Wound Healing 3 PDF

WOUND HEALING 3 Daniela Pereira Learning objectives 1) Understand tissue repair and mechanisms of regeneration. 2) Identify factors that impair healing and repair. 3) Differentiate between types of tissue healing. 1. CELL INJURY AND CELL DEATH 2. CELLULAR RESPONSE DURING WOUND HEALING 3....

WOUND HEALING 3 Daniela Pereira Learning objectives 1) Understand tissue repair and mechanisms of regeneration. 2) Identify factors that impair healing and repair. 3) Differentiate between types of tissue healing. 1. CELL INJURY AND CELL DEATH 2. CELLULAR RESPONSE DURING WOUND HEALING 3. HAEMOSTASIS 4. INFLAMMATION 5. PROLIFERATION AND ANGIOGENESIS 6. MATRIX REMODELLING 7. TISSUE REPAIR 8. FACTORS IMPAIRING HEALING AND REPAIR 9. TYPES OF TISSUE HEALING 7. TISSUE REPAIR Tissue repair can happen through regeneration or scar formation. Mild injuries can be healed through regeneration, while severe injuries need scar formation to repair underlying connective tissue. 7.1. TISSUE REGENERATION The ability of tissues to repair themselves is critically influenced by their intrinsic proliferative capacity. Mechanisms regulating cell populations. Cell numbers can be altered by increased or decreased rates of stem cell input, cell death resulting from apoptosis, or changes in the rates of proliferation or differentiation. The tissues of the body are divided into three groups according to their proliferative capacity: Labile Tissues – high proliferation capacity resulting in successful regeneration as long as the pool of stem cells is preserved. e.g. squamous surfaces of the skin, oral cavity, vagina and cervix; the columnar epithelium of the gastrointestinal tract, uterus, fallopian tubes, haemopoietic cells in the bone marrow, etc. Stable Tissues – minimal replicative activity in their normal state with limited capacity to regenerate (with the exception of the liver) however these cells are capable of proliferating in response to injury or loss of tissue mass. e.g. parenchyma of most solid tissues, such as liver, kidney, pancreas, etc. Permanent tissues – insufficient proliferative capacity to produce tissue regeneration and in these tissues the repair is typically dominated by scar formation. e.g. brain, heart, etc.  STEM CELLS  Two varieties: Embryonic stem cells and tissue stem cells  Stem cell pool present in many labile and stable populations  Are minority population in many tissues  Located in discreate compartments e.g. in epidermis there are in basal layer immediately adjacent to the basement membrane, in the hair follicle and sebaceous glands  The ability of a tissue to regenerate depends on the integrity of the stem cell population e.g. radiation injury Liver stem cells  A separate pool is available in bone marrow – haemopoietic stem cells MECHANISMS OF TISSUE REGENERATION  Tissues are constituted by continuously dividing cells (epithelia, hematopoietic tissues), normally quiescent cells that are capable of proliferation (most parenchymal organs), and nondividing cells (neurons, skeletal and cardiac muscle). The regenerative capacity of a tissue depends on the proliferative potential of its constituent cells.  Cell proliferation is regulated by the cell cycle, and is stimulated by growth factors and interactions of cells with the extracellular matrix.  The liver can regenerate itself as a form of repair through a process triggered by cytokines and growth factors in response to inflammation and loss of liver mass. Regeneration can happen through the proliferation of surviving hepatocytes or repopulation from progenitor cells depending on the situation. TISSUE REGENERATION IN DIFFERENT TISSUE TYPES The significance of tissue regeneration after injury varies depending on the tissue type and severity of damage.  In the epithelia of the intestinal tract and skin, injured cells are replaced by the proliferation of the remaining cells and differentiation of tissue stem cells if the basement membrane is intact. Growth factors are produced by residual epithelial cells for healing, and the new cells migrate to the damaged area to restore tissue integrity.  Some organs in the body, such as the pancreas, adrenal gland, thyroid, and lungs, have limited regenerative abilities, unlike the liver.  When a kidney is surgically removed, the remaining kidney undergoes both hypertrophy and hyperplasia of proximal duct cells as a compensatory response. It is believed to involve local production of growth factors and cell interactions with the extracellular matrix.  