Healing and repair - 1Healing and repair - 1

Dr H.M.D.MoratuwagamaDr H.M.D.MoratuwagamaDept of PathologyDept of Pathology

Faculty of mrdicine-RagamaFaculty of mrdicine-Ragama

Objectives

Describe the steps of cutaneous wound healing by primary intension and secondary intension

List the factors which delay wound healing

Describe the process of healing in specialized tissues

According to the potential of cell renewal 3 types of cells are present1)Labile cells Regenerate regularly Surface epithelial cells Surface epithelium of the GIT , Skin2)Stable cells Normally slowly regenerate Divide when necessary eg. Hepatocytes3)Permanent cells No effective regeneration eg. Neural cells of CNS, cardiac muscle

Definitions

RegenerationGrowth of cells to replace the lost structure ex: skin,haemopoietic system,GIT HealingTissue response 1.wound 2.Inflammatory process 3.cell necrosisTwo processes-Regeneration Scar formation-laying down of fibrous tissue

Tissue injury

Total

Scar

Partial

Labile cells

Stable cellsPermanant

RegenerateRegenerate/scar Scar

Scar formation occurs when

1)Damage to permanent cells

2)Severe destruction of connective tissue frame work

3)With extensive cell injury

4)In chronic inflammation

Steps in repair by scar tissue formation

1)Inflammatory response Polymorphs and macrophages Remove damaged and dead tissue2)Proliferation and migration of parenchymal

and connective tissue cells3)Formation of new blood vessels

(angiogenesis) and granulation tissue

Steps in repair by scar tissue formation cont.

4) Synthesis of ECM proteins and collagen deposition

5) Tissue remodeling

6) Wound contraction

7) Wound strength

What is angiogenesis?

Formation of blood vessels from existing blood vessels

From A) Endothelial precursor cells in BM B) From pre-existing vessels

What is granulation tissue?

Highly vascularized connective tissue Composed of – Newly formed capillaries Proliferating fibroblasts Inflammatory cells in oedematous stroma Macro – Pink granular Soft and fleshy

 new capillaries (result of proliferation of endothelial cells - angiogenesis or neovascularization) in an edematous atmosphere of fibroblasts (spindle shaped), myofibroblasts, mononuclear inflammatory cells, macrophages, neutrophils,

Growth factors involved in angiogenesis

1)Formation of new vessels VEGF FGF 2)Stability of new vessels Angiopoietin 1 & 2 - Periendothelial cells PDGF - Smooth muscle cells TGF – beta - ECM protein secretion

ECM protein production (Initial) VEGF - (Angiogenesis and ) increased vascular permeability

Exudation and deposition of plasma proteins Provides a stroma for the proliferating endothelial cells and fibroblasts

ECM protein production Fibroblasts migration

Macrophages , platelets , endothelium

Growth factors Cytokines TGF – beta TNF , IL -1 PDGF FGF

Fibroblast migration and proliferation

ECM deposition and scar formation

Growth factors (PDGF , FGF , TGF) & Cytokines (IL-1 & IL-13)

Stimulate fibroblast to produce collagen

Net collagen is dependant on both the production and degradation

Tissue remodeling Degradation of collagen and other ECM proteins

by a family of matrix metalloprotinases (MMPs) TIMs –(Tissue inhibitors of metaloprotinases)

inhibit their action

Net result is the formation of an avascular firm white scar tissue

Wound contraction By the contraction of a specialized cell in the

granulation tissue called myofibroblasts

Wound defect decreased in size

Harmful effect – Stenosis , contractures

Wound strength

It is acquired by1) Increase collagen deposition2) Cross linking of collagen fibers3) Change of collagen fibers from type 3 to type 1

Cutaneous wound healing1)Inflammation Early and late

2)Granulation tissue formation and

re-epithelialization

3)Wound contraction ECM deposition and

remodeling

Wound healing

1)Healing by first intension (Primary union) -wounds with opposed edges-2)Healing by second intension (Secondary union) -Wounds with separated edges-

Healing by first intension(Primary union)

In –Surgically incised Clean and uninfected Limited death of

epithelial cells and connective tissue

Edges approximated by surgical sutures

Healing by second intension

Wounds with Extensive cell

death Large defects +/-

infection Wounds not

approximated by sutures

Healing by primary intension Surgical wounds

Gap filled by clotted blood containing fibrin and blood cells

Scab forms

Healing process

Within 24 hrs Neutrophils enter

24-48hrs Epithelial cells move and fuse in the midline

Day 3 Macrophages move in Granulation tissue forms Collagen laid down epithelial cell layer forms

Day 5 Granuation tissue fills the gap Maximal neovascularization Collagen fibrils increases Epithelial cells thickens2nd Week Accumulation of collagen and fibroblast

proliferation Regression of vascular channels,

inflammation and oedema4th Week Scar Covered by epidermis Dermal appendages are absent Wound strength - over several months

Differences from primary union

1) Larger fibrin clot2) More necrotic debris and exudate3) Intense inflammatory reaction4) Abundant granulation tissue5) Wound contraction (by myofibroblasts)6) Scar formation and thinning of epidermis

Primary wound healing

Secondary Wound Healing

Secondary Wound Healing

Secondary Wound Healing

Wound strength Day 7 10% of the original tissue 2nd to 3rd month 70-80% of original tissue

Factors that retard wound healing

Local factors Poor blood supply - arteriosclerosis, venous

abnormalities(ex: varicose veins) Denervation Local infection Foreign bodies – interfere with healing and

cause infection Presence of a haematoma Mechanical stress Presence of a necrotic tissue

Systemic factors that delay wound healing

Anaemia Drugs-Steroids ( anti-inflammatory) , cytotoxic drugs Genetic disorders with collagen defects Ehlers – Danlos syndrome Osteogenesis imperfecta Marfans syndrome Diabetes Malignancy

Systemic factors that delay wound healingcont.

Nutritional deficiencies – eg- Protein, Vitamin C, Zinc Systemic infection Trauma , hypovolaemia , hypoxia Uraemia Haematological abnormalities – Defect of

neutrophil function

Other factors that influence wound healing

Age Size Location Mechanical factors

Summary The process by which healing occurs in a

tissue is dependant on several factors – Type of cell , extent of injury etc Depending on the type of wounds, healing

process follows two pathways - Healing by primary intension - Healing by second intension There are systemic and local factors that may

delay wound healing

THANK YOU