Normal Healing

• superficial wounds: only epidermis is lost
• partial thickness wounds: involve the epidermis + parts of dermis
• full thickness wounds: involve the epidermis, dermis, + subcutaneous tissue; may extend to muscles, bones, tendons, etc
• phases of normal wound healing:

  • hemostasis
  • inflammation
  • proliferation
  • maturation
• hemostasis (coagulation):

  • occurs immediately after injury
  • must occur for healing to progress
  • vasoconstriction
  • platelet aggregation
  • fibrin deposited
  • clot formation
• clot: fibrin mesh, blood cells, + platelets

  • prevents fluid loss
  • protects from contamination
  • provides temporary wound matrix into which other cells migrate
• growth factors control:

  • cell growth
  • differentiation
  • metabolism
• inflammation:

  • transition from vasoconstriction to vasodilation mediated by mast cells
  • increased vascular permeability mediated by eosinophils
  • fluid leaks into interstitial tissue causing edema
  • monocytes transform to macrophages
  • neutrophils + macrophages being cellular debridement through phagocytosis + release MMPs
  • margination occurs
  • neutrophils adhere to endothelial cells lining the capillaries
  • diapedesis occurs
  • neutrophils migrate through endothelium
• inflammatory phase characterized by:

  • redness (rubor)
  • swelling (tumor)
  • heat (calor)
  • pain (dolor)
  • acute inflammation lasts 24-48 hours
• proliferation:

  • granulation tissue appears (if full thickness)
  • angiogenesis occurs
  • wound contraction
  • epithelialization
• matrix metalloproteasis (MMP):

  • protein-degrading enzyme produced when cells need to move in order to clear a pathway
• during proliferation:

  • MMP degrade proteins needed to move out to clear pathway
  • granulation tissue fills the gap
• granulation tissue:

  • gel-like matrix
  • beefy red in color
  • supports newly formed vascular network
  • very fragile --> handle with care
• normal tissue healing:

  • balance between deposition mediated by growth factors + tissue destruction mediated by MMP's
• non-healing wounds:

  • destruction mediated by MMP's is greater than tissue deposition by growth factors
• MMP's have been shown to be present in excess in chronic non-healing wounds
• proliferation:

  • granulation tissue forms
  • macrophages secrete GF + MMP's early in the process
  • later in the process, fibroblasts dominate in healing
  • stimulate growth factors (can be impeded by debris)
• growth factors: small proteins secreted by cells that stimulate:

  • chemotaxis
  • mitosis
  • angiogenesis through angioblasts
  • production + degredation of matrix
  • apoptosis
  • regulate + coordinate healing
• granulation tissue is primarily type 3 collagen
• wound contraction (proliferation):

  • wound edges draw in toward each other - mediated by myofibroblasts
  • cytoplasmic pseudopodia attach to collagen fibers, drawing wound closed
  • occurs at a rate of .6-.7 mm/day
• contact inhibition (proliferation):

  • force resisting closure is greater than the myofibroblastic force, causing contraction to cease
  • important to remember in dressing application
  • do not be the cause of contact inhibition
• re-epitheliazation (proliferation):

  • re-establishment of the epidermis
  • epidermal cells migrate from the wound periphery
  • basement membrane formed
  • basement membrane + epidermis bond
  • fibroblast proliferation + collagen production occur
  • re-vascularization occurs
• remodeling (maturation):

  • wound is closed
  • type 1 collagen deposit continues for additional strength
  • tensile strength = 40% at 1 month + continues to strengthen for up to 1 year
  • post-injury tensile strength 80% of pre-injury
  • vascularization matures
• primary intention: edges of wounds are brought close together

  • direct closure
  • flap: nearby tissue moved into the wound bed
  • graft: skin from other locations placed on the wound
• secondary intention: wound edges can not be brought together so wound is "open"; granulation tissue matrix must be formed to fill in the open wound
• tertiary intention (delayed primary closure):

  • combination of primary + secondary intention
  • wound is allowed to remain open until it is confirmed to be free of contamination + then surgically closed
• platelets release growth factors
• margination (inflammatory phase): neutrophils adhere to endothelial cells lining the capillaries

  • involves rolling, activation, + firm adhesion of the WBC to the endothelium
• diapedesis (inflammatory phase): neutrophils migrate through endothelium where chemotaxis + phagocytosis can occur