Tissue Repair


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  • Tissue Repair

    1. 1. Repair : Regeneration of injured tissue by parenchymal cells of the same type or replacement by connective tissue. Chapter Three Repair Section A
    2. 2. Repair <ul><li>Completely regeneration: Regeneration of injured tissue by parenchymal cells of the same type. </li></ul><ul><li>Fibrous repair: Replacement by connective tissue </li></ul><ul><li>In other words </li></ul><ul><ul><li>Regeneration </li></ul></ul><ul><ul><li>Scar </li></ul></ul>
    3. 4. Cell population and cell cycle phases
    4. 6. Proliferative Potential <ul><li>Labile cells - continuously dividing </li></ul><ul><ul><li>Epidermis, mucosal epithelium, GI tract epithelium etc </li></ul></ul><ul><li>Stable cells - low level of replication </li></ul><ul><ul><li>Hepatocytes, renal tubular epithelium, pancreatic acini </li></ul></ul><ul><li>Permanent cells - never divide </li></ul><ul><ul><li>Nerve cells, cardiac myocytes, skeletal mm </li></ul></ul>
    5. 12. <ul><li>Regeneration of e pithelial t issues </li></ul><ul><li>Skin regeneration : BM not breached, repaired by the proliferation of epithelial cells. . </li></ul>
    6. 13. <ul><li>Regeneration of renal tubular cells and hepatocytes : </li></ul><ul><li>Renal tubular cells: repaired by surviving renal tubular epithelial cells. </li></ul><ul><li>If the basic framework is not intact, massive scar tissue is formed. </li></ul><ul><li>Hepatocytes are analogous to the above. </li></ul>
    7. 14. <ul><li>Regeneration of c onnective t issue </li></ul><ul><li>connective tissue includes: </li></ul><ul><li>inactive fibroblasts(fibrocyte), </li></ul><ul><li>activated fibroblasts </li></ul><ul><li>extracellular matrix </li></ul><ul><li>Fibroblasts produce collagen, elastic, and reticular fibers and amorphous material. </li></ul>
    8. 15. <ul><li>Regeneration of cartilage and bone </li></ul><ul><li>Cartilage regeneration: weak of repair capability </li></ul><ul><li>Bone tissue: a strong regenerative ability </li></ul>perichondrial cells chondrocytes with new cartilage matrix the quiescent cells and embed in the increased matrix or the wall of lacunae.
    9. 18. <ul><li>Angiogenesis: </li></ul><ul><li>by two processes: </li></ul><ul><li>Vasculogenesis: from angioblasts </li></ul><ul><li>Angiogenesis: capillary sprouts </li></ul>
    10. 20. <ul><li>Fig 4-15 </li></ul>
    11. 21. <ul><li>Muscle </li></ul><ul><li>Cardiac muscle fibe r s and s keletal muscle : </li></ul><ul><li>scar tissue. </li></ul><ul><li>skeletal muscle: Repair may be possible only when sarcolemma keeps alive and portion of myofibrils destroy in muscle fiber. </li></ul><ul><li>V ascular smooth muscle: a limited replicative protential, new small vessels can be formed. </li></ul>Sarcolemma: a coating of BM-like material adhering to the plasma membrane.
    12. 22. <ul><li>Neural tissue </li></ul><ul><li>the central nervous system: scar formation. </li></ul><ul><li>the peripheral nervous system: axonal regeneration. </li></ul>
    13. 23. 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.
    14. 24. 1. Cell-cell interaction Conditioned medium Contact inhibition 2. Growth factors 3. Extracellular matrix Laminin:  Epithelia  Fibroblasts Fibronectin :  Epithelia  Fibroblasts Factors influencing regeneration
    15. 25. <ul><li>1. Chalon and c ontact inhibition </li></ul><ul><li>Chalones is a number of growth inhibitory signals. A ny different tissues can produce and release inhibitors to control its own proliferation. </li></ul><ul><li>Contact inhibition: Cells continue dividing until they touch one another. </li></ul>
    16. 26. 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.
    17. 27. 2. Growth factor s <ul><li>Present in serum or produced locally </li></ul><ul><li>Exert pleiotropic effects: proliferation, cell migration, differentiation, tissue remodeling </li></ul><ul><li>Regulate growth of cells by controlling expression of genes that regulate cell proliferation </li></ul>
    18. 32. <ul><li>The common growth factor s: </li></ul><ul><li>Platelet-derived growth factor (PDGF) : activates fibroblasts, smooth muscle cells, and monocytes for their proliferation and migration; promotes mitosis of gliacytes. </li></ul><ul><li>Fibroblast growth factor (FGF) : mitogenic for most mesenchymal cells and induces endothelial cell to release proteolytic enzyme. </li></ul>
    19. 33. <ul><li>Epidermal growth factor (EGF) : mitogenic for epithelial cells , fibroblasts , glial cells and SMC. </li></ul><ul><li>Tr ansforming growth factors(TGF) : T wo types : </li></ul><ul><li>alpha TGF shares homology with EGF . Beta TGF acts as either a growth stimulator or a growth inhibitor. </li></ul>
    20. 34. <ul><li>Vascular endothelial growth factor (VEGF) : a central role in the growth of new blood. </li></ul><ul><li>Cytokines: IL-1 and TNF induce fibroblast proliferation and collagen synthesis. TNF can also stimulate angiogenesis. </li></ul>
    21. 36. <ul><li>Extracellular matrix( ECM ) </li></ul><ul><li>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. </li></ul>
    22. 38. <ul><li>Components of the ECMs: </li></ul><ul><li>Collagen : Fibrous structural proteins confers tensile strength. </li></ul><ul><li>Elastin : Provides the ability to recoil and return to a baseline structure after physical stress. </li></ul><ul><li>Proteoglycans: H elp regular ECM structure and permeability; modulate cell growth, differentiation and even maintain cell morphology. </li></ul>
    23. 39. <ul><li>Adhesive glycoproteins: Include fibronectin, laminin and so on. Link ECM components and link ECM to cells via cell surface integrins. </li></ul><ul><li>Integrins: A family of cell surface receptors mediating adhesion of cells to ECMs. </li></ul>
    24. 41. Section B Fibrous Repair Granulation tissues: <ul><li>Newly formed capillaries </li></ul><ul><li>Fibroblasts </li></ul><ul><li>Inflammatory cells </li></ul>
    25. 42. Repair by connective tissue <ul><li>Occurs when repair by parenchymal regeneration alone cannot be accomplished </li></ul><ul><li>Involves production of Granulation Tissue </li></ul><ul><li>replacement of parenchymal cells with proliferating fibroblasts and vascular endothelial cells </li></ul>
    26. 43. <ul><li>Granulation tissue </li></ul><ul><li>Gross: soft, pink, and granular. </li></ul><ul><li>LM: fibroblasts, new thin-walled capillaries and inflammatory cells in a loose ECM with edema. </li></ul>
    27. 44. <ul><li>Fibroblasts -- divide and secrete collagen. </li></ul><ul><li>Eeventually results in fibrosis with connective tissue matrix. </li></ul>
    28. 45. Granulation tissue : with numerous new blood vessels, fibroblasts and inflammatory cells.
