Abstract
The hydrogen ion concentration ([H+]) in intracellular cytoplasmic 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 (strong ion difference, SID), the conservation of mass, the principle of electrical neutrality, and that [H+] and bicarbonate ions [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 (Stewart. 1983. Can. J. Physiol. Pharmacol. 61: 1444-1461. Doi:10.1139/y83-207). 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 dominate regulation of [H+]. The primary strong ions are Na+, K+, and Cl-, and a few organic strong anions. The second independent variable, partial pressure of carbon dioxide (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 will potentially provide new insights into ICF pH regulation.
Highlights
Close to 40 years ago in this journal the late Peter Stewart laid out the principles of a quantitative physical–chemical approach to understanding the determinants of hydrogen ion concentration ([H+], pH, and acid–base in water-based biological solutions, Stewart 1983)
Our objective is to provide a roadmap for use of physical–chemical concepts in future studies on the regulation of intracellular cytoplasmic fluid (ICF) [H+]
The failure to consider the behavior of weak ions and buffering limits mechanistic analysis and potentially produces quantitative buffer and grown in the presence of 5% CO2, it was not stated whether the superfusate was bubbled with partial pressure of carbon dioxide (PCO2) during the experiments. pHi rises from a to b with the addition of 20 mM NH4+ which partially dissociates to NH3, enters the cell, and raises pHi by binding H+ to form the strong cation, NH4+, and NH3/NH4+ reaches a new equilibrium
Summary
Close to 40 years ago in this journal the late Peter Stewart laid out the principles of a quantitative physical–chemical approach to understanding the determinants of hydrogen ion concentration ([H+], pH, and acid–base in water-based biological solutions, Stewart 1983). When SID is positive, and the concentration is greater than the total amount of the weak acid [HA], the weak acid is essentially completely dissociated and this solution, too, behaves as if it only has strong ions; [H+] is extremely small and [OHÀ] increases linearly with increases in SID for there are no other anions to balance the SID and maintain electrical neutrality. Without the [Atot], [H+] would be K0w/SID (where K0 is the product of the dissociation constant and concentration of water at a given temperature) From this discussion, it should be apparent that buffers do not reduce changes in [H+] in response to the addition of a strong acid, but instead when SID is less than [Atot] they set the magnitude of [H+] and pH in the range of the KA or pKa of the weak acid. Quantity [Na+] (mEq/L) [K+] (mEq/L) [Mg2+] (mEq/L) [Ca2+] (mEq/L) [ClÀ] (mEq/L) Other strong anions (mEq/L) PCO2 (mmHg) SID (mEq/L) HA (mmol/L) HCO3À (mEq/L) pH [H+] (Eq/L) [OHÀ] (Eq/L)
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