16. kuliah pemulihan jaringan (1)

8/18/2019 16. Kuliah Pemulihan Jaringan (1)

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Tissue Renewal,

Regeneration and Repair

Dr. Upik A. Miskad, PhD, SpPA


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Introduction healing Process

• Injur to cells n tissues induce a series o!

e"ents that contain da#age and healing

process.

• Repair, so#eti#es called healing, re!ers to

the restoration o! tissue architecture and

!unction a!ter an injur.

• repair is often used for parenchymal andconnective tissues and healing for surface

epithelia,


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• $. Regeneration

% Proli!eration o! residual uninjured cells and tissues to

replace lost structure

% Maturation o! tissue ste# cells

% Replace#ent o! injured cells & cells o! the sa#e tpe % So#e ti#es no residual trace.

• '. Repair/ SCAR Formation

% (o#&ination o! regeneration and scar !or#ation

% Replace#ent & connecti"e tissue

% )ea"e per#anent scar.

*I+RSIS descri&e e-tensi"e deposition o! (ollagen.



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• ECM components are essential for woundhealing because provide the framework for cell

migration maintain the correct cell polarit! for

the re"assembl! of multila!er structures and

participate in the formation of new blood vessels#angiogenesis$

• Cells in the ECM #fibroblasts macrophages and

other cell t!pes$ produce growth factorsc!tokines and chemokines that are critical for

regeneration and repair.


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(M / -tracellular Matri-


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• REGENERASI

Proli!erasi sel atau jaringan untuk

#enggantikan struktur

ang hilang

• REPAIR /

PERBAIKAN

0o#&inasi regenerasi1 pe#&entukan skar.


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(ontrol o! nor#al cell proli!eration and

tissue growth

• 2u#lah populasi sel pada

jaringan ditentukan oleh /

Proli!erasi

Di!erensiasi Apoptosis

%roliferasi bisa dipicu

kondisi fisiologis

maupun patologis


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Tissue Proli!erati"e Acti"it


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$. (ontinuosl di"iding cells3 la&ile

cells• %roliferate throughout life replacing those that are

destro!ed.• &hese tissues include

% surface epithelia such as stratified s'uamous

epithelia of the skin oral cavit! vagina and cervi() % the lining mucosa of all the e(cretor! ducts of the

glands of the bod! #e.g. salivar! glands pancreasbiliar! tract$)

% the columnar epithelium of the *+ tract and uterus)

% the transitional epithelium of the urinar! tract andcells of the bone marrow and hematopoietic tissues. %

Most of them derived from A,-& S&EM CES


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'. 4uiescent3 Sta&le cells

• have a low level of replication) can undergo rapid division inresponse to stimuli and are thus capable of reconstituting the

tissue of origin.

• Consist of

% the parench!mal cells of liver kidne!s and pancreas

% mesench!mal cells such as fibroblasts and smooth musclechondroc!tes and osteoc!tes )

% vascular endothelial cells) and

% l!mphoc!tes and other leukoc!tes.

% E0AM%E the abilit! of the liver to regenerate after partialhepatectom! and after acute chemical in1ur!.

% Fibroblasts in particular can proliferate e(tensivel! as in

healing processes and fibrosis.


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5. 6ondi"iding 3per#anent cells

Contain cells that have left the cell c!cleand cannot undergo mitotic division inpostnatal life.

+nclude neurons and skeletal and cardiacmuscle cells+f neurons in the central nervous s!stem are

destro!ed the tissue is generall! replaced b! theglial cells. Recent research limited neurogenesisfrom stem cells ma! occur in adult brains.

Cardiac muscle has ver! limited if an! regenerativecapacit! and a large in1ur! to the heart muscle asma! occur in m!ocardial infarction is followed b!scar formation.


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Repair & Scar

*or#ation• • Tissues are repaired & replace#ent

with connecti"e tissue and scar!or#ation i! the injured tissue is not

capa&le o! proli!eration or i! the

structural !ra#ework is da#agedandcannot support regeneration


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STPS I6 S(AR *RMATI6

• Angiogenesis 7pe#&entukan pe#&uluh

darah &aru8

• *or#ation o! 9ranulation Tissue. 7Migrasi

dan proli!erasi !i&ro&las, "essel dan sel

radang #e#&entuk jaringan granulasi8

• Re#odelling (onnecti"e Tissue 7Deposisi

(M, Maturasi dan reorganisasi jaringan

!i&rosa #e#&entuk scar ang sta&il8


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• Macrophages pla a central

role in repair & clearing

o!!ending agents and dead

tissue, pro"iding growth !actors

!or the proli!eration o! "ariouscells, and secreting ctokines

that sti#ulate !i&ro&last

proli!eration and connecti"e

tissue snthesis and

deposition.• M' 7alternati"el Macrophage

pla a role in Repair8• M$ 7classicall Macrophage pla in

in!la##ation8


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• Pe#ulihan di#ulai dala# waktu ': ja# setelah jejas. Melalui e#igrasi dan proli!erasi sel

