More Related Content
Similar to Irreversible cell injury pathology for medicine(20)
Irreversible cell injury pathology for medicine
- 1. Irreversible cell injury Prof.J. Hewavisenthi Department of Pathology
- 2. Types of irreversibleinjury / lethal injury / cell death • Necrosis - cell death – Coagulative – Collequative – Fat necrosis – Fibrinoid necrosis • Apoptosis - single cell death • Infarction - necrosis due to ischaemia • Gangrene - necrosis with superimposed infection.
- 3. Necrosis - definition •Spectrum of morphological changes that follow cell death in living tissue, resulting largely from the degradative action of enzymes on a lethally injured cell.
- 4. Processes that bringabout changes in necrosis • Two concurrent processes • Enzymatic degradation of the cell – Autolysis - enzymes derived from the dead cell – Heterolysis - Enzymes derived from migrant leukocytes • Protein denaturation • The balance of these processes determine the type of necrosis
- 5. Factors that determinethe type of necrosis • Composition of tissue – liquefactive necrosis in brain • Speed of necrosis • Type of injury – Bacterial infection leads to Gangrene • Balance between processes of protein denaturation and enzymatic denaturation
- 6. Morphological changes in necrosis- Cytoplasm • Eosinophilia (acidophilic) - loss of normal basophilia due to the loss of RNA and increased binding of eosin to the denatured proteins. • Glassy and homogenous appearance - loss of glycogen particles • Moth eaten appearance - digestion of the cytoplasmic organelles by lysosomal enzymes
- 7. Morphological changes in necrosis- Nucleus • Karyolysis - dissolution of chromatin • Pyknosis - Tightly packed dense chromatin ball • Karyorrhexis - fragmentation of the dense chromatin ball
- 8.
- 9. Types of necrosis-Coagulative necrosis • Most common pattern of necrosis • Morphology – loss of the nucleus – Basic cellular outline and tissue architecture preserved • Pathogenesis - denaturation of proteins (structural and enzymatic) • Occurs solid organs – Eg: following ischaemia of kidney heart lungs
- 10.
- 11. Coagulative necrosis • Sequalae –Phagocytosis by macrophages and leukocytes – Proteolytic enzymes of leukocytes digesting the necrotic cells. Therefore an inflammatory response is evoked by this process. – Calcification of dead cells - Dystrophic calcification (discussed later)
- 12. Liquefactive / Colliquative necrosis •Results from – Powerful hydrolytic enzymes that occur rather than protein denaturation (compare with Coagulative necrosis) Eg: Bacterial infection with pus formation – Because of lack of substantial supporting stroma Eg: ischaemic necrosis of brain • Sequalae – Cyst formation - Eg: Glial cyst – Calcification
- 13.
- 14. Caseous necrosis • Distinctiveform of coagulative necrosis • A combination of coagulative and liquefactive necrosis • Morphology – Soft, friable, whitish - gray debris = cheesy – Outlines are neither preserved nor totally liquefied - amorphous granular debris – No polymorphs
- 15. Caseous necrosis • Attributedto the capsule of tubercle bacillus which contains lipopolysaccharides • Example - Center of a TB granuloma • Sequalae – Cavitation – Fibrosis and healing – Calcification – Ossification
- 16.
- 17. Fat necrosis • Specificpattern of necrosis occuring in adipose tissue due to the action of lipases • Morphology – Opaque chalky white nodules – Outlines of fat cells are shadowy – Cytoplasm bubbly – Surrounding inflammatory reaction • Examples – Acute pancreatitis – Trauma - Eg: Breast
- 18. Fat necrosis -Pathogenesis Adipocyte Triglycerides Free fatty acids + Ca2+ Lipases Eg: pancreas Calcium soaps (Chalky white appearance)
- 19.
- 20. Special types • Fibrinoidnecrosis - Misnomer – In malignant hypertension ) Around – In connective tissue disorders ) Blood vv. • Gummatous necrosis - Gum or rubber like – Eg: Syphilis • Necrosis of muscle - Zenker’s necrosis – Eg: Typhoid - Rectus abdominis muscle / Diaphragm
- 21.
- 22. Gangrene/ Gangrenous necrosis •Tissue necrosis with superimposed bacterial infection • Dry gangrene • Wet gangrene • Gas gangrene • Primary and secondary gangrene
- 23. Primary Gangrene • Theorganism causing the primary infection is also responsible for the supervening gangrene. • Compare with secondary gangrene – Bacterial infection supervenes on necrosis.
- 24. Cancrum oris (NOMA)– Rapidly spreading gangrenous stomatitis which occurs chiefly in debilitated or malnourished children, destroying the soft and hard tissue structures. I Founier Gangrene – necrotizing fasciitis or gangrene affecting the external genitalia or perineum. Eg: Alcoholic, diabetics and immunecompromised
- 25. Types of gangrene- Secondary • Dry gangrene – Liquefactive necrosis and bacterial infection is less dominant – Dry, shrivelled up and black (due to FeS deposited from denatured Hb) – Well demarcated from normal tissue – Eg:- Peripheral vascular disease of the limbs
- 26.
- 27. Types of gangrene- Secondary • Wet gangrene – Severe bacterial infection - Therefore liquefaction more. – Swollen, odematous reddish black and oozing. – Eg: Bowel infarction Diabetic gangrene of the peripheries.
- 28.
- 29. Types of gangrene- Primary • Primary gangrene – the organisms causing necrosis is responsible for gangrene as well. – Founiers gangrene – Cancrum oris • Gas gangrene – Infection with Clostridium perfringens producing gas – Features of wet gangrene + crepitus – Eg: In war wounds, road traffic accidents
- 30. Apoptosis • Single celldeath or death in a small group of cells • Derived from the Greek word - dropping off • Energy dependant process • Genetically programmed - DNA damage is the target • Morphology – Masses of intensely eosinophilic cytoplasm – Dense chromatin fragments – No inflammatory cell response evoked
- 31. APOPTOTIC PATHWAYS • Initiation –Extrinsic pathway – Intrinsic (mitochondrial pathway) • Execution – Caspase cleavage of DNA and cytoskeletal proteins • Phagocytosis
- 32.
- 33. FAS receptor FAS ligand FADD FASassociated death domain PRO Caspase Caspase 8 or 10 FADD adaptor protein Caspase cascade EXTRINSIC PATHWAY Death effector domain
- 34.
- 35. Apoptosis • Physiological – Inembryogenesis - Thymic involution – Atrophy of organs as an adaptive reponse – Hormone dependant involution of the endometrium – Ageing
- 36. Apoptosis • Pathological – Hepatitisinfection - Councilman bodies – HIV – Reperfusion injury – Apoptosis is inhibited in Carcinogenesis
- 37.
- 38.
- 39. Assignment • List thedifferences between apoptosis and necrosis