Wound Healing & Repair PDF

LEARNING OUTCOMES List the types of cells according to their proliferative activity Define regeneration and repair Describe the phases of wound healing Define healing by primary intention Define healing by secondary intention Outline examples of healing in various tissues List the pat...

LEARNING OUTCOMES List the types of cells according to their proliferative activity Define regeneration and repair Describe the phases of wound healing Define healing by primary intention Define healing by secondary intention Outline examples of healing in various tissues List the pathologic aspects of good and poor wound healing List the local and systemic factors which impair wound healing  TISSUE RESPONSE TO INJURY The initial response to injury is acute inflammation, this may be followed by: – Resolution No tissue destruction Damaging agent and cell debris are removed Tissue returned to its pre-injury state e.g., mild heat injury – Regeneration is replacement of the lost tissue by tissue of the same type supporting framework must be intact tissue is returned to its pre-injury state – Repair replacement of the destroyed tissue by a fibrous scar occurs when there is destruction to parenchymal cells and stromal framework, death of permanent cells  FACTORS THAT AFFECT THE HEALING PROCESS Efficiency of: – Removal of the causative agent – Clearance of inflammatory debris – Degree of architectural damage – Proliferative capacity of tissue – The extent of extracellular matrix damage  PROLIFERATIVE CAPACITY The ability of tissues to regenerate is dependent on their intrinsic proliferative capacity and/or the presence of tissue stem cells. Based on these criteria, the tissues of the body are divided into three groups. – Labile – Stable – Permanent  LABILE CELLS Continuously dividing cells Epidermis, mucosal epithelium, GI tract epithelium, etc. Cells are derived from stem cells Injury to such tissue can easily heal by regeneration if the supporting stroma is intact Ki67 small intestine  STABLE CELLS Normally low level of replication Hepatocytes, renal tubular epithelium, pancreatic acini Cells can be stimulated to divide Healing by regeneration if the supporting stroma and the regenerative stem cells are intact  PERMANENT CELLS Non dividing cells Neurons, cardiac myocytes, skeletal muscle No regeneration Replaced by connective tissue THE CELL CYCLE  POLYPEPTIDE GROWTH FACTORS Important mediators affecting cell growth Present in serum or produced locally Exert pleiotropic effects; proliferation, cell migration, differentiation, tissue remodeling Regulate growth of cells by controlling expression of genes that regulate cell proliferation  EXTRACELLULAR MATRIX It is not just a scaffold for cells to grow on Regulates cell growth, motility and differentiation Consists of  Fibrous structural proteins  Collagens  Elastin  Adhesive glycoproteins that link ECM component to one another and to cells  Proteoglycans EXTRACELLULAR MATRIX  REPAIR BY CONNECTIVE TISSUE Involves production of granulation tissue- fibroblasts (and myofibroblasts) and capillary buds Angiogenesis - New vessels budding from old Fibrosis, consisting of emigration and proliferation of fibroblasts and Granulation tissue deposition of ECM (type III collagen) Scar remodeling type III collagen is replaced by type I collagen (collagenase- requires zinc)  PHASES OF WOUND HEALING Inflammatory phase Proliferative phase  Epidermal re-growth  Dermal repair Remodelling phase  Restoration of elasticity  INFLAMMATORY PHASE Induction of acute inflammatory response by an initial injury  Haematoma formation  Infiltration by neutrophils  Infiltration by macrophages  PROLIFERATIVE PHASE Epithelial cell proliferation Granulation tissue Formation of new vessels Proliferation of fibroblasts  Synthesis of ECM proteins  REMODELLING PHASE Replacement of the granulation tissue by a fibrous tissue Remodeling of parenchymal elements to restore tissue function Remodeling of connective tissue to achieve wound strength Degradation of excessive extracellular matrix (metalloproteinases) WOUND HEALING  WOUND HEALING Types of wound healing  Primary intention  Secondary intention  STAGES OF WOUND HEALING BY PRIMARY INTENTION Day 1 Wound filled with blood clot Acute inflammation in the surrounding tissue Proliferation of epithelial cells Day 2 Macrophages Epithelial cells cover the surface  STAGES OF WOUND HEALING BY PRIMARY INTENTION Day 3 Granulation tissue formation Day 5 Collagen deposition Day 7 Sutured removed  WOUND STRENGTH After sutures are removed at one-week, wound strength is only 10% of unwounded skin By 3- months, wound strength is about 80% of unwounded skin Walker's Law, in the context of wound healing, refers to the principle that wound strength is directly proportional to the amount of collagen present within the wound.  WOUND HEALING BY SECONDARY INTENTION The process is similar to healing by primary intention The edges are not approximated - granulation tissue fills the gap Slower The inflammatory reaction is more intense Wound contraction (myofibroblast) More scarring PATHOLOGIC ASPECTS OF WOUND HEALING Deficient scar formation  Wound rupture Excessive scar formation  Keloid-type III collagen. Genetic predisposition Contracture deformity Malignant transformation (extremely rare) Keloid  EXAMPLES OF HEALING IN VARIOUS TISSUES Mucosal surfaces  Erosion is healed by regeneration  Ulceration by regeneration and fibrosis Liver  A single short-lived injury is healed by regeneration  Chronic injury by cirrhosis  EXAMPLES OF HEALING IN VARIOUS TISSUES Nervous system  Central nervous system gliosis (repair)  Peripheral nerves Regeneration Muscle  Cardiac muscle Fibrosis  Skeletal muscle Fibrosis Gliosis  FACTORS INFLUENCING HEALING YOU HAVE TO KNOW THIS! Local factors Poor vascular supply Infection Foreign material Excessive movement Poor approximation Size, site and type of injury Systemic factors Age Nutrition (proteins, Vitamin C- collagen formation, copper- cross linking of collagen, Zinc- conversion of type III to type I collagen) Metabolic status (DM) Hormones (steroids) Malignancy Chemotherapy/radiotherapy