4.0 repairs and healing


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4.0 repairs and healing

  1. 1. Basic Pathology Lecture 4 Tissue Repairs and Healing By Hermizan Halihanafiah
  2. 2. Introduction to Tissue Repair • Tissue repair refers to the restoration of tissue structure and function after injury. • It can be : 1. Regeneration: replacement of injured parenchymal cells with cells of the same type 2. Connective tissue (fibrous tissue) replacement : lead to the scar formation (fibrosis)
  3. 3. Tissue Repairs • Involve cell proliferation, differentiation and apoptosis • Cell proliferation : • Cell Differentiation : • Cell apoptosis :
  4. 4. Continue…. • Several types of cells proliferate during tissue repair including remnants of injured parenchymal cells, vascular endothelial cells fibroblast. • The proliferation of this cells driven by protein known as growth factors, hormones, cytokines • It also mediates for cells growth. For examples IGF stimulates hypertrophy of skeletal muscles.
  5. 5. Cell Cycle • Full regeneration or repair cannot occur without replacing cells lost (due to injury or disease) through the cell cycle • Cell cycle consist of several steps – Synthesis (S) – Mitosis (M) – Gaps 1 (G1) – Gaps 2 (G2) – Gaps 0 (G0)
  6. 6. CELL CYCLE
  7. 7. PROLIFERATIVE CAPACITY OF TISSUE • The capacity for regeneration varies with tissue and cell type • Based on the ability of their parenchymal cells to undergo regeneration, body tissue can be divided into: – Labile tissue/cells – Stable tissue/cells – Permanent tissue/cells
  8. 8. Labile tissues • Cells continue to divide and replicate throughout life, replacing injured/destroyed cells • Examples: epithelium cells of skin, GIT, vagina etc
  9. 9. Stable Tissues • Cells that normally stop dividing when growth ceases. • This cells remain in G0 phase in cell cycle, but capable to undergo regeneration with appropriate stimulus. • Examples : liver, kidney, smooth muscles cells, vascular endothelium.
  10. 10. Permanent Cells • Do not proliferate • Considered terminally differentiated (highly specialize) • Do not undergo mitotic division in postnatal life. • Example: nerve cells, skeletal muscle cells, cardiac cells • Once destroyed, it will replaced by fibrous connective tissue (scar formation)
  11. 11. Extracellular Matrix and Cell Matrix Interaction • ECM – network of spaces surrounding the tissue cells • 3 basic components of ECF – Fibrous structural protein (collagen and elastin fiber) – Water hydrated gel (proteoglycans and hyaluronic acid) – Adhesive glycoprotein (fibronectin, laminin)
  12. 12. Healing by Connective Tissue Repair (Fibrosis Formation) • Tissue repair highly associated with tissue regeneration – replacing the injured/destroyed cells with the same type cells • Tissue regeneration only occur in labile and stable cells • If the regeneration cant occur, healing process via fibrosis formation (scar formation) • Fibrosis – extensive the deposition of collagen fiber (lungs, kidney, liver etc) as a results of chronic inflammation or injury
  13. 13. Fibrosis Formation 4 basic processes: • In growth of granulation tissue and Formation of new blood vessels (angiogenesis) • Migration and proliferation of fibroblast and Deposition of ECM • Maturation and reorganization of the fibrous tissue (remodeling)
  14. 14. Ingrowths of granulation tissue • Formation of granulation tissue at the site of injury area • Granulation tissue : highly vascularized tissue, composed with newly formed capillaries, proliferating fibroblast and residual inflammatory cells. • Vascular proliferation, fibroblast and other cells at the site of injury is controlled by growth stimulatory and inhibitory factors (most importantly Vascular Endothelial Cells Growth Factor & Fibroblast Growth Factor) • Edamotous appearance – leaking of new blood vessels
  15. 15. Migration and proliferation of fibroblast and deposition of ECM • Migration and proliferation of fibroblast at the injury site driven by platelet derived growth factor (PDGF) • Collagen fiber synthesis by fibroblast, is critical to the development of strength in a healing site (days 3 – 5) and may continue to several weeks • Granulation tissue ------- scar tissue
  16. 16. Maturation and reorganization of the fibrous tissue (remodeling) • the collagen content of granulation tissue progressively increase in time • A young scar tissue consist of granulation tissues, collagen fiber and moderate number of capillaries and fibroblast • As the scar matures, the amount of collagen increases and the scar become less cellular and vascular.
