PATHOLOGY - lecture - Healing & Repair.pdf

Healing and repair processes

1. Ephraim Imhotep Zulu, BSc BMS, MSc Path
University of ZambiaSchool of Health Sciences,Dept. of Biomedical Sciences,
Pathology
Lecture #4
Tissue Healing & Repair


| Version 01 | April 2017

Procedural document:
Rare disease nomenclature in English


www.orpha.net www.orphadata.org

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3. Lecture Outline
•Proliferative Capacities of Tissues
•Tissue Repair
•Patterns of Wound Healing
•Factors that Influence Wound Healing
•Complications of Wound Healing
•Fracture Healing
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4. Learning Objectives:
Attheendofthislecture,thestudentisexpectedto
•KnowthedifferenttypesandPatternsofWoundHealingprocesses
•Understand the process of Tissue Repair
•AppreciatetheProliferativeCapacitiesofTissues
•Differentiate/CompareandContrastthefollowingpairsofterms:
•PrimaryunionandSecondaryunion
•KeloidsandHypertrophicscars
•UnderstandandAppreciatethedifferentFactorsthatInfluenceWoundHealing
•Know the Complications of Wound Healing
•Understand how Fracture Healing occurs
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5. Synopsis
•Healing,asusedinapathologicalcontext,referstothebody’sreplacementof
destroyedtissuebylivingtissue.
•Thehealingprocessinvolvestwodistinctprocesses:RegenerationandRepair
•Regeneration-abilityofatissuetoreplacethedamagedcomponentsandessentially
returningtoanormalstate.Itistherenewalofalosttissueinwhichthelostcellsare
replacedbyidenticalonesanditinvolvestwoprocesses:
•ProliferationofsurvivingcellstoreplacelosttissueandMigrationofsurvivingcells
intothevacantspace.
•Repair-thereplacementoflosttissuebygranulationtissuewhichmaturestoform
scartissue
•Fibrosis-extensivedepositionofcollagenthatoccursintheorgansasaconsequence
ofchronicinflammation,orafterextensiveinfarction.
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Proliferative Capacities of Tissues
The ability of tissues to repair
themselves is critically influenced
by their intrinsic proliferative
capacity.

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10. Tissue Repair
•Repairistheorderlyprocessbywhichlosttissueis
eventuallyreplacedbyascar.
•Tissuescontainingpermanentcellscannothealby
regeneration.
•Ratherthelostpermanentcellsarereplacedby
formationofgranulationtissue.
•Ingranulation-tissueformation,threephasesmaybe
observed.
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11. Phases: Granulation tissue formation
1.Phaseofinflammation
•Inflammatoryexudatecontainingpolymorphsisseenin
theareaoftissueinjury.
2.Phaseofdemolition
•Thedeadcellsliberatetheirautolyticenzymes,andother
enzymes(proteolytic)comefromdisintegrating
polymorphs.
•Macrophagesingestparticulatematter.
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12. 3.Ingrowthofgranulationtissue
•Thisischaracterizedbyproliferationoffibroblastsandaningrowth
ofnewbloodvesselsintotheareaofinjury,withavariablenumber
ofinflammatorycells.
•Fibroblastsactivelysynthesizeandsecretefibronectin,
proteoglycans,andcollagen.
•Asthecollagencontentofthewoundincreases,manyofthenewly
formedvesselsdisappear.
•Thisvascularinvolutionwhichtakesplaceinafewweeks,
dramaticallytransformsarichlyvascularizedtissueintoapale,
avascularscartissue.
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13. “Healthy” Granulation Tissue
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14. Wound Contraction
•Isamechanicalreductioninthesizeofthedefect.
•Thewoundisreducedapproximatelyby70-80%ofitsoriginal
size.
•Ifcontractionisprevented,healingisslowandalargeugly
scarisformed.
•Contractionissaidtobeduetocontractionbymyofibroblasts.
•Twotothreedaysaftertheinjurytheymigrateintothewound
andtheiractivecontractiondecreasethesizeofthedefect.
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15. Patterns of Wound Healing
•Healingofawounddemonstratesbothepithelialregeneration
(healingoftheepidermis)andrepairbyscarring(healingofthe
dermis).
•Therearetwopatternsofwoundhealingdependingontheamount
oftissuedamage:
•Healingbyfirstintention(Primaryunion)andHealingbysecond
intention(Secondaryunion)
•Thesetwopatternsareessentiallythesameprocessvaryingonlyin
amount.
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Attribute Primary healingSecondary healing
Nature of the woundWound is small in sizeWound is largein size
Wound has regular marginsWound has irregular
margins
Wounds generally uninfectedWounds maybe infected
Clot sizeSmall Large
inflammationLess intenseMore intense
Granulation tissueSmall Large
Scar tissueSmall Large
Wound contractionAbsent Present
Outcome Neat linear scarContracted irregular scar

