Wound Healing / Keloids Flashcards
A 17-year-old boy undergoes excision of a congenital nevus of the scalp. Prior to excision, he underwent placement of a subgaleal tissue expander. Which of the followinggrowth factors is most likely to be upregulated during ischemia in this patient?
A) Epidermal B) Keratinocyte C) Platelet-derived D) Transforming E) Vascular endothelial
E) Vascular endothelial
Vascular endothelial growth factor
Vascular endothelial growth factor (VEGF) is an important mediator of wound healing and is necessary for angiogenesis. It was originally discovered as a protein secreted by tumor cells to increase the permeability of local blood vessels to circulating macromolecules. It has been shown to increase endothelial growth and migration and enhance glucose transport in the endothelial cell, which is needed to match the increased energy required during angiogenesis. Hypoxia has been shown to be a potent stimulus for the expression of VEGF, and current research has been directed at utilizing VEGF to augment healing and viability in situations of tissue ischemia.
A 10-year-old girl is referred to the office because of a large, full-thickness cranial defect after sustaining a traumatic injury. Reconstruction with a split cranial bone graft is performed. Which of the following is the most likely mechanism by which the bone graft heals? A) Dural ossification B) Osteoconduction C) Osteogenesis D) Osteoinduction E) Vasculogenesis
B) Osteoconduction
Method of healing after split cranial bone grafting
The most likely mechanism of split cranial bone graft healing is osteoconduction. The split cranial bone graft is primarily cortical. After it isseparated from its blood supply, it serves as a nonviable scaffold for the ingrowth of blood vessels and osteoprogenitor cells from the recipient site. This process of osteoconduction, or creeping substitution, eventually leads to resorption and replacement of most of the graft with new bone. The graft becomes fully osseointegrated with the recipient site
Osteoconduction
The process of osteoconduction, or creeping substitution, eventually leads to resorption and replacement of most of the graft with new bone, after a graft is infiltrated as a scaffold with vessels and osteoprogenitor cells. The graft becomes fully osseointegrated with the recipient site
Spontaneous dural ossification
Spontaneous dural ossification can heal full-thickness cranial defects in infancy. After 12 to 18 months of age, the dura will not spontaneously ossify
Osteogenesis
Osteogenesis is the primary mechanism of bone graft healing for cancellous or vascularized bone grafts. Because these grafts are revascularized rapidly, osteoblasts survive the transplantation and produce new bone at the recipient site.
Osteoinduction
Osteoinduction involves the stimulation of mesenchymal cells at the recipient site to differentiate into bone-producing cells. Demineralized bone and bone morphogenetic protein produce new bone primarily by osteoinduction.
Vasculogenesis
Vasculogenesis, the de novo formation of blood vessels from precursor cells, occurs during embryogenesis.
Angiogenesis
Angiogenesis: the production of new vessels from preexisting vasculature.
A 24-year-old woman comes to the office because of painful nodules in both buttocks. She underwent buttock augmentation with injections of liquid silicone by an unlicensed practitioner 4 years ago. Excision of the affected area is performed. Histology of a specimen obtained from the excised tissue is most likely to show which of the following? A) Acellularity B) Calcification C) Granuloma D) Necrosis E) Thrombosis
C) Granuloma
Potential adverse sequelae after silicone injection
Potential adverse sequelae following silicone injection include migration, chronic induration and pigmentary changes, painful subcutaneous nodules, chronic infection, and ulceration. Many of the treated areas require radical resection and reconstruction.
Histologic study of postsilicone injection nodules
Histologic study of postsilicone injection nodules typically shows granulomas which develop after initial inflammation and fibrosis.
A 15-year-old boy undergoes negative pressure wound therapy (NPWT) of a traumatic abdominal wound. Which of the following is the most likely mechanism by which NPWT expedites the healing of this wound?
