A distributed two-pore model: Theoretical implications and practical application to the glomerular sieving of Ficoll
Published online on February 12, 2014
Abstract
In the current study, an extended two-pore theory is presented where the porous pathways are continuously distributed according to small- and large-pore mean radii (uS and uL) and standard deviations (sS and sL). Experimental glomerular sieving data for Ficoll are analyzed using the model. In addition, several theoretical findings are presented along with analytical solutions to many of the equations used in distributed pore modeling. The results of the data analysis reveal a small-pore population in the glomerular capillary wall with a mean-radius of 36.6Å with a wide arithmetic standard deviation being ~5Å and a large-pore radius of 98.6Å with an even wider standard deviation of ~44Å. The small-pore radius obtained in the analysis is close to that of human serum albumin (35.5Å). By reanalyzing the data and setting the distribution spread of the model constant, we discovered that a narrow distribution is compensated by an increased mean-pore radius and a decreased pore area to diffusion length ratio (A0/x). The wide distribution of pore-sizes obtained in the current analysis, even when considering electrostatic hindrance due to the negatively charged barrier, is inconsistent with the high selectivity to proteins typically characterizing the glomerular filtration barrier. We therefore hypothesize that a large portion of the variance in the distribution of pore-sizes obtained is due to the molecular 'flexibility' of Ficoll, implying that the true variance of the pore-system is lower than that obtained using flexible probes. This would also, in part, explain the commonly noted discrepancy between A0/x and the filtration coefficient Kf.