!i&ro&last dan endotel• Dala# 5;< hari #uncul jaringan granulasi

• Makroskopik / warna #erah #uda, halus dan&ergranula

• Mikroskopik / ditandai dengan proli!erasi!i&ro&las dan pe#&entukan pe#&uluh darahkecil 7kapiler8 &aru. Pe#& darah &aru ini#e#punai interendothelial junction ang &elu##enutup se#purna &ocor protein dansel darah #erah ke ekstraseluler ede#a.


17/382AR+3*A3 *RA3-AS+ MA&-RE SCAR


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A69I96SIS Angiogenesis is the process o! new &lood "essel de"elop#ent !ro# e-isting "essels

and consists o! the !ollowing steps /

• • =asodilation in response to nitric o-ide and increased per#ea&ilit induced &"ascular endothelial growth !actor 7=9*8

• • Separation o! perictes !ro# the a&lu#inal sur!ace and &reakdown o! the &ase#ent

#e#&rane to allow !or#ation o! a vessel sprout

• • Migration o! endothelial cells toward the area o! tissue injur

• • Proli!eration o! endothelial cells just &ehind the leading!ront 7>tip>8 o! #igrating cells

• • Re#odeling into capillar tu&es

• • Recruit#ent o! periendothelial cells 7perictes !or s#all capillaries and s#ooth

#uscle cells !or larger "essels8 to !or# the #ature "essel

• • Suppression o! endothelial proli!eration and #igration and deposition o! the

&ase#ent #e#&rane


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• The process o! angiogenesis in"ol"es se"eralsignaling pathwas, cell;cell interactions,(M proteins, and tissue en?#es.

% 9rowth *actors 7=9*, *9*;' dll8

% 6otch Signaling pathwa 7regulates thesprouting and &ranching new "essels8

% (M proteins 7integrin dll8

% n?#es 7MMPs8


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9R@T *A(TR in A69I96SIS

• Vascular endothelial growth factors (VEGFs), mainly VEGF-

A stimulates oth #igration and proli!eration o! endothelial

cells, capillar sprouting It pro#otes "asodilation &sti#ulating the production o! 6 .

• Firolast growth factors (FGFs), #ainl *9*;', sti#ulates

the proli!eration o! endothelial cells, #igration o!

#acrophages, !i&ro&lasts to the da#aged area, sti#ulatesepithelial cell #igration to co"er epider#al wounds.

• Angiopoietins ! and " (Ang ! and Ang ") are growth factors

that pla a role in angiogenesis and the structural

#aturation o! new "essels & the recruit#ent o! perictes,

s#ooth #uscle cells 1 the deposition o! connecti"e tissue.

• The growth !actors PD9* and T9*;B also participate in the

sta&ili?ation process/


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#eposition of $onnective %issue• 7$8 #igration and proli!eration o! !i&ro&lasts into the site

o! injur and• 7'8 deposition o! (M proteins produced & these cells.

• These processes are orchestrated & locall produced

ctokines and growth !actors, including PD9*, *9*;',

and T9*;+eta.• %ransforming growth factor- &eta (%GF-&eta) is the

most i#portant ctokine !or the snthesis and deposition

o! connecti"e tissue proteins. T9* +eta has an

antiin!la##ator ctokine e!!ect.


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FIGURE. Main components of the extracellular matrix (ECM), includingcollagens, proteoglcans, and adhesi!e glcoproteins. "oth epithelial andmesenchmal cells (e.g., #$ro$lasts) interact %ith ECM !ia integrins."asement mem$ranes and interstitial ECM ha!e di&erent architecture andgeneral composition, although there is some o!erlap in their constituents.

For the sa'e of simpli#cation, man ECM components (e.g., elastin, #$rillin,h aluronan and s ndecan are not included.


