Wound Healing/Keloids Flashcards
1
Q
What are the layers of the epidermis and dermis?
A
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
2
Q
What are the steps involved in wound healing?
A
- Inflammation: 1 to 2 days.
- Proliferation: 3 to 30 days (depends on bacterial load). 3. Remodeling/differentiation: up to 1 year.
3
Q
What are the cell types primarily responsible for each of these stages?
A
- Inflammation: PMNs, macrophages.
- Proliferation: macrophages, fibroblasts.
- Remodeling: myofibroblasts (wound contraction), epithelial cells (reepithelialization).
4
Q
What are the steps involved in epithelialization across a wound?
A
Mobilization, migration, mitosis, and differentiation of epithelial cells. The loss and reestablishment of contact inhibition initiate and terminate the process.
5
Q
In a healthy individual, how long does it take for a surgical incision to reepithelialize after closure?
A
After a surgical incision is 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
6
Q
What is the key cell involved in wound remodeling?
A
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.
7
Q
Which cells are responsible for wound contracture?
A
Myofibroblasts—fibroblasts that contain myofibrils permitting contractile activity similar to muscle.
8
Q
What provides tensile strength to a healing wound?
A
Collagen.
9
Q
Which cells produce collagen in the healing wound, and when does production peak?
A
Fibroblasts produce collagen; maximal net collagen production occurs at about 1 to 2 weeks.
10
Q
When is a scar fully matured, and how much tensile strength does it achieve?
A
Wounds have gained approximately 50% of their final strength by 6 weeks and a scar fully matures in 1 year, at which point it has gained approximately 80% to 90% of its initial tensile strength. The most rapid increase in tensile strength occurs between 10 and 30 days, secondary to collagen cross-linking.
11
Q
What defines a chronic wound?
A
Wounds that fail to close in 3 months are classified as “chronic wounds.”
12
Q
How does the metalloproteinase level in chronic wounds compare to that in acute wounds?
A
In chronic wounds, the metalloproteinase level is increased as compared to that of an acute wound resulting in
increased extracellular matrix degradation.
13
Q
What are the different types of collagen?
A
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.
Type IV: basement membrane.
Type V: fetal and placental tissue.
14
Q
What is the ratio of type I to type III collagen in normal skin and scars?
A
- Normal skin: 4:1 (ie, predominantly type I collagen).
- Immature scar: 2:1.
- Hypertrophic scar: 2:1.
- Keloid: 3:1 (varies).
- Fetal skin: predominantly type III collagen.
15
Q
Which conditions adversely affect key steps in collagen synthesis?
A
- Vitamin C deficiency (scurvy): inhibits hydroxylation of proline and lysine (required for collagen cross-linking).
- Colchicine: inhibits secretion of tropocollagen from the cell.
- Copper deficiency and penicillamine: prevent lysine oxidation (which is necessary for intra- and intermolecular bonding).
16
Q
Which cytokines are produced by macrophages?
A
IL-1, IL-6, IL-8, IL-10, TNFa, IFNg.
17
Q
What isomers mediate the profibrotic phenotype of TGF-b?
A
TGF-b has three isomers. TGF-b1 and TGF-b2 are profibrotic. TGF-b3 is antifibrotic.
Various fibrotic diseases (such as keloids) might result from aberrant ratios of TGF-b isomers (ie, increased TGF-b1 and TGF-b2 and decreased TGF-b3).
18
Q
What are the biologic effects of FGF?
A
Fibroblast and epithelial proliferation.
Collagen production.
Potent angiogenic factor.
19
Q
What is the role of FGF in wound healing?
A
FGF-1 and FGF-2 (acidic and basic FGF) are the major proteins in this family and drive rapid proliferation of r fibroblasts, epithelial cells, and endothelial cells.
FGF-7 (keratinocyte growth factor) is a major epidermal growth factor and is involved in dermal–epidermal r 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.
20
Q
What are the detrimental effects of corticosteroids on wound healing?
A
Corticosteroids inhibit macrophages, resulting in poor fibroblast stimulation and wound contraction.
21
Q
What strategy can overcome the effects of steroids?
A
Vitamin A (25,000 IU by mouth daily for 3 to 5 days, alternatively 200,000 IU topically three times a day).
22
Q
How long should you wait before revising a scar?
A
One year to allow scar remodeling to complete.
23
Q
What factors impair wound healing?
A
- Foreign bodies.
- Infection.
- Radiated tissue—decreases blood supply.
- Inadequate blood supply—any cause.
- Local trauma.
- Systemic factors (steroid use, obesity, edema, smoking, comorbidities, malnutrition).
