Chapter 14: Wound Healing Flashcards
Wound healing: days 1-10
Inflammation: PMNs, macrophages
Rate of epithelialization during wound healing
1-2 mm/day
Wound healing: 5 days - 3 weeks
Proliferation: fibroblasts, collagen deposition, neovascularizaiton, granulation tissue formation; type 3 collagen replaced with type 1
Wound healing: 3 weeks - 1 year
Decreased vascularity
What happens during the remodeling phase of wound healing?
Net amount of collagen does not change with remodeling, although significant production and degradation occur. Collagen cross-linking occurs.
Rate of regeneration of peripheral nerves
1 mm/day
Order of cell arrival in wound
Platelets, PMNs, Macrophages, Lymphocytes, (recent research shows arrival before fibroblasts), fibroblasts
Essential for wound healing (release of growth factors, cytokines, etc)
Macrophages
Chemotactic for macrophages; anchors fibroblasts
Fibronectin
Replace fibronectin-fibrin with collagen
Fibroblasts
Predominant cell type by day:
- Days 0-2
- Days 3-4
- Days 5 and on
- Days 0-2: PMNs
- Days 3-4: Macrophages
- Days 5 and on: fibroblasts
What comprises platelet plug?
Platelets and fibrin
What comprises the provisional matrix?
Platelets, fibrin, fibronectin
Definition: accelerated wound healing
Reopening a wound results in quicker healing the 2nd time (as healing cells are already present there)
Most important factor in healing open wounds (secondary intention)
Epithelial integrity
What does secondary intention wound healing depend on?
- Epithelial integrity.
- Migration from hair follicles (#1 site), wound edges, sweat glands. Dependent on granulation tissue in wound.
Unepithelialized wounds leak…
Serum and protein, promote bacteria.
Most important factor in healing closed incisions (primary intention)
Tensile strength
What does tensile strength / primary intention depend on?
Depends on collagen deposition and cross-linking of collagen
Strength layer of bowel
Submucosa
Weakest time point for small bowel anastomosis
3 - 5 days
- Smooth muscle cell-fibroblast; communicate by gap junctions
- Involved in wound contraction and healing by secondary intention
- Perineum has better wound contraction than leg
Myofibroblasts
Collagen: MC type of collagen; skin, bone, tendons. Primary collagen in a healed wound.
Type 1
Collagen: Cartilage
Type 2
Collagen: increased in healing wound, also in blood vessels and skin
Type 3
Collagen: Basement membrane
Type 4
Collagen: widespread, particularly found in the cornea
Type 5
Required for hydroxylation (prolyl hydroxylase) and subsequent cross-linking of proline residues in collagen
Alpha-ketoglutarate, vitamin C, oxygen, and iron
Collagen: every third amino acid
Proline
What does proline cross-linking do?
Improves wound tensile strength
Vitamin C deficiency
Scurvy
% tensile strength to pre-wound strength
80%
Predominant collagen type synthesized for days 1-2
Type 3 collagen
Predominant collagen type synthesized by days 3-4
Type 1 collagen
When is type 3 collagen replaced with type 1 collagen?
By 3 weeks
When does the wound reach maximum tensile strength?
At 8 weeks.
When is maximum collagen accumulation?
2-3 weeks. After that the amount of collagen stays the same, but continued cross-linking improves strength.
Inhibits collagen cross-linking
d-Penicillamine
Essentials for wound healing
- Moist environment (avoid desiccation)
- Oxygen delivery
- Avoid edema
- Remove necrotic tissue
How do you optimize oxygen delivery for wound healing?
Optimize fluids, no smoking, pain control, arterial revascularlization, supplemental oxygen.
What do you want transcutaneous oxygen to measure for wound healing?
Want transcutaneous oxygen measurement (TCOM) > 25 mm Hg
Impediments to wound healing
Bacteria > 10^5, devitalized tissue and foreign bodies, cytotoxic drugs, diabetes, albumin
How does bacteria 10^5 impede wound healing?
Decreased oxygen content, collagen lysis, prolonged inflammation
How does devitalized tissue and foreign bodies impede wound healing?
Retards granulation tissue formation and wound healing.
How do cytotoxic drugs impede wound healing?
5FU, methotrexate, cyclosporine, FK-506, etc can impair wound healing in first 14 days after injury
How can diabetes impede wound healing?
Can contribute to poor wound healing by impeding the early-phase inflammation response (hyperglycemia causes poor leukocyte chemotaxis)
How do steroids impede wound healing?
Inhibit macrophages, PMNs, and collagen synthesis by fibroblasts; decreases wound tensile strength as well
Counteracts effects of steroids on wound healing
Vitamin A (25,000 IU qd)
What can cause wound ischemia (hypoxia)?
Fibrosis, pressure (sacral decubitus ulcer, pressure sores), poor arterial inflow (atherosclerosis), poor venous outflow (venous stasis), smoking, radiation, edema, vasculitis
Diseases associated with abnormal wound healing
Osteogenesis imperfecta, Ehlers-Danlos syndrome, Marfan’s, Epidermyolsis bullosa, Scurvy, Pyoderma Gangrenosum
Common location of diabetic foot ulcer
Charcot’s joint (2nd MTP joint) secondary to neuropathy
90% due to venous insufficiency.
- Tx: Unna boot
Leg ulcers
What do scars contain?
A lot of proteoglycans, hyaluronic acid and water.
When can you revise a scar?
Wait for 1 year to allow maturation; may improve with age.
- Infants heal with little to no scarring.
Contains no blood vessels (get nutrients and oxygen by diffusion)
Cartilage
Has no effect on wound healing
Denervation
Has no effect on wound healing after 14 days
Chemotherapy
Autosomal dominant, dark skinned
- Collaged goes beyond original scar
- Tx: intra-lesion steroid injection; silicone, pressure garments, XRT
Keloids
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
Hypertrophic scar tissue
What are contained in alpha granules of platelets?
- Platelet factor 4: aggregation
- Beta-thrombomodulin: binds thrombin
- Platelet-derived growth factor (PDGF): chemoattractant
- Transforming growth factor beta (TGF-beta): modulates above responses
What do dense granules of platelets contained?
Contain adenosine, serotonin, and calcium
Platelet aggregation factors
TXA2, thrombin, platelet factor 4
