Tissue Repair, Wound Healing and Fibrosis

7/27/2019 Tissue Repair, Wound Healing and Fibrosis

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TISSUE REPAIR, WOUND

HEALING AND FIBROSIS


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WOUND HEALING

Wound healing is fundamentalhomeostatic process in response to

injury

The Understanding is fundamentalfor practice of surgery

Has a closed relationship since a

beginning of surgery

SURGEONTISSUE INJURY


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Tissue Renewal & Repair

Ability to replace injured or dead cells Ability to repair tissues after inflammation

injury

RegenerationRestitution of lost tissue

HealingRestore original

structure but involves

colagen deposition and

scar formation


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REGENERATION

GROWTH OF CELL TISSUE TOREPLACES LOST STRUCTURE

HEMATOPOIETIC SYSTEM,

THE EPITHELIA OF THE SKINAND GI TRACT

RARELY IN MAMMALS

ORGANS AND COMPLEXTISSUES

REQUIRES AN INTACT

CONNECTIVE TISSUE


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HEALING IS USUALLY TISSUE

RESPONSE

1. TO WOUND HEALING

2. TO INFLAMMATORY PROCESS

3. TO CELL NECROSIS IN

ORGANS INCAPABLE OF

REGENERATION

SCAR FORMATION OCCURSIF ECM FRAMEWORK

DAMAGED

CHRONIC : FIBROSIS


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Tissue Response To Injury


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NORMAL CELL PROLIFERATION

& TISSUE GROWTH


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NORMAL CELL

PROLIFERATION

& TISSUE GROWTH

The size of cell population is

determined by:

1. Cell proliferation

2. Differentiation

3. Death by Apoptosis


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CELL PROLIFERATION

PHYSIOLOGIC

Ex: Proliferation of endometrial cell

during menstruation

PATHOLOGICPathologic condition : injury, cell

death or mechanical alteration

Excessive physiologic stimuli:nodular prostatic hyperplasia resulting

from dihydrotestosterone stimulation


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TISSUE PROLIFERATIVE

ACTIVITY

DIVIDED INTO 3 GROUPS

1. CONTINUOUSLY DIVIDING TISSUES

(LABILE TISSUES), ex: surface epithelia,

lining mucosa, columnar epithelium GI tract,

etc

2. QUIESCENT TISSUE (STABLE), ex: the

parenchymal cell of kidney, liver, pacreas, etc

3. NON DIVIDING TISSUES, ex: neurons,

skeletal, cardiac muscle


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STEM CELL

Most exciting topic in modern day

Regenerative Medicine

Hope may one day be used to repair

in human tissues such as Heart,

Brain, and Skeletal muscle


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GROWTH FACTOR

Stimulating Cell Proliferation

Also have effects on

Cell locomotion

Contractility

Differentiation

Angiogenesis

EGF, TGF-, HGF, VEGF, PDGF,

FGF, TGF , Cytokines


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SIGNALING MECHANISM

IN CELL GROWTH

AUTOCRINE SIGNALING

PARACRINE SIGNALING ENDOCRINE SIGNALING


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AUTOCRINE SIGNALING

LIVER REGENERATION

PROLIFERATION OF ANTIGEN-STIMULATED LYMPHOCYTE

THE GROWTH OF SOME

TUMORS


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PARACRINE SIGNALING

CONNECTIVE TISSUE REPAIR OF

WOUND HEALING


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ENDOCRINE SIGNALING

HORMONE SECRETION INTO

BLOOD BY ENDOCRINE GLAND

CARRIED BY THE BLOOD

ACT ON DISTANT TARGET CELL


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RECEPTORS & SIGNAL TRANSDUCTION PATHWAY


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Extracellular matrix


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Mechanical support for cell anchorage

Control of cell growth

Maintenance of cell differentiation

Scaffolding for tissue renewal

Establishment of tissue microenvironments

Storage and presentation of regulatory

molecules


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Collagen

Elastin

Proteoglycans and Hyaluronana

Adhesive glycoproteins and integrins

Fibronectin

Laminin

Integrins


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Influence of ECM & GFs


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Tissue remodeling


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INJURY


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INJURY

DAERAH LUKA

PlateletKolagen dan

ECM

PELEPASAN FAKTOR PEMBEKUAN

CASCADE :

SINYAL KIMIA CITOKIN (GROWTH FACTORS)

Fungsi Fibrin

PDGF

Kemotaksis dan

stimulasi

TGF-Sekresi Sitokin,

Peningkatan kemotaksis,

Modulasi Kolagen

Ekspresi Kolagenase


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Penyembuhan Dengan Intensi Pertama

Penyembuhan insisi bedah yang bersih, tidak terinfeksi

yang diperkirakan karena jahitan operasi

Insisi hanya menyebabkan

gangguan kelangsungan

membrane basal epitel dan

kematian epitel yang relative

sedikit dan sel jaringan

penyambung.

