Tissue Repair - · PDF file•Tissue repair = restoraon of ,ssue architecture and func,on aer an injury • Occurs in two ways: • Regeneraon of injured ,ssue • Replacement by connec,ve

TissueRepairKris,neKra.s,M.D.

•  Tissuerepair=restora,onof,ssuearchitectureandfunc,ona.eraninjury

•  Occursintwoways:•  Regenera,onofinjured,ssue•  Replacementbyconnec,ve,ssue(scarring)

•  Usually,,ssuerepairinvolvesbothprocesses

•  Involvescellprolifera,on,andinterac,onbetweencellsandextracellularmatrix

TissueRepair

•  Importantbackgroundfacts•  Cellularprolifera,on•  Growthfactors•  Theextracellularmatrix

•  Theprocessof,ssuerepair•  Regenera,on•  Scarring•  Anillustra,on:skinwoundhealing•  Whydogoodwoundsgobad?

TissueRepairLectureOutline

•  Importantbackgroundfacts•  Cellularprolifera,on


•  Lotsofcellsproliferateduring,ssuerepair:•  Injured,ssueremnants•  Vascularendothelialcells•  Fibroblasts

•  Youneedtoknowafewthingsabout:•  Thecellcycle•  Theprolifera,vecapaci,esofdifferent,ssues•  Stemcells•  Growthfactors•  Theextracellularmatrix

CellularProlifera,on

The Cell Cycle

•  Con,nuouslydividing(labile),ssues•  Stable,ssues•  Permanent,ssues

Tissuesofthebodyaredividedintothreegroups:


•  Con,nuouslydividing(labile),ssues•  Cellsarecon,nuouslyprolifera,ng•  Caneasilyregeneratea.erinjury•  Containapoolofstemcells•  Examples:bonemarrow,skin,GIepithelium



Stem cells in skin

Stem cells in GI epithelium

•  Con,nuouslydividing(labile),ssues•  Stable,ssues

•  Cellshavelimitedabilitytoproliferate•  Limitedabilitytoregenerate(exceptliver!)•  NormallyinG0,butcanproliferateifinjured•  Examples:liver,kidney,pancreas



•  Con,nuouslydividing(labile),ssues•  Stable,ssues•  Permanent,ssues

•  Cellscan’tproliferate•  Can’tregenerate(soinjuryalwaysleadstoscar)•  Examples:neurons,cardiacmuscle



The Cell Cycle and Different Cell Populations

•  Importantbackgroundfacts•  Cellularprolifera,on•  Growthfactors


•  Veryimportantin,ssuerepair.

•  Ac,ons:•  S,mulatecelldivisionandprolifera,on•  Promotecellsurvival

•  Hugelist!Usuallyhave“GF”inname:•  EGF(epidermalgrowthfactor)•  TGF(transforminggrowthfactor)•  PDGF(platelet-derivedgrowthfactor)

GrowthFactors



•  ECMisthenetworkthatsurroundscells

•  Twoforms:inters,,almatrixandbasementmembrane

•  Doeslotsofthings!•  Sequesterswaterandminerals•  Givescellsascaffoldtoadhereto•  Storesgrowthfactors

TheExtracellularMatrix

The Extracellular Matrix

•  Bo`omline:ECMregulatesprolifera,on,movement,anddifferen,a,onofthecellslivinginit.

•  IfyouscrewupyourECM,youcan’tregenerate!You’llformascarinstead.

ExtracellularMatrix


•  Theprocessof,ssuerepair•  Regenera,on


•  Occursallthe,meinlabile,ssues•  Cellsareconstantlybeinglostandreplaced•  Ifdemandincreases,supplyincreaseseasily

•  Occursinlimitedforminstable,ssues•  Removeonekidney:theotheroneundergoeshypertrophyandhyperplasia

•  Removehalfoftheliver:itwillgrowback

•  Onlyoccursifresidual,ssueisintact!

