PRINCIPLES OF WOUND HEALING
What are the layers of the epidermis and dermis?
Epidermis (superficial to deep):
1. stratum corneum
2. stratum lucidum
3. stratum granulosum
4. stratum spinosum
5. stratum basalis
Dermis—contains adnexal structures and vasculature
Papillary dermis—superficial, contains vascular tissue
Reticular dermis—deep, contains denser tissue
What are the steps involved in wound healing?
1. Coagulation: Minutes to hours.
2. Inflammation: 1 to 2 days.
3. Proliferation: 3 to 30 days (depends on bacterial load).
4. Remodeling/differentiation: up to 1 year.
What are the cell types primarily responsible for each of these stages?
1. Coagulation: platelets.
2. Inflammation: PMNs, macrophages.
3. Proliferation: macrophages, fibroblasts.
4. Remodeling: myofibroblasts (wound contraction), epithelial cells (reepithelialization).
What are the steps involved in epithelialization across a wound?
Mobilization, migration, mitosis, and differentiation of epithelial cells. The loss and reestablishment of contact inhibition initiate and terminate the process.
After a surgical incision is primarily closed, it takes approximately 24 hours for the wound to reepithelialize. After this point, it is not necessary to keep the surgical area dry with an occlusive dressing.
What is the key cell involved in wound remodeling?
Macrophage. The macrophage is probably the most critical cell in wound healing in general—it initiates the growth factor cascade that results in fibroblast proliferation and thus collagen production.
Which cells are responsible for wound contracture?
Myofibroblasts: fibroblasts that contain myofibrils permitting contractile activity similar to muscle.
What provides tensile strength to a healing wound?
Which cells produce collagen in the healing wound, and when does production peak?
Fibroblasts produce collagen; maximal net collagen production occurs at about 1 to 2 weeks.
How does platelet-derived growth factor (PGDF) affect wound healing?
PGDF is released by platelets in the inflammatory phase, and attracts macrophages.
How does transforming growth factor-beta (TGF-β) affect wound healing?
TGF-β is released primarily by macrophages which attracts fibroblasts and is involved with collagen production.
What isomers mediate the profibrotic phenotype of TGF-β?
TGF-b has three isomers. TGF-β1 and TGF-β2 are profibrotic. TGF-β3 is antifibrotic.
Various fibrotic diseases (such as keloids) might result from aberrant ratios of TGF-β isomers (i.e., increased TGF-β1 and TGF-β2 and decreased TGF-β3).
What is the role of fibroblast growth factor (FGF) in wound healing?
• FGF-1 and FGF-2 (acidic and basic FGF) are the major proteins in this family and drive rapid proliferation of fibroblasts, epithelial cells, and endothelial cells.
• FGF-7 (keratinocyte growth factor) is a major epidermal growth factor and is involved in dermal–epidermal signaling.
• The sequence of events in wound healing is largely mediated by orchestration of intra- and extracellular regulation of FGF proteins in a defined pattern.
What are the biologic effects of FGF?
• Fibroblast and epithelial proliferation.
• Collagen production.
• Potent angiogenic factor.
Skin incisions have gained approximately 80% of their final strength by 6 weeks, and a scar has its full tensile strength at 12 weeks, at which point it has gained approximately 80% to 90% of its initial tensile strength. Tensile strength doubles approximately every week over the first 4 weeks, secondary to collagen cross-linking.
What defines a chronic wound?
Wounds that fail to heal in 3 months are classified as “chronic wounds.”
How does the metalloproteinase level in chronic wounds compare to that in acute wounds?
In chronic wounds, the metalloproteinase level is increased as compared to that of an acute wound resulting in increased ECM degradation.
What are the different types of collagen?
There are many types of collagen (more than 10). Critical to wound healing are:
• Type I: most common; in skin, bone, and tendon/ligament.
• Type II: hyaline cartilage.
• Type III: vessel walls; intestine; skin; early scar formation.
• Type IV: basement membrane.
• Type V: fetal and placental tissue.
What is the ratio of type I to type III collagen in normal skin and scars?
1. Normal skin: 4:1 (i.e., predominantly type I collagen).
2. Immature scar: 2:1.
3. Hypertrophic scar: 2:1.
4. Keloid: 3:1 (varies).
5. Fetal skin: predominantly type III collagen.
Which conditions adversely affect key steps in collagen synthesis?
1. Vitamin C deficiency (scurvy): inhibits hydroxylation of proline and lysine (required for collagen cross-linking).
2. Colchicine: inhibits secretion of tropocollagen from the cell.
3. Copper deficiency and penicillamine: prevent lysine oxidation (which is necessary for intra- and intermolecular bonding).
What are the detrimental effects of corticosteroids on wound healing?
Corticosteroids inhibit macrophages, resulting in poor fibroblast stimulation and wound contraction.
What strategy can overcome the effects of steroids?
Vitamin A (25,000 IU by mouth daily for 3 to 5 days, alternatively 200,000 IU topically three times a day).
One year to allow scar remodeling to complete.
What factors impair wound healing?
