Intermediate wound healing events Mesenchymal cell

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Wound healing

• Danny Silverberg M.D.

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Phases of healing

• Early
• Intermediate
• Late
• Terminal

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Early wound healing events

• Hemostasis
• Platelet aggregation
• Intrinsic and extrinsic coagulation cascade
• Thrombin, fibrin
• Vasoconstriction

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Early wound healing events

• Inflammation
• Vasodilatation
• Increase in vascular permeability
• Chemotaxis
• Cellular response

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Early wound healing events

• Homeostasis
• Neutrophils
• 48-72h- macrophages
• 5-7 days- few inflammatory cells.

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Intermediate wound healing events

• Mesenchymal cell chemotaxis and proliferation
• Angiogenesis
• Epithelisation
• 2-4 days after injury
• Mediated by cytokines

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Intermediate wound healing events

• Mesenchymal cell chemotaxis and proliferation
• Fibroblasts- migration and proliferation
• Smooth muscle
• Angiogenesis- reconstruction of vasculature
• Stimulate High lactate, acidic Ph, low O2
  tension
• Endothelial cell migration and proliferation

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Intermediate wound healing events

• Epithelisation
• Partial thickness- Cells derived from wound edges
  and epithelial appendages.
• Incisional wound cellular migration over less
  then 1 mm. Wound sealed in 24-48h.
• Cellular detachment
• Migration
• Proliferartion
• differentiation

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Late wound healing events

• Collagen synthesis
• 3 helical polypeptide chains
• Lysine and proline hydroxylation
• Required for cross-linking

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Late wound healing events

• Collagen synthesis
• 3-5 days post injury
• Primarily by fibroblasts
• Maximum synthesis rate 2-4 weeks
• Declines after 4 weeks
• Type 1 collagen most common ( 80-90 of skin
  collagen)
• Type 3- seen in early phases of wound healing

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Wound contraction

• Centripetal movement of the wound edges toward
  the center. ( 0.6-0.7 mm/day)
• Begins at 4-5 days
• Maximal contraction 12-15 days
• Trivial component in closed incisional wounds,
  significant for closure of open wounds
• Rate- depends on tissue
• Circular wounds- slower closure but avoid stenosis

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Wound contraction

• Mechanism- cell mediated processes, not requiring
  collagen synthesis
• Myofibroblasts- fibroblasts with myofilaments in
  cytoplasm
• Appear in wound day 3-21
• Located in periphery- pull wound edges together.
• Contractures- contraction across joint surface

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Terminal wound healing events

• Remodeling- turnover of collagen. Type 3 replaced
  by type 1
• Day 21- net accumulation of wound collagen
  becomes stable
• Wound bursting strength- 15 of normal.
• Week 3-6- greatest rate of increase
• 6 weeks- 80-90 of eventual strength.
• 6 months maximum strength ( 90 ). Process
  continues for 12 months

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Cytokines and growth factors

• Primary mediators in wound healing.
• Endo, para, auto, intracrine function
• EGF
• FGF
• PDGF
• TGF

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Growth factors in wound healing
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Which of the following is primarily responsible
for tensile strength in a healing wound 4 days
after injury?

• Collagen
• Elastin
• Fibrin
• Fibronectin
• Hyaluronic acid

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Which of the following is primarily responsible
for tensile strength in a healing wound 6 weeks
after injury?

• Myofibroblasts
• Fibrin
• Fibronectin
• Collagen
• Collagen cross linking

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Local factors affecting wound healing

• Infection
• foreign body/ necrotic tissue, hematomas
• local/ systemic factors
• type of surgery

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Local factors affecting wound healing

• Hypoxia and smoking
• O2 delivery necessary for cellular respiration
  and hydroxylation of proline and lysine
• Smoking- vasoconstriction, atherosclerosis,
  carboxyhemoglobin.

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Local factors affecting wound healing

• Radiation
• Collagen synthesized to abnormal degree-
  fibrosis
• Fibrosis of vessels- (media)-occlusion
• Thinned epidermis, pigmentation
• Limited access of inflammatory cells and
  cytokines- impaired healing
• Damage to fibrocytes and keratinocytes.

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Systemic factors

• Malnutrition
• Limited AA supply for collagen synthesis
• Consumption of proteins d/t CHD and fat
  deficiency.
• Vit C deficiency- diminished hydroxylation of
  lysine and proline,
• Vit D- impaired bone healing
• Zinc- inhibition in cellular proliferation and
  defficient granulation tissur formation

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Normal healing is accelerated by which of the
following?
?

• VitC
• VitA
• Zinc
• Increased local oxygen tension
• Scarlet red

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Systemic factors

• Cancer
• Cachexia, anorexia
• Altered host metabolism.
• Protein catabolism
• Abnormal inflammatory cell response

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Systemic factors

• Old Age
• Diabetes
• Impaired healing ( decreased chemotaxis and
  phagocyte function )
• Risk of infection

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Systemic factors

• Steroids, immunsuppression
• Inhibits all aspects of healing process
• Impaired cellular function, deficiency in
  inflammatory cell function, cytokine production,
  fibroblast proliferation
• All effects ( except contraction ) reversed by
  Vit A.

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Hypertrophic scars and kelloids

• Excessive healing processes- increase in net
  collagen synthesis raised thickened scar
• Keloid- Extension beyond wound margin, familial,
  may develop up to 1 year, rarely subside
• Hypertrophic scar- Confined to wound margin,
  light skinned, early after injury, may subside,
  cause contractures
• Tx- excision, steroid injection, pressure
  garments, radiation tx

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Types of wound closure

• Primary closure
• Approximation of acutely disrupted tissue with
  sutures, staples or tape

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Types of wound closure

• Delayed primary closure
• Approximation of wound margin delayed for several
  days
• Prevents wound infection in cases of
  contamination/foreign bodies/tissue trauma
• Less bacterial colonization in open wound
• Normal healing progress occurs

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Types of wound closure

• Secondary wound closure
• Open wound margins approximate by biologic
  contraction

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• If a patient requires reoperation 1 month after a
  midline abdominal incision which of the following
  promotes the most rapid gain in strength of the
  new incision
• Separate transverse incision
• Midline scar is excised with a 1 cm margin
• Midline incision reopended without scar excision
• Rate of strength ganed is not effected by
  incision technique

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