Wound Repair.pptx

Review of Inflammation • Causes of inflammation: • • • • Infection Tissue necrosis Foreign body Immune reactions (hypersensitivity) • Steps of inflammation: • • • • • Recognition Recruitment Removal Regulation Repair • Special considerations: • • • • Components of inflammation Complications of...

Review of Inflammation • Causes of inflammation: • • • • Infection Tissue necrosis Foreign body Immune reactions (hypersensitivity) • Steps of inflammation: • • • • • Recognition Recruitment Removal Regulation Repair • Special considerations: • • • • Components of inflammation Complications of inflammation Location (local or systemic) Acute or chronic inflammation Tissue Repair, Regeneration, Fibrosis • Repair of damaged tissue requires replacement of parenchymal (tissue) cells AND stromal (connective tissue) proteins • The ability for tissue to repair by regeneration is dependent on their proliferative capability and the presence of stem cells • Labile tissue: continually proliferative cells (hematopoietic cells, epithelial cells) • Stable tissue: quiescent cells that can be stimulated to proliferate (perenchyma of most solid tissue) • Permanent tissue: little/no regenerative capability (neurons, cardiomyocytes) • Cell proliferation is driven by tissue GFs and ECM proteins Tissue Repair, Regeneration, Fibrosis • Steps of tissue repair by fibrosis: • Inflammation • Proliferation • Formation of granulation tissue • Collagen matrix deposition • Remodeling Tissue Repair: Wound Healing Three stages of wound healing: 1. Inflammatory phase (generally up to 1 week) • Hemostasis (stasis, platelet aggregation, thrombus formation) • Inflammation (vasodilation, edema, leukocyte diapedesis and phagocytosis) Tissue Repair: Wound Healing 2. Proliferative phase (days to weeks) • Granulation tissue (plasma protein deposition, fibroblast ingrowth and ECM protein deposition, capillary ingrowth) fills the wound slowly (may overgrow = “proud flesh”) • Collagen deposition and wound strengthening (with initial contraction) • Epithelialization (epithelial cells grow over new granulation tissue to 3 cm) Tissue Repair: Angiogenesis • Angiogenesis is an important component of tissue repair/remodeling as it provides oxygenation and supply of vital nutrients/growth factors to the damaged tissue • The primary GFs involved are • VEGF – endothelial proliferation and migration (Notch ligands), vasodilation • FGF – endothelial proliferation, migration of macrophages and fibroblasts • PDGF/TGFβ – stabilization of new vessel; PDGF recruits VSMCs, TGF inhibits EC proliferation and promotes ECM protein deposition • Notch – regulates sprouting/spacing of new vessels Tissue Repair: Granulation Tissue Granulation tissue (capillary ingrowth, fibroblast migration, and collagen deposition) in healing by “Proud flesh” – excessive granulation Tissue Repair: Wound Healing 3.Remodeling phase (weeks to years) • Reorganization of fibrotic tissue (scar), vasculature • Tissue tensile strength increases up to ~80% its original strength • Further contraction Stages of Tissue Repair/Wound Healing Tissue Repair: Wound Healing • Healing by first intention (primary union) • Wound edges are approximated (brought together) by sutures or other mechanisms to enhance healing rate and outcome (cosmetic and functional) • Healing by second intention (secondary union) • Wound edges are not approximated, defect fills in slowly over time (usually significant scarring) Wound Healing: First Intention • Healing by first intention results when a small tissue defect is rapidly filled with granulation tissue • Less intense inflammation, short time to heal • Less scarring and wound contracture Healing by First Intention Wound Healing: Second Intention • Healing by second intention results in a large tissue defect which must be filled by gradual expansion of granulation tissue • Granulation tissue must grow in from margins • More intense inflammation, much longer to heal • Increased likelihood for significant scarring and wound contracture Wound Healing: Second Intention Granulation tissue (after surgical removal of eschar) Smaller wound with edge contraction After 3 months with scar formation (contraction) Tissue Remodeling • Result of site-specific changes in balance of collagen matrix synthesis versus degradation • Increased physical stresses enhance synthesis and decreased stresses enhances degradation • Besides physical stress, other factors also influence remodeling such as genetics (keloids), nutrition (vitamin C, zinc and protein deficiency), aging, disease (diabetes) Factors that Effect Tissue Repair/Remodeling • Infection is clinically the most important causes of delayed healing → prolongs inflammation and increases local tissue injury • Diabetes (and other metabolic diseases) compromise tissue repair and is one of the most important systemic causes of abnormal wound healing • Nutritional status has profound effects on repair → protein deficiency and vitamin C deficiency inhibit collagen synthesis and retard healing • Glucocorticoids have antiinflammatory effects → their administration may result in weakness of the scar due to inhibition of TGF-β production and diminished fibrosis (these effects are desirable in some situations in order to reduce scarring) • Mechanical factors such as increased local pressure or torsion may cause dehisce • Poor perfusion due to peripheral vascular disease, arteriosclerosis, and diabetes or due to obstructed venous drainage (varicose veins) • Foreign bodies such as fragments of steel, glass, or even bone → perpetuate chronic inflammation • The type and extent of tissue injury and the character of the tissue in which the injury occurs (labile, stabile, permanent cells) • The location of the injury: inflammation arising in tissue spaces → extensive exudates → proteolysis by PMNs → possible resolution → if extensive (or if necrosis occurs) granulation tissue grows into the exudate → fibrosis occurs (organization) Wound Repair Pathology: Dehiscence • • • • • Dehiscence is opening of a previously closed wound Causes include excessive stress, poor suture technique Usually occurs between 7 and 10 days post operatively Should be assumed that the defect involves the entire wound (full length, full depth) May also be associated with ulceration in areas of impaired vascularity (e.g., sutures too tight) Wound Dehiscence Wound Repair Pathology: Hypertrophic Scarring (Keloid) • Genetic predisposition, especially with darker skin • Excessive granulation tissue, delays re-epithelialization • Often hyperpigmented Wound Repair Pathology: Contracture Increased collagen and matrix deposition occurs as wound edges approach each other, followed by collagen crosslinking and “contraction”, pulling wound edges together. The reaction is more exaggerated with healing by second intention, extensive scarring. Post-Burn Wound Contracture