A) Decrease in bacterial burden
B) Deformation of the wound
C) Desiccation of the wound
D) Increase in matrix metalloproteinase activity
E) Maintenance of exudate from the wound
B) Deformation of the wound
NPWT Macrodeformation
Macrodeformation maintains approximation of the tissues, preventing loss of domain and facilitating earlier closure by delayed primary or secondary intention.
NPWT Microdeformation
Microdeformation at the interface of the sponge and wound bed changes cell shape, which then affects gene transcription via the cytoskeleton (mechanotransduction). These microdeformational forces, for example, stimulate cellular proliferation and angiogenesis in the wound.
NPWT and bacterial burden
The effect of NPWT on bacterial burden is unclear. Some studies have suggested that NPWT reduces bacterial counts in the wound, possibly by direct removal or by increasing blood flow. Other studies have found that NPWT may increase certain bacterial levels.
NPWT and desiccation
NPWT prevents desiccation of the wound. The semiocclusive polyurethane drape limits permeability to gases and water vapor and thus maintains a favorable, moist wound environment.
NPWT and matrix metalloproteinase activity
NPWT decreases matrix metalloproteinase activity in the wound. Elevated matrix metalloproteinases inhibit wound healing as well as neovascularization.
NPWT and exudate
NPWT decreases exudate of the wound by removing excess fluid through suction. The reduction in exudate may facilitate wound healing by removing toxic inflammatory mediators and proteinases. Minimizing wound edema also may improve the diffusion of oxygen and nutrients to the wound.
A 63-year-old man comes for evaluation of a dehisced surgical incision 3 weeks after undergoing open reduction of the right ankle. He has a history of coronary artery disease, hypertension, hypercholesterolemia, and poorly controlled type 2 diabetes mellitus. He had a myocardial infarction 2 years ago. Physical examination shows a dehisced surgical incision with exposed tibialis anterior tendon without paratenon. A photograph is shown. The patient refuses free tissue transfer. Which of the following is the most appropriate skin substitute for the wound?
A) Biodegradable bilaminate neodermal matrix (Integra)
B) Biosynthetic wound dressing (Biobrane)
C) Cryopreserved neonatal fibroblast-derived dermal substitute (Dermagraft)
D) Human fibroblast-derived composite skin substitute (TransCyte)
E) Living bilayered skin substitute (Apligraf)
A) Biodegradable bilaminate neodermal matrix (Integra)
Integra
Integra is a bilaminate neodermal replacement product that is composed of a biodegradable bovine collagen-glycosaminoglycan (collagen-GAG) matrix underlayer with a silicone outer layer. Although its on-label indication is for burn reconstruction, it also has utility in reconstruction of wounds of exposed bone without periosteum, exposed cartilage without perichondrium, and exposed tendon without paratenon, such as in the scenario described. The collagen-GAG matrix serves as scaffolding for the ingrowth of cells and neovascularization. After regeneration, which takes between 2 to 4 weeks, the silicone outer later is removed and a thin split-thickness skin graft completes the reconstruction by providing epithelial cells over the neovascularized dermal replacement.
Biobrane
Biobrane is a temporary, rather than permanent, bilaminar skin substitute that is constructed of an inner layer, composed of nylon and collagen, which is covered by an outer silicone film. Biobrane serves as a temporary wound dressing, usually in burn patients, where it helps prevent evaporative loss (due to the silicone outer layer) and subsequent wound desiccation. It decreases wound pain and provides a barrier to bacterial infection. Biobrane is removed either before permanent grafting or after epithelialization of the wound has occurred.
