tissue repair
TRANSCRIPT
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Repair :Repair :Regeneration of injured tissue by parenchymal cells of the same type or replacement by connective tissue.
Chapter Three RepairChapter Three Repair Section ASection A
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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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1. Regeneration of epithelial tissues Skin regeneration : BM not breached,
repaired by the proliferation of epithelial cells. .
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Regeneration of renal tubular cells and hepatocytes :
1) Renal tubular cells: repaired by surviving renal tubular epithelial cells.
If the basic framework is not intact, massive scar tissue is formed.
2) Hepatocytes are analogous to the above.
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2. Regeneration of connective tissue
• connective tissue includes:
1) inactive fibroblasts(fibrocyte),
2) activated fibroblasts
3) extracellular matrix
Fibroblasts produce collagen, elastic, and reticular fibers and amorphous material.
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3. 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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4. Angiogenesis:
by two processes:
1) Vasculogenesis: from angioblasts
2) Angiogenesis: capillary sprouts
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• Fig 4-15
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5. Muscle
1) Cardiac muscle fibers and skeletal muscle :
• scar tissue.
• skeletal muscle: Repair may be possible only when sarcolemma keeps alive and portion of myofibrils destroy in muscle fiber.
2) Vascular smooth muscle: a limited replicative protential, new small vessels can be formed.
Sarcolemma: a coating of BM-like material adhering to the plasma membrane.
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6. Neural tissue
• the central nervous system: scar formation.
• the peripheral nervous system: axonal regeneration.
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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.
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1. Cell-cell interaction1. Cell-cell interaction Conditioned mediumConditioned medium Contact inhibitionContact inhibition2. Growth factors2. Growth factors3. Extracellular matrix3. Extracellular matrix Laminin: Laminin: Epithelia Epithelia FibroblastsFibroblasts Fibronectin : Fibronectin : Epithelia Epithelia FibroblastsFibroblasts
Factors influencing regenerationFactors influencing regeneration
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1. Chalon and contact inhibition
• Chalones is a number of growth inhibitory signals. Any different tissues can produce and release inhibitors to control its own proliferation.
• Contact inhibition: Cells continue dividing until they touch one another.
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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.
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2. Growth factors
• 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 factors:
1) Platelet-derived growth factor (PDGF): activates fibroblasts, smooth muscle cells, and monocytes for their proliferation and migration; promotes mitosis of gliacytes.
2) Fibroblast growth factor (FGF): mitogenic for most mesenchymal cells and induces endothelial cell to release proteolytic enzyme.
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3) Epidermal growth factor (EGF): mitogenic for epithelial cells, fibroblasts, glial cells and SMC.
4) Transforming growth factors(TGF): Two types:
alpha TGF shares homology with EGF. Beta TGF acts as either a growth stimulator or a growth inhibitor.
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4) Vascular endothelial growth factor (VEGF): a central role in the growth of new blood.
5) Cytokines: IL-1 and TNF induce fibroblast proliferation and collagen synthesis. TNF can also stimulate angiogenesis.
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3. 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:
1) Collagen: Fibrous structural proteins confers tensile strength.
2) Elastin: Provides the ability to recoil and return to a baseline structure after physical stress.
3) Proteoglycans: Help regular ECM structure and permeability; modulate cell growth, differentiation and even maintain cell morphology.
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4) Adhesive glycoproteins: Include fibronectin, laminin and so on. Link ECM components and link ECM to cells via cell surface integrins.
5) Integrins: A family of cell surface receptors mediating adhesion of cells to ECMs.
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Section BSection BFibrous RepairFibrous Repair
Granulation tissues:Granulation tissues:• Newly formed Newly formed
capillariescapillaries• FibroblastsFibroblasts• Inflammatory cellsInflammatory cells
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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
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Granulation tissue• Gross: soft, pink, and granular.
• LM: fibroblasts, new thin-walled capillaries and inflammatory cells in a loose ECM with edema.
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•Fibroblasts -- divide and secrete collagen.
•Eeventually results in fibrosis with connective tissue matrix.
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Granulation tissue : with numerous new blood vessels, fibroblasts and inflammatory cells.
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Granulation tissue
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Components of the processof 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
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Roles of granulation tissue:
1) Anti-infection and protecting the wound surface from further injure.
2) Filling incision or wound and any defect of tissue.
3) Replacing necrosis tissue, effusion and other foreign body.
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• Fig 4-14
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Scar formation (Fibrosis)
1. Angiogenesis - New vessels budding from old
2. Fibrosis: emigration and proliferation of fibroblasts and deposition of ECM.
3. Scar remodeling: tightly regulated by proteases and protease inhibitors
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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.
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Scar tissue: dense collagen, fibrocytes, scattered fibroblasts and sparse vessels.
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Advantage of scar:
1) provides a resilient permanent patch
2) provides a tensile strength and can keep the reparative site solid.
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• Fig 4-19
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• Healing by first intentionHealing by first intention
• Healing by second intentionHealing by second intention
• Healing under scabHealing under scab
Section CSection CWound healingWound healing
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Wound healing
• Induction of acute inflammatory response by an initial injury
• Parenchymal cell regeneration
• Migration and proliferation of parenchymal and connective tissue cells
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Wound healing (cont’d)
• Synthesis of ECM proteins
• Remodeling of parenchymal elements to restore tissue function
• Remodeling of connective tissue to achieve wound strength
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Healing byFirst Intention
Focal Disruption of Basement Membrane and loss of only a
few epithelial cellse.g. Surgical Incision
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Healing by Second Intention
Larger injury, abscess, infarction
Process is similar butResults in much larger Scar and then CONTRACTION
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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)
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Healing Skin wound
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Healing - Skin Scar
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Factors affecting Healing:
SystemicSystemic
• Age
• Nutrition
• Vitamin def.
• Immune status
• Other diseases
LocalLocal
• Infection
• Size or extent.
• apposition
• Blood supply
• Mobility
• Foreign body
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• Fig 4-18
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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