  17. 17. Healing of Epithelium Tissue (Wound Healing) • Involve epithelial cells regeneration and scar formation • Wound healing mechanism can be divided into two ways: 1. Healing by first intention (primary union) • Simple repair, clean incised wound and laceration in which the edges of the wound are in close apposition. 2. Healing by second intention (secondary union) • When the wound can’t be heals by 1st intention • Large wound or Tissue lost more extensive • Maybe due to infarction, inflammatory ulceration, abscess formation, infections.
  18. 18. Wound Healing Mechanism • Cutaneous wound healing commonly can be divided into three phases 1. Inflammatory phase 2. Proliferative phase 3. Remodeling / maturational phase
  19. 19. Inflammatory Phase • Crucial period – it prepares suitable environment for tissue healing • Hemostasis : constriction of injured blood vessels, blood clot formation with platelet aggregation • Then vasodilatation, and increase it’s permeability allowing blood plasma and its component to leak into injured area. • Then follows by cellular phase ; migration of phagocytic WBC (neutrophil and macrophage) • Macrophage : release of growth factor – promote epithelial cell growth, angiogenesis and attraction of fibroblast
  20. 20. Proliferative Phase • The major cells during this phase : fibroblast • Synthesizes and secretes collagen and other intercellular elements that needed for wound healing’ • Fibroblast also produce growth factor (FGF) that needed for angiogenesis, wound contraction and matrix deposition. • Fibroblast and vascular epithelial cells begin proliferating and form granulation tissue that serves as the foundation for scar tissue development.
  21. 21. Continue… • The final component of proliferation phase is epithelialization, which is the migration, proliferation and differentiation of epithelial cells and the wound edges.
  22. 22. Remodeling Phase • Begins approximately 3 weeks after injury and continue for 6 months or maybe longer • There is continued remodeling of scar tissue by synthesis of collagen by fibroblast and lysis by collagenase enzyme. • As a results the architecture of the scar become reoriented to increase the tensile strength of the wound • An abnormality in healing by scar tissue repair is keloid formation • Keloid are benign tumorlike masses caused by excess production of scar tissue (excessive collagen).
  23. 23. Factor That Affect Wound Healing • Failure of collagen synthesis • Excessive collagen production – keloid formation • Local factors : – Foreign or necrotic tissue or blood – Infections – Abnormal blood supply (ischemic) – Decrease viability of cells – irradiation of the tissue/antimitotic drugs • Diabetes mellitus – poor microcirculation / infections incidence • Excessive levels of adrenal corticosteroid (depress WBC function)
  24. 24. Bone Healing/repairs • The repair of the bone fracture involves the following steps: 1. Formation of fracture hematoma 2. Fibrocartilaginous callus formation 3. Bony callus formation 4. Bone remodelling
  25. 25. 1.Formation of fracture hematoma • Haemorrhage within the bone from ruptured blood vessels and forming blood clot - - - - -haematoma • Haematoma facilitates repair and tissue healing • Forms 6-8 hours after injury
  26. 26. 2. Fibrocartilaginous callus formation (soft tissue callus) • Formation of collagen fiber by fibroblast and fibrocartilage by chondroblast • Lead to formation of fibrocartilaginous callus and become bridge of the broken area
  27. 27. 3. Bony callus formation • Ossification --conversation of fibrocartilaginous callus into bony callus • Osteogenic cells developed into osteoblast and then developed into spongy bone trabeculae • Begins 3 – 4 weeks after injury
  28. 28. 4. Bone remodelling • Final phase • Remodeling of the bony callus • Compact bone replace by spongy bone at the periphery site • Osteoclast – resorps the fragment of broken bone
  29. 29. Factors That Influence Bone Healing 1. Malunion • Healing with deformity at fracture site • Inadequate reduction or malalignment of fracture at time of mobilization
  30. 30. 2. Delayed union • Failure to unite within normal period • Contributing factors: – Large displaced fracture – Inadequate immobilization – Large hematoma – Infection at fracture site – Excessive lost of bone – Inadequate circulation
  31. 31. 3. Nonunion • Failure to produce union / cessation of bone repairs process • Contributing factors: – – – – – – – – – Inadequate reduction Mobility at fracture site Severe trauma Soft tissue between bone fragment Infection Extensive loss of bone Inadequate circulation Malignancy Bone necrosis