Wound Healing Flashcards
A 23-year-old African-American man presents with a raised thickened scar on his anterior chest that he complains is pruritic and unattractive. It was removed by another provider 4 years earlier and has slowly recurred over the past year. On examination, the lesion extends beyond the initial borders of the scar and is firm and hyper-pigmented. On review of his prior pathology report, which of the following histologic characteristics is most likely?
A) Greater ratio of type III to type I collagen
B) Multitude of myofibroblasts and smooth muscle actin
C) Parallel collagen bundles
D) Thick, wavy, and randomly oriented collagen fibers
The correct response is Option D.
In patients with abnormal or excessive scar tissue formation, treatment and prognosis will be driven by the correct diagnosis of a keloid versus a hypertrophic scar. This patient presents with a recurrent keloid of the chest. His clinical history supports this diagnosis by recurrence after resection, growth extending beyond the original border of the lesion, late recurrence after several years, and continued growth over several years without regression or improvement. Hypertrophic scars are less likely to recur, contained within the original boundaries of the lesion, often regress somewhat within a year, and recur earlier in the postoperative period if they are to recur. Both hypertrophic scars and keloid scars can be pruritic.
Pathologic analysis of keloids reveals more type I collagen than type III collagen, similar to normal skin. Hypertrophic scars will exhibit increased type III collagen and pro-fibrotic collagen cross-linking. Keloid growth is thought to be impacted by cell-signaling between keratinocytes and fibroblasts, but hypertrophic scar production requires an abundance of myofibroblasts expressing smooth muscle actin. While hypertrophic scars have parallel collagen fibrils and bundles, keloids are characterized histologically by thick, randomly oriented collagen fibrils that are not organized into bundles.
A 45-year-old African American woman who underwent cardiac surgery 6 months ago seeks cosmesis of the surgical scar. Physical examination shows a raised, thick keloid scar that is pruritic. Which of the following nonsurgical treatments is likely to produce the most rapid improvement in the scar with the fewest adverse effects?
A) Intralesional 5-fluorouracil
B) Intralesional triamcinolone
C) Radiation therapy
D) Silicone sheeting
E) Topical triamcinolone
The correct response is Option A.
Injection of 5-fluorouracil demonstrates similar efficacy to intralesional corticosteroid therapy (triamcinolone) and has the advantage of a lower risk of hypopigmentation.
Silicone sheeting is effective for hypertrophic scars but requires serial application and is slower in visible effect. Topical corticosteroids are not as effective as intralesional treatment. Radiation carries the risk of adjacent tissue toxicity and also includes the risk of skin pigmentation changes.
A 7-year-old boy presents with a chief complaint of multiple wide and thin scars from skin lesion excisions. The patient’s mother reports a history of late walking, hypermobile joints, and easy bruising. On the basis of these complaints, which of the following is the most likely diagnosis?
A) Capillary fragility syndrome
B) Cutis laxa
C) Ehlers-Danlos syndrome
D) Marfan syndrome
E) Osteogenesis imperfecta
The correct response is Option C.
Ehlers-Danlos syndrome (EDS) is the only diagnosis listed which encompasses all of the mentioned patient complaints. EDS encompasses a range of connective tissue disorders that share joint hypermobility, skin hyperextensibility, and tissue fragility. The different types of EDS have varying modes of inheritance and a variety of identified genetic mutations in collagen formation. Classical EDS is caused by an autosomal dominant mutation involving the COL5A1 or COL5A2 genes, which are involved in collagen type V synthesis. Common symptoms include skin hyperextensibility, widened atrophic “cigarette paper” scars, generalized joint hypermobility involving three or more joints, and easy bruising. Vascular EDS carries major risks, including arterial (aortic) dissection, rupture, or aneurysm. Cutis laxa is not associated with easy bruising. Capillary fragility syndrome typically does not present with late walking. Osteogenesis imperfecta and Marfan Syndrome are not associated with atrophic scarring.
A 63-year-old man undergoes microdermabrasion for scar irregularity following treatment of facial skin cancer. Which of the following intraoperative findings signals the endpoint of treatment?
