A model of human microvascular exchange: parameter estimation based on normals and nephrotics

A mathematical model is formulated and used to describe the distribution and transport of fluid and albumin in the human circulation, interstitium and lymphatics. Two transcapillary mass exchange mechanisms are investigated: a homoporous 'coupled Starling model', in which transcapillary albumin diffusion and convection occur within the same pathway, and a heteroporous 'plasma leak model', in which variations in structure and pressure are permitted along the length of the capillary. Parameters used in the transport models are determined based on statistical fitting of simulation predictions to experimental data from normal humans and nephrotic patients. The data consists of interstitial fluid volumes and interstitial colloid osmotic pressures as functions of plasma colloid osmotic pressure. Model validation is carried out based on comparison of (i) simulation predictions with experimental data used in parameter estimation, (ii) estimated transport parameters with experimentally determined values, and (iii) simulation predictions with a set of dynamic data from an albumin infusion study. While both models with their best-fit parameter estimates provide a good representation of experimental data, the drawbacks of the plasma leak model are three-fold: it requires more estimated parameters than the coupled Starling model, little experimental information exists with which to compare these parameters and, with the best fit values obtained, the plasma leak mechanism becomes insignificant. The model that employs a Starling-type exchange mechanism will therefore be favoured in future applications.