24
Q
What are the escalating strategies that can be used to close a defect (the “reconstructive ladder”)?
A
secondary intent
primary intent
skin graft
local tissue rearrangement
transposition flap
free tissue transfer
25
How do the following tissues differ in healing?
Bone, Tendon, Nerve, Liver.
Bone: Following fracture, bony healing is accomplished via osteoinduction and osteoconduction. Osteoinduction refers to precursor cells in the bony tissue becoming osteoblasts, and osteoconduction refers to these osteoblasts entering the fracture site. A bony callus forms, which is remodeled by osteoclasts and osteoblasts into lamellar bone (endocohondral ossification).
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.
26
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).
27
What is the Fitzpatrick classification of skin types?
Based on density of melanin pigment:
Type I: White or freckled skin (always burns, never tans). Type II: White skin (usually burns, sometimes tans). Type III: White to olive skin (equally burns and tans). Type IV: Brown skin (tans easily, rarely burns).
Type V: Dark brown skin (always tans, very rarely burns). Type VI: Black skin (deeply tans, never burns).
28
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.
29
How are nerve injuries classified?
There are two accepted classification systems for nerve injuries, Seddon and Sunderland. Seddon
1. Neuropraxia—transient block of conduction, rapid recovery expected.
2. Axonotmesis—axonal damage within the nerve, Wallerian degeneration occurs, prolonged recovery expected.
3. Neurotmesis—nerve is transected, Wallerian degeneration occurs, surgical repair needed.
Sunderland
1. First degree—demyelinate nerve, rapid recovery expected (neuropraxia).
2. Second degree—axons disrupted, but sheath intact (axonotmesis), undergoes Wallerian degeneration, slow recovery expected.
3. Third degree—some endoneurial sheaths disrupted, incomplete recovery.
4. Fourth degree—loss of perineurium, little to no recovery, requires operative intervention.
5. Fifth degree—nerve is completely transected, no recovery without operative intervention.
6. Sixth degree—combination injury, including areas with first- to fifth-degree damage.
30
What organisms are associated with bite 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.
31
What is the staging of pressure ulcers?
Stage 1: Skin intact; non-blanching 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/muscle.
Stage 4: Full-thickness skin loss with extension into bone, joint, tendon.
32
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.
33
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.
34
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.
35
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.
36
Where can pressure ulcers occur?
Anywhere bony prominences exist. In order of prevalence: 1. ischial tuberosity
2. trochanter
3. sacrum
4. calcaneus
5. occiput
6. scapula
37
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. 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.
38
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.
39
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.
40
Which wounds are “tetanus prone”?
1. Wounds that are contaminated.
2. Contain devitalized tissue.
3. Are open for more than 6 hours. 4. Are deeper than 1 cm.
41
What tetanus measures are required for a wound in a “fully immunized” patient?
A fully immunized patient is one who has received complete tetanus toxoid immunization (three to five doses) with a booster within 5 years of the current injury. If the wound is “tetanus prone,” give tetanus toxoid (0.5 mL of adsorbed toxoid intramuscularly). If the wound is not “tetanus prone,” do nothing.
42
What tetanus measures are required for a wound in a patient of unknown or inadequate immunization status?
These patients need to receive tetanus toxoid for all wounds. In addition, if the patient has received less than two
injections of immunization, also give immune globulin (250 units of human tetanus immune globulin).
43
What organisms are typically associated with necrotizing fasciitis?
Necrotizing fasciitis is a severe infection that leads to liquefaction necrosis along fascial planes. Beta-hemolytic streptococci are commonly associated with this devastating process; however, mixed aerobes and anaerobes can also be found.
44
What organism is responsible for “gas gangrene”?
The Clostridia species (typically Clostridium perfringens) cause gas gangrene. They are obligate anaerobes and so in addition to radical debridement, hyperbaric oxygen has been shown to be beneficial in the treatment of gas gangrene.
45
What is the difference between keloids and hypertrophic scars?
1. Keloids extend beyond the margin of the initial scar, whereas hypertrophic scars do not.
2. Keloids have an increased ratio of types I/III collagen unlike hypertrophic scars.
3. More significant cellular and biochemical abnormalities are found in keloids.
4. Keloids are commonly found on the face, earlobes, chest, and upper back, whereas hypertrophic scars are commonly found across flexor surfaces.
46
What are the chemical and histological differences between keloids and normal scar tissue?
Keloids contain elevated levels of TGF-. In addition, they have increased collagen (especially type III) and vascularity compared with normal tissue.
47
What are the principles of keloid and hypertrophic scar management?
