Normal Process of Healing 2

To continue after WaiKit's.
Am posting up the whole story of the process.
For a brief summary, please get ppt slides from me. =)

The proliferative phase

Collagen deposits, angiogenesis, granulation, tissue development, wound contraction

Ideal repair is complete restoration of normal anatomy and function by regeneration of the anatomy and specialized functional (parenchymal) cells of the organ.
Healing is a process that occurs when regeneration is not possible or is incomplete and additional mending of the site is required by fibrous repair – the production of a scar. Occurs under following circumstances:
- The damage to tissue is extensive that the supporting framework is destroyed.
- The injured tissue is composed of permanent cells such as myocardium, skeletal muscle or brain.

Fibrous repair
1. Fibrocyte migration and proliferation – to provide raw material for repair
2. Angiogenesis – growth of new blood vessels to nourish the process
3. Scar development – the synthesis of extracellular matrix proteins and deposition of collagen followed by contraction (shrinking), reshaping (remodelling) and strengthening of the fibrous tissue

Cell migration
Leucocytes produce cytokines that stimulate migration and proliferation of fibroblasts
Fill space not occupied by regenerating parenchymal cells, synthesize collagen fibers to knit back together the disrupted tissue
Provide permanent structure to support additional cell growth
Endothelial cells fr nearby bv sprout angioblast

Angioneogenesis
Vascular endothelial growth factor and other factors stimulate new vessels to sprout fr existing veesels
1. Normal capillary with intact basement membrane and endothelial cells
2. Dissolution of the basement membrane of the parent vessels in the injured site by proteolytic enzymes released by inflammatory cells
3. Migration and proliferation of angioneoblastic endothelial cells through the defect and up the gradient of cytokines released by inflammatory cells and injred cells
4. Organization of a new capillary branch as the tube of endothelial cells generates a basement membrane.

Scar development
Follows angioneogenesis
1. Migration and proliferation of fibroblasts and new blood vessels into the injured site
2. Deposition of an extracellular matrix of collagen and other supportive proteins
3. Maturation, remodelling, contraction and strengthening of fibrous tissue

Granulation tissue
= mixture of capillaries, fibroblasts, residual edema, small no of leucocytes
 
Fibroblast contract, pulling edges of the wound inwards, decreasing the volume to be healed
At the same time, fibroblast produce collagen and other extracellular components to bind the wound firmly and give strength
Fluid is resorbed, inflammatory cells disappear, site becomes more collagenous tissue.
Blood vessels shrink or disappear as workload decreases.
More collagen accumulates to bind the wound tightly, fibroblast shrink and disappear


Healing by first intention
Day 1 : Neutrophils accumulate at the margin of the fibrinous clot in the cut. Stem cells in the epidermis (near basement membrane) begin to proliferate
Day 2-3: Neutrophils are gradually replaced by macrophages, new capillaries begin to appear. Fibroblasts and endothelial cells begin to migrate into the wound
Days3-7: Angiogenesis peaks and richly vascular granulation tissue fills the incision space.
Fibroblasts produce large amounts of collagen to bridge the space between the edges of the wound. Growth of epidermal stem cells has produced a thin layer of epithelium to cover the wound

Second week: Fibroblastic proliferation continues and collagen accumulates. Inflammatory cells, edema fluid, and blood vessels are disappearing rapidly.
End of first month: Pink (vascularised) scar is present. It is composed largely of collagen, is devoid of imflammatory cells, has a declining number of blood vessels, and is covered by normal epidermis. The tensile strength of the wound countinues to improve as fibroblasts contract and continue to add collagen.
After several months or a year: A narrowed, white, fitted scar is present. Skin tensile strength has returned to near normal.

Freshly sutured wound has about 70% of normal tensile strength if sutures are placed After sutured removal at one week, tensile strength is about 10%. Strength improves to about 75% at three months and after a year has returned to near normal.

Healing by second intention is much the same as healing by first intention: inflammation first, followed by macrophage clean-up, neovascularization and scarring. However, the volume of necrotic tissue to be removed is greater, the reepithelialisation of the surface is slower because the wound is wider. Healing by second intention is characteristic of ulcers, infarcts, abscesses, or other wounds where the defect is largeand wound edges are not close together. A greater volume of necrotic and inflammatory debris must be removed, and a large amount of granulation tissue is required to fill the gap. The granulation tissue is replaced by scar tissue, which in turn contracts so that the filnal volume of the scar may be as little as 10% of the original defect. In tissue covered by epithelium, new epithelial cells advanced inward from the edges, first forming a thin membrane of immature cells that rest on underlying granulation tissue and then differentiate into mature epithelium as the wound below matures into scar.

Maturation Phase

 Remodelling of scar occurs
- structural modifications of collagen
eg. Cross linking
Increasing fiber size
 Recovery of tensile strength results from collagen synthesis exceeding degradation during the first 2 months.
 Wound strength reaches 70%-80% of normal by 3 months.