A re-evaluation of the properties of the three-compartment model of intestinal weak-electrolyte absorption

The three-compartment model for intestinal weak-electrolyte transport provides an equation which predicts the flux ratio (the ratio of the forward and reverse fluxes of weak electrolyte across the intestine) from the dissociation constant, given that coefficients in the equation are specified. Using the equation to evaluate the coefficients from flux ratio and dissociation constant data fails to provide a unique set of values for the coefficients, although it does provide four dissimilar but related sets of values. Differentiation to determine the position and size of the maximum flux ratio provides a relationship between the model coefficients which shows why it is that four sets of coefficients can be used in the equation when it is applied to experimental data. Coefficient sets are derived for all available flux ratio data in the literature. These always contain a variant which requires the intermediate compartment to be more acid than the end compartment. Further specification of the flux ratio equation either by combining data from different physiological circumstances or by adding voltage terms, reduces the four possible coefficient sets to a single set, again requiring the intermediate compartment to be more acid than the end compartment. Estimates of the intermediate-compartment pH agree well with electrode estimates of mucosal surface pH. The present re-evaluation of the three-compartment model resolves an apparent contradiction between experimental and previous theoretical results which indicated a more alkaline intermediate compartment. Instead of contradicting experimental findings, results from the modelling process confirm that the "acid microclimate" version of the model is the better representation of the system that causes asymmetry in weak electrolyte flows across the small intestine.