LAUSR

The concentration H+ ([H+]) in intracellular fluid (ICF) must be maintained in a narrow range in all species for normal protein functions. Thus, mechanisms regulating ICF are of fundamental biological importance. Studies on the regulation of ICF [H+] have been hampered by use of pH notation,failure to consider the roles played by differences in the concentration of strong ions ( SID), the conservation of mass, the principle of electrical neutrality and that [H+] and [HCO3-] are dependent variables. This argument is based on the late Peter Stewart's physical- chemical analysis of [H+] regulation reported in this journal nearly forty years ago. We start by outlining the principles of Stewart's analysis and then provide a general understanding of its significance for regulation of ICF [H+]. The system may initially appear complex, but it becomes evident that changes in SID dominanate regulation of [H+]. The primary strong ions are Na+, K+ and Cl-, and a few organic strong anions. The second independent variable, PCO2, can easily be assessed. The third independent variable, the activity of intracellular weak acids ([Atot]), is much more complex but largely plays a modifying role. Attention to these principles potentially will provide new insights into ICF pH regulation.