Akibatnya, regenerasiepitel lebih menonjol

dibandingkan fibrosis.

Ruang insisi yang sempit dengan cepat akan

terisi fibrin-bekuan darah; dehidrasi

permukaan yang menghasilkan luka scab

untuk menutupi dan melindungi daerah

perbaikan dan penyembuhan luka.

Dalam 24 jam tampak netrofil pada


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Dalam 24 jam, tampak netrofil pada

bagian tepi insisi, bermigrasi ke arah

bekuan fibrin

Hari ketiga, netrofil secara luas

digantikan oleh makrofag, dan jaringangranulasi dengan cepat memasuki celah

insisi. Saat ini serat kolagen tampak pada

tepi insisi

Selama minggu kedua, akumulasi

kolagen proliferasi fibroblast berlanjut.Infiltrasi leukosit, edema dan

peningkatan vaskularisasi menjadi

sangat berkurang

Pada akhir bulan pertama, bekas lukaterdiri dari jaringan penyambung

seluler yang sama sekali tanpa sel

inflamasi dan ditutupi oleh epidermis

normal. Kulit tubuh yang rusak pada

garis insisi hilang secara permanen.


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Kehilangan sel atau jaringan lebih luas

infark, peradangan ulserasi, pembentukan

abses, atau luka yang besar

Penyembuhan sekunder :

Defek jaringan yang besar secaraintrinsic memiliki volume debris

nekrotik, eksudat dan fibrin. Secarakonsekuen, reaksi inflamasi lebih

intens, dengan potensi sekunder,

media-inflamasi dan luka yang lebih

besar.

Terbentuk jaringan granulasi yang lebihbanyak. Volume jaringan granulasi yanglebih besar secara menyeluruh

menghasilkan masa jaringan parut yang

lebih besar. Penyembuhan sekunder

menampakan fenomena kontraksi luka.


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Satu minggu, daya luka mendekati

10 % dari kulit yang tidak luka

Meningkat secara cepat setelah 4

minggu

Sintesa kolagen

Modifikasi structural

kolagen

Daya luka mencapai hampir 70 %-80

% dari normal dalam 3 bulan


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PATHOLOGIC ASPECTS OF REPAIR

Factors that influence the wound healing :

Infection

The type (and volume) of tissue injured

The location of the injury or the character of the tissue

in which the injury occurs, is also important.Aberrations of the cell growth and ECM production may

occurs even in what begins as normal wound healing.

The mechanism underlying the disabling fibrosis

associated with chronic inflammatory dissease such as

rhematoid arthritis, pulmonary fibrosis, and cirrhosis

are essentialy identical to those that are involved in

normal wound healing.


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Normal wound healing


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PLATELET GRANULES AND


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PLATELET GRANULES AND

MEDIATORS OF PLATELET

AGGREGATION

PLATELET GRANULESa. Granules: Contain

Platelet-Specific Proteins

Platelet factor 4

b-Thromboglobulin

Platelet-derived growthfactor

Transforming growthfactor

b. Dense Granules Adenosine diphosphate

Serotonin

Calcium

MEDIATORS OF

PLATELET

AGGREGATION

Thromboxane A2 Thrombin

Platelet factor 4


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Open wound healing


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Factors that retard wound healing

Local Factors

Blood supply Mechanical stress

Denervation Necrotic tissue

Local infection Protection (dressings)

Foreign body Surgical techniques

Hematoma Type of tissue


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Factors that retard wound healing

Systemic Factors

Age Malnutrition

Anemia Obesity

Drugs (steroids, cytotoxic medications,

intensive antibiotic therapy)

Systemic infection

Temperature

Trauma, hypovolemia, and hypoxia

Genetic disorders (osteogenesis

imperfecta, Ehlers-Danlos

syndromes, Marfan syndrome)

Uremia

Vitamin deficiency (vitamin C)

Hormones Trace metal deficiency (zinc, copper)

Diabetes

Malignant disease


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Chronic Wound

Fails to heal within 3 months Classification :

pressure sores,diabetic foot, leg ulcers

Most have the potential to heal Due to inadequate cleansing,

debridement, edema control,treatment of ischaemia, &achievement of moist woundhealing.

Increased proteases & collagenase,

but decreased growth factors


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Four general components of this process.

Formation of new blood vessels(angiogenesis)

Migration and proliferation of fibroblasts

Deposition of EMC

Maturation and reorganization of the fibrous

tissue (remodeling)


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Proses fibrosis terjadi dalam dua tahap:

(1) Emigrasi dan proliferasi fibroblast ke dalam

daerah luka

(1) Deposisi ECM oleh sel-sel ini


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Tissue Repair, Wound Healing and Fibrosis