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Renin-Angiotensin System

FIGURE 8 Effect of molecular size and charge on filtration of macromolecules in the glomerulus. The ratio of the concentrations of the macromolecule in the ultrafiltrate compared to the plasma is plotted as a function of the molecular radius of the test molecule. These experiments were performed with different sizes of uncharged polymers of dextran (A) or polyvinylpyrrolidone (PVP; □) and with the negatively charged polymer dextran sulfate (■). Note that concentration ratios for dextran sulfate were significantly lower throughout the size range tested, and that the ratio for the largest molecule of dextran sulfate tested closely approximated that of albumin, which is also negatively charged. For comparison, the concentration ratios for inulin, myoglobin, and hemoglobin are also included. (Replotted data from Chang et al., Kidney Int 1975;8:212-218; Lambert etal, Pfliigers Arch 1975;359:1-22; Vanrenterghem etal., ClinSci 1980;58:65-75; and Whiteside, Silverman, Am J Physiol Renal Fluid Electrolyte Physiol 1983;245:F485-F495.)

FIGURE 8 Effect of molecular size and charge on filtration of macromolecules in the glomerulus. The ratio of the concentrations of the macromolecule in the ultrafiltrate compared to the plasma is plotted as a function of the molecular radius of the test molecule. These experiments were performed with different sizes of uncharged polymers of dextran (A) or polyvinylpyrrolidone (PVP; □) and with the negatively charged polymer dextran sulfate (■). Note that concentration ratios for dextran sulfate were significantly lower throughout the size range tested, and that the ratio for the largest molecule of dextran sulfate tested closely approximated that of albumin, which is also negatively charged. For comparison, the concentration ratios for inulin, myoglobin, and hemoglobin are also included. (Replotted data from Chang et al., Kidney Int 1975;8:212-218; Lambert etal, Pfliigers Arch 1975;359:1-22; Vanrenterghem etal., ClinSci 1980;58:65-75; and Whiteside, Silverman, Am J Physiol Renal Fluid Electrolyte Physiol 1983;245:F485-F495.)

that are available in a wide range of molecular sizes such as polyvinylpyrrolidone or dextran (a sucrose polymer to which anionic sulfate residues can be bonded), as well as naturally occurring protein molecules.

The ultrafiltration coefficient, Kf, can be altered not only by changes in the thickness or composition of the basement membrane and the podocyte slits, but also by their effective areas. It has been proposed that this filtration area may be regulated by humorally regulated contraction or relaxation of mesangial cells within the glomerulus. Disease processes can also change the number and size of the endothelial fenestrae, the shape and size of the epithelial podocytes, or the thickness and properties of the basement membrane. Any of these processes may change the permeability characteristics of the filtration barrier, leading to changes in Kf as well as the loss of proteins into the filtrate. When the filtration of proteins exceeds the ability of the proximal tubule to reabsorb them, they appear in the final urine, a condition known as proteinuria. Excessive albumin losses in the urine may exceed the capacity of the liver to synthesize albumin, leading to a reduction in plasma albumin concentration and a decrease in plasma coP. This can contribute to the severe edema (see chapter 16), which is a characteristic of the nephrotic syndrome (see earlier clinical Note).

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