    29. 47. Granulation tissue
    30. 48. Components of the process of fibrosis <ul><li>Angiogenesis - New vessels budding from old </li></ul><ul><li>Fibrosis, consisting of emigration and proliferation of fibroblasts and deposition of ECM </li></ul><ul><li>Scar remodeling, tightly regulated by proteases and protease inhibitors </li></ul>
    31. 49. <ul><li>Roles of granulation tissue: </li></ul><ul><li>Anti-infection and protecting the wound surface from further injure. </li></ul><ul><li>Filling incision or wound and any defect of tissue. </li></ul><ul><li>Replacing necrosis tissue, effusion and other foreign body. </li></ul>
    32. 50. <ul><li>Fig 4-14 </li></ul>
    33. 51. <ul><li>Scar f ormation (Fibrosis) </li></ul><ul><li>Angiogenesis - New vessels budding from old </li></ul><ul><li>Fibrosis: emigration and proliferation of fibroblasts and deposition of ECM. </li></ul><ul><li>Scar remodeling: tightly regulated by proteases and protease inhibitors </li></ul>
    34. 52. <ul><li>Scar tissue </li></ul><ul><li>a pale, avascular scar with largely inactive fibroblasts, dense collagen, fragments of elastic tissue, and other ECM components. </li></ul><ul><li>may undergo a reduction in size of 90 percent. </li></ul>
    35. 53. Scar tissue: dense collagen, fibrocytes, scattered fibroblasts and sparse vessels.
    36. 54. <ul><li>Advantage of scar: </li></ul><ul><li>provides a resilient permanent patch </li></ul><ul><li>provides a tensile strength and can keep the reparative site solid. </li></ul>
    37. 56. <ul><li>Fig 4-19 </li></ul>
    38. 57. <ul><li>Healing by first intention </li></ul><ul><li>Healing by second intention </li></ul><ul><li>Healing under scab </li></ul>Section C Wound healing
    39. 58. Wound healing <ul><li>Induction of acute inflammatory response by an initial injury </li></ul><ul><li>Parenchymal cell regeneration </li></ul><ul><li>Migration and proliferation of parenchymal and connective tissue cells </li></ul>
    40. 59. Wound healing (cont’d) <ul><li>Synthesis of ECM proteins </li></ul><ul><li>Remodeling of parenchymal elements to restore tissue function </li></ul><ul><li>Remodeling of connective tissue to achieve wound strength </li></ul>
    41. 60. Healing by First Intention Focal Disruption of Basement Membrane and loss of only a few epithelial cells e.g. Surgical Incision
    42. 61. Healing by Second Intention Larger injury, abscess, infarction Process is similar but Results in much larger Scar and then CONTRACTION
    43. 62. Wound Strength <ul><li>After sutures are removed at one week, wound strength is only 10% of unwounded skin (Walker’ Law) </li></ul><ul><li>By 3-4 months, wound strength is about 80% of unwounded skin (Walker’s Law) </li></ul>
    44. 63. Healing Skin wound
    45. 64. Healing - Skin Scar
    46. 65. Factors affecting Healing: <ul><li>Systemic </li></ul><ul><li>Age </li></ul><ul><li>Nutrition </li></ul><ul><li>Vitamin def. </li></ul><ul><li>Immune status </li></ul><ul><li>Other diseases </li></ul><ul><li>Local </li></ul><ul><li>Infection </li></ul><ul><li>Size or extent. </li></ul><ul><li>apposition </li></ul><ul><li>Blood supply </li></ul><ul><li>Mobility </li></ul><ul><li>Foreign body </li></ul>
    47. 66. <ul><li>Fig 4-18 </li></ul>
    48. 67. Summary: <ul><li>Healing – Proliferation & Differentiation. </li></ul><ul><li>Labile, Stabe & Permanent cells </li></ul><ul><li>Stages of Healing: 1-2-3-4…. </li></ul><ul><li>Healing by First or Second intention. </li></ul><ul><li>Skin wound healing - bone healing. </li></ul><ul><li>Factors affecting healing – Local / Systemic </li></ul>