Cell Injury and Adaptation PDF

Cell injury and adaptatin Cell injury Nirmally cells if the bidy are in equilibrium with the external micri-envirinment this is called Homeostasis. The equilibrium between cells and their micrienvirinment includes bith Chemical (electrilytes, glucise, pH, etc...

Cell injury and adaptatin Cell injury Nirmally cells if the bidy are in equilibrium with the external micri-envirinment this is called Homeostasis. The equilibrium between cells and their micrienvirinment includes bith Chemical (electrilytes, glucise, pH, etc.) and Physical (e.g. temperature) states. Stress is any insult disturbances if cellular chemical and physical states. Internal regulatiry mechanisms ciunteract stress and lead ti cellular changes, these changes are called cellular adaptations that aim ti preserve cell viability and prevent cell injury. If the adaptve ability if the cell is exceeded ir the stress inherently harmful (e.g. high temperature), cell injury iccurs. Cellular adaptationn Cellular changes that aim ti preserve cell viability and prevent cell injury. The adaptve respinses include: 1. Atriphy 2. Hypertriphy 3. Hyperplasia 4. Metaplasia 5. Hypiplasia 6. dysplasia 1. Atrophy: decrease in cell size by liss if cell substances. When sufcient numbers if cells are invilved, the entre irgan decreases in size. The cells becime smaller with diminished functin and reduced metabilic needs ti escape injury. Causes: 1. Decrease wirkliad e.g. muscular atriphy due ti immibilizatin in fracture limb. 2. Denervatin (liss if nerve supply) as in paralysis. 3. Ischemia (decrease if bliid supply)as in aging 4. Malnutritin as in starvatin 5. Liss if endicrine stmulatin eg atriphy if uterus and endimetrium afer menipause. 2. Hypertriphy: increase in the size if the cells which may lead ti increase if the size if the tssue ir irgan. Hypertriphy iccurs due ti synthesis if mire structural cimpinents within the cells (mire enzymes, mitichindria, flaments … etc) ti cimpensate the increased demand. it ciuld be: a) Physiiligical: eg uterus during pregnancy and skeletal muscles in athlete. b) Pathiligical: lef ventricle hypertriphy due ti systemic hypertensiin. 3. Hyperplasia: increase in number if cells. Hypertriphy and hyperplasia are clisely related and ifen iccur tigether. Nit all cell type has the same capacity fir divisiin and hyperplasia and accirdingly cells are divided ti: 1. Labile cells: include epidermis, mucisal surface, hepaticytes fbriblasts and bine marriw cells. 2. Permanent cells: include nerve cells, myicardium and skeletal muscle fbers 3. Intermediate cells: include bine, cartlage and smiith muscle cells. Hyperplasia ciuld be: a) Physiiligic: either Hirminal as hirminal efect in breast during puberty and pregnancy ir Cimpensatiry when part if tssue is remived: kidney, liver b) Pathiligical: eg endimetrial hyperplasia afer excessive hirminal therapy and pristatc hyperplasia 4. Metaplasia: replacement if ine mature cell type by anither mature cell type. It may represent replacement if cells sensitve ti stress by anither cells which are mire resistant. It is a genetc reprigramming” if stem cells and nit changing if already diferentated cells. examples fir metaplasia include: 1. Squamius metaplasia if laryngeal and brinchial respiratiry epithelium due ti habitual smiking. 2. Squamius metaplasia if urithelium if urinary bladder due ti bilharzia ir stine. 3. Cilumnar metaplasia if esiphageal squamius epithelium as aresult if gastric juice reflex (Barrett esopha us). 5. hypoplasian Incimplete develipment if an irgan si that it fails ti reach adult size. It can iccur at any irgan in the bidy especially paired irgans.eg hypiplastc kidney ir hypiplastc ivary. 6. Dysplasia: Disturb irganizatin and irientatin if the cells. Sever dysplasia equal intraepithelial neiplasia. Chrinic irritatin by radiatin, inflammatin cinsidered the majir cause. Cell injury Occur in twi situatins: i. The limits if adaptve respinse are exceeded. ii. When there is ni eniugh tme fir adaptve respinses ti take place as in sever injuriius agent. Cell injury divided ti: 1. Reversible cell injury: cellular changes will regress and disappear when the injuriius agent is remived i.e. cells return ti nirmal bith mirphiligically and functinally e.g. cellular swelling (hydripic changes) and faty changes. 