1. Integumentary System & Wound Care October 24, 2005 Michael S. Brogan, PT, PT, PhD, CWS

2. WOUND HEALING MODELS Superficial Wound Healing Primary Intention Wound Healing Delayed Primary Intention Wound Healing Partial-Thickness Wound Healing Secondary Intention Wound Healing

3. Superficial Wound Healing Superficial Skin Lesions –Pressure (shearing & friction) –First degree burns –Contusions Stimulates an inflammatory repair process Soft tissues heal themselves over time Interventions can hasten process (athletes) prevention of further complication (MO)

4. Primary Intention Wound Healing Drawing wound edges together (sutures) –Three considerations No major loss of subcutaneous tissue edges are smooth and clean cut Wound is not contaminated with microorganisms or foreign bodies –Result Minimal scarring, closure 3-7 days

5. Delayed Primary Intention Wound Healing Wounds contaminated with microorganisms or foreign bodies Wounds with large tissue loss Wounds where intolerable tissue tension would occur Wound is at risk of infection (time) –* Wound is left open –* Sutures are placed in subcutaneous & fascial layers –* Wound is usually closed (sutures) in 5 -7 days after infection risk is significantly decreased or tissue loss is replaced

6. Partial Thickness Wound Healing Partial-Thickness loss of the dermis –Abrasions –Skin tears –Stage II pressure ulcers –Second degree burns Following injury body immediately begins repair process Inflammation Epithelialization

7. Secondary Intention Wound Healing (by contraction) Chosen method when wound extends through full thickness of the skin –When large amounts of tissue are lost –Irregular wound edges cannot be approximated –Non-viable wound margins –High microorganism count –Debris or necrosis

8. Three Overlapping Phases of Repair With Secondary Intention Inflammation Repair (Proliferation) –Epithelialization Remodeling Inflammation Proliferation Remodeling

9. Secondary Intention (by contraction) Occurs with contraction forces by myofibroblast draw the wound edges together Little epithelialization Scar tissue formation Scar does not replicate the tissue replaced –Ex (muscle, tendons, nerves) Surface tissue is less elastic with decreased tensile strength Following Wound Closure, remodeling continues 6 months to 2 years

10. Skin Grafts If wound is in an area where contraction will disfigure or create non-functional deformation, secondary intention used to allow for the development of a good healthy wound bed. With healthy wound bed a Split-Thickness Graft can be placed on the granulating wound bed.

11. Secondary Intention Mechanism for Healing of Chronic Wounds

12. Acute Wound Healing Biology Cascade of Overlapping Events (organized & predictable) –Inflammation –Repair (proliferation - epithelialization) –Remodeling Biologic Repair Process Same for all Wounds, Open & Closed, Regardless of Etiology Sequence hastened with primary intention or with superficial/partial-thickness wounds Slower process with Full-Thickness Wounds with extension to subcutaneous tissue

13. Acute Wound Healing Inflammatory Phase 1-10 days –Essential for healing Repair Phase 3-20 days Remodeling Phase 9 days and on Remodeling Inflammation Repair

14. Inflammatory Phase Vascular & Cellular Response Hemostatic Mechanisms –Curtail blood flow –Reduces oxygen delivery to the wound –Produces hypoxia Key signal to control wound healing Too much O2 will impede wound healing Hypoxia recruits endothelial cells & serves as facilitator for angiogenesis for repair phase Local hypoxia causes shift to anaerobic glycolysis, which increases lactate production which also activates angiogenesis and collagen synthesis Wound space thus becomes hyperlactic & acidotic

15. Hemostatic Mechanisms Platelets First to arrive at injury site Release Serotonin ADP PDGF Changes Thromboplastin -Thrombin -Fibrinogen - Fibrin Clot Protection of Injured Area, delays bacterial invasion

16. Hemostatic Mechanisms Continued Vessel Wall –Endothelial Cell Damage activates Hageman Factor XII Neutrophils Marginate –Prevent pathogenic invasion

17. Vascular Reactions Vasoconstriction Vasodilation Edema/Drainage

18. Vasoconstriction First response to trauma Vasoconstriction/ norepinephrine Vasoconstriction/serotonin Adhesion of opposing endothelial surfaces

