A 55-year-old man is evaluated due to a nonhealing left forearm wound. The patient had an excisional biopsy of a suspicious skin lesion at the site of the wound several weeks ago. He has a history of uncontrolled type 2 diabetes mellitus and hypertension. Vital signs are within normal limits. Physical examination shows a 2.5-cm wound surrounded by erythema on the left forearm. Upregulation of which of the following would most likely improve fibroblast proliferation and reepithelization in this nonhealing wound?

Question

A 55-year-old man is evaluated due to a nonhealing left forearm wound.  The patient had an excisional biopsy of a suspicious skin lesion at the site of the wound several weeks ago.  He has a history of uncontrolled type 2 diabetes mellitus and hypertension.  Vital signs are within normal limits.  Physical examination shows a 2.5-cm wound surrounded by erythema on the left forearm.  Upregulation of which of the following would most likely improve fibroblast proliferation and reepithelization in this nonhealing wound?

Quizplus · Accepted Answer

This patient with a history of uncontrolled diabetes mellitus has a nonhealing wound with evidence of ongoing inflammation (eg, erythema). Wound healing normally progress through the inflammatory, proliferative, and remodeling phases. In the days after the initial injury, neutrophils and other immune cells are recruited to the wound and produce an inflammatory response that helps prevent bacterial overgrowth in the nutrient-rich environment of a healing wound. However, this inflammation also impairs formation of granulation tissue that is needed for normal wound healing. As healing progresses, release of growth factors and anti-inflammatory cytokines (eg, IL-10) by macrophages and regulatory T cells suppresses the inflammatory response, facilitating fibroblast proliferation and reepithelialization of the wound. In patients with diabetes mellitus, constitutively elevated blood glucose increases inflammation by stimulating the release of proinflammatory cytokines and reactive oxygen species from neutrophils (Choice E). Elevated glucose also leads to a marked decrease in IL-10 production that contributes to the increased susceptibility for chronic, nonhealing wounds and ulcers in patients with uncontrolled diabetes. (Choice A) Bradykinin is a vasoactive inflammatory mediator that is normally produced by endothelial cells, macrophages, and platelets during the inflammatory phase of wound healing. Further upregulation of inflammatory mediators in patients with diabetes would most likely have a negative effect on fibroblast proliferation and reepithelialization. (Choice B) Although a baseline level of cortisol production is required for normal wound healing, excess cortisol can impair both the inflammatory and proliferative components of wound healing. Patients with diabetes tend to have elevated cortisol levels; therefore, further cortisol elevation would not improve wound healing. (Choice C) Excess glucose inhibits fibroblast migration and results in the nonenzymatic glycation of collagen fibers, which can prevent collagen cross-linking and can impair the structural integrity of a healing wound. Educational objective: Elevated blood glucose induces the release of reactive oxygen species and proinflammatory cytokines from neutrophils while inhibiting the production of anti-inflammatory cytokines (eg, IL-10) and growth factors needed for fibroblast proliferation and reepithelialization in a healing wound. As a result, patients with uncontrolled diabetes frequently have nonhealing wounds with evidence of ongoing inflammation.

A 55-Year-Old Man Is Evaluated Due to a Nonhealing Left