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RMD))I69 * (66(TI= TISSU

• A!ter its deposition, the connecti"e tissue in the scar

continues to &e #odi!ied and re#odeled. The outco#e o!the repair process is in!luenced & a &alance &etween

snthesis and degradation o! (M proteins.

• The degradatio o! collagens and other (M & a !a#il o!

matri' metalloproteinases (s)*

• MMPs include interstitial collagenases, which clea"e !i&rillar

collagen 7MMP;$, ;' and ;58C gelatinases 7MMP;' and 8,

which degrade a#orphous collagen and !i&ronectinC and

stro#elsins 7MMP;5, ;$E, and ;$$8, which degrade a

"ariet o! (M constituents, including proteoglcans,la#inin, !i&ronectin, and a#orphous collagen


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*actors That In!luence

Tissue Repair

• In!ection

• Dia&etes is a #eta&olic disease

• 6utritional status, "ita#in (de!icienc, inhi&its collagen

snthesis

• 9lucocorticoids 7steroids8 inhi&i

T9*+eta


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*actors That In!luence

Tissue Repair • Mechanical factorsC local pressure or torsion

• %oor perfusion due either to arteriosclerosis or

o&structed "enous drainage 7e.g., in "aricose "eins8

• Foreign bodies such as !rag#ents o! steel, glass,or e"en &one i#pede healing.

• &he t!pe and e-tent o! tissue injur a!!ects the

su&seFuent repair. (o#plete restoration can occur

onl in tissues co#posed o! sta&le and la&ile cellsC

• &he location o! the injur and the character o! the

tissue in which the injur occurs are also i#portant.


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(6T P6GM+UA6 )U0A

• (ontoh paling sederhana/ pene#&uhan suatu insisi

&edah ang &ersih dan tidak terin!eksi

• H penyatuan primer atau penyemuhan primer

• @hen the injur in"ol"es onl the epithelial laer, the

principal #echanis# o! repair is epithelial regeneration,

also called pri#ar union or healing & !irst intention.

• +ealing y First ntention

%E34EM5-6A3 %R+MER%E34EM5-6A3 %R+MER


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P6GM+UA6 S0U6DR

• (ontoh seperti pada in!ark, ulserasi, pe#&entukan a&ses

atau &ahkan luka &esar • H penyatuan seunder atau penyemuhan seunder*

• @hen cell or tissue loss is #ore e-tensi"e, such as in large

wounds, a&scesses, ulceration, and ische#ic necrosis7in!arction8 in parench#al organs, the repair process

in"ol"es a co#&ination o! regeneration and scarring.

• In healing o! skin wounds & second intention, also nown

as healing & secondary union


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Pene#&uhan sekunder &er&eda dengan

pene#&uhan pri#er /

• 0erusakan jaringan ang luas #engaki&atkan ju#lah de&ris nekrotik, eksudat dan !i&rin angle&ih &anak ang harus disingkirkan, se&agaiaki&atna reaksi radang #enjadi le&ih he&at.

• 2aringan granulasi ang ter&entuk jauh le&ih&esar. Pada u#u#na, jaringan granulasi angle&ih &esar akan #enghasilkan suatu #assa

jaringan parut ang le&ih &esar

• Pene#&uhan sekunder #enunjukkan!eno#ena ontrasi lua.


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0MP)I0ASI 3 P6GIMPA69A6

P6GM+UA6 )U0A

• 0eloid

% Penu#pukan kolagen g &erle&ihan

• granulasi esueran atau proud flesh

% 2aringan granulasi &erle&ihan

•0ontraktur


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KELOID


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• *i&rosis in

Parench#al

organ• *i&rosis is a pathologic

process induced &

persistent injurious sti#uli

such as chronic in!ections

and i##unologic

reactions, and is tpicall

associated with loss o!

tissue 7*ig. 5;5$8.

• It #a &e responsi&le !orsu&stantial organ

ds!unction and e"en

organ !ailure.


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• Pene#&uhan luka dapat diringkas #enjadiserangkaian proses seperti &erikut /.

%Induksi respons peradangan akut %Migrasi dan proli!erasi, &aik sel

parenki# #aupun sel jaringan ikat

%Pe#&entukan pe#&uluh darah &aru dan

jaringan granulasi %Sintesis protein (M dan deposisi

kolagen

%Re#odelling jaringan

%0ontraksi luka

%Penge#&alian kekuatan


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Repair, regeneration and fbrosis ater injuryand inamation


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