19. Vasodilation Secondary response to trauma Histamine released from mast cells increases capillary permeability Capillary permeability allows clotting proteins, WBC’s and other fluids from blood into injured area

20. Edema/Drainage Serous………….……………Clear, Watery Sanguineous……………Tinge of Red, Thin Purulent..…………………Creamy, Thick – Yellow/Brown/Green/Blue

21. SEROUS Sanguineous Purulent Sussman, C., Bates Jensen, B. (2001). Wound Care 2 nd addition. Aspen, Gaithersberg, Md

22. Plasma Proteins Albumin –Small plasma protein Gamma Globulins –Medium size protein Fibrinogen –Large size plasma protein –Converted to fibrin by thrombin –Fibrin plugs seal off lymphatics to prevent spreading infection Venous Insufficiency

23. Necrotic Tissue Scab –Dehydrated crust formed by coagulated blood, pus, serum Eschar –Thick, dry, black, leathery necrotic tissue Mechanical Impediment –Impedes epithelial cell migration –Delays granulation tissue formation Prolongs Inflammation –Wounded tissues are struggling to achieve homeostasis –WBC’s are trying to digest, dissolve and remove necrotic tissues –Provides a source for pathogens

24. Cardinal Signs of Inflammation Erythema (change in color, red, blue, purple) Heat (temperature) Edema (turgor, swelling) Pain (sensation) Loss of function “flare” –Sudden response - color & temperature “flaring up a fire” From: Myers, B.A. (2004).Wound ManagementPrinciples and Practice. Prentice Hall, Saddle River, NJ)

25. Talking Points –Perfusion & Nutrition Biologic Basis for Signs & Symptoms of Inflammation Vasodilation- increased perfusion & capillary pressure Allows plasma proteins to migrate into surrounding tissues Fibrin plugs seal off lymphatic flow Increased blood flow brings nutrients, to meet high metabolic needs High metabolic activities & increased blood flow increases tissue temperature Rise in Temperature provides an environment favorable for cell mitosis and enhanced cellular activities

26. Talking Points Pain –Bleeding into tissues releases histamine and protaglandins, which stimulate dilation of injured blood vessels in adjacent tissues & pain afferents of the SNS (Reflex Hyperemia) Infection –Oxygen essential to prevent infection & to meet metabolic demands of the tissue as well as hydroxylation of proline in the biosynthesis of collagen for remodeling wound

27. How to Facilitate Inflammatory Phase Keep Wound Moist Remove Necrotic Tissue Prevent re-injury to wound (From: Myers, B.A. (2004).Wound Practice. Prentice Hall, Saddle River, NJ)

28. Cellular Reactions in Inflammatory Phase Granulocytes –Term for WBC containing many secretory granules –Polymorphonuclear leukocyte (PMNL) common term for neutrophil granulocyte (nucleus divided into lobes) –65% of leukocytes in circulating blood are granulocytes 3 types –Neutrophils (PMNL) –Eosinophils –Basophils

29. Neutrophils Present in early phase of inflammation (within 24 hrs.for 6 hrs to several days) Length of stay depends on bacterial count Most phagocytic of WBC (along with macrophages) Proliferate in hypoxic acidotic environment Produce superoxide to fight bacteria Secrete proteases and collagenases (enzymes) Destroys pathogens and hydrolyzes necrotic tissue Primary cell responsible for cleansing the wound of microorganisms Lack of neutrophils will inhibit healing in infected wounds

30. Neutrophils If bacterial count exceeds 100, 000 infection becomes apparent Wound pours forth pus (accumulation of dead neutrophils that have phagocytized debris in the wound) Short lifetime because it cannot regenerate spent lysosomal and other enzymes used for destruction of foreign substances Produces numerous toxic byproducts (OH, superoxide), if excessive neutrophil activity due to high bacterial counts wound tissue & healthy tissue can be negatively affected.

