Fiser Chapter 14. WOUND HEALING Flashcards
Order of wound healing
- Inflammation
- Proliferation
- Remodeling
Inflammation phase (days 1-10)
PMNs, macrophages, EPITHELIALIZATION (1-2 mm/day)
Proliferation phase (5 days to 3 weeks)
Fibroblasts, COLLAGEN DEPOSITION, neovascularization, GRANULATION TISSUE, type 3 collagen replaced with type 1
Remodeling phase (3 weeks to 1 year)
Decreased vascularity, net amount of collagen does not change, although significant production and degradation occur, collagen CROSS LINKING occurs
How fast do peripheral nerves regenerate?
1mm/day
Order of cell arrival to wound?
- Platelets
- Neutrophils
- Macrophages
- Lymphocytes
- Fibroblasts (proliferation and remodeling)
Predominant cell type in days 0-2?
PMNs
Predominant cell type in days 3-4?
Macrophages
Predominant cell type in days 5 onward?
Fibroblasts
True or false, reopening a wound results in quicker healing the 2nd time?
True, as cells are already present there
Most important factor in healing open wounds (secondary intention)
Epithelial integrity
-unepithelialized wounds leak serum and protein, and promote bacteria
Most important factor in healing close wounds (primary intention)
Tensile strength
-Depends on collagen deposition and cross-linking of collagen
Strength layer of bowel
Submucosa
Weakest time point for small bowel anastomosis
3-5 days
How do myofibroblasts communicate?
Gap junctions
-Involved in wound contraction and healing by secondary intention
Does the perineum or leg has better wound contraction?
Perineum
Collagen types
I: Most common; skin, bone, tendon; primary collaged in a HEALED WOUND
II: Cartilage
III: Increased in HEALING wound; vessels; skin
IV: BM
V: Cornea, widespread
Hydroxylation (prolyl hydroxylase) and cross-linking of proline residues in collagen need what?
- Alpha-ketoglutarate
- Vitamin C
- Oxygen
- Iron
-d-Penicillamine inhibits collagen cross-linking
Collagen has a lot of what amino acid?
Proline (every 3rd aa): proline cross-linking improves wound tensile strength
Tensile strength of a wound gets how good?
80% pre-wound max
Predominant collagen type in healing wound
1-2 days: type 3
3-4 days: type 1, and replaces type 1 by 3 weeks
When does a wound reach maximum tensile strength?
8 weeks (80%)
When is maximum collagen accumulation in a healing wound reached?
2-3 eweks, after that the amount stays the same, but you have continued cross-liking to improve strength
What is essential for wound healing?
- Moist environment
- Oxygen delivery (fluids, no smoking, pain control, revasc, supplemental O2 if needed): want transcutaneous oxygen measurement TCOM > 25 mm Hg
- Avoid edema (leg elevation)
- Remove necrotic tissue
Impediments to wound healing
- Bacteria > 10^5/cm^2
- Devitalized tissue and foreign bodies
- Cytotoxic drugs (5FU, methotrexate, cyclosporine, FK-506, etc can impair wound healing in 1st 14 days after injury)
- DM: impedes early-phase inflammation response, hyperglycemia causes poor leukocyte chemotaxis
- Albumin <3.0
- Steroids: inhibit macrophages, PMNs, and collagen synthesis by fibroblast; also decreases wound tensile strength
- Wound ischemia: fibrosis, pressure, atherosclerosis, venous stasis, smoking, radiation, edema, vasculitis
How does DM impede wound healing?
Hyperglycemia causes poor leukocyte chemotaxis
How do steroids prevent wound healing?
Inhibiting macrophages, PMNs, and collagen synthesis by fibroblasts; decrease wound tensile strength
How can you counteract effect of steroids on wound healing?
Vitamin A 25,000 IU per day
Diseases associated with abnormal wound healing
Osteogenesis imperfect: type 1 collagen defect
Ehlers-Danlos syndrome
Marfan’s syndrome: fibrillin defect
Epidermolysis bullosa: excessive fibroblasts, tx phenytoin
Scurvy (vit D def)
Pyoderma gangrenosum
Leg ulcers usually due to what?
90% due to venous insufficiency
Tx: unna boot (elastic wrap)
Scar revisions
Scars have a lot of proteoglycans, hyaluronic acid, and water
Wait for 1 year to allow maturation; may improve with age
Infants heal with little or no scarring
How does cartilage get nutrients without blood vessels?
Diffusion of oxygen and nutrients
What effect does denervation have on wound healing?
None
What effect does chemo have on wound healing?
None after 14 days
Keloid versus hypertrophic scars
Keloids: dark skinned, autosomal dominant; collagen goes beyond original scar; tx intra-lesional steroid injection, silicone, pressure garments, XRT
Hypertrophic scar tissue: dark skinned; flexor surfaces of upper torso; collagen stays within confines of original scar; often occurs in burns or wounds that take a long time to heal; tx steroid injection, silicone, pressure garments
Plateletgranules: alpha and dense
Alpha granules: PF4 (aggregation), beta-thrombomodulin (binds thrombin), PDGF (chemoattractant); transforming growth factor beta TGF-beta (modulates above responses)
Dense: contain adenosine, serotonin, calcium
What are the platelet aggregation factors?
PF4, TXA2, thrombin