2. Irreversible cell injury (cell death)n in which cell death is inevitable e.g. mitichindrial damage and autilysis by lysisimal enzymes. Causes if cell injury: 1. Hypixia: ixygen deprivatin 2. Physical agents: trauma, heat, cild and radiatin 3. Chemical: piisins (cyanide), pillutants, alcihil, smiking 4. Infectius agents: bacteria, viruses, fungi and parasites. 5. Immuniligical: hypersensitvity reactins and autiimmune diseases. 6. Genetc derangements: chrimisimal genetc defect eg diwns syndrime ir single gene defect sickle cell anemia. 7. Nutritinal imbalance: include bith excess and defciency Injuriius agents induce cell injury thriugh their efect in ine ir mire if the filliwing fve cellular targets: 1) Aeribic respiratin 2) Cell membranes 3) Pritein synthesis 4) Cytiskeletin 5) Genetc apparatus (chrimisimes) Mechanisms of cell injuryn Firstn ATP depletionn Hypixia and tixic chemicals are the main causes fir ATP depletin. Depletin if ATP priduces the filliwings: A. Reduction of the activity of ener y dependent plasma membrane sodium pump. This causes Na+ ti be restricted inside the cell and K+ iutside. An increased intracellular Na+ results in water retentin that leads ti cell edema. B. Switch to anaerobic lycolysis. If ATP depletin due ti hypixia, this will blick ixidatve phisphirylatin fir ATP priductin and cells undergi anaeribic glycilysis ti maintain energy and ATP priductin. This anaeribic glycilysis will priduce lactc acid that decreases intracellular PH (acidic cytiplasm) which interferes with the iptmal actvity if many cellular enzymes. C. increase in intracellular Ca+n failure if Ca+ pump leads ti influx if Ca+ that have damaging efect in many cellular cimpinents. D. Structural disruption of the protein synthesis apparatus. with priling ATP depletin there will be reductin in pritein synthesis due ti: 1) Detachment if ribisimes frim riugh endiplasmic retculum riugh ER. 2) Dissiciatin if pilysimes ti minisimes. E. Unfolded protein response. A pritein is initally a linear pilymer if amini acids linked tigether by peptde binds synthesized within ribisimes. Then these linear priteins are drawn inti ER where they acquire their filded cinfguratin. They are transpirted by vesicles ti Gilgi apparatus. ATP depletin leads ti misfilded ir unfilded priteins. These abnirmally cinfgured pritens cannit be mibilized and this leads ti their accumulatin within the ER. Secondn Loss of cell membranes permeability and cell membrane dama e. The damage is nit limited ti the cell membrane inly but may alsi invilve that if mitichindria, ribisimes and lysisimes. Cell membrane damage in cell injury result frim actvatin if intracellular enzymes that include: ATPase, phisphilipases, priteinases and endinucleases which iccur due ti increase in intracellular Ca+. Sime bacteria like bacteria if gas gangrene can directly damage cell membrane by phisphilipase enzyme that elabirated frim these bacteria. Thirdn accumulation of oxy en derived free radicals (oxidative stress). Oxygen-derived free radicals (OFR) are priduced as a bypriduct if mitichindrial respiratin. These are chemically reactve, having single unpaired electrin in the - iuter irbit. OFR include: i2 (superixide), H2O2 (hydrigen perixide), OH- (hydrixyl radicle) and 1 O (singlet ixygen). OFR can damage lipids, priteins and nucleic acids leading ti variius firms if cell injury. Cells nirmally have defense against OFR by antioxidant materials like glutathiine, vit C and ithers. An imbalance between generatin if OFR and level if antixidant materials in the bidy called oxidative stress. Fourthn mitochondrial dama e. It is the reliable cause fir irreversible cell injury.Mitichindria can be damaged by: 1. Increase in cytiplasmic Ca+ 2. Oxidatve stress 3. Breakdiwn if mitichindrial membrane phisphilipid by actvated phisphilipases. All the abive causes lead ti increase mitichindrial membrane permeability and release if H+ iin and cytichrime-C. H+ iin essental fir ixidatin phisphirylatin and ATP synthesis si leakage if H+ iin depletes ATP. Release if cytichrime-C triggers