Dermagraft
Dermagraft is a dermal substitute composed of neonatal foreskin fibroblasts cultured on a polyglactin mesh, and it is generally used in the treatment of diabetic foot ulcers, where it often is combined with meshed skin grafts
TransCyte
TransCyte is a temporary wound dressing. It is a emporary, rather than permanent, bilaminar skin substitute plus an added biologic layer derived from neonatal fibroblasts that are seeded onto the nylon matrix to produce type I collagen, fibronectin, and glycosaminoglycans. TransCyte is removed either before skin grafting or after epithelialization of the wound. It has been shown to significantly decrease pain and time to epithelialization
Apligraf
Apligraf, another permanent replacement product, is constructed of type I bovine collagen and cultured neonatal human fibroblasts and keratinocytes. After construction of the dermal matrix equivalent, cultured keratinocytes are applied. It is generally used in the treatment of venous ulcers and diabetic foot ulcers (may take more than one application). Its long-term durability, however, makes it an inappropriate choice in situations with a full-thickness defect with exposed vital structures
A 67-year-old woman comes to the office for follow-up examination 6 months after debridement of a chronic nondiabetic wound to the lower leg. Following the procedure, the patient was treated with moist dressings. Physical examination shows that the wound is healing less than 15% weekly. Persistent bacteria are suspected. Application of which of the following is the most appropriate nonsurgical management at this time? A) Alginate dressings B) Collagenase C) Film or transparent dressings D) Hydrogel dressings E) Silver ion-impregnated dressing
E) Silver ion-impregnated dressing
Silver ion-impregnated dressing
Silver ions kill a broad spectrum of bacteria. No resistant organisms have been identified, and it is nontoxic to human cells.
Alginate dressings
Alginates absorb up to 20 times their weight ad are used to exudate wounds
Epithelial cell migration across an acute skin laceration is initiated by which of the following mechanisms?
A ) Contraction of myofibroblasts
B ) Deposition of collagen into the wound
C ) Formation of a fibrin-fibronectin plug
D ) Loss of contact inhibition
E ) Secretion of anti-inflammatory products
D ) Loss of contact inhibition
Epithelial cell migration in wounds
Epithelial cell migration is initiated by loss of contact inhibition and occurs from the periphery of the wound and adnexal structures. Cell division occurs in 48 to 72 hours, resulting in a thin epithelial cell bridge across the wound
A 65-year-old woman is evaluated because of nonhealing sores on her lower extremities. She has a history of alcoholism and is homeless. She appears cachectic, pale, and severely malnourished. She has lost most of her teeth; the gums are purplish and spongy in appearance. Skin examination shows numerous petechiae. Large, superficial, nongranular sores are noted on the legs. Scurvy is suspected. Which of the following processes is most likely to be adversely affected by this patient's nutritional deficiency? A ) Collagen cross-linking B ) DNA synthesis C ) Epithelialization D ) Fibroblast proliferation E ) Immune modulation
A ) Collagen cross-linking
Vitamin C deficiency in wounds
The patient described most likely has a vitamin C deficiency. Vitamin C is an essential nutrient for collagen cross-linking via the hydroxylation of proline and lysine to hydroxyproline andhydroxylysine, respectively. The lack of cross-linking results in impaired collagen synthesis and a decrease in collagen tensile strength. Collagen-containing tissues, such as skin, dentition, bone, and blood vessels, are therefore affected, leading to the development of scurvy. The hallmark signs of scurvy are hemorrhaging in any organ (ie, petechiae, swollen gums), loss of dentition, and a lack of osteoid formation. Deficiency of vitamin C is rare in the United States; however, it can be seen in patientswho are severely malnourished; have a history of alcoholism; or have restrictive diets for medical, social, or economic reasons.
Nutrients integral to DNA synthesis and cellular proliferation
Folate and vitamin B6 (pyridoxine) are integral in DNA synthesis and cellular proliferation.
Vitamin A in wound healing
Vitamin A is an essential factor in epithelialization and fibroblast proliferation.
Can improve impaired wound healing caused by corticosteroids.
Vitamin E in wound healing
Vitamin E is a strong antioxidant and immune modulator.
