Necrosis and apoptosis

Brief discussion about necrosis and apoptosis and their differences

1. Necrosis and Apoptosis Presentor : Dr. Bishal Paudel 1 st 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 .

8. Necrosis: nuclear changes NORMAL PYKNOSIS KARYORHHEXIS KARYOLYSIS

9. Types of Necrosis 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 9 th edition First Aid 2019

26. Thank you