A distributed two-pore model: theoretical implications and practical application to the glomerular sieving of Ficoll

Carl Öberg, Bengt Rippe

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

Sammanfattning

In the present study, an extended two-pore theory is presented where the porous pathways are continuously distributed according to small-and large-pore mean radii and SDs. Experimental glomerular sieving data for Ficoll were analyzed using the model. In addition, several theoretical findings are presented along with analytic solutions to many of the equations used in distributed pore modeling. The results of the data analysis revealed a small-pore population in the glomerular capillary wall with a mean radius of 36.6 angstrom having a wide arithmetic SD of similar to 5 angstrom and a large-pore radius of 98.6 angstrom with an even wider SD of similar to 44 angstrom. The small-pore radius obtained in the analysis was close to that of human serum albumin (35.5 angstrom). 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. The wide distribution of pore sizes obtained in the present 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 the pore area-to-diffusion length ratio and the filtration coefficient.
Originalspråkengelska
Sidor (från-till)F844-F854
TidskriftAmerican Journal of Physiology-Renal Physiology
Volym306
Nummer8
DOI
StatusPublished - 2014

Ämnesklassifikation (UKÄ)

  • Urologi och njurmedicin

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