Oxygen, pH, Lactate, and Metabolism—How Old Knowledge and New Insights Might Be Combined for New Wound Treatment

Abstract

Over time, we have come to recognize a very complex network of physiological changes enabling wound healing. An immunological process enables the body to distinguish damaged cells and begin a cleaning mechanism by separating damaged proteins and cells with matrix metalloproteinases, a complement reaction, and free radicals. A wide variety of cell functions help to rebuild new tissue, dependent on energy provision and oxygen supply. Like in an optimized “bio-reactor,” disturbance can lead to prolonged healing. One of the earliest investigated local factors is the pH of wounds, studied in close relation to the local perfusion, oxygen tension, and lactate concentration. Granulation tissue with the wrong pH can hinder fibroblast and keratinocyte division and proliferation, as well as skin graft takes. Methods for influencing the pH have been tested, such as occlusion and acidification by the topical application of acidic media. In most trials, this has not changed the wound’s pH to an acidic one, but it has reduced the strong alkalinity of deeper or chronic wounds. Energy provision is essential for all repair processes. New insights into the metabolism of cells have changed the definition of lactate from a waste product to an indispensable energy provider in normoxic and hypoxic conditions. Neovascularization depends on oxygen provision and lactate, signaling hypoxic conditions even under normoxic conditions. An appropriate pH is necessary for successful skin grafting; hypoxia can change the pH of wounds. This review describes the close interconnections between the local lactate levels, metabolism, healing mechanisms, and pH. Furthermore, it analyzes and evaluates the different possible ways to support metabolism, such as lactate enhancement and pH adjustment. The aim of wound treatment must be the optimization of all these components. Therefore, the role of lactate and its influence on wound healing in acute and chronic wounds will be assessed.

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“…Even though the pH of human skin surface ranges between 5.4 and 5.9, it was found to gradually increase with skin depth, and a pH close to neutral (pH 7.4) was observed after skin destruction in an acute wound [ 55 ]. The wound as scar tissue becomes acidic during healing and reestablishing the intact stratum corneum [ 56 ]. In contrast, the pH in chronic wounds varies between 5.45 and 8.65, due to the alkaline shift [ 57 ] caused by dissolved CO 2 , a reduction in oxygen tension and, possibly, by alkaline anions accumulation from bacterial metabolism.…”

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“…Since the median blood pH of 7.2 ( Figure 5 ) for these individuals was measured only on the fifth day of the experiment, the tissue alkalosis during the first days after the injection can be explained both by systemic and local pH increases. In the former case, it could be the consequence of the applied anesthesia, which may provoke systemic hypoxia-mediated respiratory alkalosis [ 52 ]; in the latter case, it may reflect a local hypocapnia in the wound area [ 53 ]. Thus, this effect requires further investigation.…”

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