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19. Secondary Wound Healing
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20. Factors that Influence Wound Healing
•Infection
•Nutrition
•Glucocorticoids
•Mechanicalvariables
•Poorperfusion,
•Foreignbodies
•Type (and volume) of
tissue injured
•Type and size of wound
•Location of the wound
•Movement
•Ionizingradiation
•Metabolicstatus
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21. Factors That Influence Wound Healing..,
Infection
•isthesinglemostimportantcauseofdelayinhealing;it
prolongstheinflammationphaseoftheprocessand
potentiallyincreasesthelocaltissueinjury.
Nutrition
•proteinandvitaminCdeficiency,inhibitscollagensynthesis
andretardshealing.
Poorperfusion,
•Alsoimpairshealing.
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22. Glucocorticoids (steroids)
•have an anti-inflammatory effects,
and may result in poor wound
strength due to diminished fibrosis.
Mechanical variables
•such as increased local pressure or
torsion may cause wounds to pull
apart, or dehisce (see picture).
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Dehiscence

23. •Foreignbodies
•suchasfragmentsofsteel,glass,orevenboneimpede
healing.
•Type(andvolume)oftissueinjured
•Completerestorationcanoccuronlyintissuescomposed
ofstableandlabilecells;eventhen,extensiveinjurywill
probablyresultinincompletetissueregeneration.
•Injurytotissuescomposedofpermanentcellsmust
inevitablyresultinscarring
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24. Type, size, and location of the wound
•Aclean,asepticwoundproducedbythesurgeon’sscalpel
healsfasterthanawoundproducedbyblunttrauma,which
exhibitsabundantnecrosisandirregularedges.
•Smallbluntwoundshealfasterthanlargerones.
•Injuriesinrichlyvascularizedareas(e.g.,theface)healfaster
thanthoseinpoorlyvascularizedones(e.g.,thefoot).
•Inareaswheretheskinadherestobonysurfaces,asininjuries
overthetibia,woundcontractionandadequateappositionof
theedgesaredifficult.
•Hence,suchwoundshealslowly.
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25. •Movement
•Earlymotion,particularlybeforetensilestrengthsubjects
awoundtopersistenttrauma,thuspreventingor
retardinghealing.
•Ionizingradiation
•Priorirradiationleavesvascularlesionsthatinterfere
withbloodsupplyandresultinslowwoundhealing.
•Acutely,irradiationofawoundblockscellproliferation,
inhibitscontraction,andretardstheformationof
granulationtissue.
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26. Metabolic status
•Poorlycontrolleddiabetesmellitusisassociatedwith
delayedwoundhealing.
•Theriskofinfectionincleanwoundapproachesfivefold
theriskinnon-diabetics.
•Indiabeticpatients,therecanbeimpairedcirculation
secondarytoarteriosclerosisandimpairedsensationdue
todiabeticneuropathy.
•Theimpairedsensationrendersthelowerextremity
blindtoeverydayhazards.
•Hence,indiabeticpatients,woundshealveryslowly.
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27. Complications of Wound Healing
Abnormalitiesinbasichealingprocessesresultinthe
complicationsofwoundhealing.
•Infection
•DeficientScarFormation(wounddehiscenceandulceration).
•ExcessiveScarFormation(HypertrophicscarandKeloid)
•ExcessiveContraction
•Epidermalcysts
•Pigmentation
•Neoplasia
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28. Complications.,
•Infection.Infectedwoundmayprovidetheportalofentryfor
manyorganisms.
•Epidermalcystscandevelopduetopersistenceofepithelial
cellsatthesiteofwoundhealing.
•Pigmentationmaydevelopduetoeithercoloredparticleleft
inthewoundorduetohemosiderinpigment.
•Neoplasia:Forexamplesquamouscellcarcinomamay
developinMarjolin’sulcer,whichisthescarthatfollowsburns
inskin..
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29. Deficient Scar Formation
•Inadequateformationofgranulationtissueoradeficientscarformationcancause
wounddehiscenceandulceration.
•1.Dehiscence(thewoundsplittingopen)orruptureofawoundismostcommonlife-
threateningcomplicationafterabdominalsurgery.Itisduetoincreasedabdominal
pressure/mechanicalstressontheabdominalwoundfromvomiting,coughing,or
ileus.
•2.Ulceration:Woundscanulcerateduetoinadequateangiogenesisduringhealing.
Nonhealingwoundsalsodevelopinregionsdevoidofsensation..
•3.Incisionalherniaresultingfromweakscarsoftheabdominalwallduetoadefect
causedbypriorsurgery.Theyareduetoinsufficientdepositionofextracellularmatrix
orinadequatecross-linkinginthecollagenmatrix.
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30. Excessive Contraction
•Adecreaseinthesizeofawoundduetomyofibroblastsisknownascontraction.
Anexaggerationofthiscontractionistermedcontracture(cicatrisation)and
resultsindeformitiesofthewoundandthesurroundingtissues.
•Contractureisalsosaidtoariseasaresultoflatereductioninthesizeofthe
wound.
•Consequencesofcontractures:
•–Compromisemovements:forexample,contracturesthatfollowsevereburns
cancompromisethemovementoftheinvolvedregionandjointmovements.
•–Obstruction:forexample,inGItractcontracture(stricture)cancause
intestinalobstruction.
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31. Contracture.,
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Exam Preparatory Manual for Undergraduates—General and Systemic Pathology72
Excessive Contraction
xA decrease in the size of a wound due to myo!broblasts is known as contraction.
xAn exaggeration of this contraction is termed contracture and results in deformities of the
wound and the surrounding tissues.
xConsequences of contractures:
–Compromise movements: for example, contractures that follow severe burns can
compromise the movementof the involved region (Fig. 3.8) and joint movements.
–Obstruction: for example, in GI tract contracture (stricture) can cause intestinal
obstruction.
Others
1. Infection of wound by microbes.
2. Epidermal cysts can develop due to persistence of epithelial cells at the site of wound
healing.
3. Pigmentation may develop due to either colored particle left in the wound or due to
hemosiderin pigment.
4. Neoplasia: For example squamous cell carcinoma may develop in Marjolin’s ulcer,
which is the scar that follows burns in skin.
Fibrosis
xNormal wound healing is associated with deposition of collagen.
x"e excessive deposition of collagen and other ECM components in a tissue is termed as
!brosis. It is usually observed in chronic in#ammation.
xTGF-E is an important !brogenic agent.
xExamples of disorders with fibrosis: Cirrhosis of liver, pneumoconioses, chronic pancreatitis
and glomerulonephritis.
Contracture: Exaggeration
of wound contraction.
Common sites for
contractures are palms,
the soles and the anterior
aspect of the thorax.
Infection of the wound is
an important and common
complication of wound
healing.
TGF-!: Important
"brogenic agent.
Fig. 3.7: Exuberant granulation tissue at
the tip of the finger
Keloids: Excessive
deposition of type III
collagen.
Fig. 3.8: Wound contracture—Severe contracture of a
wound on the right side of neck, following burns
Scar contracture in a boy after scald

