Fig. 33.15 shows how electric charge affects filtration of macromolecules (e.g., dextrans) by the glomerulus. Dextrans are a family of exogenous polysaccharides manufactured in various molecular weights. They can be electrically neutral or have either negative (polyanionic) or positive (polycationic) charges. As the size (i.e., effective molecular radius) of a dextran molecule increases, the rate at which it is filtered decreases. For any given molecular radius, cationic molecules are more readily filtered than anionic molecules. The reduced filtration rate for anionic molecules is explained by the presence of negatively charged glycoproteins on the surface of all components of the glomerular filtration barrier. These charged glycoproteins repel similarly charged molecules. Because most plasma proteins are negatively charged, the negative charge on the filtration barrier restricts filtration of anionic proteins more than the filtration of neutral and polyanionic proteins with a molecular radius between approximately 18 to 42 Å. For example, serum albumin, an anionic protein that has an effective molecular radius of 35.5 Å, is poorly filtered. Because the small amount of filtered albumin is normally reabsorbed avidly by the proximal tubule, almost no albumin appears in urine.
The importance of the negative charges on the filtration barrier in restricting filtration of plasma proteins is shown in
Figs. 33.15 33.16 . Removal of the negative charges from the filtration barrier causes proteins to be filtered solely on the basis of their effective molecular radius (
Fig. 33.16 ). Hence at any molecular radius between approximately 18 and 42 Å, filtration of polyanionic proteins will exceed the filtration that prevails in the normal state (in which the filtration barrier has anionic charges). In a number of glomerular diseases the negative charges on the filtration barrier are reduced because of immunological damage and inflammation. As a result, filtration of anionic proteins between approximately 18 and 42 Å in radius is increased. When the filtered proteins exceed the ability of the proximal tubule to reabsorb and catabolize them, anionic proteins begin to appear in urine (proteinuria), which is a marker of kidney disease.
Dynamics of Ultrafiltration
The forces responsible for glomerular filtration of plasma are the same as those in other capillary beds. Ultrafiltration occurs because the Starling forces (i.e., hydraulic and oncotic pressures) combine to drive fluid from the lumen of glomerular capillaries across the filtration barrier and into Bowman’s space (
Fig. 33.17 ). The hydraulic pressure inside the glomerular capillary (PGC) is oriented to promote movement of fluid from the glomerular capillary into Bowman’s space. Because the glomerular ultrafiltrate is essentially protein free under normal conditions, owing in large part to the paucity of proteins in serum smaller than 18 Å in radius 1.0 0.8 0.6 0.4 0.2 0 • Fig. 33.16 Reduction of the negative charges on the glomerular wall results in filtration of proteins on the basis of size only. In this situation the relative filterability of proteins depends only on the molecular radius. Accordingly, excretion of polyanionic proteins (18–42 Å) in urine increases because more proteins of this size are filtered.
that can be effectively filtered, the reflection coefficient (σ) for proteins across the glomerular capillary is essentially 1. Thus the oncotic pressure in Bowman’s space (πBS) is near zero. Therefore PGC is the principal force favoring filtration. In contrast, the hydraulic pressure in Bowman’s space (PBS) and the oncotic pressure in the glomerular capillary (πGC) both oppose filtration.