Regenera,on

Liver before

resection

Liver 1 week

after resection

right lobe to be

resected

left lobe now

enlarged


•  Theprocessof,ssuerepair•  Regenera,on•  Scarring


•  Ifinjuryissevere,regenera,oncan’thappen

•  So,fibrosis(ascar)replacestheinjured,ssue

•  Fourcomponentstothisprocess:•  Newvesselforma,on(angiogenesis)•  Fibroblastprolifera,on•  Synthesisofcollagen(scarforma,on)•  Remodelingofscar

Scarring

•  By24hours:•  Endothelialcellsstartprolifera,ng•  Fibroblastsemigrate

•  By3-5days:•  Granula,on,ssuepresent

•  Weekslater:•  Densefibrosis(scar)•  Scarisremodeledover,me

Scarring

Summary:

1.Makegranula,on,ssue

2.Turnitintoachunkofcollagen

Scarring

Granula,on,ssue

Scar

Q.Is“granula,on,ssue”thesamethingas“granuloma”?


A.No!

Granuloma


A.No!

Q.Isitthesamethingas“chronicgranulomatousdisease”?


A.No!

Q.Isitthesamethingas“chronicgranulomatousdisease”?

A.No!


•  Theprocessof,ssuerepair•  Regenera,on•  Scarring•  Anillustra,on:skinwoundhealing


•  Firstinten,on

•  Secondinten,on

SkinWoundHealing

first intention healing second intention healing

•  Occursinsmallwoundsthatcloseeasily

•  Epithelialregenera,onpredominatesoverfibrosis

•  Healingisfast,withminimalscarring/infec,on

•  Examples:•  Papercuts•  Well-approximatedsurgicalincisions•  Replacedperiodontalflaps

HealingbyFirstInten,on

•  By24hours•  By3-7days•  Weekslater


•  By24hours•  clotforms•  neutrophilscomein•  epitheliumbeginstoregenerate


•  By24hours•  By3-7days•  Macrophagesarrive•  Granula,on,ssueisformed•  Collagenbeginstobridgeincision•  Epitheliumincreasesinthickness


•  By24hours•  By3-7days•  Weekslater•  Granula,on,ssueisgone•  Collagenisremodeled•  Epidermisisfullandmature

(butwithoutdermalappendages)•  Eventually,scarforms


6 hours 24 hours

2 days

1 week

•  Occursinlargerwoundsthathavegapsbetweenwoundmargins

•  Fibrosispredominatesoverepithelialregenera,on

•  Healingisslower,withmoreinflamma,onandgranula,on,ssueforma,on,andmorescarring.

•  Examples:•  Infarc,on•  Largeburnsandulcers•  Extrac,onsockets•  External-bevelgingivectomies

HealingbySecondInten,on

•  Moreinflamma,on

•  Moregranula,on,ssue

•  Woundcontrac,on

Secondinten,onhealinghas:

SkinWoundHealing

Pressureulcerofskin

Skinulcer:largegapbetweenedges

Skinulcer:granula,on,ssue

Skinulcer:re-epithelializa,on

•  Atsutureremoval:10%

•  Rapidincreaseovernext4weeks

•  Atthirdmonth:70-80%

Woundstrength

SkinWoundHealing




•  Extrinsicfactors•  Infec,on•  Diabetes•  Steroids

•  Typeof,ssueinjured(labilevs.permanent)

•  AberrantcellgrowthorECMproduc,on•  Keloidscars•  Proudflesh

Whydogoodwoundsgobad?

Keloidscar

Keloidscar

Proudflesh

Proudflesh

Proudflesh




•  Notallinjuriesresultinpermanentdamage;someareresolvedalmostcompletely.

•  Moreo.en,thereissomedegreeofscarring.

•  Scarringisusuallygood(providesaresilientpatch)butoccasionallybad(cancausepermanentdysfunc,on)

TissueRepairSummary

Documents

Tissue Repair - · PDF file•Tissue repair = restoraon of ,ssue architecture and func,on aer an injury • Occurs in two ways: • Regeneraon of injured ,ssue • Replacement by connec,ve