A mechanistic physicochemical model of carbon dioxide transport in blood

A number of mathematical models have been produced that, given the Pco₂ and Po₂ of blood, will calculate the total concentrations for CO₂ and O₂ in blood. However, all these models contain at least some empirical features, and thus do not represent all of the underlying physicochemical processes in an entirely mechanistic manner. The aim of this study was to develop a physicochemical model of CO₂ carriage by the blood to determine whether our understanding of the physical chemistry of the major chemical components of blood together with their interactions is sufficiently strong to predict the physiological properties of CO₂ carriage by whole blood. Standard values are used for the ionic composition of the blood, the plasma albumin concentration, and the hemoglobin concentration. All K_m values required for the model are taken from the literature. The distribution of bicarbonate, chloride, and H⁺ ions across the red blood cell membrane follows that of a Gibbs-Donnan equilibrium. The system of equations that results is solved numerically using constraints for mass balance and electroneutrality. The model reproduces the phenomena associated with CO₂ carriage, including the magnitude of the Haldane effect, very well. The structural nature of the model allows various hypothetical scenarios to be explored. Here we examine the effects of 1) removing the ability of hemoglobin to form carbamino compounds; 2) allowing a degree of Cl^- binding to deoxygenated hemoglobin; and 3) removing the chloride (Hamburger) shift. The insights gained could not have been obtained from empirical models.

This study is the first to incorporate a mechanistic model of chloride-bicarbonate exchange between the erythrocyte and plasma into a full physicochemical model of the carriage of carbon dioxide in blood. The mechanistic nature of the model allowed a theoretical study of the quantitative significance for carbon dioxide transport of carbamino compound formation; the putative binding of chloride to deoxygenated hemoglobin, and the chloride (Hamburger) shift.