Healing & Repair PDF

Whenever injury & the associated inflammatory response resulted in tissue damage, the host response include attempts at replacement of the dead cells by healthy tissue. This response is referred to as healing. Dr.Nazar Jawhar Repair refers to the restoration of tissue architect...

Whenever injury & the associated inflammatory response resulted in tissue damage, the host response include attempts at replacement of the dead cells by healthy tissue. This response is referred to as healing. Dr.Nazar Jawhar Repair refers to the restoration of tissue architecture and function after an injury. It occurs by two types of reactions (in many cases both): -Some tissues are able to replace the damaged components and essentially return to a normal state; this process is called regeneration. - If the injured tissues are incapable of complete restitution, or if the supporting structures of the tissue are severely damaged, repair occurs by laying down of connective (fibrous) tissue, a process termed healing that results in scar formation. Although the fibrous scar is not normal, it provides enough structural stability that the injured tissue is usually able to function Dr.Nazar Jawhar Repair of damaged tissue separated into 2 processes: regeneration & healing by connective tissue Dr.Nazar Jawhar NOTE: The term fibrosis is most often used to describe the extensive deposition of collagen that occurs in various organs as a consequence of chronic inflammation, or ischemic necrosis (infarction). If fibrosis develops in a tissue space occupied by an inflammatory exudate it is called organization. Repair involves the proliferation of various cells, and close interactions between cells and the extracellular matrix (ECM). Dr.Nazar Jawhar Several cell types proliferate during tissue repair. These include the remnants of the injured tissue (which attempt to restore normal structure), vascular endothelial cells (to create new vessels that provide the nutrients needed for the repair process), and fibroblasts (the source of the fibrous tissue that forms the scar to fill defects that cannot be corrected by regeneration). The proliferation of these cell types is driven by proteins that are collectively called growth factors Dr.Nazar Jawhar Healing & repair include the following steps: ❑ Scavenging: Removal of dead tissue by macrophages. ❑ Regeneration: ❑ Granulation tissue formation: ❑ Synthesis & deposition of ECM: ❑ Tissue remodelling: Dr.Nazar Jawhar  REGENERATION: Means replacement of dead & lost cells by multiplication of their neighbors. This occurs in cells that have the ability to proliferate (labile &stable cells). Body cells are classified into 3 groups on the basis of their proliferative capacity: Dr.Nazar Jawhar Dr.Nazar Jawhar  GRANULATION TISSUE: A specialized type of tissue representing the hallmark of healing. It appears pink , soft and granular & it has two main components: angiogenesis & fibroblastic proliferation. It is often leaky (edematous). Dr.Nazar Jawhar  1- Angiogenesis: ❖ Means formation of new small blood vessels. ❖ This done by two main mechanism: Formation of capillary sprouts from adjacent vessels & mobilization of Endothelial Precursor Cells from bone marrow to the site of injury. ❖ Angiogenesis is stimulated by growth factors mainly VEGF & angiopoietin. ( secreted by many cells). ❖ Angiogenesis is critical for healing, tumor growth & revascularization of ischemic tissue. Dr.Nazar Jawhar Dr.Nazar Jawhar  2-Fibroblastic proliferation: Fibroblasts proliferate &migrate into the granulation tissue framework. This is done by the effect of growth factors &cytokines ( as PDGF, FGF,TNF,IL1,..). Dr.Nazar Jawhar  ECM DEPOSITION: - As the process continue, the emigrated fibroblasts deposited increasing amount of ECM (as fibrillar collagen) which is important for the development of strength in healing wounds. Such process begins 3-5 days after the injury & continue for weeks. Again this process is enhanced by growth factors as PDGF,FGF & cytokines. Dr.Nazar Jawhar - What are the components of ECM? Dr.Nazar Jawhar  REMODELLING: -Maturation & organization of the fibrous tissue (scar). - It results from balance between deposition & degradation of ECM , ending in remodelling of connective tissue framework (to increase the strength). - Degradation is achieved by a family of enzymes called metalloproteinases ( as collagenases), they depend on zinc ions & are stimulated by same growth factors (PDGF, FGF, cytokines,..). - As the scar matures, vascular regression occurs, so it becomes pale and avascular. Dr.Nazar Jawhar  CUTANEOUS WOUND HEALING: Skin wounds are classically described to heal by: - Primary intention or by -Secondary intention. This is based on the nature of the wound rather than the healing process itself. Dr.Nazar Jawhar  HEALING BY 1ST INTENTION (WOUNDS WITH OPPOSED EDGES): The least complicated example of wound repair is the healing of a clean, uninfected surgical incision approximated by surgical sutures. Such healing is referred to as primary union or healing by first intention. The incision causes death of a limited number of epithelial and connective tissue cells. The narrow incisional space immediately fills with clotted blood containing fibrin and blood cells; dehydration of the surface clot forms the well-known SCAB that covers the wound. The healing process follows aJawhar Dr.Nazar series of sequential steps: The healing process follows a series of sequential steps: Within 24 hours, neutrophils appear at the margins of the incision, moving toward the fibrin clot. In 24 to 48 hours, spurs of epithelial cells move from the wound edges along the cut margins of the dermis. They fuse in the midline beneath the surface scab, producing a continuous but thin epithelial layer that closes the wound. Dr.Nazar Jawhar By day 3, -The neutrophils have been largely replaced by macrophages (scavengers). - Granulation tissue progressively invades the incision space. Epithelial cell proliferation thickens the epidermal layer. Dr.Nazar Jawhar By day 5, the incisional space is filled with granulation tissue. Neovascularization is maximal. Collagen fibrils appear & begin to bridge the incision. The epidermis recovers its normal thickness. Dr.Nazar Jawhar During the second week, there is continued accumulation of collagen and proliferation of fibroblasts. The leukocytic infiltrate, edema, and increased vascularity have largely disappeared. Dr.Nazar Jawhar By the end of the first month, the scar is made up of a cellular connective tissue devoid of inflammatory infiltrate, covered now by intact epidermis. The dermal appendages that have been destroyed in the line of the incision are permanently lost. Tensile strength of the wound increases thereafter, but it may take months for the wounded area to obtain its maximal strength. Dr.Nazar Jawhar  HEALING BY SECOND INTENTION (WOUNDS WITH SEPARATED EDGES): When there is more extensive loss of cells and tissue, as in surface wounds that create large defects, the reparative process is more complicated. Regeneration of parenchymal cells cannot completely restore the original architecture, and hence abundant granulation tissue grows in from the margin to complete the repair. This form of healing is referred to as secondary union or healing by second intention. Dr.Nazar Jawhar Secondary healing differs from primary healing in several respects: The large tissue defects generate a larger fibrin clot that fills the defect and more necrotic debris and exudate that must be removed. Consequently the inflammatory reaction is more intense. Much larger amounts of granulation tissue are formed. Dr.Nazar Jawhar  Perhaps the feature that most clearly differentiates primary from secondary healing is the phenomenon of wound contraction, which occurs in large surface wounds. This results from the action of myofibroblasts (altered fibroblasts that have the ultrastructural characteristics of smooth muscle). Substantial scar formation and thinning of the epidermis. Dr.Nazar Jawhar  WOUND STRENGTH At the end of the first week, wound strength is approximately 10% of that of unwounded skin. Then wound strength increases gradually over the next few weeks, reaching about 70-80% of the tensile strength of the unwounded skin. It result from excessive collagen synthesis. Dr.Nazar Jawhar  Factors that influence healing: Healing is modified by a no. of systemic and local host factors including: Systemic factors: ❑. ❑. ❑. ❑. Dr.Nazar Jawhar  Factors that influence healing: LOCAL FACTORS: ❑. ❑. ❑. ❑! Dr.Nazar Jawhar  COMPLICATIONS IN CUTANEOUS WOUND HEALING: I- Excessive formation of scar tissue. - HYPERTROPHIC SCAR: Accumulation of excessive amounts of collagen giving rise to a raised scar. - KELOID: Accumulation of excessive amounts of collagen in which the scar tissue grows beyond the boundaries of the original wounds & does not regress. It appears to be of individual predisposition & is more common in black people. Dr.Nazar Jawhar  COMPLICATIONS IN CUTANEOUS WOUND HEALING: II- Deficient scar formation & inadequate granulation tissue formation can lead to wound dehiscence (more common in abdominal surgery, decrease blood supply). III- Formation of contracture: Exaggerated wound contracture can leads to deformity of wounds & surrounding tissue. Dr.Nazar Jawhar Dr.Nazar Jawhar