells
  7. • Nuclear changes : - Karyolysis - gradual fading away of the basophilic nuclear material, presumably due to action of DNAses. - Karyorrhexis - fragmentation of nucleus and the debris is either phagocytosed by other cells or just disappears. - Pyknosis - condensation of nucleus into a deep basophilic mass. This stage is often followed by karyorrhexis.
  9. Types of Necrosis 1) Coagulative necrosis: - denaturation of cytoplasmic proteins with preservation of the framework of the coagulated cell - lschemia/infracts in most tissues (except brain)
  10. • Liquefaction necrosis - autolysis and heterolysis prevail over protein denaturation - necrotic area is soft and filled with fluid with obliteration of normal architecture - localized bacterial infection (abscesses) and brain
  11. Caseation necrosis- - Cellular death with complete loss of architectural pattern - Necrotic area is dry, cheesy and friable - Example: Tuberculosis
  12. • Fat necrosis: - Enzymatic: acute pancreatitis (saponification of peripancreatic fat) - Nonenzymatic: traumatic (eg injury to breast tissue}
  13. • Fibrinoid necrosis: - Immune vascular reactions (eg, PAN) - Nonimmune vascular reactions (eg. Hypertensive emergency, preeclampsia)
  14. • Gangrenous necrosis: - Distal extremity and GI tract, after chronic ischemia
  15. Apoptosis • named after the Greek designation for “falling off” • Tightly regulated suicide program in which cells destined to die activate enzymes capable of degrading the cells own nuclear DNA and nuclear and cytoplasmic proteins • Dead cells are rapidly cleared before its content are leaked out • Hence does not elicit inflammatory reaction in the host
  16. Causes of apoptosis Apoptosis in physiologic situation: - programmed destruction of cells during embryogenesis, including implantation, organogenesis, developmental involution, and metamorphosis - Involution of hormone-dependent tissues upon hormone withdrawal, such as endometrial cell breakdown during the menstrual cycle - Elimination of potentially harmful self-reactive lymphocytes, either before or after they have completed their maturation - Death of host cells that have served their useful purpose, such as neutrophils in an acute inflammatory response
  17. • Apoptosis in pathologic conditions: - DNA damage. Radiation, cytotoxic anticancer drugs, and hypoxia - Accumulation of misfolded proteins- damage caused by free radicals - Cell death in certain infections, particularly viral infections, in which loss of infected cells is largely due to apoptosis- adenovirus or HIV infection
  18. Morphologic and biochemical changes in Apoptosis • Morphology: - Cell shrinkage : cell is smaller in size; the cytoplasm is dense and the organelles are more tightly packed - Chromatin condensation: chromatin aggregates peripherally, under the nuclear membrane, into dense masses of various shapes and sizes - Formation of cytoplasmic blebs and apoptotic bodies - Phagocytosis of apoptotic cells or cell bodies, usually by macrophages
  19. Mechanism of Apoptosis
  20. Intrinsic(mitochondrial) pathway • result of increased mitochondrial permeability and release of pro-apoptotic molecules (death inducers) into the cytoplasm Triggered by: -Loss of survival signal - DNA damage -Accumulation of misfolded proteins Inhibited by: - Survival signals- growth factors
  21. Extrinsic death receptor pathway Responsible for elimination of self-reactive lymphocytes and damage by cytotoxic T lymphocytes
  22. Disorders associated with Dysregulated Apoptosis • Defective apoptosis and increased cell survival - Cancer - Autoimmune disorders • Increased apoptosis and excessive cell death - Neurodegenerative diseases - Ischemic injury - Death of virus infected cells
  23. Different between necrosis and apoptosis
  24. Necrosis vs Apoptosis
  25. References • Robbins Basic Pathology 9th edition • First Aid 2019
  26. Thank you