PowerPoint Presentation

Wound healing

WoundAny violation of live tissue integrity may be regarded as a woundSkin is the largest organ of the human body.Acute wound- orderly and timely reparative process - laceration, puncture, abrasion, avulsion, amputation, contusionChronic wound wound not healed in 4 weeks. Venous and arterial ulcers, diabetic ulcers, pressure ulcers.Three techniques of wound treatmentPrimary intention- all tissue including skin are closed with suture material.

Secondary intention in which wound is left open and close naturally.

Tertiary intention in which wound is left open for number of days and then closed if it found to be clean.DEFINITION wound healingWound healing is a mechanism whereby the body attempts to restore the integrity of the injured part.

Can be achieved by 2 processes: scar formation & tissue regeneration.

Dynamic balance between these 2 is different in different tissues.IntroductionDuring healing, a complex cascade of cellular events occur to achieve resurfacing, reconstitution and restoration of tensile strength of injured tissue.

3 classic but overlapping phases occur: inflammation, proliferation & maturation.Phases of HealingInflammatory (Reactive)

Proliferative (Regenerative/Reparative)

Maturational (Remodeling)

Stages of Wound Healing

Early Wound Healing Events Inflammatory or reactive phase - Immediate response to injury. - Goals: homeostasis, debridement , sealing of the wound. - last for 2-3 days. EventsVasoconstriction and thrombus formationIncrease vascular permeabilityChemotaxisSecretion of cytokinesGrowth factor

Inflammatory PhaseBlood vessels are disrupted, resulting in bleeding. Haemostasis is achieved by formation of platelet plug & activation of extrinsic & intrinsic clotting pathways.

Formation of a provisional fibrin matrix.

Recruitment of inflammatory cells into the wound by potent chemoattractants. Inflammatory PhaseFibrin and fibronectin form a lattice that provides scaffold for migration of inflammatory, endothelial, and mesenchymal cells.

Neutrophilic infiltrate appears: removes dead tissue & prevent infection.

Monocytes/macrophages follow neutrophils:- production of growth factors & phagocytosis.Inflammatory cellsPMN Migration of PMN stops when wound contamination has been controlledDont survive more than 24 hoursIncrease contamination stimulates PMN resulting to delayed wound healing and destruction of tissues.Not essential for wound healingInflammatory cellsMacrophagesRelease of cytokines/ Process of wound healing/ release of growth factors24 48 hoursSource of TNF /interleukin 1, 6, 8

Macrophage Activities During Wound HealingActivityMediatorsPhagocytosisReactive oxygen species Nitric oxideDebridementCollagenase, elastaseCell recruitment and activationGrowth factors: PDGF, TGF-, EGF, IGF Cytokines: TNF-, IL-1, IL-6 FibronectinMatrix synthesisGrowth factors: TGF-, EGF, PDGF Cytokines: TNF-, IL-1, IFN-Enzymes: arginase, collagenase ProstaglandinsNitric oxideAngiogenesisGrowth factors: FGF, VEGFCytokines: TNF- Nitric oxideLate Events in InflammationEntry of lymphocytes.

Appearance of mast cell: aberrant scarringInflammatory cellsLymphocytes ( In chronic inflammation )Peak on 7th dayAffects fibroblastStimulate cytokinesNot essential for acute wound healingProliferative Phase (3rd day Third week)Proliferative phaseGoal: granulation tissue formationEvents: AngiogenesisFibroplasiaEpithelization

Proliferative PhaseGranulation tissue formation (composed of fibroblasts, macrophages and endothelial cells).

Contraction.

Re-epithelialization (begins immediately after injury)Decrease collagen synthesis at 4 weeks after injury

Proliferative phaseExtracellular matrix Scaffold for cellular migrationComposed of fibrin, fibrinogen, fibronectinFibronectin and Type 3 collagen = early matrix Type 1 collagen later (Enhance strength)

Proliferative phaseHydroxylation results in stable triple stranded helix

Vitamin C, TGF B, IgF 1, IgF 2- increase collagen synthesis

Interferon Y , steroids decreases collagen synthesis

Mesenchymal cell proliferationFibroblasts are the major mesenchymal cells involved in wound healing, although smooth muscle cells are also involved.

Macrophage products are chemotactic for fibroblasts. PDGF, EGF, TGF, IL-1, lymphocytes are as well.