31. Eosinophils Term based on the staining (Red) of cytoplasmic granules Modulate allergic inflammatory responses

32. Basophils Release histamine –Increases inflammation –Increases vasodilation –Increases capillary permeabilty

33. Mast Cells Specialized secretory cells, granules contain several biologically active substances including neutrophil chemotactic factor which attracts leukocytic cells that in turn act as chemical signals for the recruitment of macrophages. Histamine released from mast cell initially following injury for vasodilation and increased permeability - mild edema In low amounts histamine has been shown to stimulate collagen formation and healing Mast cells also release heparin which stimulates the migration of endothelial cells. Heparin also accelerates the activity of the leukocytes in the phagocytosis of the hematoma following initial wounding of the blood vessels

34. Macrophages Differentiate from monocytes once they leave the bloodstream Perform several vital functions during inflammatory phase Large phagocytic cell, can ingest large microorganisms & debris controlling infection by excreting ascorbic acid, hydrogen peroxide and lactic with a build up of these substances more macrophages will be recruited resulting in an intense prolonged inflammatory phase Important regulatory cell and is long lived (months to years) Macrophages attract fibroblasts, endothelial cells, and vascular smooth muscle cells Both Neutrophils & Macrophages function in a low-oxygen high acidotic environment Macrophages are essential for the transition between the inflammatory and repair phases

35. Macrophages Secrete Angiogenesis Growth Factor (AGF) which stimulates the budding of endothelial from damaged blood vessels Reestablishment of the blood supply is essential to deliver nutrients, oxygen and toilet the newly forming tissue Secretions of Macrophages and dead platelets combine to produce fibroblast- stimulating factor which provide a chemotactic message to the fibroblasts during the late stages of the inflammatory phase Macrophages transcend all phases of healing

36. Lymphocytes Immunologically important Responsible for primary immune response to pathogens

37. B Lymphocytes B cells release antibodies into bloodstream (referred to as the humerol response) Antibodies are immunoglobin (protein) which bind to an antigen (pathogenic)

38. T Lymphocytes T cells responsible for cell- mediated responses “helper cells” assist in B cloning “suppressor cells” cause B cells to stop cloning

39. Defense Against Microorganisms Epithelium Neutrophils & Macrophages T & B Cells

40. Chemical Mediators Inflammatory Phase Histamine –Released primarily from mast cells, also from basophils & platelets –Vasodilator which increases permeability of capillaries & arterioles Serotonin –Powerful vasoconstrictor, from platelets & mast cells –Early phase of inflammation stimulates smooth muscle contraction

41. Chemical Mediators Inflammatory Phase (cont.) Kinins –Polypeptides (two or more a.a.) –Relax smooth muscle cells of vasculature –Produces vasodilation, increased permeability –Ex. Bradykinin one type of plasma kinins

42. Chemical Mediators Inflammatory Phase (cont.) Prostaglandins (PG’s) –PG’s, fatty acid derivatives –Local mediators, many tissues & fluids –Extremely active biological substances –Increase vascular permeability –Chemotactic substances (attracts other cells) –* steroids and aspirins reduce prostaglandin production

43. Chronic Inflammation Inefficient cellular activity Misuse of cytotoxic agents Frequent irritation Presence of pathogens Infection Granuloma Repeated trauma (spitting silk)

44. Repair/ Proliferative Phase Fibroplasia Granulation/Angiogenesis Contraction Reepithelialization From: Myers, B.A. (2004).Wound ManagementPrinciples and Practice. Prentice Hall, Saddle River, NJ)

45. Fibroplasia Fibroblasts –Respond to chemotactic substances from the macrophages –build the collagen matrix (polypeptide chains) –Procollagen - tropocollagen - collagen fibril - array of filaments –Cross-linkage welding together of the collagen matrix Produces durability and tensile strength the better the organization & cross-linkage, the better the tensile strength of the scar –Elastin- provides elastic properties Hunt & Dunphy (1979). Appleton-Century Crofts, NY

46. Fiboplasia Fibroblasts (cont.) –Glycoproteins Laminin & Fibronectin provide structure & metabolic support to other tissues Myofibroblasts (contain actin & myosin) –Differentiate from fibroblasts –Contract & extend –Draw the edges of the wound together –Influence rate & amount of wound contraction

47. Collagen Matrix Collagen, Fibronectin, Laminin, Elastin, Acid & new vascular network produced by endothelial cells Looks like red granules piled on top of each other Granulation Tissue Pink granulation buds may be the first sign of repair in a wound