1. Excision plus adjuvant therapy (intradermal steroids, silicone gel, radiation therapy). 2. Meticulous tissue handling and closure with intradermal sutures.
3. Pressure earrings/garments.
48
What are the contraindications to radiation therapy for keloids?
1. Pediatric patients.
2. Pregnant women.
3. Tissue with underlying visceral structures.
Despite the theoretical risk of neoplastic transformation, fewer than 10 cases of cancer due to radiation therapy for keloids have been reported.
49
What is the mechanism of intralesional steroid (triamcinolone acetonide) therapy for keloids?
1. Inhibits fibroblast proliferation and collagen production.
2. Stimulates collagenase production.
3. Normalizes collagen ultrastructural organization that is disrupted in keloid nodules.
50
What is the optimal treatment for earlobe keloids?
Surgical excision with or without steroid injection, followed by wearing of pressure earrings.
51
Can a partial-thickness burn scar be left to heal by secondary intention?
Generally, partial-thickness burn scars can be given up to 3 weeks to close by secondary intent. If not closed by
3 weeks, they need to be grafted to avoid hypertrophic scar formation.
52
Where does scarless wound healing occur?
Wound healing occurs without scar in the early mammalian fetus (including human). Levels of hyaluronic acid are
significantly higher in fetal skin and appear to correlate with scarless wound healing.
53
During wound therapy with leeches, which bacteria grow in the leech gut?
Aeromonas hydrophila. Ciprofloxacin, Bactrim, or tetracycline can be used for prophylaxis.
54
What is the antibacterial mechanism of Acticoat?
Acticoat contains silver ions that are directly bactericidal. It needs to be moistened with distilled water prior to application (ions in normal saline will negate the antibacterial effect of Acticoat). It is efficacious against Pseudomonas, MRSA, VRE, and some species of yeast.
55
What are the associated side effects of topical antimicrobial agents?
Silvadene (silver sulfadiazine)—leukopenia.
Sulfamylon (mafenide acetate)—acidosis (secondary to carbonic anhydrase inhibition). Silver nitrate—hyponatremia.
Bacitracin—vesicular rash.
56
What are the clinical indications for Regranex gel (becaplermin, PDGF)?
Regranex is indicated for lower extremity ulcers:
of diabetic neuropathy
that extend into the subcutaneous tissue
that have a good vascular supply and
that are not infected.
Regranex is not FDA approved for use in ischemic, infected, or superficial wounds, or those that are being closed primarily.
57
Which biologic dressings contain cultured cells?
1. TransCyte: a dermal substitute that is composed of cultured neonatal dermal fibroblasts seeded on a
silicone/collagen matrix, covered with a nylon sheet.
2. Dermagraft: contains neonatal fibroblasts on a sheet of Dexon (polyglycolic acid) or Vicryl.
3. Epicyte: a matrix of cultured autologous keratinocytes (ie, from the same patient).
4. Apligraf: contains both neonatal keratinocytes and fibroblasts; these cells are seeded onto a collagen matrix.
58
Which other biologic dressings contain dermal matrix?
1. Biobrane: a nylon sheet covering a silicone layer containing dermal collagen.
2. Integra: a silicone sheet coated with collagen and glycosaminoglycan obtained from bone tendon cartilage. 3. AlloDerm: cadaveric acellular dermis that has been de-epithelialized.
59
Which wounds are best treated with alginates?
Highly exudative wounds. Calcium alginate gels are made from seaweed and are hydrophilic, so they can absorb
significant amounts of fluid. Alginates prevent tissue maceration, trap bacteria, and can be rinsed off.
60
What is the mechanism of vacuum-assisted closure?
Continuous or intermittent negative pressure is applied to the wound bed increasing collagen production by fibroblasts and fibroblast mitotic activity. The actual mechanism is believed to involve structural realignment of fibroblast cells that triggers collagen production and mitosis.
61
How does a split-thickness skin graft initially receive nutrition?
Plasma imbibition for the first 48 hours until an adequate vascular supply is established.
Inosculation: Connection of recipient and donor vessels in the graft and recipient bed. Neovascularization: Sprouting of new blood vessels.
62
What are the steps in adherence of a skin graft?
Phase 1: fibrin phase (first 72 hours).
Phase 2: fibrovascular phase (after 72 hours)—vascular ingrowth and anastomosis.
63
What are the causes of skin graft failure?
1. hematoma
2. seroma
3. infection
4. shearing forces disrupting skin graft adherence and thus nutrition
64
What bacterial load is required to cause clinical infection in a split-thickness skin graft?
105 bacteria per cm3 of tissue.
65
Which flap type offers the greatest resistance to bacterial infection?
