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37 Cards in this Set
- Front
- Back
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healing |
- outcome of inflammation characterized by regeneration and/or scarring - often involves both processes with one dominating over other |
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regeneration |
replacement of injured cells by healthy cells of same type |
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scarring |
AKA fibrosis or connective tissue replacement - replacement of injured cells by connective tissue - scar formation - occurs in tissue not capable of regneration |
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repair |
- synonym for healing? - repair by? look at context |
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cell growth in healing |
- always involves cell growth (division, proliferation) - regeneration: tissue's own cells are dividing as well as stem cells in tissue that divide and mature - scar formation: fibroblasts and vascular endothelial cells dividing |
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cell cycle phases |
cell preparing for mitosis - S = actively synthesizing DNA - G1 - presynthetic phase - G2 = postsynthetic (premitotic) phase - G0 = intermitotic (resting) phase - cell is out of cell cycle |
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three groups based on proliferative capacity |
- labile: continuously dividing cells - stable: quiescent cells - permanent: non-dividing cells |
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characteristics labile cells |
- short G0 - actively dividing throughout life (high turnover) - examples: 1) epithelial cells: basal cells of skin, endometrium, mucosa lining GI tract, respiratory tract, biliary tract, etc. 2) hematopoietic cells: bone marrow stem cells |
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characteristics stable cells |
- low rate cell division - prolonged G0, could last years - re-enter cell cycle only under certain conditions, like healing - example: 1) vascular endothelial cells 2) parenchymal cells of solid organs (liver, kidney, pancreas, etc) 3) mesenchymal cells: fibroblasts, smooth muscle |
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characteristics permanent cells |
- cells that have left cell cycle forever - never undergo mitosis again - examples: 1) neurons of CNS 2) cardiac muscle 3) skeletal muscle |
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requirements for healing regeneration |
1) tissue composed of labile or stable cells 2) area of injury must contain some surviving (viable) cells capable of undergoing cell division 3) connective tissue framework, to which cells are attached, is intact - scaffolding for replicating cells |
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healing by scarring occurs in cells incapable of regeneration because: |
1) tissue consists of permanent cells AND/OR 2) no surviving tissue cells remain AND/OR 3) connective tissue framework is disrupted/destroyed |
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growth factor characteristics |
- polypeptides present in serum or produced by cells - may promote cell proliferation by recruiting G0 cells into cell cycle (mitogenic) - may inhibit cell proliferation by blocking cells from entering cell cycle - may influence other cell functions (differentiation, cell migration through tissues - chemotactic) |
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mitogenic |
factor able to push cell into cell cycle and do mitosis |
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chemotactic |
give cell ability to move through tissue |
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angiogenic |
factor generating new blood vessels in injured tissue |
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fibrogenic |
can bind to cell and get it to secrete collagen |
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epidermal growth factor family |
- EGF - transforming growth factor-alpha (TGF-alpha) |
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EGF |
epidermal growth factor - produced by several cells, including macrophages - mitogenic for epithelial cells,hepatocytes and fibroblasts - binds to EGF cell membrane receptor ERB B1 |
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TGF-alpha |
transforming growth factor-alpha - identical in structure and function to EGF - also binds ERB B1 |
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platelet derived growth factor (PDGF) |
- stored in alpha granules as platelets - released when platelets activated - also produced by macrophages, endothelial cells, smooth muscle cells and some tumor cells - mitogenic and chemotactic for fibroblasts, smooth muscle cells and monocytes |
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fibroblast growth factors (FGF) |
- acidic FGF and basis FGF - produced by activated macrophages and other cells - chemotactic and mitogenic for fibroblasts and endothelial cells - induce angiogenesis - important in granulation tissue formation |
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Transforming growth factor beta family (TGF-beta) |
- produced by platelets, endothelial cells, lymphocytes, activated macrophages - inhibit or stimulate cell growth depending on circumstances - mitogenic for fibroblasts but inhibit most epithelial cells - stimulate fibroblast chemotaxis and production of collagen and fibronectin - scar formation |
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fibrogenic cytokines |
- interleukin-1 (IL-1) - tumor necrosis factor (TNF) - mitogenic and chemotactic for fibroblasts - stimulate collagen production by fibroblasts - important for scar formation |
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Extracellular matrix (ECM) made up of |
- interstitial matrix: collagen, elastin, fibronectin (adhesive glycoprotein), others - basement membrane: laminin (adhesive glycoprotein), collagen, others |
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ECM characteristics |
- non cellular part of connective tissue framework - most cells in direct, intimate contact with ECM (epithelial, parenchymal, endothelial, smooth muscle, fibroblasts) - integrins bind to ECM (especially adhesive glycoproteins) - cell binding to ECM critical for regeneration and scar formation - binding triggers molecular pathways affecting cell growth,movement and differentiation |
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repair by fibrosis |
occurs when healing tissue is incapable of regeneration and results with replacement of original tissue with connective tissue |
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four main components fibrosis |
- formation new blood vessels (angiogenesis, neovascularization) - migration and proliferation fibroblasts - deposition of ECM components, including collagen - organization of fibrous tissue into mature scar |
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sequence of cellular/biochemical events in fibrosis |
1) 24 hours after injury: fibroblasts and vascular endothelial cells proliferate 2) formation (3-5 days later) of granulation tissue (pink, soft, granular appearance) 3) weeks to months after, granulation tissue is mature scar |
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important features granulation tissue |
- proliferation of newly formed small blood vessels - fibroblast proliferation |
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angiogenesis in granulation tissue
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- new vessels bud off of pre-existing blood vessels within area of repair - new vessels are immature and leaky - exudate forms - granulation tissue is edematous - involves growth factors FGF and vascular endothelial growth factor (VEGF) - stimulate endothelial mitosis and migration to new blood vessels |
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fibroblast proliferation in granulation tissue |
- triggered by growth factors EGF, TGF-beta, PDGF, others - TGF-beta stimulates newly created fibroblasts to synthesize/secrete collagen (beginning of fibrosis) |
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formation mature scar from granulation tissue |
- amount of collagen and other ECM proteins increases - fibroblasts and vascularity decreases - fully mature scar practically avascular, few cells, much dense collagen |
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healing of surgical incision |
1) scalpel blade injures limited number of epidermal cells and underlying connective tissue 2) incisional space immediately fills with clotted blood 3) 24 hrs - cellular evidence of acute inflammation appears (neutrophils) 4) day 3 - acute replaced with chronic (macrophages) 5) day 3 - granulation tissue forms - growth factors secreted by platelets, macrophages and endothelial cells. TGF-beta stimulates production collagen and other ECM proteins 6) growth factors induce regeneration of basal cells of epidermis 7) day 5 - granulation tissue filled incisional space 8) second week - collagen accumulates - leukocytes, edema and vascularity begin to disappear 9) end of first month - connective tissue scar formed and epidermis regenerated 10) healing by regeneration and scarring complete |
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scar formation - red blood cells red - purple lines: collagen - clear space: edema |
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mature scar collagen is blue |
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liver with connective tissue framework outlined |