A) Cobblestoned, yellow adiposity
B) Confluent patches of bleeding lakes on a yellowish background
C) Minimal dermis with visible subdermal plexus
D) Pinpoint, punctate bleeding on a white background
E) Thinned but present epidermis
The correct response is Option D.
When performing microdermabrasion, the most appropriate endpoint is removal of soft tissue into the papillary dermis. The appropriate level in the papillary dermis is visualized as pinpoint bleeding in a white dermal background. Epithelial removal would be insufficient. Removal of tissue into the reticular dermis, either superficial or deep, increases the risk for scarring. The superficial reticular dermis demonstrates a yellowish white coloration and would reinforce the need to discontinue treatment before deeper injury occurs. Furthermore, dermal excisional depth would manifest as confluent red bleeding in a yellowish background of dermis or nearly complete dermal removal with a visible subdermal vascular plexus. If a full-thickness skin removal is performed (into the subcutaneous adipose layer), significant deformity could result. Preservation of adnexal structures to allow reepithelialization is a key tenet in determining the appropriate depth of treatment. Posttreatment changes include thickened epidermis and increased elastin and collagen.
An 80-year-old woman undergoes excision and direct closure of a nasal sidewall carcinoma. The wound is closed with cuticular nylon suture and dressed with a temporary sterile gauze bandage in an uncomplicated office procedure with immediate discharge home. How long after surgery should this patient be advised to refrain from wetting the suture line with tap water rinses?
A) 48 Hours after surgery
B) 48 Hours after suture removal
C) Until suture removal
D) Until wound edge epithelization is complete
E) No restriction
The correct response is Option E.
Several studies have compared wet, moist, and dry wound healing following skin surgery without demonstrating an increase in infection rate when washing the wound with tap water at any point postoperatively as opposed to keeping the site dry for various lengths of time. This includes a rigorous randomized control trial in which patients with defects following skin lesion removal were divided into groups with tap water wound washing within 12 hours of surgery versus those asked to keep wound dry for 48 hours, where the incidence of surgical site infection in the wash group was not inferior to the dry group. On the other hand, unrestricted wound washing improves patient comfort, and multiple studies have demonstrated that wet or moist wounds promote reepithelialization and result in reduced scar formation with less inflammatory reaction compared to dry wounds.
Which of the following is the primary role of adipose-derived stem cells (ADSC) in wound healing?
A) Assist in chemotaxis of platelets and granulocytes
B) Differentiate directly into fibroblasts and keratinocytes
C) Induce development of hair and sweat follicles
D) Provide a scaffold for deposition of granulation tissues
E) Register and organize pro-collagen fibrils
The correct response is Option B.
Adipose-derived stems cells (ADSC) have had extensive study in vitro and in vivo because there are ready sources of them from adult patients, which bypasses many ethical and regulatory issues of embryonic stem cells.
ADSC have both direct structural and paracrine roles in wound healing. They can directly differentiate into keratinocytes, endothelial cells, and dermal fibroblasts. ADSCs, through paracrine phenomena, are modulators of the inflammatory environment of the wound healing milieu but are not involved in the immediate chemotaxis during the inflammatory period nor do they function as a scaffold during the proliferative phase. Lysyl oxidase is the extracellular enzyme responsible for final alignment of collagen fibrils.
Presence of skin adnexa such as hair follicles and sweat glands are hallmarks of scarless, fetal healing. Hair follicle formation typically only occurs during embryonic development and involves interaction of ectodermal and mesenchymal cells influenced by signaling pathways including Wnt/b-catenin and BMPl but not ADSCs.
Which of these situations is best suited for the use of a topical skin adhesive (polymerizing cyanoacrylate) for closure?
A) Burst laceration along the eyebrow
B) Over an intradermal repair of a vertical forehead laceration
C) Over a suture repaired dog bite of the ear
D) Straight line laceration on the cheek with 4 mm of separation
E) Well apposed lip laceration crossing the vermilion cutaneous border
The correct response is Option B.
Cyanoacrylate skin adhesives are sold as monomers that polymerize by an exothermic reaction on contact with air and fluids. They can be used in conjunction with other skin closure mechanisms such as sutures or as a primary skin closure device. There is evidence across multiple surgical specialties and situations that skin glues can save time in the operating room. When used correctly, the cosmesis is similar or better than external suturing. There are in vitro studies suggesting inhibition of Gram-positive cocci and clinical anecdotal evidence of decreased infection.