Replacement of provisional fibrin matrix with type III collagen.AngiogenesisAngiogenesis reconstructs vasculature in areas damaged by wounding, stimulated by high lactate levels, acidic pH, decreased O2 tension in tissues.Recruitment & assembly of bone marrow derived progenitor cells by cytokines.FGF-1 is most potent angiogenic stimulant identified. Heparin important as cofactor, TGF-alpha, beta, prostaglandins also stimulate.EpithelializationBasal cell layer thickening, elongation, detachment & migration via interaction with ECM proteins via integrin mediators.

Epithelial cells proliferation contributes new cells to the monolayer. Contact inhibition when edges come together.Late Wound Healing Events (Days 21-1 yr)Remodeling PhaseGoal: scar contraction with collagen cross-linking, shrinking and loss of edema

Programmed regression of blood vessels & granulation tissue.

Wound contraction.

Collagen remodeling.Maturation phaseWound contraction centripetal movement of full thickness of skinDecreases amount of disorganized scarWound contracture, physical restriction, limitation of function- result of wound contractionAppearance of stimulated fibroblast known as myofibroblast

Collagen19 types identified. Type 1(80-90%) most common, found in all tissue. The primary collagen in a healed wound.

Type 3(10-20%) seen in early phases of wound healing. Type 5 in smooth muscle, Types 2,11 in cartilage, Type 4 in BM.Wound ContractionBegins approximately 4-5 days after wounding by action of myofibroblasts.

Represents centripetal movement of the wound edge towards the center of the wound.

Maximal contraction occurs for 12-15 days, although it will continue longer if wound remains open.Wound ContractionThe wound edges move toward each other at an average rate of 0.6 to .75 mm/day.

Wound contraction depends on laxity of tissues, so a buttock wound will contract faster than a wound on the scalp or pretibial area.

Wound shape also a factor, square is faster than circular.Wound ContractionContraction of a wound across a joint can cause contracture.

Can be limited by skin grafts, full better than split thickness.

The earlier the graft the less contraction.

Splints temporarily slow contraction.RemodelingAfter 21 days, net accumulation of collagen becomes stable. Bursting strength is only 15% of normal at this point. Remodeling dramatically increases this.

3-6 weeks after wounding greatest rate of increase, so at 6 weeks we are at 80% to 90% of eventual strength and at 6months 90% of skin breaking strength.RemodelingThe number of intra and intermolecular cross-links between collagen fibers increases dramatically.A major contributor to the increase in wound breaking strength.Quantity of Type 3 collagen decreases replaced by Type 1 collagenRemodeling continues for 12 months, so scar revision should not be done prematurely.Disturbances in Wound HealingLocal FactorsIschemia

Infection: impairs healing.

Smoking: increased platelet adhesiveness, decreased O2 carrying capacity of blood, abnormal collagen.

Radiation: endarteritis, abnormal fibroblasts.

Systemic FactorsMalnutritionCancerOld AgeDiabetes- impaired neutrophil chemotaxis, phagocytosis.Steroids and immunosuppressant suppresses macrophage migration, fibroblast proliferation, collagen accumulation, and angiogenesis. Reversed by Vitamin A 25,000 IU per day.Abnormal Response to InjuryInadequate RegenerationCNS injuries

Bone nonunion

Corneal ulcersInadequate Scar FormationDiabetic foot ulcers.

Sacral pressure sores.

Venous stasis ulcers.Excessive RegenerationNeuroma

Hyperkeratosis in cutaneous psoriasis

Adenomatous polyp formation.Excessive Scar FormationExcessive healing results in a raised, thickened scar, with both functional and cosmetic complications.If it stays within margins of wound it is hypertrophic. Keloids extend beyond the confines of the original injury.Dark skinned, ages of 2-40. Wound in the presternal or deltoid area, wounds that cross langerhans lines.Keloids and Hypertrophic ScarsKeloids more familial

Hypertrophic scars develop soon after injury, Keloids up to a year later.

Hypertrophic scars may subside in time, Keloids rarely do.

Hypertrophic scars more likely to cause contracture over joint surface.Keloids and Hypertrophic ScarsBoth from an overall increase in the quantity of collagen synthesized.

Recent evidence suggests that the fibroblasts within Keloids are different from those within normal dermis in terms of their responsiveness.

No modality of treatment is predictably effective for these lesions.

Keloids Hypertrophic scar

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