Repair DR .HALA Badawi Lecturer of pathology Repair • Definition: Repair is the replacement of damaged tissue by new healthy one • Types of Repair I- Regeneration II- Healing by fibrosis Cell Cycle and Proliferative Potential • The cells of the body are divided into three groups on the basis of their proliferative capacity and their relationship to the cell cycle. • 1- Continuously dividing cells (also called labile cells) e.g. skin, urinary& GIT mucosa and blood & lymphoid tissue • 2- Quiescent (or stable) cells: e.g. liver, kidney, pancrease & fibroblasts • 3- Nondividing (permanent) cells: e.g. nerve cells and cardiac& striated muscles CONTROL OF NORMAL CELL GROWTH • Cell replication is controlled largely by chemical factors (growth factors) in the microenvironment, which either stimulate or inhibit cell proliferation. Regeneration • Definition: • Regeneration is the replacement of damaged cells by new cells of the same kind • Examples of Regeneration: • Regeneration of skin • Regeneration of liver cells • Repair of bone fracture • Healing of peripheral nerve Regeneration of Liver Cells 1- When the injury is limited and the fibrous framework is preserved, complete regeneration occurs 2- when the damage is severe and the framework is destroyed, regenerating nodules and fibrosis resulting in cirrhosis Healing of bone fracture Phases of fracture healing There are three major phases of fracture healing; 1. Reactive Phase i. Fracture and inflammatory phase ii. Granulation tissue formation 1 2 2. Reparative Phase iii. Callus formation iv. Lamellar bone deposition 3. Remodeling Phase v. Remodeling to original bone contour 3 Repair of Peripheral Nerve Nerve injury and repair (a)Normal axon and target organ (striated muscle). (b)Following nerve injury the distal part of the axon disintegrates and the myelin sheath breaks up. The nerve cell nucleus becomes eccentric and Nissl granules decreased. (c)New axonal tendrills grow into the mass of proliferating Schwann cells. One of the tendrill will find its way into the old endoneurial tube (d)the axon will slowly regenerate Healing by fibrosis • Definition: Replacement of damaged tissue by fibrous tissue through formation of granulation tissue. Granulation tissue : Consists of new capillary loops and proliferating fibroblasts Granulation tissue 1- Red granular surface 2- Moist 3- Bleeds easily 4- Insensitive Healing of Wounds I- Primary Union of Wounds (Healing by First Intention) Clean incised wound with minimal tissue destruction II- Secondary Union of Wounds (Healing by Second Intention) Gaping septic wounds with marked tissue destruction Healing of Wounds I- Primary Union of Wounds Is the healing of a clean, uninfected surgical incision approximated by surgical sutures. • The narrow incisional space immediately fills with clotted blood and the surface is covered by scab. • Within 24 hours, neutrophils infiltrate the clot. • Within 24 to 48 hours the epidermis grow along the cut margins of the dermis producing a continuous thin epithelial layer beneath the surface scab. Healing of Wounds • I- Primary Union of Wounds (continue) • By day 3, the neutrophils have been largely replaced by macrophages and granulation tissue started to appear. • By day 5, the incisional space is filled with granulation tissue. • The epidermis recovers its normal thickness by day 5-7 • During the second week, there is continuous maturation of granulation tissue to fibrous tissue • By the end of the first month, complete deposition of collagen with formation of thin incisional scar 24 hours 6 hours 2 days 1 week Wound healing Wound healing ( 1ry union) ( 1ry union) Healed wound Healing of Wounds II- Secondary Union of Wounds (Healing by Second Intention) When there is extensive loss of tissue and surface wounds that create large defects, the reparative process is more complicated. Healing of Wounds Secondary healing differs from primary healing in several respects: 1. Large tissue defects, have more fibrin and more necrotic debris with intense inflammatory reaction. 2. Much larger amounts of granulation tissue formed. 3. The most clear difference between primary and secondary healing is the phenomenon of wound contraction, which occurs in large surface wounds. first intention healing second intention healing Wound Strength • When sutures are removed, usually at the end of the first week, wound strength is approximately 10% of the strength of unwounded skin. • But it increases rapidly over the next 4 weeks. • This rate of increase then slows at approximately the third month after the original incision and then reaches a plateau at about 70 to 80% of the tensile strength of unwounded skin, which may persist for life. • The recovery of tensile strength results from increased collagen synthesis exceeding collagen degradation during the first 2 months and from structural modifications of collagen fibers. Factors Affecting Wound Healing Systemic factors include the following: • Nutrition has intense effects on wound healing. Protein deficiency, for example, and vitamin C deficiency inhibit collagen synthesis and retard healing. • Metabolic status can change wound healing. Diabetes mellitus, for example, is associated with delayed healing. • Blood supply, Inadequate blood supply usually caused by arteriosclerosis or venous abnormalities that retard venous drainage also impair healing. • Hormones, such as glucocorticoids, have anti-inflammatory effects and inhibit collagen synthesis Factors Affecting Wound Healing Local factors that influcence healing include the following: • Infection is the single most important cause of delay in healing. • Mechanical factors, as early motion of wounds, can delay healing. • Foreign bodies, such as unnecessary sutures or fragments of steel, glass, or even bone, constitute impediments to healing. • Size, location, and type of wound influence healing. Wounds in richly vascularized areas, such as the face, heal faster than those in poorly vascularized ones, such as the foot. Small injuries and surgical wounds heal faster than larger ones caused by blunt trauma. Complications of Wounds Healing 1. Wound rupture and ulceration: Rupture of a wound is most common after abdominal surgery. Ulceration occur due to inadequate vascularization. Complications of Wounds Healing 2- Keloid: The accumulation of excessive amounts of collagen may give rise to a raised tumorous scar known as a keloid, which is more common in blacks. Complications of Wounds Healing 3- Exuberant granulation: formation of excessive amounts of granulation tissue. Complications of Wounds Healing 4- Desmoids tumour: proliferations of fibroblasts and collagen forming a mass that recur after excision. Complications of Wounds Healing 5- Contractur exaggeration of wound contraction, results in deformities of the wound and the surrounding tissues. Contractures are commonly seen after serious burns and can compromise the movement of joints. TISSUE REPAIR SUMMARY • Not all injuries result in permanent damage; some are resolved with almost perfect return of normal structure and function (resolution). • Resolution occurs with minimal or no tissue damage. • More often, there is some degree of scarring • Scar is usually good (provides a resilient patch) but occasionally bad (can cause permanent dysfunction)