There is evidence that when wounds are closed with skin glue as the only closure device that dehiscence rates are increased.
If the adhesive leaks below the skin when applied, it can hold the edges open and delay or prevent healing with increased scarring or poorer cosmesis. Adhesives should be applied to well apposed skin edges only.
The U.S. Food & Drug Administration–approved package insert for a major brand of skin adhesive (eg, Johnson & Johnson, Ethicon Dermabond) specifically indicates use on mucosa and over dirty wounds such as dog bites to be contraindicated.
A burst laceration along the eyebrow and a straight line laceration on the cheek with 4 mm of separation would be contraindicated because of the lack of excellent epithelial continuity. Adhesive over a suture-repaired dog bite of the ear and a well-opposed lip laceration crossing the vermilion cutaneous border are specifically contraindicated on the package insert. Studies across multiple surgical specialties are supportive of cyanoacrylate skin adhesives over an intradermal repair of a vertical forehead laceration.
A 46-year-old woman undergoes a fleur-de-lis abdominoplasty following successful gastric bypass surgery. She has a 94-lb (43-kg) weight loss and current BMI is 28 kg/m2. To ensure the best outcome for wound healing, which of the following is the recommended postoperative daily intake of protein for this patient?
A) 20 to 30 g/day
B) 40 to 50 g/day
C) 60 to 70 g/day
D) 80 to 90 g/day
E) More than 100 g/day
The correct response is Option C.
Nutritional status in postbariatric subjects is essential in achieving successful healing of surgical wounds. Anatomical changes to the gastrointestinal tract following bariatric surgery can exacerbate nutritional deficiencies and inadequacies. Reduced protein intake has been associated with significantly lower healing rates in massive weight loss patients. It is recommended that postbariatric patients consume 60 to 70 g/day of protein 2 to 4 weeks prior to surgery and for 1 to 2 months postoperatively.
A 58-year-old woman develops full-thickness dermal necrosis in a 4 × 4 × 2-cm area of her lower breast following reduction mammaplasty. After debridement to healthy tissue, she starts daily wound packing with a calcium alginate fiber dressing. The main advantage of calcium alginate versus saline gauze dressings is a decrease in which of the following?
A) Dressing change frequency
B) Healing time
C) Keloid scarring
D) Treatment cost
E) Wound infection rate
The correct response is Option A.
An effective dressing should aid in surface debridement, absorb wound exudate, and maintain a moist healing environment. Normal saline wet-to-dry gauze dressings have been a mainstay of wound management for generations because they are easy to perform, widely available, and inexpensive. They are best changed 2 to 3 times daily to remove exudative material because they can quickly become saturated. Some of the wound healing byproducts, such as metalloproteinases and elastase, can slow down wound healing and result in chronic wounds. By wicking away these potentially harmful agents, more absorptive wound dressings can help simplify care. Alternatives to conventional saline wet-to-dry gauze dressing materials include hydrogels, hydrocolloids, foams, alginates, and negative pressure dressings. They are more expensive than traditional saline-gauze dressings but are typically far more absorptive, allowing for less frequent dressing changes. Daily dressing changes versus two to three times a day are far more convenient for patients and may ultimately save total treatment costs by allowing for fewer nursing visits or allowing for outpatient care. Many studies show no difference in healing times, though some studies suggest a mild benefit in diabetic foot ulcers. Current recommendations call for additional studies, as evidence of faster healing times is lacking. No studies show lower infection or scarring.
Calcium alginates are fibers made of brown seaweed fibers, and they can hold more than ten times their weight in fluid. Some manufacturers claim that they are able to deactivate metalloproteinases and stimulate healing, although in vitro data are lacking. They are a comfortable and effective alternative to saline wet-to-dry dressings, albeit at a higher product cost.
A 30-year-old man presents with a large open wound to the right thigh. The proposed treatment plan after debridement and establishing a clean wound is to use negative pressure wound therapy (NPWT). Which of the following is the main direct mechanism for wound healing by this method?
A) Improvement in tissue auto-debridement
B) Increase in collagen synthesis
C) Reduction in wound bacterial load
D) Removal of interstitial fluid leading to increased blood flow
The correct response is Option D.
