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The relationship between pH and wound healing

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The relationship between pH and wound healing


In intact dermal tissue (i.e. effectively sealed from the environment by the epidermis), the products of oxidative respiration, CO 2 and anaerobic respiration (lactic acid), are removed from the local environment by the return flow of venous blood. An indicator of this is the lower pH of venous blood (7.35) compared to that of arterial blood (7.45). The pH of intact skin ranges from about 4.8 to 6.0, while the interstitial fluid exhibits a near neutral pH. The low skin pH is attributed mainly to the presence of the so-called "acid mantle," a natural barrier to the external environment.


Two approaches have been taken to determine the role that pH plays in wound healing:


a. direct measurement of wound pH

determination of the effect of modifying wound pH on healing rates.


Direct measurement of wound pH is restricted by the availability of suitable probes: even a needle-style pH probe will cause tissue disruption and localised cell death, while the assay technique itself will modify the pH. As a result of these limitations, available data are restricted to measurement of wound surface pH or wound exudate pH.


The role of wound bed pH has proven to be of fundamental importance during the healing of chronic wounds, with prolonged chemical acidification of the wound bed having been shown to increase the healing rate in chronic venous leg ulcers 13. The principal explanation for the mechanism of interaction between the acidic wound bed and the wound healing process is related to the potential to increase tissue oxygen availability through oxygen dissociation and to reduce the histotoxicity of bacterial end products, thus stimulating the wound's healing process.


Chronic wound fluid contains elevated protease levels. These increased levels have deleterious effects on wound healing, degrading de novo granulation tissue and endogenous, biologically active proteins such as growth factors and cytokines. An effective therapeutic approach for chronic wounds would therefore be to modify this ‘hostile' environment and redress this proteolytic imbalance. One approach would be to reduce pH and thus inhibit excess protease activity. The wound bed pH of chronic venous leg ulcers and pressure ulcers was found to be alkaline or neutral when compared to intact surrounding skin; it was also found to change pH according to the stage of healing of the ulcer, moving to an acidic state during epithelialisation.


Protease activity is extremely pH sensitive. Protease activity peaks at between pH7 to pH8 and decreases rapidly in the presence of acidity. Below pH4, some proteases are permanently inactivated. The pH of wounds is neutral to alkaline whereas the pH of normal skin is acidic: pH5.5. When a wound is kept in an acidic condition, the fibroblasts proliferate more actively and the wound's healing process is stimulated more than when it is in a neutral or alkaline condition.


If wound healing is to be initiated or assisted then it is important that the wound is maintained above pH4, given that the aforementioned enzymes are essential for wound healing. Modulation of protease activity may therefore be significant in accelerating wound healing.


There is thus a strong correlation between prolonged proteolytic activity in the wound environment and wound chronicity: the activity profiles of proteases are highly pH dependent, with optimum activity being in the same range as that of chronic wound fluid. Chronic wound fluids have been found to have a pH range of 7-8, which is consistent with published literature.


It has been shown that excessive proteases are a contributory factor in slowing down the healing process and in some instances locking the wound into a cycle of chronicity. Reducing the pH of the wound fluid is therefore an ideal method of inhibiting protease activity yet without causing permanent protease deactivation, which could also potentially destroy beneficial proteins present in the wound fluid. The net result is that the cycle of chronicity is broken, enabling the wound to progress to healing - achieved by the inactivation of harmful proteases, the alleviation of excessive protease activity and the control of unhelpful proteolytic activity.


Lowering pH below 7 slows down enzyme activity of proteases such as elastase, plasmin, cathepsin G and MMP-2. See diagram below


Enzyme activity graph