Brewing complications: the effect of acute ethanol exposure on wound healing

Abstract

Ethanol consumption is linked to a higher incidence of traumatic wounds and increases the risk for morbidity and mortality following surgical or traumatic injury. One of the most profound effects of acute ethanol exposure on wound healing occurs during the inflammatory response, and altered cytokine production is a primary component. Acute ethanol exposure also impairs the proliferative response during healing, causing delays in epithelial coverage, collagen synthesis, and blood vessel regrowth. The accumulated data support the paradigm that acute ethanol intoxication prior to injury significantly diminishes a patient's ability to heal efficiently.

Figure 1.

Schematic of the process of wound repair. Uninjured skin is composed of an outer layer of epidermal cells (keratinocytes) and a dermal layer composed of fibroblasts, ECM components, and vasculature. Immediately following wounding, degranulation of platelets occurs following damage to the vasculature (1). Hemostasis is then achieved through the release of clotting factors and fibrin, which acts as a provisional matrix for the migration of immune cells (2). Neutrophils are the first immune cells to arrive at the wound site, followed by macrophages, both of which participate in host defense (3). The initial fibrin matrix is degraded slowly and replaced by newly synthesized ECM components by the fibroblasts (4). The robust fibroblast and endothelial cell proliferation result in the synthesis of fibrillar collagen and revascularization (5). Vessel regression occurs along with matrix remodeling, and 80–90% of the skin’s original integrity is restored (6).

Figure 2.

Probable effects of ethanol on reparative angiogenesis. Ethanol inhibits the hypoxia-associated translocation of HIF-1α and subsequent production of VEGF. Ethanol also decreases expression and phosphorylation (p) of VEGFR2 in endothelial cells. Through a combination of these effects, endothelial function is impaired, including the ability to form cord-like structures, ultimately resulting in a reduction in capillary density, wound vascularity, and angiogenesis.

Figure 3.

Probable effects of ethanol on ECM reconstitution in wounds. Ethanol impairs synthesis of collagen at the mRNA and post-translational level. Additionally, ethanol increases production and activity of collagen degradation enzymes, including MMP-8, u-PA, and t-PA. Glutathione, a substrate for ROS that modulates MMP activity, is depleted by ethanol, removing inhibition of the degradative enzymes. The cumulative effect is a decrease in collagen content as a result of a reduction in production and an increase in breakdown.

Figure 4.

Schematic of the metabolic, hemodynamic, and pathologic consequences of ethanol consumption prior to injury. Following injury, the metabolic, hemodynamic, and immunologic alterations are exacerbated by ethanol exposure. These effects interact with one another and negatively influence the capacity of the body to heal. The net result of these effects is an increase in wound-healing complications.