Cell Injury, Cell Death & Adaptations - PDF

normalcell reversibleinjury Adffainan ÉÉiinjury janging mildtransient severeprogressive notesmesses ofdifferenttypes...

normalcell reversibleinjury Adffainan ÉÉiinjury janging mildtransient severeprogressive notesmesses ofdifferenttypesmayinduce 99ftp.idgg mmenothert han seainsureates adaptation lfa fcagm irrepressible ThEuh necromosis ftp.feiyygmf ttisiaao causes inadequate oxygenation bloodof 0 carrying capacity of blood physical agents mechanical temp pressure radiation electric chemical agents infectiousagents immune reactions genetic nutritional Reversible cell injury 2features consistentlyseen Generalised cellularswelling ofmembrane blebbing of detachment fromERclumpingofnuclearc hromatin ribosomes small clearvacuoles pinchand off cytoplasm of injuredcells in H E appearred because theblue RNAbinds hydropic changevacuolardegeneration Fatty changein lipid metabolising organs 9 denaturation ofcellular proteinsleakageof cellularcontentsthrough damaged membraneslocalinflammation enzymah digestionof lethally injuredcell DAMPS ATPuricacid clinically cardiac muscles troponin E Morphology ingepsne.gghoPhi Bielpadnytestrains aminases Myelinfigures NuclearchangesfromDNA breakdown pyhs Thinkinconfesses intodense shrunnermassalsoseen inapoptoticc ell death hangormexis nucleus f ragmentation undergoes Thepointof no return Notdefined BUT 2 phenomena consistently characterise irreversibility inabilityto reverse mitochondrial dysfx lackofoxidativephosphorylation ATP p roduction profound membrane disturbances 919ktechie so has a firm texture ofdead tissueis preservedforaspanof atleastsomedays occurs afterischaemiaforall organsexcept brain localisedarea of ischaemia infarct Edisisintaemadan9 feaimentlacieh.I1at9 infections ftp.iyigggygiggggy ggg.gg gag ggggggg p.gg gggggiigg gggggggggggpgg.gg ggygggggcggggg.mg g I notethese are all usually resolved through enzymatic digestion and phagocytosis of debrisbyleukocytes BUT iftheyare not provides a nidusfor calcium saltsother minerals dystrophic calcification PPfignHy regulated cellsuicide Cellsdestined to die activate intrinsic enzymesthatdegrade cell's genomic DNAand nuclearcytoplasmicproteins 0 fear imaminflammation Physiologic apoptosis removal ofexcesscellsduringdevelopment involution of hormonedependenttissuesonwithdrawa hormone cellturnoveregBonemarrowintestinalcrypts elimination of potentially harmfulselfreactive lymphocytes deathofhostc ells after it hasserved purpose pathologic apoptosis DNAdamage accumulation of misfolded proteins viralinfections virus itself 4 host response cytotoxicT cellsinduce apoptosis to eliminate reservoirs of infection duct obstruction can contributeto pathologicatrophy in parenchymalorgans morphology Ihhdn.hn Endensation Formation of cytoplasmic blebsand apoptoticbodies ofapoptotic cells cellbodiesby macrophages phagocytosis Processes are duetoactivationof caspases exist as pro e nzymesand must undergo enzymatic cleavagetobecomeactive terminal caspases trigger cellularfragmentation Yasps aol.ie branded eEgeasaaes and the death receptor pathway pathways converge upon caspase activation mitochondrial The mitochondrial intrinsic pathway occursin most situations mitochondrial membrane regulated byBCL2 protein family when compromised leaus Cytochrome C induces apoptosis Antia poptotic BCL2BCLXL MCLI four possess BHdomains Proapoptotic BAXBAK thefirst3 contain BHdomains BIDPumaNoxa are Blesonlyproteins BIM RegulatedapoptosisinhibitorsBAD p p.gg p p ggggigggpggpp.gg aggggggpgggppg.gg gggggggggggg ggggggpggggggg.gg main binds bringsmore as form a o Fas when Fast Fasligand receptors together cytoplasmicdeathdomains bindingsite for FADD Fasassoc.de fgy caspase 8 andactivatesit inhalt pilaspare blockingthis p rocess These are separatebutcan occur simultaneously eg hepatocytespancreatic cells p caspase8 produced byFas cleaves andactivates BID activating the mitochfathday Necroptosis Thinkof it as looking like necrosis biochemicallylikethestartof extrinsicapoptosis but w o caspase activation Involves kinases RIPKIand RIPK3 ligation of TNFRI kinasesare recruited into a multiprotein complex plasma membrane dysruption physiologic formation ofgrowth plate pathologic celldeath in steato hepatitisacutepancreatitis neurodegendiseases Parkinson's pyrophosis form of apoptosis accompanied byrelease of feverinducing cytokine 11 1 Ferrophosis  distinctform ofcelldeath triggeredby excess iron or ROS causes unchecked lipidperoxidation looks like necrosis butis regulated by specific signals Autophagy Celleatsitsown contents to survive regulated morethan a dozen proteinsthat actto sequestrate by cellularorganelles intocytoplasmic autophagic vacuoles autophagosomes thatfusewith lysosomes Dysregulation islinkedwith cancer neurodegenerativedisorders infectiousdisease IBD alzheimers Huntingtons Artifitautophagyrelated geneassoctangothami Mechanisms of cellular injury Mitochondrialdamage ATP depletion even 5 10 hasmanywidespreadeffects NatK ATPase pumps regulate water Failureofsodiumpumps cell