Wound Healing Physiology Trisha Sando, DPT Bi 145a Lecture 5,

Who cares? “You just put a bandaid on it” “Let it dry out” “Just get stitches” “Use wet gauze and change it 3 times/day”

Who cares?

Who cares? Impact on Society Health Care Cost –Pressure wounds in 2007, Medicare 257,412 cases preventable $43,180 per wound –Neuropathic/Diabetic wounds $14 billion/year in US 50-84% amputations due to wound development Mortality rate 50% in 5 years after amputation Quality of Life

Wound Healing Skin structure Classification of Wounds –Depth –Etiology Acute wound healing Chronic wound healing Collagen in wounds Tissue mechanics of wounds

Skin structure

Epidermis Begins as columnar cells Ultimately Stratified squamous epithelium Cell types –Keratinocytes –Melanocytes –Langerhans cells.

Epidermis 15µm Sloughs every 30 days Protective layer –waterproof –Prevents moisture loss –Resists friction –Low pH (4-6.5)

Keratinocytes Ectoderm derived Produce keratin –Intermediate filaments –Crosslink to form protective layer Also form nails

Dermis Below basement membrane Supports and provides nutrition for epidermis Regulates temperature

Classification of wounds Depth of injury Type of injury Etiology –Vascular, pressure, neuropathic, burn, surgical, atypical

Superficial Wounds Involve epidermis only No breach of basement membrane No bleeding Can be painful Ex- sunburn, “rug burn”

Partial Thickness Wounds Epidermis and basement membrane breached Into dermis Ex- blisters, skin tears

Full Thickness Wounds Epidermis, basement membrane and dermis breached Extends into subcutaneous fat, muscles, bone, etc

Arterial Wounds Inadequate arterial flow –Tissue lacks nutrients and oxygen to maintain Causes: peripheral vascular disease, diabetes, embolism Often located on tips of toes and fingers

Venous Wounds Inadequate venous drainage Causes: vein valve disfunction, post vein removal, DVT, vein dilation Often located LE, above ankle Weepy wound

Pressure Wounds Aka- “bedsore” Excessive or unrelieved pressure Often over bony prominences Impaired mobility

Neuropathic Wounds Wound develops in area with impaired sensation Commonly on foot Often patients with diabetes, s/p chemothepy, neurodegenerative diseases, nerve compression Often lead to amputation

Acute Surgical Wounds Often sutured or stapled and heals quickly Left open due to swelling Infection, poor nutrition can lead to chronic wound

Atypical Wounds Dermal disease –dermatitis, pemphigus, autoimmune, fungal infection Trauma Malignancy Necrotizing fasciitis

Acute Wound Healing

Fetal Wound Healing No scarring No inflammatory phase –Underdeveloped immune system –TGF-ß levels very low Environment rich in hyaluronic acid, fibronectin, growth factors Skin with lower levels of collagen And many other unknown reasons…

Hemostasis/Coagulation Goals: –Control bleeding Clotting cascade –Begins immediately upon injury –Activate platelets

Hemostasis/Coagulation Cellular component The Platelet –Activates to form fibrin clot –Stems blood flow –Release cytokines PDGF TGF-ß EGF

Hemostasis/Coagulation Cytokines Platelet derived growth factor (PDGF) –Directs collagen expression –Released with platelet activation –Neutrophil, macrophage chemotaxis TGF-ß –Directs collagen expression

Inflammatory Phase 0-3 days Begins with clotting cascade and platelets Characterized by: –Rubor (redness) –Turgor (swelling) –Calor (heat –Dolar (pain)

Inflammatory Phase Goals: –Destroy pathogens White blood cells –Clean wound site Breakdown cellular and extracellular debris –Signal cells of repair Cytokines, growth factors,

Inflammatory Phase Cellular Component Neutrophils –Migrate into wound within 24 hours Initially largest proportion of WBCs –Remain 6 hours to 4 days –Called to wound by presence of fibrinogen, fibrin degradation products –Move into wound from vasculature by diapedesis

Inflammatory Phase Cellular Component Macrophages –Most active in late inflammatory phase –Main regulatory cell of inflammation –Remain through proliferative and remodeling phases

Inflammatory Phase Cellular Component Macrophages –Phagocytize bacteria and exogenous debris –Secrete collagenases to remove damaged extracellular matrix –Release nitric oxide to kill bacteria –Release fibronectin to recruit fibroblasts –Can stimulate angiogenesis

Inflammatory Phase Molecular Component Compliment –Immunology course –Bacterial destruction Opsization Bacterial lysis –Chemotactic factors Phagocytic cells, neutrophils, macrophages

Inflammatory Phase Molecular Component Macrophage Derived PDGF TNF-  Proinflammatory Induce MMPs IL-1 –Proinflammatory –Stimulates NO synthesis –Amplifies inflammatory response –IL-6 Proinflammatory –G-CSF proinflammatory –CM-CSF ECM degradation

Proliferative Phase Overlaps inflammatory phase Begins 3-5 days post injury Length of phase dictated by wound size (~3 weeks for closed surgical wounds) Includes angiogenesis, re-epithelialization, fibroplasia

Proliferative Phase Angiogenesis Neovascularization Granulation tissue –Buds of new capillaries Does not occur if ECM absent Stimulated by FGF, VEGF, TGF-ß, EGF, wound angiogenesis factor

Proliferative Phase Matrix Formation Aka- fibroplasia Begins hours post injury Fibroblasts secrete collagen (type III) and ground substance Maximally secretes for 5-7 days Forms scaffold for endothelial migration Binds cytokines, growth factors

Wound Extracellular Matrix Composed of collagen and ground substance Produced by fibroblasts Provide structure for cells and tissues Bind growth factors, helps create gradient

Ground Substance Amorphous viscous gel produced by fibroblasts Comprised of glycosaminoglycans (GAGs) and proteoglycans Occupies space between cells and fibers Allows medium for diffusion of nutrients and wastes

Proliferative Phase Re-epithelialization Resurfaces wound Restores integrity of epithelium Keratinocytes migrate into and proliferate over wound bed –Inhibited by scabs REQUIRES basement membrane

Proliferative Phase Re-epithelialization Begins within 24 hours of injury Closed surgical wounds complete in hours New skin tensile strength ~15% of original skin After remodelling tensile strength only 70-80%

Remodeling Phase Begins during proliferative phase Continues 1-2 years post injury Scar tissue/ECM remodeled Increases tensile strength of scar –Type III collagen replaced by type I

Types of Healing Primary intention Secondary intention Tertiary or delayed primary Chronic

Moist Wound Healing DRY IS DEAD! Moist environment allows: –Cell function –Diffusion of chemical factors –Migration of cells –Autolytic debridement

Moist Wound Healing Dressings Gauze is bad Absorb or give moisture Antimicrobial Conform to wound Limit dressing changes

Chronic Wounds Wound “fails to proceed through an orderly and timely process to produce anatomic and functional integrity, or proceeded through the repair process without establishing a sustained anatomic and functional result” No definitive amount of time to be considered chronic

Chronic Wounds Wound gets “stuck” in one phase of healing Causes can be intrinsic, extrinsic or iatrogenic

Chronic Wounds Intrinsic causes Age Chronic disease Perfusion/oxygenation Immunosuppression Neurologic impairments

Chronic Wounds Extrinsic causes Medication Nutrition Irration/chemotherapy Psychophysiologic stress Wound bioburden

Chronic Wounds Iatrogeneic causes Local ischemia Poor wound care Trauma Wound extent Wound duration

Chronic Wounds Treatment Cleansing Debriding Antimicrobials Advanced dressings Growth factors Scar remodeling

Questions?