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Introduction to Wound Healing Physiology Content Creators: Members of the South West Regional Wound Care Programs Clinical Practice and Knowledge Translation Learning Collaborative Last Updated August 27, 2015 Learning Objectives 1.

  1. Introduction to Wound Healing Physiology Content Creators: Members of the South West Regional Wound Care Program’s Clinical Practice and Knowledge Translation Learning Collaborative Last Updated August 27, 2015

  2. Learning Objectives 1. Describe the various Wound Healing Models 2. Describe the three phases of wound healing: • Inflammatory • Proliferative Care Program South West Regional Wound • Remodeling 3. Understand the various factors that may impact wound healing: • Intrinsic • Extrinsic • Iatrogenic 2

  3. Photographs and Illustrations • Most images/illustrations obtained via Google Images • Some images obtained from the CAWC slide series Care Program South West Regional Wound 3

  4. What is ‘Wound Healing’? • Cascade of immunologic and biologic events resulting in a closed wound • Acute wounds proceed through the processes involved in Care Program South West Regional Wound wound healing in an orderly and timely manner • Chronic wounds fail to heal in a timely and orderly manner • Viability of tissues will determine the course and quality of healing 4

  5. WOUND HEALING MODELS South West Regional Wound 5 Care Program

  6. Wound Healing Model Types • Superficial wound healing • Primary intention wound healing • Delayed primary intention wound healing • Partial thickness wound healing Care Program South West Regional Wound • Full thickness/secondary intention healing 6

  7. Superficial Wound Healing • Ulcerations in the superficial skin • Soft tissues heal themselves over time via inflammatory repair process Care Program South West Regional Wound • I.e. stage I pressure ulcer, superficial burn, or contusion 7

  8. Primary Intention Wound Healing • A.k.a. Surgical wound healing • Connective tissue deposition and epithelialization Care Program South West Regional Wound • No granulation tissue formation or wound contraction 8

  9. Delayed Primary Intention • Wound left open to: • Promote drainage • Reduce bacterial burden Care Program South West Regional Wound • Later (often within seven days) surgically closed 9

  10. Partial Thickness Wound Healing • Wounds with loss of the epidermis or partial thickness skin loss of the dermis • Heal by epithelialization/regeneration • Wound edges Care Program South West Regional Wound • Dermal appendages • Normal appearance and function • I.e. abrasions, skin tears, stage II pressure ulcers, blisters, and partial thickness burns 10

  11. Full Thickness/Secondary Intention Healing • Most effective method when: • The wound extends through all layers of skin • High microorganism count • Debris or non-viable tissue present Care Program South West Regional Wound • Involves inflammation, epithelialization, proliferation, and remodeling • Scar tissue formation and contraction • Replacement tissue will have less 11 elasticity/tensile strength

  12. What Healing Model do These Wounds Represent? Care Program South West Regional Wound 12

  13. Chronic Wound Healing • Associated with secondary intention • A chronic wound is one that has “failed to proceed though an orderly and timely process to produce anatomic and Care Program South West Regional Wound functional integrity, or proceeded through the repair process without establishing a sustained anatomic and functional result” 6 13

  14. PHASES OF WOUND HEALING South West Regional Wound 14 Care Program

  15. Wound Healing Phases • Every wound is unique, “with a unique set of physiologic and social circumstances preventing or retarding wound healing” 1 . • The normal wound repair process consists of three phases Care Program South West Regional Wound that occur in a predictable sequence 1 : ▫ Inflammation ▫ Proliferation ▫ Remodeling 15

  16. Healing Phases • “The end result of uncomplicated healing is a fine scar with little fibrosis, minimal if any wound contraction, and a return to near normal tissue architecture and organ function” 1 Care Program South West Regional Wound • If a wound does not heal in an timely and/or orderly fashion or if there is a lack of structural integrity, then the wound is considered chronic 1,2 16

  17. The Inflammatory Phase South West Regional Wound 17 Care Program

  18. Inflammatory Phase 1 • Immediately initiated by tissue injury • Body’s immune system reaction: • Redness, heat, swelling, pain, loss of function Care Program South West Regional Wound • Typically lasts 3-7 days • Goals: • Hemostasis (coagulation cascade – stops bleeding and prevents bacterial infiltration) • Breakdown and removal of debris (natural autolysis) • Major cell types: platelets (clot formation and cytokine release) and 18 white blood cells

