Structure and Properties of the Filtration Barrier: Overview

As described in Chapter 3 of this section, the filtration barrier of the glomerular capillaries consists of three major elements. The first of these is the endothelial cells that line the inside of the glomerular capillary. The second is the basement membrane of the capillary itself, and the third is the epithelial cells containing podocytes or foot process projections that lie on the outside of the capillary in the urinary space of Bowman’s capsule. The glomerular filtration barrier is about 1000 times more porous than other capillaries. It excludes cells and behaves as a molecular sieve restricting solute filtration based on molecular size, shape and charge.

Endothelium:

The nuclei of the endothelial cells are usually found in an area of the basement membrane that is attached to the messangium. The remainder of each cell is distributed around the inner wall of the glomerular capillary. The endothelial cell cytoplasm becomes quite thin and contains 70 nm pores called fenestrae. Thin single membranes, possibly of a protein-polysaccharide film, cover these fenestrae. These are highly permeable, and do not pose a significant barrier to the movement of even large molecules but do exclude passage of cellular elements of the blood

Basement Membrane: The basement membrane of the glomerular capillary consists of three layers, but these layers do not contain pores. In the middle of the basement membrane is a dense inner layer called the lamina densa. The lamina densa separates two thinner layers, the lamina rara interna, nearest the capillary lumen, and the lamina rara externa nearest the urinary space. The lamina densa is made of type IV collagen which selectively filters molecules between the fibers based on size. The lamina rara layers contain heparin sulfate, a polyanionic molecule that may act as a charge barrier to large negatively charged molecules such as protein Epithelium; Cell Types: Two types of epithelial cells are found within the urinary space of Bowman’s capsule. The first of these are the parietal epithelial cells that line the inside of Bowman’s capsule. These cells are not part of the filtration barrier. The second type of epithelial cells are the visceral epithelial cells or podocytes, which rest on the basement membrane of the glomerular capillary and which are the largest of the cells in the glomerulus. Extending from the main cell body of the podocytes are primary processes from which pedicels or foot processes extend and actually contact the lamina rara externa of the basement membrane. Additional pedicels also arise from secondary and tertiary processes. Glomerular Filtration: Composition of Glomerular Filtrate The glomerular filtration barrier allows fluid to be filtered at a high rate while remaining nearly impermeable to cells and larger molecules. Up to molecular weights of about 7000 daltons molecules are freely filtered across the barrier. As molecular weight increases above 7000 daltons filterability decreases progressively and essentially ceases at molecular weights of about 70000. Plasma albumin, with a molecular weight of 66000 daltons is very poorly filtered and appears in the filtrate at about 0.02% of its concentration in plasma. The resultant glomerular filtrate is, as expected, very close to plasma in composition of small solutes, while being nearly devoid of protein. Because the contribution of protein to total plasma osmolarity is quite small and that of the filtrate even less the filtrate is essentially isosmotic with the plasma from which it is derived. In animals with easily accessible surface glomeruli, the micropuncture technique has allowed the direct sampling of the glomerular filtrate. These studies have shown that small molecules such as inulin ( molecular weight 5500) are filtered freely while larger molecules such as albumin are cleared at a rate thGlomerular Filtration Rate: The glomerular filtration rate (GFR) is defined as the volume of plasma filtered by all the glomeruli in a given period of time. In the discussion of renal function the GFR is often referred to as the "First Factor." This is because the GFR determines the volume of fluid, both water and solutes, available to the nephron to act on in performing its major function of regulation of water and electrolyte balance. In the normal adult male, the GFR is equal to about 125 ml/minute. In the normal adult female the GFR is 10% less. At this GFR, about 180 L of fluid are filtered in 24 hours. Urine output, however, is only about 1 to 2 L per day. From these values it may be assumed that about 99% of the glomerular filtrate is reabsorbed by the renal tubules. at is less than 1% of inulin. Forces Driving the Glomerular Filtration Rate The formula on the right characterizes the GFR in terms of the forces that contribute to filtration across the glomerular capillary wall. These forces are essentially the same as those affecting movement across the other capillaries in the body and are as follows: KF = filtration coefficient which is a product of the glomerular capillary permeability and the glomerular capillary surface area; PGC = mean capillary hydraulic pressure; PT = mean tubule hydraulic pressure; PGC = oncotic (protein osmotic) pressure in the plasma in the glomerular capillaries; and P T = oncotic pressure of the glomerular filtrate in the renal tubules. Because filtrate protein concentration is very low P T is low and plays a minimal role in determining the force driving filtration. Measurement of Glomerular Filtration Rate