Wound Healing Physiology

1. Wound Healing Physiology Trisha Sando, DPT Bi 145a Lecture 5, 2008-09

2. 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”

3. Who cares?

4. 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

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

6. Skin structure

7. Skin structure

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

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

10. Keratinocytes • Ectoderm derived • Produce keratin • Intermediate filaments • Crosslink to form protective layer • Also form nails

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

12. Classification of wounds • Depth of injury • Type of injury • Etiology • Vascular, pressure, neuropathic, burn, surgical, atypical

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

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

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

16. 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

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

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

19. 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

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

21. Atypical Wounds • Dermal disease • dermatitis, pemphigus, autoimmune, fungal infection • Trauma • Malignancy • Necrotizing fasciitis

22. Acute Wound Healing

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

24. Hemostasis/Coagulation • Goals: • Control bleeding • Clotting cascade • Begins immediately upon injury • Activate platelets

25. Hemostasis/CoagulationCellular component • The Platelet • Activates to form fibrin clot • Stems blood flow • Release cytokines • PDGF • TGF-ß • EGF

26. Hemostasis/CoagulationCytokines • Platelet derived growth factor (PDGF) • Directs collagen expression • Released with platelet activation • Neutrophil, macrophage chemotaxis • TGF-ß • Directs collagen expression

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

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

29. Inflammatory PhaseCellular 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

30. Inflammatory PhaseCellular Component • Macrophages • Most active in late inflammatory phase • Main regulatory cell of inflammation • Remain through proliferative and remodeling phases

31. Inflammatory PhaseCellular 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

32. Inflammatory PhaseMolecular Component • Compliment • Immunology course • Bacterial destruction • Opsization • Bacterial lysis • Chemotactic factors • Phagocytic cells, neutrophils, macrophages

33. PDGF TNF- Proinflammatory Induce MMPs IL-1 Proinflammatory Stimulates NO synthesis Amplifies inflammatory response IL-6 Proinflammatory G-CSF proinflammatory CM-CSF ECM degradation Inflammatory PhaseMolecular ComponentMacrophage Derived

34. 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

35. Proliferative PhaseAngiogenesis • Neovascularization • Granulation tissue • Buds of new capillaries • Does not occur if ECM absent • Stimulated by FGF, VEGF, TGF-ß, EGF, wound angiogenesis factor

36. Proliferative PhaseMatrix Formation • Aka- fibroplasia • Begins 48-72 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

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

38. 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

39. Proliferative PhaseRe-epithelialization • Resurfaces wound • Restores integrity of epithelium • Keratinocytes migrate into and proliferate over wound bed • Inhibited by scabs • REQUIRES basement membrane

40. Proliferative PhaseRe-epithelialization • Begins within 24 hours of injury • Closed surgical wounds complete in 48-72 hours • New skin tensile strength ~15% of original skin • After remodelling tensile strength only 70-80%

41. 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

42. Types of Healing • Primary intention • Secondary intention • Tertiary or delayed primary • Chronic

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

44. Moist Wound HealingDressings • Gauze is bad • Absorb or give moisture • Antimicrobial • Conform to wound • Limit dressing changes

45. 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

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

47. Chronic WoundsIntrinsic causes • Age • Chronic disease • Perfusion/oxygenation • Immunosuppression • Neurologic impairments

48. Chronic WoundsExtrinsic causes • Medication • Nutrition • Irration/chemotherapy • Psychophysiologic stress • Wound bioburden

49. Chronic WoundsIatrogeneic causes • Local ischemia • Poor wound care • Trauma • Wound extent • Wound duration

50. Chronic WoundsTreatment • Cleansing • Debriding • Antimicrobials • Advanced dressings • Growth factors • Scar remodeling