CHAPTER 14- WOUND HEALING.txt

• Inflammation (days 1-10)-
• 1) PMNs, macrophages
• 2) epithelialization 1-2mm/day

• Proliferation (5 days-3 weeks)
• 1) fibroblasts, neovascularization, production of collagen, granulation tissue

• Remodeling (3 weeks- 1 year)
• 1) type III collagen replaced with type I
• 2) decreased vascularity
• 3) net amount of collagen does not change, although significant production and degradation occurs
• 4) collagen cross-linking occurs

• 1) days 1-10
• 2) PMNs, macrophages
• 3) epithelialization 1-2mm/day

• 1) 5 days-3 weeks
• 2) fibroblasts
• 3) neovascularization
• 4) production of collagen
• 5) granulation tissue

• 1) 3 weeks- 1 year
• 2) type III collagen replaced with type I
• 3) decreased vascularity
• 4) net amount of collagen does not change, although significant production and degradation occur
• 5) collagen cross-linking occurs
• 6) peripheral nerves regenerate at 1mm/day

• 1) platelets
• 2) PMNs
• 3) macrophages
• 4) fibroblasts
• 5) lymphocytes

are essential for wound healing (release of growth factors, cytokines, etc)

replace fibronectin-fibrin with collagen

• 1) chemotactic for macrophages
• 2) anchors fibroblasts

also act as growth factors for endothelial cells and fibroblasts

• day 0-3: PMNs
• day 3-4: macrophages
• day 5-on: fibroblasts

platelets and fibrin

• 1) platelets
• 2) fibrin
• 3) fibronectin

reopening a wound results in quicker healing the 2nd time (as healing cells are already present there)

• Alpha granules
• 1- Platelet factor 4- aggregation
• 2- Beta-thrombomodulin- binds thrombin
• 3- PDGF- chemoattractant

• Dense granules
• 1- adenosine
• 2- serotonin
• 3- calcium

• 3) Platelet aggregation factors:
• 1- TXA₂
• 2- thrombin
• 3- platelet factor 4

• 1) Platelet activating factor
• 2) transforming growth factor alpha (TGF-alpha
• 3) Fibroblast growth factor
• 4) Beta lysin (antimicrobial)
• 5) PGE₂ and PGI₂ (vasodilators)
• 6) PGF₂ (vasoconstrictors)

• 1) most important factor in healing open wounds (secondary intention)
• 2) migration from wound edges, sweat glands, and hair follicles
• 3) dependent on granulation tissue
• 4) unepithelialized wounds leak serum and protein, promote bacteria

• 1) most important factor in healing closed incisions (primary intention)
• 2) depends on collagen deposition and cross-linking of collagen
• 3) Submucosa- strength layer of bowel
• 4) weakest time point for small bowel anastomosis: 3-5 days

• 1) smooth muscle cell-fibroblast, communicate by gap junctions
• 2) involved in wound contraction and healing by secondary intention
• 3) perineum has better wound contraction than leg

Type I- most common type of collagen: skin, bone, and tendons. Primary collagen in a healed wound

Type II- cartilage

Type III- Increased in healing wound, also in blood vessels and skin

Type IV: basement membrane

Type V- widespread, particularly found in the cornea

• 1) alpha-ketoglutarate
• 2) vitamin C
• 3) oxygen
• 4) iron

All of the above are required for hydroxylation of proline (prolyl hydroxylase) and subsequent cross-linking of proline residues.

Hydroxylysine also undergoes cross-linking

has proline every 3rd amino acid; also has abundant lysine

vitamin C deficiency

80%

• 1) Type III collagen- predominant collagent type synthesized for days 1-2
• 2) Type I collagen- predominant collagen type synthesized by days 3-4
• 3) Type III replaced by type I collagen by 3 weeks
• 1- at 6 weeks, wound is 80% of its final strength and 60% of its original strength
• 2- at 8 weeks, wound reaches maximum tensile strength, which is 80% of its original strength
• 3- maximum collagen accumulation at 2-3 weeks after that--> the amount of collagen stays the same but continued cross-linking improves strength

d-penicillamine

• 1) moist environment (avoid desiccation)
• 2) Oxygen delivery:
• 1-optimal fluids
• 2- no smoking
• 3- pain control
• 4- arterial reconstruction
• 5- supplemental oxygen
• 6- want transcutaneous oxygen measurement (TCOM) >25mmHg
• 3) avoid edema- leg elevation, compression
• 4) remove necrotic tissue

• 1) Bacteria >10⁵/cm²
• 1- decreaed oxygen content
• 2- collagen lysis
• 3- prolonged inflammation

2) Devitalized tissue and foreign bodies- retards granulation tissue formation and wound healing

• 3) Cytotoxic drugs:
• 1- 5FU
• 2- methotrexate
• 3- cyclosporine
• 4- FK-506 etc
• can all impair wound healing

4) Diabetes- can contribute to poor wound healing by impeding the early-phase response

5) Albumin <3.0- risk factor for poor wound healing

6) Steroids- prevent wound healing by inhibiting macrophages, PMNs, and collagen synthesis by fibroblasts; decreases wound tensile strength as well

7) Vitamin A (25,000 IU qD)- counteracts effects of steroids on wound healing

• 8) Wound ischemia
• 1- fibrosis
• 2- pressure (sacral decubitus ulcers
• 3- poor arterial inflow
• 4- poor venous outflow
• 5- smoking
• 6- radiation
• 7- edema
• 8- vasculitis

type I collagen defect

• 1) 10 types identified
• 2) all collagen disorders

fibrillin (collagen) defect

• 1) excessive fibroblasts
• 2) Tx: phenytoin

vit C deficiency

• cause not clear.
• Pyoderma gangrenosum is a disease that causes tissue to become necrotic, causing deep ulcers that usually occur on the legs. When they occur, they can lead to chronic wounds. Ulcers usually initially look like small bug bites or papules, and they progress to larger ulcers. Though the wounds rarely lead to death, they can cause pain and scarring.

• 1) charcot's joint (2nd MTP joint)
• 2) secondary to neuropathy
• 3) pressure leads to ischemia

• 1) 90% of leg ulcers due to venous insufficiency
• 2) Tx: unna boot, elastic wrap

• Contain a lot of:
• 1- proteoglycans
• 2- hyaluronic acid
• 3- water

• 2) Scar revisions- wait for 1 year to allow maturation; may improve with age
• 3) Infants heal with little or no scaring

contains no blood vessels

denervation has no effect on wound healing

has no effect on wound healing after 14 days

• 1) autosomal dominant
• 2) dark skinned
• 3) collagen goes beyond scar
• 4) Tx:
• 1-XRT
• 2- steroids
• 3- silicone
• 4- pressure garments

• 1) dark skinned
• 2) flexor surfaces of upper torso
• 3) collagen stays within confines of scar
• 4) often occurs in burns or wounds that take a long time to heal
• 5) Tx: steroids, silicone, pressure garments