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    Irzan Gustanto

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    THE RESPONSE TO INJURYWound healing : the repair or reconstitution of a

    defect in an organ or tissue

    Inflammatoryphase, proliferative phase, remodelingphase

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    PHASES OF NORMAL

    WOUND HEALING Inflammatory Phase

    Proliferative Phase

    Remodeling Phase

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    Inflammation is the first stage of wound healing

    Hemostasis

    Removal of dead and devitalized tissues

    prevention of colonization and invasive infectionby microbial pathogens, principally bacteria.

    Platelets aggregate and form the initialhemostatic plug

    The coagulation and complement cascades areinitiated

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    Intrinsic and extrinsic coagulation

    cascades is the conversion of fibrinogen tofibrin and subsequent polymerization intoa gel-> fibrin matrix

    There is neutrophilic infiltrate into thefibrin matrix filling the wound cavity. Roleof these cells:

    to remove dead tissue by phagocytosis and to prevent infection by oxygen-dependent

    and independent killing mechanisms.

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    INFLAMMATORY PHASE

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    Monocyte/macrophages followneutrophils into the wound and appear 48to 72 hours after injury

    By the third day after wounding they arethe predominant cell type in the healingwound,

    Phagocytose debris and bacteria,

    Critical for orchestrated production of growth factorsnecessary for production of the extracellular matrixby fibroblasts and the production of new blood

    vessels in the healing wound

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    Macrophages role, Phagocytose debris and bacteria,

    Critical for orchestrated production of growth factorsnecessary for production of the extracellular matrix

    by fibroblasts and the production of new bloodvessels in the healing wound

    These peptide growth factors activate and

    attract local endothelial cells, fibroblasts,and keratinocytes to begin their respectiverepair functions

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    Occurring from days 4 to 21 following injury

    Keratinocyte migrate to restore epithelial continuity Platelets, macrophages,and local ECMgrowth factorinitiate fibroblast activation

    Fibroblast migrate into the woundactivated

    increase protein synthesis

    cell division The provisional fibrin matrix is gradually replaced by a

    new platform for migration: granulation tissue

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    Granulation tissue begins to appear in human

    wounds by about day 4 postinjury Fibroblasts produce the extracellular matrix

    that fills the healing scar and provides aplatform for keratinocyte migration

    Macrophages produce growth factors(PDGF,TGF-1) that induce fibroblasts toproliferate, migrate, and deposit extracellularmatrix, as well as stimulating endothelial cellsto form new vessels

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    Contraction is the process in which thesurrounding skin is pulledcircumferentially toward the wound

    Open wounds are characterized

    Occur after trauma, burns or when

    previously closed wounds are secondarilyopened cause infection

    Wound contractiondecreases the sizeof the woundwithout new tissueformation

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    Clinically, wound contraction can lead tocontracture,

    which distorts tissue and leads todecreased function

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    The process of epithelial renewal after injury.

    Particularly important in partial thicknessinjuries, but plays a role in all healing.

    Partial thickness wounds have epidermis anddermis damaged, with some dermis preserved.Epithelial cells involved in healing come from

    wound edges and sweat glands, sebaceousglands in the more central portion of wound.

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    Within hours after injury, morphologic changesin keratinocytes at the wound margin are

    evident Epidermis thickens, marginal basal cell enlarge

    and migrate over the wound defect

    epithelial cells begin migrating, they do notdivide until epidermal continuity is restored.

    New epithelial cells for wound closure areprovided by fixed basal cells in a zone near the

    edge of the wound

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    In humans is believed to last from 21 daysup to 1 year.

    Rate increases rapidly, and continues at arapid rate for 2-4 weeks in most wounds.

    As more collagen is synthesized, itgradually replaces fibrin as the primarymatrix in the wound.

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    Reorganization of previously synthesizedcollagen

    Collagen is broken down by matrixmetalloproteinase, and the net woundcollagen content is the result of balancebetween collagenolysis and collagensynthesis

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    The number of intra and intermolecularcross-links between collagen fibers

    increases dramatically.Once collagen matrix has filled in thewound cavity, fibroblasts rapidly disappear

    and newly formed blood regressA major contributor to the increase inwound strength. Remodeling continues for12 month, so scar revision should not be

    done prematurely.

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    At 3 weeks, the beginning of theremodeling phase, wounds only haveapproximately 20% of the strength ofunwounded skin,

    Eventually only possess 70% of the

    breaking strength of unwounded skin.

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    The final result of tissue repair is scar,which is brittle, less elastic than normalskin, and does not contain any skinappendages such as hair follicles or sweatglands.

    The major benefit of repair by scar is therelatively rapid reformation of tissueintegrity

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    Primary

    Secondary

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    Primary intention healing occurs in closedwounds, which are wounds with the edgesapproximated

    Uncomplicated wounds healing with primaryintention epithelialize within 24-48 h

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    Open wounds heal with the same basic processes

    of inflammation, proliferation, and remodeling asclosed wounds

    The major difference is that each sequence is

    much longer, especially the proliferative phase.There is much more granulation tissue formationand contraction

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