Based on the original studies by Moryk, it was hypothesized that the beneficial wound-healing effects of negative pressure wound therapy (NPWT) was a combination of a fluid-based mechanism and a mechanical stress mechanism. The fluid-based mechanism involves the removal of excess interstitial fluid from the wound bed by the vacuum, which results in the interstitial pressure decreasing below the capillary filling pressures, thus allowing “re-opening” of these wound bed capillaries. This leads to improved blood flow within the wound, allowing for granulation tissue formation. The mechanical strain mechanism is created by micro-strain forces created by the vacuum on the cells within the wound. Cellular deformation leads to numerous molecular changes, including activation of the vascular endothelial cell growth factor (VEGF) pathway, which enhance angiogenesis.
Collagen synthesis is not directly affected by NPWT. There is equivocal evidence for whether there is a positive or negative effect of NPWT on wound bacterial loads.
NPWT does not auto-debride wounds. It is important when using NPWT to ensure adequate mechanical debridement of nonviable tissues from the wound bed prior to initiating NPWT.
A 23-year-old woman comes to the office for evaluation of bilateral ear keloids. She reports that the keloids developed after she had her ears pierced 5 years ago. She has not had previous surgery for this problem. Which of the following is the most likely recurrence rate after surgical excision with injection of a corticosteroid?
A) 5%
B) 15%
C) 35%
D) 50%
E) 75%
The correct response is Option B.
Earlobe keloid formation after piercing is reported to affect approximately 2.5% of the population. Various adjuvant therapeutic modalities, including radiation therapy, intralesional corticosteroids, interferon, 5-fluorouracil, topical silicone, and pressure devices, are used to decrease recurrence rate after surgical excision. A recent meta-analysis looked at the recurrence rate of keloid formation after surgical excision with the use of radiation therapy and intralesional corticosteroids. Recurrence rate after excision with radiation therapy was found to be 14%. The recurrence rate after excision with intralesional corticosteroids was 15.4%. Although radiation therapy had an overall reduced recurrence rate, it was associated with higher cost and more significant potential complications. Five cases of carcinogenesis after radiation therapy have been reported. The main disadvantage of corticosteroid injections was found in most studies to be the pain of injection. Adjuvant corticosteroid injections in conjunction with surgery were performed preoperatively, intraoperatively, or postoperatively in various studies.
E-cigarettes are similar to traditional cigarettes in that the negative effect of nicotine on wound healing is primarily due to which of the following?
A) Endothelial cell injury
B) Increased inflammatory response
C) Increased prostacyclin production
D) Peripheral microvascular vasoconstriction
E) Platelet aggregation
The correct response is Option D.
Cigarette smoke contains thousands of different chemical substances including chemical toxins and carcinogens in addition to nicotine. While e-cigarettes are believed to have fewer health risks because tar and many other harmful chemicals have been removed, they do deliver vaporized nicotine. Nicotine-induced vasoconstriction in the periphery leads to relative skin ischemia and poor wound healing.
Platelet aggregation is incorrect. Nicotine does not have a direct effect on platelets. In some studies, platelet aggregation appears to be reduced with long-term administration of nicotine. Increased prostacyclin production is incorrect.
Prostacyclin is a local vasodilator with effects that minimize platelet aggregation.
Nicotine has been shown to inhibit synthesis of prostacyclin. Increased inflammatory response is incorrect. Nicotine causes a diminished inflammatory response by a weakened chemotaxis, reduced migration, impaired bacterial killing by inflammatory cells and a subnormal release of proteolytic enzymes and inhibitors. Endothelial cell injury is incorrect. While nicotine can alter the structural and functional characteristics of vascular smooth muscle and endothelial cells, it does not cause cell injury. Several studies show increased number of endothelial cells in venous blood after nicotine administration in cigarette smokers, but not in non-cigarette smokers, suggesting that other harmful chemicals found in tobacco may contribute to cell injury.
Hyperbaric oxygen therapy (HBOT) is most appropriate for a patient with which of the following conditions?
A) Acute osteomyelitis of the tibia
B) Anaerobic necrotizing soft-tissue infection
C) Chemical burn because of lye exposure
D) Stevens-Johnson syndrome
E) Wagner grade 2 diabetic foot ulcer
The correct response is Option B.
