Tissue Repair
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Tissue Repair

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Tissue Repair Tissue Repair Presentation Transcript

  • Repair : Regeneration of injured tissue by parenchymal cells of the same type or replacement by connective tissue. Chapter Three Repair Section A
  • Repair
    • Completely regeneration: Regeneration of injured tissue by parenchymal cells of the same type.
    • Fibrous repair: Replacement by connective tissue
    • In other words
      • Regeneration
      • Scar
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  • Cell population and cell cycle phases
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  • Proliferative Potential
    • Labile cells - continuously dividing
      • Epidermis, mucosal epithelium, GI tract epithelium etc
    • Stable cells - low level of replication
      • Hepatocytes, renal tubular epithelium, pancreatic acini
    • Permanent cells - never divide
      • Nerve cells, cardiac myocytes, skeletal mm
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    • Regeneration of e pithelial t issues
    • Skin regeneration : BM not breached, repaired by the proliferation of epithelial cells. .
    • Regeneration of renal tubular cells and hepatocytes :
    • Renal tubular cells: repaired by surviving renal tubular epithelial cells.
    • If the basic framework is not intact, massive scar tissue is formed.
    • Hepatocytes are analogous to the above.
    • Regeneration of c onnective t issue
    • connective tissue includes:
    • inactive fibroblasts(fibrocyte),
    • activated fibroblasts
    • extracellular matrix
    • Fibroblasts produce collagen, elastic, and reticular fibers and amorphous material.
    • Regeneration of cartilage and bone
    • Cartilage regeneration: weak of repair capability
    • Bone tissue: a strong regenerative ability
    perichondrial cells chondrocytes with new cartilage matrix the quiescent cells and embed in the increased matrix or the wall of lacunae.
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    • Angiogenesis:
    • by two processes:
    • Vasculogenesis: from angioblasts
    • Angiogenesis: capillary sprouts
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    • Fig 4-15
    • Muscle
    • Cardiac muscle fibe r s and s keletal muscle :
    • scar tissue.
    • skeletal muscle: Repair may be possible only when sarcolemma keeps alive and portion of myofibrils destroy in muscle fiber.
    • V ascular smooth muscle: a limited replicative protential, new small vessels can be formed.
    Sarcolemma: a coating of BM-like material adhering to the plasma membrane.
    • Neural tissue
    • the central nervous system: scar formation.
    • the peripheral nervous system: axonal regeneration.
  • Nerve fiber regeneration Normal nerve fiber Regeneration of Schwann cells and axon filaments at site of nerve lesion or section New axon extending into original channel.
  • 1. Cell-cell interaction Conditioned medium Contact inhibition 2. Growth factors 3. Extracellular matrix Laminin:  Epithelia  Fibroblasts Fibronectin :  Epithelia  Fibroblasts Factors influencing regeneration
    • 1. Chalon and c ontact inhibition
    • Chalones is a number of growth inhibitory signals. A ny different tissues can produce and release inhibitors to control its own proliferation.
    • Contact inhibition: Cells continue dividing until they touch one another.
  • Cells anchor to dish surface and divide. When cells have formed a complete single layer, they stop dividing. If some cells are scraped away, the remaining cells divide to fill the dish with a single layer and then stop.
  • 2. Growth factor s
    • 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
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    • The common growth factor s:
    • Platelet-derived growth factor (PDGF) : activates fibroblasts, smooth muscle cells, and monocytes for their proliferation and migration; promotes mitosis of gliacytes.
    • Fibroblast growth factor (FGF) : mitogenic for most mesenchymal cells and induces endothelial cell to release proteolytic enzyme.
    • Epidermal growth factor (EGF) : mitogenic for epithelial cells , fibroblasts , glial cells and SMC.
    • Tr ansforming growth factors(TGF) : T wo types :
    • alpha TGF shares homology with EGF . Beta TGF acts as either a growth stimulator or a growth inhibitor.
    • Vascular endothelial growth factor (VEGF) : a central role in the growth of new blood.
    • Cytokines: IL-1 and TNF induce fibroblast proliferation and collagen synthesis. TNF can also stimulate angiogenesis.
