Repair: Regeneration, Healing & Fibrosis PDF

Repair : Regeneration ,Healing &fibrosis Repair: Refers to the restoration of tissue architecture and function after an injury. It occurs by two types of reactions : (1) Regeneration: When tissues are able to replace the damaged components and essentially return to a normal state. (2) scar formation...

Repair : Regeneration ,Healing &fibrosis Repair: Refers to the restoration of tissue architecture and function after an injury. It occurs by two types of reactions : (1) Regeneration: When tissues are able to replace the damaged components and essentially return to a normal state. (2) scar formation: When repair occurs by laying down of connective (fibrous) tissue, which results in scar formation. Repair involves the proliferation of various cells, and close interactions between cells and the extracellular matrix (ECM). Proliferative Capacities of Tissues: 1. Labile tissues : Continuously dividing tissue. Lost cell replaced by maturation from stem cells and by proliferation of mature cells. E.g : hematopoietic cells in the bone marrow and surface epithelia. 2.Stable Tissues: Cells of these tissues have only minimal replicative activity. These cells are capable of proliferating in response to injury or loss of tissue mass. E.g: liver, kidney, and pancreas, fibroblasts, and smooth muscle cells. 3.Permanent Tissues: Terminally differentiated and nonproliferative in postnatal life. Thus, injury these tissue is irreversible and results in a scar. E.g: neurons and cardiac muscle cells. REPAIR BY CONNECTIVE TISSUE Repair by connective tissue deposition consists of : 1.Formation of blood vessels (angiogenesis) 2.Migration and proliferation of fibroblasts 3.Deposition of ECM (scar formation) 4.Maturation and reorganization of the fibrous tissue (remodeling) Angiogenesis: occur by two processes: 1.vasculogenesis in which the vascular network is formed from angioblasts (endothelial cell precursors)coming from the bone marrow. 2.neovascularization in which preexisting vessels send out capillaries to produce new vessels (sprouting angiogenesis). Sprouting angigenesis; Is important in wound healing. And in formation of collateral circulation in hypoxic tissues. Is driven mainly by VEGF. Steps: 1.vasodilation (due to NO)and increased vascular permeability by VEGF 2.Seperation of pericytes and breakdown of the BM. 3.migration and proliferation of endothelial cells (by VEGF). 4.Capillary tubing. 5.recruitment of pericytes. Suppression of proliferation.formation of the BM. Migration of Fibroblasts and ECM Deposition (Scar Formation) : It occurs in two steps: (1) migration and proliferation of fibroblasts into the site of injury (2) deposition of ECM by these cells. The recruitment and stimulation of fibroblasts is driven by many growth factors, including PDGF, FGF-2 and TGFB(produced mainly by macrophages). Tissue Remodeling: Is The outcome of the repair process it is, a balance between ECM synthesis and degradation. Involves strengthening and contracting the scar. Strength is achieved by cross linking of collagen fibers, shifting its type. contracting the scar occurs by degradation of collagens and other ECM components is accomplished by a family of matrix metalloproteinases (MMPs). MMPs are rapidly inhibited by tissue inhibitors of MPs(TIMPs). CUTANEOUS WOUND HEALING 1.Healing by First Intention: known as primary union, or healing by first intention. Occur when there is only focal disruption of epithelial basement membrane. The narrow incisional space first fills with hemostatic plug, which is rapidly invaded by granulation tissue and covered by new epithelium. Epithelial regeneration predominates over fibrosis. 2. Healing by Second Intention: Occur When cell or tissue loss is more extensive, suchas in large wounds, abscess formation, and ulceration. The inflammatory reaction is more intense. There is abundant development of granulation tissue. The wound contracts by the action of myofibroblasts. This is followed by accumulation of ECM and formation of a large scar. Factors affect healing : 1.Infections and diabetes. 2.Nutrition , protein deficiency, vitamin C deficiency, inhibits collagen synthesis and retards healing. 3.Glucocorticoids (steroids) result in poor wound strength due to diminished fibrosis(inhibiting TGFbeta). 4.Mechanical variables such as increased local pressure or torsion. 5. Poor perfusion due either to arteriosclerosis to obstructed venous drainage (e.g. in varicose veins). 6. foreign bodies such as fragments of steel, glass, or even bone impede healing. 7.The type (and volume) of tissue injured is critical. A, Granulation tissue showing numerous blood vessels, edema, and a loose ECM containing occasional inflammatory cells. B, Trichrome stain of mature scar, showing dense collagen with only scattered vascular channels. A, Excess collagen deposition in the skin forming a raised scar known as a keloid.