An analysis of the permeability of a fenestra.

In this analysis of published data we evaluate the permeabilities of unit area of fenestral pathway to water and small solutes. These properties are then used to assess the functional significance of the fenestral diaphragm which, along with the glycocalyx and basement membrane, makes up the fenestral pathway. Endothelial hydraulic conductance and permeability to small lipophobic solutes increase with fenestral density in a variety of mammalian tissue. The increase in conductance per unit increment in fenestral area (Kfen) averages 0.38 micron X s-1 X mm Hg-1 (regression analysis). This value means that a single fenestra (diam 0.06 micron, area 0.003 micron2) has a greater conductance than 1 micron2 of continuous (skeletal muscle) endothelium. Similarly the diffusional permeability of unit fenestral area (Pfen) to B12 and inulin is high. But neither Kfen nor Pfen is as great as might be expected from the extreme thinness of the diaphragm (less than or equal to 5 nm). Pfen depends on diffusivity (D) and pathlength (delta chi): Pfen = D'/delta chi. D' depends on the fraction of the fenestral surface available for exchange and on restriction to diffusion. These relations were applied to test the view that the diaphragm, rather than the glycocalyx or basement membrane, is the major barrier to fluid and small solutes in the fenestral pathway. If this were turn, over 98 1/2% of the diaphragm's area would have to be totally impermeable in order to yield the observed values of Pfen--a result consequent upon the extreme thinness of the diaphragm. In this event there would be less than one equivalent pore (radius 5-11 nm) per diaphragm on average-which is incompatible with ultrastructural evidence. The resistance of a 5-nm-thick diaphragm containing one or more pores is not high enough to account for fenestral resistance. It is concluded that much thicker structures, such as the glycocalyx and/or basement membrane, and not the diaphragm, account for fenestral resistance to small-solute and water transport.