48. Granulation/Angiogenesis Endothelial cells –Respond to AGF secretions of macrophages & from hypoxic environment –Development of new blood vessels or vascularization of the tissue that will grow on the collagen matrix (gives bright red appearance of granulation tissue)

49. Granulation/Angiogenesis Endothelial cells form new capillaries Capillaries perfuse the collagen matrix Red granular appearance GT matrix of collagen, acid, laminin, fibronectin, elastin, Provides matrix upon which epithelial cell migration can occur Sussman, C., Bates Jensen, B. (2001). Wound Care 2 nd addition. Aspen, Gaithersberg, Md

50. Contraction Occurs in full-thickness wounds The entire thickness of the periwound tissue moves centripetally by action of the myofibroblasts From: Myers, B.A. (2004).Wound ManagementPrinciples and Practice. Prentice Hall, Saddle River, NJ)

51. Re-Epithelialization Superficial wounds heal by reepithelialization Epithelial cells respond to a break in the skin & from the dermal appendages Epithelial cells line skin appendages (hair follicles, sebaceous glands, sweat glands) The resurfacing process immediately following injury

52. Epithelial Cells Specialized function - debridement of necrotic tissue by release of lytic enzymes- lyse the attachment of necrotic tissue to the wound bed Migration of epithelial cells O2 dependent –Low levels of O2 & epithelial cells cannot migrate to debride the wound

53. Reepithelialization (cont.) Epithelial cell migration occurs towards the center of wound from edges Contact inhibition stops migration (curled/rolled edges) Reepithelialization 4 step process –Mobilization - migration - proliferation- differentiation (mature into Type I collagen).… new skin 15 % strength of original 70% to 80% of original strength

54. Remodeling Phase Scar maturation occurs Fibroblasts disappear Collagen reorganizes and scar exhibits greater strength Compression garments - burn patients Appropriate to massage soft tissue in early maturation phase Sussman, C., Bates Jensen, B. (2001). Wound Care 2 nd addition. Aspen, Gaithersberg, Md

55. Collagen Lysis Collagenase - enzyme responsible to regulate fibroplasia, creates balance between synthesis & lysis of collagen Cleaving or breaking the cross-linkage of the tropocollagen molecules Collagenase as a debriding agent (Santyl) As wound matures collagen lysis increases

56. Balance Collagen synthesis oxygen dependent - collagen lysis is not Too much oxygen can cause hypertrophy of the granulation tissues (hypergranulation) Better organization of the collagen produces a better functional outcome, more elastic, smoother, and stronger

57. Remodeling Errors Hypertrophic Scar Keloid Formation –Genetic inhibition of lysis, unbalanced synthesis and lysis of collagen

58. Remodeling Errors (cont.) Control- –pressure garments to reduce perfusion & oxygen inflow, synthesis is suppressed & lysis continues –Silver nitrate “knock down the granulation tissue, allowing epithelial migration –Electrical stimulation; + polarity

59. Talking Point Wound is considered Closed when the epithelial integrity has been restored Wound is considered Healed after it has been resurfaced, and tissue strength approaches normal

60. Chronic Wound Healing Deviation from normal sequence of repair in terms of time, appearance, and response to appropriate treatment 2 - 4 weeks Halo of redness

61. Abnormal Wound Healing Healing is slower than expected Abundance or reduction of the typical characteristics of each phase of wound healing Underlying causes should be investigated –Local & systemic factors –Iatrogenic factors –Other factors (drugs, radiation, age, etc)

62. Absence of Inflammation Inflammation is a necessary & desirable element of wound healing Reduced or absent inflammation may be seen in patients taking high doses of steroids, malnutrition, elderly, immune disorders (HIV, AIDS)

63. Chronic Inflammation May continue for months or years Characterized by an increase in macrophages & fibroblast proliferation New tissue cannot be built in an inflammatory environment –Causes Presence of foreign body in the wound bed Repetitive mechanical trauma Use of cytotoxic agents

64. Hypogranulation Absence of a successful proliferative phase Insufficient granulation tissue to fill wound defect (pot-hole type wound) Epithelial cells cannot bridge the gap Rolled edges