Zinc in wound healing
Zinc is one of the most important micronutrients, as it acts as a cofactor for numerous metalloenzymes and proteins. It is essential for proper protein (like collagen) and nucleic acid synthesis
During which of the following phases of wound healing is the net rate of collagen synthesis greatest? A ) Contraction B ) Fibroblastic C ) Hemostasis D ) Inflammatory E ) Remodeling
B ) Fibroblastic
Fibroblastic stage of wound healing
During the fibroblastic (proliferative) phase, three to five days after injury, fibroblasts migrate into the wound and lay new collagen. Type 3 collagen predominates early in normal wound healing but is later replaced by Type 1 collagen. It is during this time that the greatest rate of collagen synthesis occurs in the wound.
Days 3-5 after injury
During the fibroblastic phase, three to five days after injury, fibroblasts migrate into the wound and lay new collagen. Type 3 collagen predominates early in normal wound healing but is later replaced by Type 1 collagen. It is during this time that the greatest rate of collagen synthesis occurs in the wound.
Contraction during wound healing
Contraction begins during the fibroblastic stage (proliferative) and continues well into the remodeling phase.
Hemostasis and wound healing
Hemostasis is the brief period before healing starts.This allows for vasoconstriction and clotting to be activated.
Maximum tensile strength and wound healing
Maximum tensile strength is achieved after approximately 12 weeks
A 62-year-old man is scheduled to undergo repair of an abdominal wall hernia. A preoperative photograph is shown. He has a 15-year history of chronic lung disease and receives daily corticosteroids to control his symptoms. Supplementation with which of the following is most likely to decrease impairment of wound healing in this patient? A ) Vitamin A B ) Vitamin B1 (thiamine) C ) Vitamin B2 (riboflavin) D ) Vitamin B6 (pyridoxine) E ) Vitamin C
A ) Vitamin A
Impairment of wound healing by corticosteroids and be treated by:
Animal studies have shown that impairment of wound healing caused by use of corticosteroids can be reversed by the oral administration of vitamin A (retinoic acid), 15,000 IU daily for seven days.
An 11-year-old girl has full-thickness dermal necrosis in the infusion zone of an antebrachial intravenous catheter which was used for treatment of a metastatic lower extremity sarcoma. Localized swelling was noted five days earlier after approximately 100 mL of the medication extravasated into the subcutaneous tissues. Total parenteral nutrition and intravenous doxorubicin had been administered as well as intravenous cefazolin and vancomycin. CT of the leg with intravenous contrast medium had also been performed in the past week. Which of the following is the most likely causative agent of the dermal necrosis from extravasation injury? A ) Cefazolin B ) Doxorubicin hydrochloride C ) Radiographic contrast medium D ) Total parenteral nutrition E ) Vancomycin
B ) Doxorubicin hydrochloride
While any of the agents listed could be harmful in sufficient volume, doxorubicin hydrochloride (Adriamycin) is the one agent that should raise particular alarm. Adriamycin is associated with severe soft-tissue necrosis and warrants close follow-up for early surgical debridement,
Treatment of doxorubicin hydrochloride extravasation
Adriamycin is associated with severe soft-tissue necrosis and warrants close follow-up for early surgical debridement, if needed. Dilution of the agent with saline or hyaluronidase may be helpful. Other early interventions, which are standard to all extravasation injuries, include splinting, elevation, local dressings, and close serial examination
Treatment of extravasation injuries
Early interventions, which are standard to all extravasation injuries, include splinting, elevation, local dressings, and close serial examination.
An 80-year-old woman has been receiving papain-ureaointment for management of a pressure necrosis wound over the lateral aspect of the right calf. A 4 * 10-cm diameter zone of black, dry, insensate eschar is noted on the right calf. A 1-cm zone of mild erythema and slight liquefaction of the eschar edges are noted. No tenderness to palpation is noted. Pedal pulses are present. Which of the following is the main disadvantage of using a papain-urea ointment in this patient? A ) Elevation of compartment pressures B ) Inadequate debridement C ) Painful dressing changes D ) Renal toxicity E ) Resistant organism infection
B ) Inadequate debridement
The patient described has a full-thickness dermal injury with ensuing liquefactive necrosis that requires sharp debridement to healthy tissue. Enzymatic ointments are not sufficient for this level of necrotic tissue burden.