1. Foreign bodies.
3. Radiated tissue—decreases blood supply.
4. Inadequate blood supply—any cause.
5. Local trauma.
6. Systemic factors (steroid use, obesity, edema, smoking, comorbidities, malnutrition).
What are the escalating strategies that can be used to close a defect (the “reconstructive ladder”)?
• Secondary sintent
• Primary intent
• Skin graft
• Local tissue rearrangement
• Transposition flap
• Free tissue transfer
How do the following tissues differ in healing?
Bone, Tendon, Nerve, Liver.
Bone healing is accomplished via osteoinduction, osteoconduction, or osteogenesis. Osteoinduction refers to precursor cells in the bony tissue being induced to become osteoblasts, often by demineralized bone or bone morphogenic protein (BMP). Osteoconduction refers to osteoblasts entering the site, along a nonviable bony scaffold such as cortical grafts or cadaveric bone which is replaced by new bone, by “creeping substitution.” Osteogenesis refers to healing with vascularized bone grafts or cancellous bone, where osteoblasts survive the transplantation and produce new bone.
Tendons heal by intrinsic (minimal inflammation with epitenon cells producing collagen) and extrinsic (inflammation, proliferation, remodeling) healing. Extrinsic healing produces adhesions and is increased with immobilization.
Peripheral nerves heal by a combination of degeneration and regeneration. The degenerative process is called Wallerian degeneration and occurs distal to the site of nerve injury.
Hepatic tissue undergoes regeneration.
What adult tissues are able to heal without scarring?
Bone and liver are the only adult tissues that are able to heal without scar formation. Chronic damage can cause hepatic scarring (cirrhosis).
How are operative wounds classified?
Class I: Clean—atraumatic, uninfected, no entry into GI/GU/respiratory tract.
Class II: Clean-contaminated—entry into GI/GU/respiratory tract.
Class III: Contaminated—traumatic wounds or gross spillage of enteric contents.
Class IV: Dirty—drainage of abscess or soft tissue infection.
TYPES OF WOUNDS
Cat and dog bites are associated with Pasteurella multocida as well as Staphylococcus and Streptococcus species.
Human bites are associated with Eikenella corrodens as well as Staphylococcus and Streptococcus species and Bacteroides.
Bite wounds are typically treated with Augmentin for prophylaxis.
What is the staging of pressure ulcers?
Stage 1: Skin intact; nonblanching erythema.
Stage 2: Partial-thickness skin loss, abrasions, and blisters included (so into epidermis or dermis).
Stage 3: Full-thickness skin loss with extension into subcutaneous tissue but not through the underlying fascia.
Stage 4: Full-thickness skin loss with extension into muscle, bone, joint, or tendon.
How long does it take for pressure ulcers to arise?
Early (stage I, nonblanching erythema) pressure ulcer formation can occur within 30 minutes of unrelieved pressure. Partial-thickness skin loss (stage II) can be seen in as little as 2 to 6 hours.
How much pressure is required to cause a pressure sore?
Unrelieved pressure above 32 mm Hg (capillary arterial pressure) can lead to tissue ischemia and pressure sores.
What are the principles of sacral wound management?
1. Remove pressure.
2. Maintain hygiene in region (diverting colostomy if needed).
3. Optimize medical issues.
4. Serial wound debridements.
5. Dressing changes (wet-to-dry; enzymatic therapy if necrotic tissue or dilute acetic acid if infected, especially with pseudomonas).
6. Repair with excision and choice of flap once above factors addressed.
In the evaluation of a pressure ulcer, what is the imaging modality of choice for diagnosis of osteomyelitis?
MRI is the current imaging modality of choice.
Bone biopsy is the gold standard to confirm osteomyelitis.
Where can pressure ulcers occur?
Anywhere bony prominences exist. In order of prevalence:
1. ischial tuberosity
Fasciocutaneous flaps preserve muscle and do not affect ambulation.
What is frostbite, and how is it classified?
Frostbite occurs with extremely cold temperatures that cause tissue freezing and formation of intracellular ice crystals and microvascular occlusion. After thawing, tissue inflammation and coagulation lead to cell death. It is classified similarly to burns:
First degree: involves epidermis only with hyperemia.
Second degree: involves dermis with blister formation.
Third degree: full-thickness skin and subcutaneous tissue involvement.
Fourth degree: necrosis of deeper tissues such as muscle and bone.
What are the steps of frostbite management?
2. Rapid rewarming
3. Thrombolytic therapy
4. Watchful waiting
Which animals can potentially transmit rabies?
Carnivores: dog, cat, raccoon, bat, fox, skunk, coyote. Incidence of rabies from cats is increasing. Exposure alone without a bite can transmit rabies and is an indication for prophylaxis (entering a cave harboring rabid bats).
Rodents do not carry rabies.
How is a rabies exposure managed?
1. Wash the wound in virucidal agent (dilute Betadine).
2. Rabies immune globulin: give single dose of 20 IU/kg around the wound.
3. Rabies vaccine (human diploid cell vaccine): give five 1-cc doses over a 28-day period (days 0, 3, 7, 14, and 28); intramuscular injection in the deltoid.
4. Give both rabies immune globulin and vaccine to all patients, except for patients with a documented antibody titer, who do not need immune globulin.