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Apoptosis
Apoptosis
Apoptosis
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Apoptosis

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this is a series of notes on general pathology, useful for undergraduate and post graduate pathology students. Notes have been prepared from standard textbooks and are in a format easy to reproduce …

this is a series of notes on general pathology, useful for undergraduate and post graduate pathology students. Notes have been prepared from standard textbooks and are in a format easy to reproduce in exams.

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  • 1. 1 General Pathology Notes (Robbins) By Dr. Ashish Jawarkar Chapter 1 : CELLULAR RESPONES TO STRESS AND TOXIC INSULTS: ADAPTATION, INJURY AND CELL DEATH TOPIC 1. APOPTOSIS aka Programmed cell death OVERVIEW 1. definition 2. causes – 1 physiologic 2 pathologic 3. morphology – 1 Light microscopy 2 Electron Microscopy 4. Mechanisms – 1. Initiation – a. Intrinsic pathway b. extrinsic pathway 2. Execution 3. Removal of dead cells 5. Disorders of dysregulated apoptosis * Definition 1. a pattern of cell death 2. affecting single cells 3. marked by fragmentation into cell membrane bound apoptotic bodies, Condensation of chromatin 4. these apoptotic bodies are eliminated by phagocytosis * Causes of Apoptosis Physiologic 1.During embryogenesis – implantation, organogenesis, involution and metamorphosis 2. Due to hormone withdrawl - endometrial cycle - ovarian follicular atresia at menopause - breast after weaning - prostate after castration 3. In homeostasis - lymphocytes that recognize self antigens - epithelial cells in intestinal crypts - neutrophils and lymphocytes at the end of immune response Pathologic 1. DNA damage – due to radiation/hypoxia/ Anticancer drugs 2. Accumulation of misfolded proteins – ER stress - apoptosis This is the basis of degenerative diseases of the CNS 3. Certain viral infections lead to cell death by apoptosis – like adenovirus, HIV and hepatitis 4. Atrophy of parenchymal organs after duct obstruction – pancreas, parotid, kidney * Morphology Notes on apoptosis.. By Dr. Ashish Jawarkar Contact: pathologybasics@gmail.com Website: pathologybasics.wix.com/notes
  • 2. 2 LIGHT MICROSCOPY Apoptotic bodies seen as 1. shrunken cell 2. no damage to plasma membrane 3. intensely eosinophilic cytoplasm 4. dense nuclear chromatin 5. no inflammation ELECTRON MICROSCOPY 1. intact nuclear membrane 2. chromatin condensation under nuclear membrane 3. formation of cytoplasmic blebs * Mechanisms Initiation – execution – clearing of dead cells INITIATION INTRINSIC PATHWAY (mitochondrial) Cell injury due to 1. growth factor withdrawl 2. ROS 3. Toxins 4. Protein misfolding 5. radiation Receptor-ligand interactions (Fas, TNF receptor) Adapter proteins (FADD) Activation of Apoptotic sensors (Bcl-2 family – Bim, Bid, Bad) Activation of Apoptotic activators (Bcl-2 family – Bax, Bak) Insert into mitochondrial membrane and create channels EXTRINSIC PATHWAY (death receptor) # by Bcl regulators (Bcl-2, Bcl-x, Mcl-1) (# of apoptosis) Initiator caspases (Caspase 8, in human caspase 10) Mitochondrial cyto-c leakage Notes on apoptosis.. By Dr. Ashish Jawarkar Contact: pathologybasics@gmail.com Website: pathologybasics.wix.com/notes
  • 3. 3 Cyto c in cytoplasm Cyto C binds to apaf-1 and forms cytoC-apaf1 complex Executioner Caspase (Caspase 3&6) complex activates initiator caspase 9 inhibited by SMAC/DIABLO (# of apoptosis) caspase 9 activates executioner caspase 3 Endonuclease activation Breakdown of cytoskeleton DNA fragmentation Formation of cytoplasmic blebs and apoptotic bodies Phagocytosis of apoptotic bodies Removal of dead cells The apoptotic bodies are recognized by phagocytes by – 1. alterations in plasma membrane 2. thrombospondin is expressed on the outer leaflet 3. coatin with complements eg. C1q * disorders of dysregulated apoptosis 1. disorders due to too little apoptosis - cancer - autoimmune disorders 2. disorders due to too much apoptosis - neurodegenerative diseases Notes on apoptosis.. By Dr. Ashish Jawarkar Contact: pathologybasics@gmail.com Website: pathologybasics.wix.com/notes

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