32. Excessive Scar Formation
•Excessiveformationofthecomponentsoftherepairprocesscanresultin:
•Hypertrophicscar:Theaccumulationofexcessiveamountsofextracellularmatrix,
mostlycollagenmaygiverisetoaraisedscaratthesiteofwoundknownasa
hypertrophicscar.
•Theyusuallydevelopafterthermalortraumaticinjury,whichinvolvesthedeeplayers
ofthedermis.
•Keloid:Ifthescartissuegrows/progressbeyondtheboundariesoftheoriginal
woundanddoesnotregress,itiscalledakeloid.Thus,keloidisanexuberantscarthat
recurswithstilllargerkeloidaftersurgicalexcision.
•Thecauseisunknownandisthoughttobeduetolackoftheproper
metalloproteinases(collagenases)todegradetypeIIIcollagen
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33. Keloids.,
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Excess collagen deposition in the skin
forming a raised scar known as a keloid

34. Hypertrophic Scars
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36. Keloid Vs Hypertrophic Scars
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37. Keloid Vs Hypertrophic Scars
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Fracture Healing

39. References & Credits
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•BaroneJ,CastroM.A.(2016),USMLEStep1PathologyLectureNotes,
PublishedbyKaplanMedical,adivisionofKaplan,Inc.750ThirdAvenue,New
York,NY10017:ISBN:978-1-5062-0772-8
•RobbinsSLandKumarV(2013).BasicPathology(9thEdition).WBSaunders
Co.London.
•BezabehM,TesfayeA,ErgichoB,ErkeM,MengistuS,BedaneA,DestaA(2004);
StudentsLectureNoteSeriesGeneralPathologyForHealthsciencestudents
JimmaUniversity,Ethiopia.
•RubinE,RubinR,StrayerD.S.(2012)Rubin`sPathology:Clinicopathologic
FoundationsofMedicine(6thEdition),LippincottWilliams&Wilkins,aWolters
Kluwerbusiness.Philadelphia,PA.
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End of Lecture
Ephraim Imhotep Zulu
Pathology
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