65. Hypergranulation Granulation continues after the wound defect has been filled Appears as a mound of granulation tissue extending above the surface of the epithelium (proud flesh) Epithelialization cannot proceed

66. Hypertrophic Scarring Over production of immature collagen More likely to occur in wounds that cross lines of tension in the skin or in wounds with a prolonged inflammatory phase (large or infected wounds) Burns because of their lengthy proliferative phase Often associated with contractures (random over production of collagen Darker skin individuals greater propensity ** contained within the confines of the wound

67. Keloids Result from excessive immature collagen synthesis More common in individuals with more highly pigmented skin & in areas of increased tissue tension Extend outside the confines of the wound Commonly associated with tissue trauma

68. Contracture Pathological shortening of scar tissue resulting in deformity Likely to occur in wounds crossing a joint (especially burns) Position of comfort are usually maintained resulting in adhesions and adaptive shortening of muscles, tendons, and joint capsules Decreases movement & limits function

69. Dehiscence Separation of wound margins due to insufficient collagen production or tensile strength Common misconception is that infection causes dehiscence Longtime steroid use, diabetes mellitus, & malnutrition increase Kloth, L.C., McCulloch, J.M. (2002)

70. Types of Wounds Arterial Venous Pressure (STG I, II, III, IV) Neuropathic (Diabetic) Traumatic (injury/surgery) Rheumatoid

71. Wound Healing Model - Review Inflammatory Phase –Vasoconstriction –Hemostasis –Vasodilation –Phagocytosis

72. Key Cells of the Inflammatory Phase Platelet –Forms platelet plug to control bleeding –Secretes growth factors & chemotactic agents Polymorphonuclear Leukocyte – Neutrophil –First cells to the site of injury –Scavenger –Kills bacteria –Cleans wound –Secretes inflammatory mediators Mast Cell –Secretes several biologically active substances –Secretes inflammatory mediators Macrophages –Directs repair process –Assists with killing bacteria and cleaning wound –Secretes growth factors

73. Proliferative Phase Angiogenesis/Granulation Collagen Synthesis/Fibroplasia Contraction Reepithelialization

74. Proliferative Phase Key Cells –Angioblast Forms new blood vessels –Fibroblast Builds granulation tissue –Myofibroblast Causes Wound Contraction –Keratinocyte Reepithelializes wound surface

75. Remodeling Phase Collagen Synthesis - Lysis Balance Collagen Fiber Re-organization

76. Wound Healing Model Wound –Inflammatory Phase –Repair Phase –Remodeling Phase Closed Wound Healed Wound

77. Fetal Wound Healing Research Lack of Scar tissue in fetuses that have fetal surgery in utero Amniotic fluid rich in Hyaluronic acid & fibronectin with other growth factors Low oxygen levels, differences in immune systems, histology, fibroblasts, absence of myofibroblasts

78. References Arndt, A.A., Wintroub, B.U., Robinson, J.K., LeBoit, P.E. (1997). Primary Care Dermatology. W.B. Saunders Company: Philadelphia, Plate 5, 12, 57-81. Du Vivier, A. (1995). Dermatology in Practice. Mosby-Wolfe: New York, 1-11, 25, 53, 94, 97, 100. Fitzpatrick, T.B., Johnson, R.A., Wolff, K., Polano, M.K., Suurmond D. (1997). Color Atlas and Synopsis of Clinical Dermatology: Common and Serious Diseases. McGraw-Hill: Health Professions Division: New York. Kloth, l.C., McCulloch, J.M. (2002). Wound Healing Alternatives in Management (3 rd ed.). F.A. Davis Company, Philadelphia, PA. Plate 17. Myers, B.A. (2004). Wound Management: Principles and Practice. Prentice Hall: Upper Saddle River, New Jersey, 37-45, 369-391. Sussman, C., Bates-Jensen (1998). Wound Care: A collaborative Practice Manual for Physical Therapists and Nurses. Aspen: Gaithersburg, Maryland. White, G.M., Cox, N.H. (2002). Diseases of the Skin: A Color Atlas and Text. Mosby: New York, 1, 3, 5.