Musculocutaneous flaps bring in a large proportion of blood supply that best wards off bacterial infection.
66
What histologic layer mediates skin graft contraction?
Elastin within the dermis—thicker skin grafts mean more dermis, which means more elastin which means more
primary or immediate contraction.
Conversely, elastin inhibits delayed (secondary) graft contraction so those grafts without dermis, such as cultured epithelial cells, demonstrate the most delayed contraction.
67
Hyperbaric oxygen therapy might be beneficial in which clinical situations?
Osteomyelitis.
Necrotizing infections.
Ischemia-reperfusion injury.
Diabetic lower extremity wounds.
68
What are the effects of tissue expansion on flap properties?
1. Increased tissue surface area, collagen and ground substance content. 2. Increased vascularity (similar to flap delay).
3. Decreased tensile strength and elasticity (since thinner dermis).
4. Markedly increased sensitivity to epinephrine-induced necrosis.
Tissue expansion results in a net gain of tissue that is due to both stretching of existing tissue and de novo tissue generation.
69
What are the histologic changes seen following tissue expansion?
1. Subcutaneous fat atrophies.
2. Dermis becomes thinner.
3. Epidermis becomes thicker, particularly the stratum spinosum (increased mitotic activity). 4. Rete ridges become flatter.
70
What are the tissue zones that result from tissue expansion?
Tissue expansion results in formation of a capsule surrounding the expander, which is essentially a foreign body
reaction. These zones are, from inside to outside, as follows: Zone A: inner zone, cellular (predominantly macrophages).
Zone B: central zone, fibrous, with fibroblasts and myofibroblasts. Zone C: transitional zone, with loose collagen.
Zone D: vascular zone.
71
What is mechanical creep?
1. A response to constant mechanical force.
2. Collagen realigns and results in a change in tissue elasticity. 3. Interstitial fluid and ground substance are displaced.
4. Depends on viscoelastic properties of skin.
72
What is stress relaxation?
Less force is needed to keep tissue stretched to a given length the longer it is held at that length.
73
Which tissue expansion protocol results in maximal tissue recruitment?
Cyclic loading: repeated cycles of stretching followed by relaxation
74
How can extra tissue be recruited intraoperatively?
Approximately 15% to 20% tissue expansion can be gained with a brief 1- to 2-hour session (acute tissue expansion). Clinical studies suggest acute tissue expansion provides tissue of comparable quality to that expanded over a much longer time frame (weeks).
75
What are the concerns with lower extremity tissue expansion, especially below the knee?
1. Extensive tissue expansion can cause sural nerve neuropraxia.
2. The region below the knee has relatively limited lymphatic outflow (compared with the trunk), and a tissue expander is at increased risk for cellulitis.
3. Tissue expansion in the lower extremity is particularly problematic in the pediatric population.
76
What effect does tissue expansion have on hair growth?
Tissue expansion, such as in the scalp, decreases the telogen, or growth arrest, phase.
77
How does irradiated tissue differ from normal during tissue expansion?
Irradiated tissue does not undergo the histologic changes that are seen with normal tissue during tissue expansion. Previous irradiation decreases the net tissue gain from expansion by approximately 25%.
78
What is the maximal dose of lidocaine and bupivicaine that can be used for local anesthesia?
Plain lidocaine: 4 mg/kg.
Lidocaine with epinephrine: 7 mg/kg.
Tumescent technique: up to 35 mg/kg has been suggested to be safe. Bupivicaine: 3 mg/kg.
79
Which local anesthetics can produce a true allergic reaction?
Esters (NOT AMIDES) can be responsible for causing allergic reactions once administered.
80
How long do sutures retain tensile strength?
Catgut—1 week or less.
Monocryl (Poliglecaprone 25)—7 to 10 days. Chromic gut—1 week.
Vicryl, Dexon—2 to 4 weeks.
PDS—4 to 6 weeks.
81
Which conditions associated with impaired wound healing preclude elective rejuvenation surgery?
Ehlers-Danlos syndrome: inherited disorder of collagen polymerization, characterized by joint laxity, r hyperextensible skin, and poor wound healing.
Progeria: autosomal recessive disorder (rare) of premature aging, characterized by premature aging, loss of subcutaneous fat, poor wound healing, atherosclerosis.
82
In which inherited skin disorders is it possible to perform rejuvenation surgery?
Cutis laxa: have nonfunctioning elastase inhibitor characterized by coarsely textured drooping skin due to r degeneration of dermal elastic fibers.
Pseudoxanthoma elasticum: associated with increased collagen degradation and deposition of calcium in elastic fibers.