  19. Inflammatory Phase Continued • Key processes: • Coagulation cascade (platelet activation and hemostasis) • Mitogenesis and chemotaxis of growth factors • Controlled tissue degradation Care Program South West Regional Wound • Perfusion • Hypoxia and regulatory function of oxygen-tension gradient • Complement system activation to control infection • Neutrophil, macrophage, mast, fibroblast cell functions • Keratinocyte activation • Current of injury stimulus 19 Results in typical signs/symptoms of inflammation: redness, heat, swelling  pain and functional limitations

  20. Inflammatory Phase Continued 1 Trauma to skin (and bleeding) Release of epinephrine and intense vasoconstriction (5-10 minutes) to blood loss Care Program South West Regional Wound Release of inflammatory mediators (histamine, prostaglandins) from mast cells Active vasodilation and increased capillary permeability (within 10-30 minutes) = blood, O2, nutrients 20 Platelet adhesion at the site of injury and clot formation/hemostasis (wound is temporarily closed)

  21. Inflammation Continued 1 Neutrophils appear, followed by macrophages (kill bacteria and emulsify necrotic tissue) Influx of polymorphonuclear leukocytes and mononuclear Care Program South West Regional Wound leukocytes, which mature to macrophages, and later to lymphocytes Protein rich serum enters the interstitial space Fibronectin is deposited, which creates a scaffolding on which fibroblasts can migrate into 21

  22. Inflammation Activated neutrophils release free O2 radicals and lysosomal enzymes (proteases, collagenases, elastases) which fight infection and clean the wound 1,3 Care Program South West Regional Wound Lymphocytes appear in greater numbers, which attract fibroblasts and clear the wound of old neutrophils 1,4 Click on the film strip to watch a short video on the Inflammatory Phase of wound healing 22

  23. Slough • NOTE: • The formation of slough during the inflammatory phase is not uncommon • Slough is the result of the accumulation of cellular debris • Slough may be creamy and yellow Care Program South West Regional Wound • May be combined with fibrin 23

  24. The Proliferative Phase South West Regional Wound 24 Care Program

  25. Proliferation Phase 1,5 • Occurs 2-21 days after injury • Goal: • Formation of granulation tissue (fills in the wound) Care Program South West Regional Wound • Angiogenesis • Contraction (pulling edges together) • Epithelialization (covering of wound) • Major cell types: • Fibroblasts (scar formation) • Endothelial cells (angiogenesis) 25 • Epithelial cells (re-epithelization)

  26. Proliferation Continued Macrophages stimulate the fibroblasts to produce GAGS and immature collagen (increases wound tensile strength) Macrophages promote the formation of new blood vessels from Care Program South West Regional Wound endothelial cells of damaged vessels (angiogenesis) New blood vessels = new blood supply to granulation tissue Collagen fibers cross-link to increase their strength Click on the film strip to watch a short video on angiogenesis 26

  27. Proliferative Phase Continued Wound contraction Wound re-epithelialization Care Program South West Regional Wound 27

  28. Wound Contraction • Wound contraction: • Starts one week after wounding (once wound filled with granulation tissue) • Some fibroblasts will transform to smooth muscle actin (myofibroblasts) Care Program South West Regional Wound • Secure attachments, drawing the wound edges closer • At the same time, collagen is synthesized, deposited, and cross linked, holding the wound in place • Process results in: • Increased scaring • Decreased risk of infection • Increased wound closure rate 28

  29. Wound Epithelialization • Wound re-epithelialization: • Mobilization • Migration Of epithelial cells • Mitosis Care Program South West Regional Wound • Cellular differentiation 29

  30. Schematic of Epithelialization South West Regional Wound 30 Care Program

  31. The Maturation Phase South West Regional Wound 31 Care Program

  32. Maturation Phase 1 • Starts by 3 weeks after injury • Homeostasis between collagen synthesis and degradation, and wound remodeling begins • Process continues for up to 2 years – collagen structurally re- Care Program South West Regional Wound organized to increase tensile strength • A plateau is reached – healed wound will never exceed 80% strength • Major cell types: • Growth factors • Collagenases 32

  33. Maturation Continued ECM degraded and re-synthesized Mature collagen laid down and realigned Care Program South West Regional Wound Decrease in the number of fibroblasts Increase in tensile strength of wound 33

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