Hyperbaric oxygen therapy (HBOT) is an accepted adjunct to surgical debridement, appropriate antibiotic therapy, and indicated critical care measures for necrotizing soft-tissue infections such as necrotizing fasciitis and Fournier gangrene. The increased oxygen delivery of HBOT improves leukocyte function and can enhance penetration of certain antibiotics such as aminoglycosides. The clinical effects include slowing of the progress of the infection and decreased risk of both amputation and mortality.
There is not adequate evidence to justify HBOT in diabetic foot ulcers (DFUs) with Wagner grade 2 (extension to bone, tendon, or capsule) or less. However, there is moderate evidence to suggest benefit in DFUs with Wagner grade 3 (deep ulcer with osteomyelitis or abscess) or greater.
HBOT may be indicated in the treatment of chronic osteomyelitis but not in the acute setting. It plays no role in the treatment of Stevens Johnson syndrome, and may be beneficial in acute thermal burns but is not indicated for chemical burns.
The complete list of approved indications for HBOT, as determined by the Undersea and Hyperbaric Medical Society and the U.S. Food and Drug Administration, includes the following:
Air or gas embolism
Carbon monoxide poisoning
Clostridial myositis and myonecrosis (gas gangrene)
Crush injury, compartment syndrome, and other acute traumatic ischemias
Decompression sickness
Arterial insufficiency
Severe anemia
Intracranial abscess
Necrotizing soft-tissue infections
Refractory osteomyelitis
Delayed radiation injury (soft tissue and bony necrosis)
Compromised grafts and flaps
Acute thermal burn injury
Idiopathic sudden sensorineural hearing loss
Which of the following mechanisms is most likely to inhibit normal wound healing in a patient who smokes cigarettes?
A) DNA strand breaks and helical cross-linking
B) Increased cosubstrate for enzymes involved in collagen production
C) Increased platelet aggregation
D) Increased tissue oxygen delivery
E) Nicotine-induced vasodilation
The correct response is Option C.
The detrimental effects of smoking on wound healing are due primarily to nicotine, carbon monoxide, and hydrogen cyanide. One of the effects of nicotine is increased platelet aggregation due to enhanced adhesiveness of the platelets themselves. This leads to thrombus formation and decreased oxygen delivery. Nicotine does not produce vasodilation, but rather vasoconstriction. Both of these effects can lead to local tissue ischemia, which inhibits the normal wound healing process.
One of the major mechanisms by which ionizing radiation inhibits wound healing is production of DNA strand breaks and helical cross-linking, but smoking is not significantly involved.
Vitamin C is the vitamin which plays the greatest role in wound healing. It is required as a cosubstrate for hydroxylase enzymes, which are involved in the production of collagen. Vitamin C deficiency has long been known to inhibit wound healing (scurvy). However, supplemental vitamin C in the nondeficient patient has not been shown conclusively to produce any beneficial wound-healing effects.
Compared with standard wound dressings, postoperative negative pressure wound therapy is most likely to produce which of the following outcomes?
A) Better delayed primary fascial closure rates for salvage laparotomy
B) Better split-thickness skin graft incorporation
C) Increased inflammatory response
D) Increased postoperative dressing changes
E) Increased risk of infection
The correct response is Option B.
Multiple studies have shown the benefits of negative pressure wound therapy (NPWT) when used in conjunction with skin grafts, both as a bolster over a skin graft as well as wound bed preparation.
NPWT has been shown to decrease the risk of infection in complex and traumatic wounds in some studies, while others have shown no difference in infection rates in complex wounds when the patient has multiple comorbidities or when used to cover uncomplicated incisions for elective orthopedic operations. However, there is no evidence to suggest NPWT increases infection risk compared with standard wound dressings.
NPWT reduces both inflammatory response and edema formation.
When used for damage control laparotomy and abdominal compartment syndrome, studies have failed to show any benefit of NPWT over standard dressings. Furthermore, at least one study has suggested an increased rate of enteric fistula formation is associated with NPWT.
NPWT has been shown to decrease both the number of postoperative dressing changes and the number of additional operative interventions in complicated diabetic wounds.
