Microvascular Permeability to Water Hydraulic Conductivity Lp

Although cell membranes are freely permeable to the diffusion of water, they have a high resistance to fluid flow down a hydrostatic pressure gradient. Lp is given by the fluid flow per unit pressure per unit area.

What Is the Site of the Resistance to Fluid Flow?

The main pathway of fluid flow across the walls of continuous capillaries is the intercellular cleft, and in fenestrated endothelium through fenestrae. The conductance is determined the viscosity of the fluid (h), the path length (Ax), and the fourth power of the radius of the pathway (r4). The cleft of most endothelial cells in the capillary and postcapillary beds is approximately 20 to 30nm wide throughout its length (see Figure 1) with at least one tight junction. Breaks in the tight junction strand, approximately every 2 to 3 mm and usually 50 to 200nmlong and overlapping junc-tional strands further into or out of the cleft, give rise to a tortuous pathway for fluid flow through the cleft. The path length is therefore greater than the cleft length, and the radius is smaller than the cleft width, but greater than the space between the tight junction molecules.

How Can Lp Be Measured?

Cell Culture Models

Lp can be measured of endothelial cells in culture. A monolayer grown on polycarbonate filters is pressurized and the flow rate through the monolayer measured. The area of the monolayer and the pressure difference are known, so Lp can be calculated. Two main problems with this technique are the lack of formation of a perfect monolayer and the compression of endothelial cells and the underlying basement membrane onto the filter (sealing). The Lp of mono-layers is up to two orders of magnitude greater than in vivo.

Measurement of Lp in Single Vessels in Vivo

Lp can be measured in single arterioles, capillaries, and postcapillary venules using the Landis-Michel technique. A single microvessel in a thin flat tissue such as the mesentery is cannulated and perfused with a solution of known oncotic pressure and containing flow markers (erythrocytes). The vessel is then occluded by a glass rod, and the rate of filtration per unit area of vessel wall per unit pressure (Lp) is determined from the rate of movement of the flow markers, the radius of the vessel, and the length of the vessel.

Measurement of Filtration Capacity in Whole Organs Lp can be estimated in whole tissues by measuring the gain of weight or volume induced by an increase in fluid filtration after an increase in capillary pressure. The venous

Figure 1 Three-dimensional reconstruction of an endothelial cell cleft from ultrathin serial sections. Endothelial cell 1 (EC1) has been cut away to reveal the tight-junction structure of endothelial cell 2 (EC2) to be visible in the cleft. Tight junction strands run along the cleft and have small breaks in them that allow fluid and solutes through.

Figure 1 Three-dimensional reconstruction of an endothelial cell cleft from ultrathin serial sections. Endothelial cell 1 (EC1) has been cut away to reveal the tight-junction structure of endothelial cell 2 (EC2) to be visible in the cleft. Tight junction strands run along the cleft and have small breaks in them that allow fluid and solutes through.

pressure of the tissue can be increased, either by cannulating the draining vein or by inflating a cuff. The increase in weight or volume of the tissue per unit pressure is the capillary filtration coefficient (CFC, or Kf), which is the product of the mean Lp and the surface area available for exchange.

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