Glomerular Filtration-The First Step in Urine Formation
Urine formation begins with filtration of large amounts of fluid through the glomerular capillaries into Bowman’s capsule. Like most capillaries, the glomerular capillaries are relatively impermeable to proteins, so that the filtered fluid (called the glomeru-lar filtrate) is essentially protein-free and devoid of cellular elements, including red blood cells.
The concentrations of other constituents of the glomerular filtrate, including most salts and organic molecules, are similar to the concentrations in the plasma. Exceptions to this generalization include a few low-molecular-weight substances, such as calcium and fatty acids, that are not freely filtered because they are partially bound to the plasma proteins. Almost one half of the plasma calcium and most of the plasma fatty acids are bound to proteins, and these bound portions are not filtered through the glomerular capillaries.
As in other capillaries, the GFR is determined by (1) the balance of hydrostatic and colloid osmotic forces acting across the capillary membrane and (2) the cap-illary filtration coefficient (Kf), the product of the per-meability and filtering surface area of the capillaries. The glomerular capillaries have a much higher rate of filtration than most other capillaries because of a high glomerular hydrostatic pressure and a large Kf. In the average adult human, the GFR is about 125 ml/min, or 180 L/day. The fraction of the renal plasma flow that is filtered (the filtration fraction) averages about 0.2; this means that about 20 per cent of the plasma flowing through the kidney is filtered through the glomerular capillaries. The filtration fraction is calculated as follows:
Filtration fraction = GFR/Renal plasma flow
The glomerular capillary membrane is similar to that of other capillaries, except that it has three (instead of the usual two) major layers: (1) the endothelium of the capillary, (2) a basement membrane, and (3) a layer of epithelial cells (podocytes) surrounding the outer surface of the capillary basement membrane (Figure 26–10). Together, these layers make up the filtration barrier, which, despite the three layers, filters several hundred times as much water and solutes as the usual capillary membrane. Even with this high rate of filtra-tion, the glomerular capillary membrane normally pre-vents filtration of plasma proteins.
The high filtration rate across the glomerular capil-lary membrane is due partly to its special charac-teristics. The capillary endothelium is perforated by thousands of small holes called fenestrae, similar to the fenestrated capillaries found in the liver. Although the fenestrations are relatively large, endothelial cells are richly endowed with fixed negative charges that hinder the passage of plasma proteins.
Surrounding the endothelium is the basement mem-brane, which consists of a meshwork of collagen andproteoglycan fibrillae that have large spaces through which large amounts of water and small solutes can filter. The basement membrane effectively prevents filtration of plasma proteins, in part because of strong negative electrical charges associated with the proteoglycans.
The final part of the glomerular membrane is a layer of epithelial cells that line the outer surface of the glomerulus. These cells are not continuous but have long footlike processes (podocytes) that encircle the outer surface of the capillaries (see Figure 26–10).
The foot processes are separated by gaps called slit pores through which the glomerular filtrate moves.The epithelial cells, which also have negative charges, provide additional restriction to filtration of plasma proteins. Thus, all layers of the glomerular capillary wall provide a barrier to filtration of plasma proteins.
Filterability of Solutes Is Inversely Related to Their Size. The glomerular capillary membrane is thickerthan most other capillaries, but it is also much more porous and therefore filters fluid at a high rate. Despite the high filtration rate, the glomerular filtration barrier is selective in determining which molecules will filter, based on their size and electrical charge.
Table 26–1 lists the effect of molecular size on fil-terability of different molecules. A filterability of 1.0 means that the substance is filtered as freely as water; a filterability of 0.75 means that the substance is fil-tered only 75 per cent as rapidly as water. Note that electrolytes such as sodium and small organic com-pounds such as glucose are freely filtered. As the molecular weight of the molecule approaches that of albumin, the filterability rapidly decreases, approach-ing zero.
Negatively Charged Large Molecules Are Filtered Less Easily Than Positively Charged Molecules of Equal Molecular Size.
The molecular diameter of the plasma protein albumin is only about 6 nanometers, whereas the pores of the glomerular membrane are thought to be about 8 nanometers (80 angstroms). Albumin is restricted from filtration, however, because of its negative charge and the electrostatic repulsion exerted by negative charges of the glomerular capillary wall proteoglycans.
Figure 26–11 shows how electrical charge affects the filtration of different molecular weight dextrans by the glomerulus. Dextrans are polysaccharides that can be manufactured as neutral molecules or with negative or positive charges. Note that for any given molecular radius, positively charged molecules are filtered much more readily than negatively charged molecules. Neutral dextrans are also filtered more readily than negatively charged dextrans of equal molecular weight. The reason for these differences in filterability is that the negative charges of the basement mem-brane and the podocytes provide an important means for restricting large negatively charged molecules, including the plasma proteins.
In certain kidney diseases, the negative charges on the basement membrane are lost even before there are noticeable changes in kidney histology, a condition referred to as minimal change nephropathy. As a result of this loss of negative charges on the basement membranes, some of the lower-molecular-weight proteins, especially albumin, are filtered and appear in the urine, a condition known as proteinuria or albuminuria.
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