The liver has an exceptional regenerative capacity.  Tissue architecture can only be restored if the remaining tissue is structurally intact, as in the case of partial surgical resection of the liver.  Complete damage to the tissue from infection or inflammation results in incomplete regeneration and scarring. For example, liver abscesses cause extensive destruction of the liver, leading to scar formation despite the remaining cells' ability to regenerate. 7.2. SCAR FORMATION  If regeneration alone is insufficient, injured cells are replaced by connective tissue, forming a scar, or a combination of regeneration and scar formation can occur.  As previously discussed, scarring can occur when tissue damage is severe or long-lasting, resulting in harm to both parenchymal cells, epithelia, and the connective tissue framework. It may also occur when non-dividing cells are damaged. Scar formation is different from tissue regeneration, which involves the restoration of tissue components. Scar formation is a response that "patches up" tissue rather than fully restoring it.  The term scar is commonly associated with the healing of skin wounds, but it can also refer to the replacement of parenchymal cells in any tissue by collagen, such as in the case of the heart after a myocardial infarction. SCAR FORMATION  The main steps: clot formation, inflammation, angiogenesis and formation of granulation tissue, migration and proliferation of fibroblasts, collagen synthesis, and connective tissue remodelling.  Repair by connective tissue starts with the formation of granulation tissue and culminates in the laying down of fibrous tissue.  Macrophages are critical for the elimination of the offending agents and for the production of cytokines and growth factors that stimulate the proliferation of the cells involved in repair.  TGF-β is a strong contributor to fibrosis, and the deposition of extracellular matrix (ECM) is dependent on the balance between fibrogenic agents, matrix metalloproteinases (MMPs), which break down ECM, and the tissue inhibitors of MMPs (TIMPs).  GRANULATION While new blood vessels emerge, resident fibroblasts proliferate and invade the clot to form contractile granulation tissue.  The combination of proliferating fibroblasts, loose connective tissue, new blood vessels and scattered chronic inflammatory cells, forms a type of tissue that is unique to healing wounds and is called granulation tissue.  This term derives from its pink, soft, granular gross appearance, such as that seen beneath the scab of a skin wound. Become pro-fibrotic Laying down ECM proteins Resident and mesenchymal derived fibroblasts Differentiate into myofibroblasts Driving wound contraction GRANULATION Granulation tissue with numerous blood Trichrome stain of mature scar, showing vessels, oedema, and a loose extracellular dense collagen (stained blue) and matrix containing occasional inflammatory scattered vascular channels. cells. Collagen is stained blue by the trichrome stain. 8. FACTORS IMPAIRING HEALING AND REPAIR  Tissue repair may be impaired by a variety of factors that reduce the quality or adequacy of the reparative process.  Factors that interfere with healing may be extrinsic (e.g., infection) or intrinsic to the injured tissue, and systemic or local.  FACTORS IMPAIRING HEALING AND REPAIR Ischemia Nutritional Denervatio status (Bone) Continuing movement of bone ends n Glucocorticoid s Neoplastic disorders Poor blood supply Location of injury Diabetes mellitus Ag Steroid therapy and anti-cancer e Vascular disturbances drugs Poor blood supply Type and extent of tissue injury Infection Immunosuppressio n 9. TYPES OF TISSUE HEALING  Summary  Tissue repair can occur through regeneration (replacing damaged cells) or scar formation (especially in severe injuries).  Regeneration depends on the proliferative capacity of the tissue and involves cell proliferation, driven by growth factors and the extracellular matrix.  If regeneration is insufficient, scar formation replaces damaged cells with connective tissue. This process includes clot formation, inflammation, angiogenesis, granulation tissue formation, and collagen synthesis.  Several factors can impair healing, such as age, nutritional status, diabetes, infection, and vascular disturbances. These factors can be systemic or localised, affecting the reparative process.