swelling 4 glycogenstoresrapidlydepleted acidfromanaerobicresp lactic apr 4 structural disruptionof ER synthesis protein Cellmembrane damage DNAdamage triggers p53 dependentpathways apoptosisvia mitochondrial pathway oxidative stress ROS oxygenderivedfreeradicalunpaired electron inouterorbit of Generation free radicals redoxreactionthatoccurin normal metabolic processes UVlight Xrays inflammationfromleukocytes metabolism of certain chemicals drugs Transition metals NO mange Removal free radicals usually occur spontaneously butsome mechanisms in placeto reduce injury of Antioxidants vit E A C glutathione bound versions of transition metals eg Transferrin ferritinlactoferrin centoplasmin enzymes such as catalase Superoxide dismutase SOD Gluatione peroxidase Whyarethey bad these all getreleased 1 Lipid peroxidation in membranes daintyc oktan.me mes9Msheana 2 oxidativemodification of proteins 3 can cause single or doublestranded DNA breaks intoextracellularstress CalciumHomeostasisdisturbances usually canserveas second messengers but if releasedintothe cytoplasm excessively cellinjury also usually intracell Cast is v low and in the mitochondria andER when elevated causes mitochondrial permeability transitionporeto open ATP ableto be generated Can activate a lot of enzymes l ipases proteases endonucleases Atpases eg phospho Endoplasmic Reticulum stress accumulation of misfolded proteins inthe ER trigger apoptosis unfolded protein response loweredtranslation rates increased chaperone production more foldedproteinsless unfoldedones Clinicopathologic correlations Hypoxia Ischaemia often ischaemiaworsebe ofmetabolitebuildup ATPleadsto necrosis hypoxia inducible factor HIF 1 transcriptionfactoractivateduponHypoxicstress butbestapproach isto brieflylower angiogenesisstimulatecell s urvival pathways corebodytemp to 33 C glycolysis ischaemia reperfusion injury reducing ATPdemand severaltheories asto why it causesparadoxicalcelldeath systemactivation s tress intracell Castoverload inflammation complement oxidative Chemical Toxic injury ahhhhh ftp Mmeith9eshcegmte fa eccl by cytochrome 1450 Adaptations to cellgrowthand differentiation Hypertrophy resultsfrom increased cellularprotein production egmyofilaments afterdetecting increasedload eventually reaches a limitofcoping Ppath Ing with burden rpggsje 9f.am cardiacfailure realasiapiyii.ge iieat iii regeneration.si iiiontctons pathologicatpatghqsfnam.fm cancer pathologic hyperplasia constitutes a fertilesoilinwhich cancerous proliferationsmayeventuallyrise response toviralinfections egHPV skinwarts endometrialcancer eg fromhyperpaggmoetm.fm Atrophy reduction in cellsize and number Resultsfrom proteinsynthesis degradation in cells causes of pathologic atrophy and decreased workload disuse often happenswith autophagy but lossof innervation sometimes cell residualbodiesstayinthe eglipofuscingranule reducedblood supply ayiiata.n.it Tg inadequate nutrition loss of endocrine stimulation pressure Metaplasia change of cell type riskof cancer mostcommon columnar squamous g smover l ungsn'tAdeficiency squamous columnar barrett's esophagus connectivetissuemetaplasia notlinkedto cancerriskthough eg myositis ossificans externalStimuli promote specificgeneexpressions muscle bone Intracellular accumulations Lipids Triglycerides steatosis fattychange Cholesterol Cholesterol esters foam cells atherosclerosis Xanthomas Cholesterolosis Neimann Pick QYsghffahtihaknn.ge Proteins usuallyappearasrandedeosininicdroplets aggregates in cytoplasm mhñ Foragedisease gestation proteinhutia in Resorptiondropletsin gdefective proximalrenal tubules orprotein multipleorgans resorption intracellular transportsecretion of proteins x def antinypsin calleepikhalantammipagopy accumulation of cytoskeletal proteins eg in Alzheimerdisease neurofibrillarytangles aggregationof misfolded proteins proteinopathies ERfullofproteins Russellb odies distended Hyaline change glassypink Glycogen clearvacuoles pigments exogenous egcarbon anthracosis blackening endogenous eg Lipofuscin It itself isharmless buttelltalesignof oxidativeinjury ochronosis Melanin blackendogenous brown only pigment loyalsystemic Fe Hemosiderin whenthereis excess ferritinforms haemosigning  he grammes Pathologic calcification 9ii.isii'sa mean heketeifintanmii deposition indyingtissuedespitenormalserumlevels Dystrophic If local normaltissue andalmostalways Hypercart Metastatic if deposition in Dystrophic calcification encounteredin areas necrosis of psamomma bodies singlenecroticcell of layers mineraldeposits Abestos bodies beadeddumbbell looningthingsfrom asbestosis Metastatic calcification Hyperca causes PTH T.FI Renal naiteahaisaaers failure Locations gastric mucosakidneyslungsarteries palmveins all excreteacidmeaningthey haveaninternalaphlen Cellular Aging lessincreaseslongevity paradoxicallyeating damage Wernersyndrome Bloom syndrome Attaingectaria app cellularsenescence allcells havea limited capacity forreplication Telomere attrition iiiiiiii.in Arivation oftumoursuppressorgenes iie readYemaidioactivatesirmins in