Extracellular and local tissue pH (pHe)

Extracellular and local tissue pH (pHe) refers to the hydrogen ion concentration in the interstitial fluid surrounding cells, a parameter that is strictly maintained at approximately 7.4 in healthy tissues [1]. In pathological states such as cancer, ischemia, and chronic inflammation, this balance is disrupted, leading to a significantly more acidic microenvironment (pHe 6.5–6.9) [2]. This localized acidosis is a hallmark of the tumor microenvironment, where it promotes extracellular matrix degradation, facilitates tumor invasion, and impairs the anti-tumor immune response [3]. Therapeutic strategies targeting pHe involve the use of systemic alkalizing agents like sodium bicarbonate to neutralize acidity or the development of pH-sensitive drug delivery systems that exploit the acidity for localized release [4]. Additionally, targeting the proteins that regulate pHe, such as carbonic anhydrases and sodium-hydrogen exchangers, represents a major pharmacological approach to normalizing the tissue environment and enhancing the efficacy of conventional therapies [5].

Other names

Extracellular pHInterstitial pHTissue acidityHydrogen ion concentrationpHe

Chemical buffering and neutralization of extracellular protons; inhibition of membrane-bound proton pumps and exchangers to modulate the interstitial pH gradient.