病理學(xué)教學(xué)課件：3-組織更新與修復(fù)：再生和纖維化

ChapterIII

TissueRenewalandRepair:RegenerationandFibrosis組織更新與修復(fù)：再生和纖維化FibrosisTissuescar

Stimuliremovedsoon(acuteinjury)PersistenttissuedamageIntacttissueframeworkDamagedtissueframeworkSuperficialwoundsSomeinflammatoryprocessesDeepwoundsPerfectreturnofnormalstructure&function

Functionalimperfect

Permanentdysfunction

RegenerationRestitutionofnormalstructureHealingOrganizationofexudateScarformationTissueRenewalandRepairCelldeathPluripotent-cangiverisetoallthetissues.

Regenerativemedicine:stemcellsmayonedaybeusedtorepairinjuryinhumantissues,includingheart,brain,andskeletalmuscle.EmbryonicStemCellsmorerestricteddifferentiationcapacityandusu.lineage-specificAdultStemCellsProlongedself-renewalcapacity+AsymmetricreplicationCellcycleProliferativeCapacityofDifferentCellsLabilecells:

proliferatethroughoutlifeusu.bystemcellssurfacecells;cellsofbonemarrowandhematopoietictissuesRegenerationofsquamouscellsStable(quiescent)cells:normallyhavealowlevelofreplication,butcanundergorapiddivisioninresponsetostimuliandarethuscapableofreconstitutingthetissueoforigin

glandularepitheliaandmesenchymalcellsRegenerationofhepatocytesRegenerationofglandularepithelia

RegenerationofhumanliverCTscansofthedonorliverinlivingdonorhepatictransplantationTheliverofthedonorbeforetheoperation.Therightlobe,whichwillbeusedasatransplant,isoutlined.Oneweekafterperformanceofpartialhepatectomytoremovetherightlobe.Notethegreatenlargementoftheleftlobe(outlined),withoutregrowthoftherightlobe.RegenerationofMesenchyamlcellsRegenerationofChondrocytesRegenerationofosteocytesRegenerationofcapillariesRegenerationofneuralfibersPermanent(nondividing)cells:haveleftthecellcycleandcannotundergomitoticdivisioninpostnatallifeneurons,skeletalandcardiacmusclecellsRegenerationofskeletalmusclecellsCell-cellinteraction

ConditionedmediumContactinhibitionExtracellularmatrix

Laminin:EpitheliaFibroblastsFibronectin:EpitheliaFibroblastsGrowthfactors

EGF,TGF-A,PDGF,aFGF,bFGF,IGF-1,IGF-2,VEGF,HGF,G-CSF,M-CSF,G-CSF,RYTHROPOITIN,ILs,TNF,IFN,NGFRegeneration-factorsinfluencingregenerationHealing

-cutaneouswoundhealingTheprototypeoftissuerepairMediatedthroughGFsandCytokinesDynamic,changingandoverlappingprocessesGrossly:

pink,soft,granularappearanceGranulationTissue-hallmarkofhealingHistologically:Newbloodvessels;Inflammatorycells;FibroblastsGranulationtissueNumerousbloodvessels,edema,andalooseECM,occ.InflammatorycellsTrichomestain:minimalmaturecollegen(blue)MaturescarScatteredvascularchannelsTrichomestain:densecollagen(blue)HealingbyfirstintentionHealingbysecondintentionWoundNarrowsurgicalincisionalspace,cleananduninfectedLargedefects,morenecroticdebrisandexudateInflammationmildmoreintenseRegenerationintactepidermisthinnerepidermisdermalappendageswillbepermanentlylostinbothsituationsGranulationTissuessmallamountabundantRemodelingCharacteristic“woundcontraction”,todecreasethegapbetweentheedgesofthewoundScarformationlittlesubstantialBasedonthenatureofthewound,twotypesofhealingComplicationsinCutaneousWoundHealingDeficientscarformationWounddehiscencebymechanicalstressUlcerationduetoinadequatevasculationExcessivecollagenoftherepaircomponentsAraisedscar:hypertrophicscarScargrowsbeyondtheboundariesoftheoriginalwoundanddoesnotregress:keloid

Exuberantproliferationoffibroblastsandotherconnectivetissueelements,mayrecurafterexcision:desmoidoraggressivefibromatoses,itisalow-gradetumorKeloid：excesscollagendepositionintheskin,formingaraisedscar，andgrowsbeyondtheboundariesoftheoriginalwoundsNormalscarFactorsinfluencingwoundhealingSystemic

NutritionMetabolicstatusCirculatorystatusHormonesLocalInfectionMechanicalfactorsForeignbodiesSize,locationandtypesofwoundAlteredphysiologicstimuliInjuriousstimuliInabilitytoadaptAdaptationMetabolicstimuliDegenerationCellinjuryCelldeathToomuchoverloadedCellularResponsesforKeepingTheir“Homeostasis”AtrophyHypertrophyHyperplasiaMetaplasiaHydropicFatty,

CholesteralHyaline,AmyloidosisLipofuscin,HemosiderinApoptosisNecrosis:Coagulative,Liquefactive,Caseous,Gangrene,Fat,FibrinoidErosion

&Ulcer;Sinus&Fistula;Cavitation&EncapsulationCalcification&PsammomaBodyTissueRenewalandRepai