In acid-base homeostasis, homeostatic mechanisms regulate the acid-base status of the extracellular fluid (ECF) and intracellular fluid (ICF) compartments of the body, targeting for stabilization the concentration of the positively charged hydrogen ion, [H+], a proton, the concentration often expressed in terms of the common acidity index, pH.[1]
That homeostatic targets of ECF and ICF pH makes sense from a biological chemistry perspective for the following reasons:
Hydrogen ions, protons, in aqueous solution bind to water molecules, molecules of H2O, forming so-called hydronium ions, H3O+. By hopping from one water molecule to an adjacent one, kicking a proton off the adjacent molecule, which repeats the hop, which kicks another proton on etc. — in a kind of concerted transport through water, similar to the way electrons conduct along a copper wire — protons diffuse along their concentration gradients through the solution very rapidly. In their attachment to the tiny water molecule — tiny by comparison to the numerous macromolecules (proteins, nucleic acids, lipids) present in body fluids — they jiggle and swirl vigorously, driven by the thermal (heat) energy of the body fluids. Accordingly, they frequently encounter a macromolecule, their small size giving them access to the interstices of the macromolecule as well as their outer surfaces, and their charged status giving them the ability to disrupt the charges on the macromolecules, charges that importantly help maintain the convoluted structure of the macromolecule critical for its normal biological/biochemical function.
Small changes in pH can exert large or small functional disruptions of proteins, leading to acute serious biological disturbances in such activities as enzyme catalysis, cell signaling, gene regulation, and many others, very many more in the ICF than in the ECF.[1]