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Flashcards in Wound Repair Deck (35):
1

definition of a wound

an acquired defect in the structural and functional integrity of tissue caused by physical or chemical insults

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two subtypes of wound healing

regeneration & replacement

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wound regeneration

restoration of lost tissue structures via cell division and growth of new parenchymal cells

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wound replacement/repair

filling of the wound with less specialized connective tissue, principally collagen resulting in a scar

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three types of regeneration

1) division of parenchymal cells in intact stroma
2) division of parenchymal cells in remaining structure
3) stem cell division and differentiation

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labile cells

cells that can undergo high regeneration due to highly proliferative tissues (GI epithelium, epidermis, bone marrow)

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stable cells

tissues that undergo limited regeneration bc they divide at low rates. (liver, kidney, vascular endothelium)

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permanent cells

post-mitotic tissue (neurons, cardiac muscle)

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chronic inflammation and wound repair

inhibits regeneration and therefore leads to replacement

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milder injury & regeneration

when accompanied with persistence of underlying stromal framework, enables regeneration

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severe injury & regeneration

destroys stromal framework precluding regeneration or triggering abnormal regeneration

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characteristics of replacement of a wound with a scar

destruction of tissue stromal architecture, limited proliferation of tissue stem cells, chronic inflammation

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primary union

straight wound, well apposed edges, clean. minimal scar formation. minimized formation of granulation tissue and scar formation.

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secondary union

irregular wound, unappeased edges, dirty/infected, significant scar formation. extensive inflammation and granulation tissue, wound contraction. attempts to close via primary union can prevent infection from clearing.

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tertiary union

wound that is allowed to begin healing by secondary union and is sutured after resolution of infection to allow further healing by primary union

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5 steps in wound healing

1. clot formation
2. inflammatory cell recruitment
3. proliferation/migration of parenchymal/stromal cells
4. synthesis of ECM proteins
5. remodeling

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PDGF (platelet derived GF)

released by activated platelets and macrophages, stimulates proliferation of fibroblasts and vascular endothelial cells

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FGF (fibroblast GF)

produced by macrophages and fibroblasts. potent activator of angiogenesis via stimulation of proliferation of endothelial cells and via directing their formation into tubular vessels

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KGF (keratinocyte GF)

produced by fibroblasts, stimulates growth of keratinocytes during reepithelialization of the wound

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VEGF (vascular endothelial GF)****

synthesis is stimulated by hypoxia, released from many cells including endothelial cells, fibroblasts, macrophages. stimulates endothelial cell proliferation and angiogenesis. also increases permeability of vessels

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TGF-beta (transforming GF-beta)

produced by many cells including platelets, macrophages, fibroblasts, keratinocytes. regulates multiple target cells and all stages of wound healing

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wound healing steps (simple version)

clot, inflammation, epithelialization, granulation, collagenization, maturation

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clot phase of wound healing

initial coverage of the wound via clot, entry of acute inflammatory cells (PMNs) via leaky/damaged vessels, which release chemokines and GFs that attract cellular components of epithelialization

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first line of defense against wound

clot

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scab

superficial aspect of a clot that has become dehydrated

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epithelialization phase of wound healing

keratinocytes migrate under the clot

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granulation tissue phase of wound healing

epithelial regrowth has reached surface. underneath there is ingrowth of fibroblasts, new/leaky endothelial bus (create edema), macrophages

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functions of fibroblasts in a wound

secrete ECM (collagen, glycoproteins, etc), secrete growth factors, contract to reduce size of wound

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functions of endothelial cells in wound

migration and angiogenesis=leaky vasculature

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collagenization phase of wound healing

replacement of granulation tissue with disorganized collagen (type 3)

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maturation phase of wound healing

collagen deposition stops and it is reorganized into tensile bundles. vascularity and cellularity decrease, production of GF ceases

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matrix metalloproteinases (MMPs)

key regulators of wound healing. set of 24 proteins that help keratinocyte migration, modulate chemokine activities, help remodel ECM,

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principle components of granulation tissue

leaky capillaries and macrophages

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examples of pathologic scarring

nodule formation in cirrhosis, contractures, keloids, strictures

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keloids

growth of the scar beyond the boundaries of the original wound. over exuberant deposition of collagen and ECM