These are slow-acting agents that allow separation of superficial eschar over days to weeks.
Papain
Papain is a potent digestant of nonviable protein material but does not affect healthy tissues.
Urea
Urea increases the digestive potency of papain, which is a potent digestant of nonviable protein material but does not affect healthy tissues.
Papain is inactivated by:
Dressings containing silver ions inactivate papain and they should not be used together.
A 52-year-old woman (shown) is evaluated six years after bilateralmastectomies and radiation therapy for cancer of the left breast because of a new, small open area near the left axillary fold which she first noted three weeks ago. She has been compliant with postoperative oncologic surveillance. Temperature is 98.9°F (37.2°C), pulse is 80 bpm, respirations are 16/min, and blood pressure is 140/75 mmHg. Physical examination shows a 2 * 2-cm open ulcer on the left chest wall with exposed rib. Which of the following is the most likely cause of the ulcer?
A ) Abscess
B ) Loss of skin integrity from intertriginous shearing forces
C ) Lymphedema drainage tract
D ) Osteoradionecrosis of the underlying ribs
E ) Recurrent breast cance
D ) Osteoradionecrosis of the underlying ribs
Mechanism of injury from ionizing radiation
The mechanism of injury from this radiation is through free radical production which, in turn, directly damages the DNA.
Acute effects of radiation -> over time
In the acute period, the effects of radiation may manifest themselves as erythema and edema of the skin, vasodilation with endothelial edema, and lymphatic obliteration. This eventually leads to capillarythrombosis and subsequent inadequate tissue oxygenation. Over time, nonhealing ulcers can spontaneously develop, sometimes years later.
When do most recurrences of breast cancer occur
Most recurrent breast cancer occurs within the first five year
Intertriginous shearing presentation
Intertriginous shearing would most often present as superficial epidermal loss with possible superinfection with yeast due to moisture
Recurrence rate of keloid scars after surgical excision
Keloid scars are associated with an extremely high recurrence rate. Surgical excision alone is associated with a recurrence rate of up to 80%.
Methods investigated to improve success in treatment of keloids and success rate
Methods investigated to improve success in treatment of these lesions include intralesional injection of corticosteroids, interferon, retinoic acid, and 5-fluorouracil. Even with these interventions, the rate of recurrence is approximately 50%.
Pressure therapy for keloid recurrence
Pressure therapy has been found to be helpful in decreasing keloid recurrence but requires ongoing treatment for three to ten months, which may not be acceptable
Radiation therapy for keloid recurrence
Radiation therapy has emerged as an effective method to prevent keloid scarring. External beam irradiation has been shown to decrease recurrence rates to 12%–27%, but it may be associated with pigmentary changes.
A 42-year-old man develops a dehiscence of the abdominal incision six weeks after undergoing a lower body lift. Medical history includes a 100-lb (45-kg) weight loss during the past three years. Which of the following is the most likely cause of the wound-healing problem? A ) Hematoma B ) Patient movement C ) Seroma D ) Skin necrosis E ) Wound infection
C ) Seroma
Body lift procedures after massive weight loss: overall rate, and most common complication and rate
Body lift procedures after massive weight loss have a complication rate of approximately 50%. The most common complication is wound dehiscence, which occurs in greater than 30% of patients.
Although infection and skin necrosis can occur in the postoperative period and result in wound dehiscence, seroma is much more common.
Early wound dehiscence after body lift after massive weight loss
Wound dehiscence can be characterized as either early (in the immediate postoperative period) or late. Early wound dehiscence may be caused by patient movement.
Late wound dehiscence after body lift after massive weight loss
Wound dehiscence can be characterized as either early (in the immediate postoperative period) or late. Late wound dehiscence is often due to underlying seroma.
