TISSUE RENEWAL/WOUND HEALINGDr. ANAND

HEALING VS REPAIR

• Healing is body’s response to injury in an attempt to restore normal structure and function.

• It involves• A. Regeneration• B. Repair

• Regeneration is restoration to original tissue by proliferation of parenchymal cells

• Repair is healing of proliferation of connective tissue resulting in fibrosis and scaring

• WHAT ARE THE ORGANS IN THE BODY WHICH REGENERATES

TYPES OF CELLS

TYPES OF CELLS IN BODY• LIABLE CELLS— epidermis, endometrium, blood

cells

• STABLE CELLS--- decrease proliferation after adolescence– bone cartilage, liver, pancreas

• PERMANENT CELLS– stop proliferation after birth– neurons, skeletal mucles, cardiac muscles

Why ??

• Each of these cells have separate wound healing process

FACTORS

• CELL CYCLE SIGNALLING PATHWAYS[UBIQUINTIN PATHWAYS]

• CDK

• ANGIOGENESIS[ Formation of new blood vessels]

• NEOVASCULARISATION– Formation of new blood vessels

• GROWTH FACTORS-TGF, FGF, PDGF

• NEUTROPHILS• MACROPHAGES• PLASMA CELLS

TABLE 3-4 -- Growth Factors and Cytokines Affecting Various Steps in Wound Healing Monocyte chemotaxis Chemokines, TNF, PDGF,

FGF, TGF-β Fibroblast migration/replication

PDGF, EGF, FGF, TGF-β, TNF, IL-1

Keratinocyte replication HB-EGF, FGF-7, HGF Angiogenesis VEGF, angiopoietins, FGF Collagen synthesis TGF-β, PDGF Collagenase secretion PDGF, FGF, TNF; TGF-β

inhibits

HOW WOUND IS STRENGTHENED??

• FIBROSIS HAS OCCURRED

• EXTRACELLULAR MATRIX COMPONENTS

• COLLAGEN

• FIBRONECTIN

• ELASTIC FIBRES

• PROTEOGLYCANS

REPAIR

• Repair is the replacement of injured tissue by fibrous tissue.

• Two processes are involved in repair:• 1. Granulation tissue formation; and• 2. Contraction of wounds

• Repair response takes place by participation of• mesenchymal cells (consisting of connective

tissue stem cells, fibrocytes and histiocytes), endothelial cells,

• macrophages,• platelets, • parenchymal cells of the injured organ

STEP-1 BLOOD CLOT

• Clot is reffered as SCAB…. Forms as a barrier of wound preventing microbial invasion

• Factors involved:• - Transforming growth factors[TGF]• -Platelet derived growth factors[PDGF]

• Source:: Platelets and plasma

Step-II Inflammation• Neutrophils infiltrate the wound to remove the microbes

and necrotic debris

• Plasma derived fibronectin and neutrophil debris acts as chemoattractants from macrophage and fibroblasts

• Macrophage eats neutrophil debris and release factors for fibrogenesis and angiogenesis

• Factors: TGF

• Source: Neutrophils

III--Granulation tissue formation

• It is transient specialised organ of repair• Composed of:• Erythrocytes and fibroblasts• Single cell lined capillaries

• Factors involved: FFG, TGF• Source:: Macrophages , fibroblasts

IV– Fibroblast proliferation and matrix accumulation

• 2 or 3 days after injury, fibroblasts start secreting collagen

• 5-7 days later,, collagen is more in amount and tightly grips the wound

• Source: macrophages, fibroblasts

STEP—V ANGIOGENEIS

i) Angiogenesis (neovascularisation). Formation of new blood vessels at the site of injury takes place by proliferation of endothelial cells from the margins of severed blood vessels.

• Initially, the proliferated endothelial cells are solid buds but within a few hours develop a lumen and start carrying blood.

• The newly formed blood vessels are more leaky, accounting for the oedematous appearance of new granulation tissue. Soon, these blood vessels differentiate into muscular arterioles, thin-walled venules and true capillaries

• FACTORS INVOLVED: Vascular endothelilal growth factors[VEGF]

• Source Macrophages, monocytes

VI– WOUND CONTRACTION– It is done by specialize type of fibroblasts called as– MYOFIBROBLASTS[ MYO + FIBROBLASTS]

MF contains actin – contractile

Forms a tight junctions and contract leading to wound contraction

Factors involved: TGF

Source: Platelets, macrophages

VII- Accretion of tensile strength and remodelling

• Remodelling is done cross linking of collagen fibres

• Occurs as wound site devascularies

• Factors; PDGF, FGF MMP• Source: platelets, fibroblasts

Mechanism of Wound healingMacrophages

CytokinesFree radicalsEnzymesNO

TGF-BFGE

Tissue

damage

+EGF

AngiogenesisFibrosis

Granulation tissueHealing

Activation

TH

© Dr.yasir 2oo7

GRANULATION TISSUE

• Granulation tissue= granular and pink appearance

• Granule stands for histologically proliferation of small sized blood vessels

• DOES GRANULATION TISSUE NORMALLY PRESENT IN BODY??

• WHAT IS THE DIFFERENCE BETWEEN• GRANULATION TISSUE VS• BLOOD VESSEL

TYPES OF WOUND HEALING

• PRIMARY INTENTION

• SECONDARY INTENTION

• Healing by First Intention (Primary Union)This is defined as healing of a wound which has the• following characteristics:• i) clean and uninfected;• ii) surgically incised;• iii) without much loss of cells and tissue; and• iv) edges of wound are approximated by surgical

sutures.

• 1. Initial haemorrhage• 2.Acute inflammatory response.-Neutrophils• 3. Epithelial changes– Granulation tissue• 4. Organisation- fibroblasts• 5. Suture tracks- fibrous union

Healing by Second Intention (Secondary Union

• This is defined as healing of a wound having the following characteristics:

• i) open with a large tissue defect, at times infected;

• ii) having extensive loss of cells and tissues; and• iii) the wound is not approximated by surgical

sutures but is left open.

HEALING IN SPECIALISED TISSUES

FRACTURE HEALING

• CALLUS FORMATION

• Fracture Healing• Healing of fracture by callus formation

depends upon some• clinical considerations whether the fracture is:• traumatic (in previously normal bone), or

pathological (in previously diseased bone)

• Primary union of fractures occurs in a few special situations when the ends of fracture are approximated as is done by application of compression clamps

• Secondary union is the more common process of fracture healing. Though it is a continuous process,

Secondary bone union is described under the 3headings:• i) Procallus formation• ii) Osseous callus formation• Remodelling

FACTORS AFFECTING WOUND HEALING

• LOCAL FACTORS

• SYSTEMIC FACTORS

• BLOOD SUPPLY• INFECTION• FOREIGN BODY• MECHANICAL STRESS

• SYSTEMIC FACTORS• AGE• ANAEMIA• DIABETES• SEPTICEMIA• COLLAGEN GENETIC DISEASES• DRUGS

• DIABETES MELLITUS

COMPLICATION OF WOUND HEALING

• DEFICIENT SCAR FORMATION

• KELOID

• CONTRACTURES

OVERVIEW OF WOUND HEALING MECHANISM

THANKU