NECROSIS

1. NECROSIS Prof C V Raghuveer MBBS Class Dec 2014

2. Necrosis Defn. Spectrum of morphological changes that follow cell death in living tissue resulting from the progressive degradative action of enzymes on a lethally injured cell;

3. Necrosis Classification: • Coagulation necrosis, • Liquefaction necrosis, • Gangrenous • Caseous • Fat ( traumatic, enzymatic ) • Fibrinoid necrosis

4. Necrosis – General Morphology • Cell membrane - fragmented, • Cytoplasm - eosinophilic, glassy, vacuolated • Nucleus - pyknosis, karyolysis, karyorrhexis, • Dystrophic calcification

5. Coagulative Necrosis • Preservation of basic outline of the cell • Denaturation of structural protiens & proteolytic enzymes • Hypoxic death in all tissues except Brain

8. Liquifactive Necrosis • Focal bacterial or fungal infections • Hypoxic death in CNS • Tissue is converted into liquid viscous mass

9. 45 yrs old man, alcoholic suddenly aspirated after a bout of alcoholic drink in a local shop. He came to hospital with fever and cough and suffered a heart attack and died What is the lesion

11. 33 years old man with fever, vomiting and neck stiffness . Before anything could be done he succumbed to it and died. Post Mortem showed the lesion in brain

12. Gangrenous Necrosis • Loss of blood supply to a limb – DRY GANGRENE • Superimposition of bacterial infection over coagulative necrosis – WET GANGRENE

13. Gangrene

14. Caseous Necrosis • Tuberculosis • Cheesy white • Amorphous granular debris enclosed within inflammatory border • Tissue architecture is completely destroyed

15. 35 years old immunocompromised man with evening rise of temperature and sweating. He died in a RTA. Post Mortem showed a lesion. Explain

17. Fat Necrosis • Acute Pancreatitis • Necrotic fat cells with basophilic calcium deposits sorrounded by inflammatory reaction

18. 45 years old executive from Delhi, obese person died due in shock after suffering from severe pain abdomen after heavy drinking

20. Fibrinoid Necrosis • Seen in immunologic tissue injury • Deposition of fibrin like material • Morphology – brightly eosinophilic hyaline like deposition in the vessel wall

22. Gangrene C V Raghuveer, 27th December 2014 2012 IR Batch

23. Definition • A form of ischemic necrosis with superadded putrefaction. • Types : • 1. Dry Gangrene. • 2. Wet Gangrene. • 3. Gas Gangrene.(Variant of Wet Gangrene)

24. Dry Gangrene • Affects distal parts of limbs-ischemia • Typical ex, Atherosclerotic Gangrene. • Other ex- TAO, Trauma, Ergot poison, Diabetes • Spreads slowly upwards • Line of demarcation clear

25. Morphology of Dry Gangrene • Affected part is dry, shrunken, mummified, • Dark due to iron sulfide formed from Hb by H2S liberated from bacteria.

26. Another example of dry gangrene • Dry shrunken black with a line of demarkation

27. Wet Gangrene • Occurs in naturally moist organs • Ex: Mouth,GIT,Lung,Appendix etc • Diabetic foot is another example • Bed sores is another example. • Usually rapid in onset. • Ischemia is the root cause venous/arterial blockade • No clear line of demarcation seen

28. Morphology of Wet gangrene • Swollen, putrid,rotten, dark • Classic ex is Gangrene of GIT

29. Gas Gangrene • Special form of Wet Gangrene due to gas forming Cl. Welchi infection. • Morphology- swollen, crepitant, painful, gas bubbles.

30. APOPTOSIS • Definition: Form of cell death designed to eliminate unwanted host cells through the activation of a coordinated internally programmed series of events effected by dedicated set of genes

31. Apoptosis Physiologic events: • Embryogenesis, • Hormone dependent involution; Pathologic events: • Cellular death in tumors, • Death of neutrophils during infection • Viral diseases

32. Apoptosis - morphology • Cell shrinkage • Chromatin condensation, • Formation of cytoplasmic blebs and apoptotic bodies, • Phagocytosis

34. Histopathology • Single cell / small groups of cells • Round / oval mass of intensely eosinophilic cytoplasm with dense chromatin • No inflammation

36. Biochemical Features • Protein cleavage Caspases • DNA breakdown • Phagocytic recognition

37. Mechanisms of Apoptosis • Initiation phase • Execution phase

38. Initiation • Extrinsic ( Receptor mediated ) pathway • Intrinsic ( mitochondrial ) pathway Both pathways converge to activate caspases

42. Execution phase Caspases cleave cytoskeletal & nuclear matrix proteins Disrupt cytoskeleton & lead to breakdown of nucleus

43. Removal of dead cells Phagocytes

44. Decreased Apoptosis • Cancers • Autoimmune diseases

45. Increased Apoptosis • Neurodegenerative diseases • Ischemic injury • Death of virus infected cells

46. THANK YOU

47. Sub cellular Responses to Injury • Could coexist with acute lethal injury • Chronic forms of cell injury • Adaptive response

48. Lysosomal Catabolism • HETEROPHAGY • AUTOPHAGY

49. Effects of Lysosomal Catabolism • Lipofuscin pigment deposition • Carbon pigment deposition in Tatoos • Hereditary Lysosomal storage Disorders • Drugs can disturb lysosomal function