A 76-year-old woman with type 1 diabetes mellitus is scheduled to undergo surgical intervention for chronic ulceration of the lower extremities. Which of the following factors is NOT likely to impair wound healing in this patient? A ) Advanced age B ) Chronic anemia C ) Chronic use of corticosteroids D ) Malnutrition E ) Poor control of diabetes
B ) Chronic anemia
Increased age vs healing
Aging is associated with reduced production of collagen and angiogenesis and a diminished response to environmental stresses.
Steroid impairment of healing
By reducing inflammation, steroids impair angiogenesis, fibrogenesis, wound contraction, reduced wound strength, and delay healing. O
Anemia vs healing
Does not impair healing
Malnutrition vs healing
Malnutrition, including caloric, protein, vitamin, and mineral insufficiency, impairs the immune system, prevents tissue repair, and may lead to progression or recurrence of a wound. A
Diabetes vs healing
Diabetes mellitus adversely affects healing by altering circulation, attenuating inflammation, reducing tissue oxygenation, and adversely affecting glucose metabolism resulting in stress hyperglycemia.
Factors which impair wound healing
Diabetes mellitus Malnutrition Aging Steroids Infection Smoking Poor tissue oxygenation Radiation Chemotherapy Presence of foreign bodies Cancer
A 26-year-old man comes to the emergency department because he has a laceration of the anterior aspect of the right lower leg. Physical examination shows a superficial 2-cm full-thickness skin laceration. Sutures are placed. If the wound heals normally, which of the following is the earliest time that the epidermis is likely to be restored? (A)12 Hours (B)24 Hours (C)2 to 3 Days (D)4 to 5 Days (E)6 to 7 Days
(B)24 Hours
When is it safe to get a surgical incision wet?
After closing a surgical incision, epithelialization usually occurs within24 hours, at which point it is no longer necessary to keep the wound dry. Washing to remove dried blood can reduce bacterial proliferation and improve wound healing. This process may take longer in patients in whom wound healing may be compromised, such as elderly patients or patients with diabetes.
Reaction after destroying basement membrane
If the basement membrane has been destroyed, epithelial cells and keratinocytes located on wound edges proliferate and send out projections to reestablish a protective barrier against fluid loss and bacterial invasion. The stimuli for epithelial proliferation and chemotaxis are epidermal growth factor and transforming growth factor (TGF)-α produced by activated platelets and macrophages.
In an acute wound, which of the following structures initiate coagulation, hemostasis, and the inflammatory cascade? (A)Endothelial cells (B)Eosinophils (C)Macrophages (D)Neutrophils (E)Platelet
(E)Platelet
Initial changes in a wound after injury are _______ in nature:
Initial changes in a wound after injury are vascular in nature. Blood vessels are disrupted and hemorrhage ensues, damaging the epidermal barrier. After vasoconstriction occurs, the coagulation cascade is activated to reduce blood loss.
Platelet initiation of hemostasis/normal inflammatory response
Platelets release:
- adenosine diphosphate (ADP), which, in the presence of calcium, stimulates further platelet aggregation.
Alpha granules in the platelets release
- cytokines such as platelet-derived growth factor (PDGF), transforming growth factor (TGF)-β, TGF-α, basic fibroblast growth factor (bFGF), platelet factor IV, and β-thromboglobulin. These proteins initiate the wound healing cascade by attracting and activating fibroblasts, endothelial cells, and macrophages.
Platelets also contain lysosomes, which include proteases
Platelet dense bodies:
- store vasoactive amines, such as serotonin, which increase microvascular permeability.
Result of extrinsic and intrinsic coagulation pathway activation:
The extrinsic and intrinsic coagulation pathways are activated, resulting in a fibrin mesh with aggregated platelets embedded in it.
The early inflammatory phase following coagulation activates _________, and initiates the __________, which leads to ____________.
The early inflammatory phase following coagulation activates complement and initiates the classic molecular cascade, which leads to infiltration of the wound with neutrophils within 24 to 48 hours of injury.
Neutrophils reach a wound within __________ (time) of injury
Neutrophils reach a wound within 24 to 48 hours of injury
