A new view of Starling's hypothesis at the microstructural level.

In this paper we quantitatively investigate the hypothesis proposed by Michel (Exp. Physiol. 82, 1-30, 1997) and Weinbaum (Ann. Biomed. Eng. 26, 1-17, 1998) that the Starling forces are determined by the local difference in the hydrostatic and colloid osmotic pressure across the endothelial surface glycocalyx, which we propose is the primary molecular sieve for plasma proteins, rather than the global difference in the hydrostatic and oncotic pressure across the capillary wall between the plasma and tissue, as has been universally assumed until now. A spatially heterogeneous microstructural model is developed to explain at the cellular level why there is oncotic absorption at low capillary pressures in the short-lived transient experiments of Michel and Phillips (J. Physiol. 388, 421-435, 1987) on frog mesentery capillary, but a small positive filtration once a steady state is achieved. The new model also predicts that the local protein concentration behind the surface glycocalyx can differ greatly from the tissue protein concentration, since the convective flux of proteins through the orifice-like pores in the junction strand will greatly impede the back diffusion of the proteins into the lumen side of the cleft when the local Peclet number at the orifice is >1. The net result is that the filtration in the capillaries is far less than heretofore realized and there may be no need for venous reabsorption.