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    • Extracellular matrix( ECM )
    • ECM provides turgor to soft tissue and rigidity to bone, and supplies a substratum for cell adhesion and critically regulates the growth, movement, and differentiation of the cells living within it.
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    • Components of the ECMs:
    • Collagen : Fibrous structural proteins confers tensile strength.
    • Elastin : Provides the ability to recoil and return to a baseline structure after physical stress.
    • Proteoglycans: H elp regular ECM structure and permeability; modulate cell growth, differentiation and even maintain cell morphology.
    • Adhesive glycoproteins: Include fibronectin, laminin and so on. Link ECM components and link ECM to cells via cell surface integrins.
    • Integrins: A family of cell surface receptors mediating adhesion of cells to ECMs.
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  • Section B Fibrous Repair Granulation tissues:
    • Newly formed capillaries
    • Fibroblasts
    • Inflammatory cells
  • Repair by connective tissue
    • Occurs when repair by parenchymal regeneration alone cannot be accomplished
    • Involves production of Granulation Tissue
    • replacement of parenchymal cells with proliferating fibroblasts and vascular endothelial cells
    • Granulation tissue
    • Gross: soft, pink, and granular.
    • LM: fibroblasts, new thin-walled capillaries and inflammatory cells in a loose ECM with edema.
    • Fibroblasts -- divide and secrete collagen.
    • Eeventually results in fibrosis with connective tissue matrix.
  • Granulation tissue : with numerous new blood vessels, fibroblasts and inflammatory cells.
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  • Granulation tissue
  • Components of the process of fibrosis
    • Angiogenesis - New vessels budding from old
    • Fibrosis, consisting of emigration and proliferation of fibroblasts and deposition of ECM
    • Scar remodeling, tightly regulated by proteases and protease inhibitors
    • Roles of granulation tissue:
    • Anti-infection and protecting the wound surface from further injure.
    • Filling incision or wound and any defect of tissue.
    • Replacing necrosis tissue, effusion and other foreign body.
    • Fig 4-14
    • Scar f ormation (Fibrosis)
    • Angiogenesis - New vessels budding from old
    • Fibrosis: emigration and proliferation of fibroblasts and deposition of ECM.
    • Scar remodeling: tightly regulated by proteases and protease inhibitors
    • Scar tissue
    • a pale, avascular scar with largely inactive fibroblasts, dense collagen, fragments of elastic tissue, and other ECM components.
    • may undergo a reduction in size of 90 percent.
  • Scar tissue: dense collagen, fibrocytes, scattered fibroblasts and sparse vessels.
    • Advantage of scar:
    • provides a resilient permanent patch
    • provides a tensile strength and can keep the reparative site solid.
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    • Fig 4-19
    • Healing by first intention
    • Healing by second intention
    • Healing under scab
    Section C Wound healing
  • Wound healing
    • Induction of acute inflammatory response by an initial injury
    • Parenchymal cell regeneration
    • Migration and proliferation of parenchymal and connective tissue cells
  • Wound healing (cont’d)
    • Synthesis of ECM proteins
    • Remodeling of parenchymal elements to restore tissue function
    • Remodeling of connective tissue to achieve wound strength
  • Healing by First Intention Focal Disruption of Basement Membrane and loss of only a few epithelial cells e.g. Surgical Incision
  • Healing by Second Intention Larger injury, abscess, infarction Process is similar but Results in much larger Scar and then CONTRACTION
  • Wound Strength
    • After sutures are removed at one week, wound strength is only 10% of unwounded skin (Walker’ Law)
    • By 3-4 months, wound strength is about 80% of unwounded skin (Walker’s Law)
  • Healing Skin wound
  • Healing - Skin Scar
  • Factors affecting Healing:
    • Systemic
    • Age
    • Nutrition
    • Vitamin def.
    • Immune status
    • Other diseases
    • Local
    • Infection
    • Size or extent.
    • apposition
    • Blood supply
    • Mobility
    • Foreign body
    • Fig 4-18
  • Summary:
    • Healing – Proliferation & Differentiation.
    • Labile, Stabe & Permanent cells
    • Stages of Healing: 1-2-3-4….
    • Healing by First or Second intention.
    • Skin wound healing - bone healing.
    • Factors affecting healing – Local / Systemic