cell death by apiptisis. Cell death There are twi mides if cell death: A. Necrisis B. Apiptisis Necrosisn cell death due to de radin action of enzymes on irreversibly dama ed cells with denaturation of cellular proteins. It include cytoplasmic as well as nuclear chan es Cytoplasmic chan esn in hematixylin-eisin stain (H&E stain) hematixylin stains the acidic cell materials (nucleus) blue whereas eisin stains alkaline cell materials (cytiplasm) pink. Necritc cells cytiplasm becimes mire alkaline and stains deeply with eisin (eisiniphilic) than viable cells because: Liss if cytiplasmic RNA (RNA acidic material) and increase binding if eisin ti denatured pritein. Nuclear chan esn include chromatin clumpin (chrimatn aggregatin) which is the earliest nuclear changes.afer that nucleus Either shrinks and transfirmed ti a wrinkled mass (pyknosis) with subsequent disintegratin if chrimatn and disappearance if nucleus (karyolysis). Or the nucleus breaks inti many clumps (karyorrhexis). Types of cell Necrosisn A/Coa ulative necrosisn result frim sudden sever ischemia in irgans such as heart kidney…. B/Liquefactive necrosisn characterized by cimplete digestin if dead cells by enzymes and the lesiin cinverted inti cyst flled with debris. It was seen in twi situatins: 1. Brain infarct: ischemic destructin if brain tssue. 2. Abscess that iccur afer suppuratve bacterial infectin. C/Fat necrosisn specifc patern if cell death seen in adipise tssue due ti actin if lipase enzyme as in acute pancreatts. Alsi can be seen afer trauma if faty tssue e.g. if trauma if female breast. D/Caseous necrosis (caseation)n have the cimbined features if bith ciagulatve and liquefactve necrisis seen in the center if TB granulima. E/Gan renous necrosisn it is surgical term represents cimbinatin if ciagulatve necrisis (ischemia) if tssue filliwed by liquefactve necrisis by liquefactve actin if enzymes derived frim bacteria and inflammatiry cells. Apoptosisn distnct patern if cell death difers frim necrisis in that it is an internally cintrilled energy - dependent pricess fir deletin if unwanted cells withiut damage ti the tssue that cintaining them (without infammation). Apiptisis can iccur in: 1. During embryigenesis fir irgan mirphigenesis and remideling. 2. Hirmine dependent invilutin eg shedding if endimetrium during menstrual cycle. 3. Physiiligical Deletin if aged cells if bliid, skin, intestnal epithelia 4. Deletin if inappripriately priliferated cells eg tumir cells. Intracellular accumulatin Under certain circumstances, cells may accumulate abnirmal amiunts if variius substances. The accumulated substances may be:  1. Nirmal cellular cinsttuents accumulated in excess eg lipid, pritein and CHO. they are examples if reversible cell injury and include faty liver changes and accumulated pritein drips in the epithelia if priximal cinviluted tubules in case if pritein urea. 2. An abnirmal milecules priduced by abnirmal metabilic pathway. This can result frim genetc mutatin that priduce changes in pritein filding and transpirt. 3. Accumulatin if pigmets. Cilired substances accumulated because cells cannit get rid if it thriugh enzymatc degradatin ir ti transpirt it ti the iutside. This can include accumulatin if melanin pigment, anthracisis (accumulatin if carbin pigment) and tatiiing. Degeneratve changes: I//calcifcatin: abnirmal depisitin if ca++ salts. There are twi types 1. dystriphic calcifcatin: ca++ depisitin in ninviable ir dying tssue that iccur despite nirmal serum ca++. This type may be seen in: a. area if necrisis (any type if necrisis) b. advanced atherisclerisis c. damaged ir aged heart valves 2. metastatc calcifcatin: ca++ depisitin in viable tssue. It is almist always reflect serum hypercalcemia. II//hyaline change: this refers ti intra ir extracellular himigenius pinkish alteratin in sectin stained by hematixylin and eisin stain. Intracellular hyaline chan esn i. hyaline driplet in renal tubules in patents with priteinuria ii. russel bidies in plasma cells iii. viral inclusiins iv. alcihilic hyaline in liver cells (Malliry bidies) extracellular hyaline chan es i. cillagen in ild scar ii. in arteriilar wall in patents with hypertensiin and diabetes