The first step in urine formation is the filtration of large amounts of fluid through the glomerular capillaries into Bowman’s capsule—almost 180 liters each day. Most of this filtrate is reabsorbed, leaving only about 1 liter of fluid to be excreted each day, although the renal fluid excretion rate may be highly variable depending on fluid intake. The high rate of glomerular filtration depends on a high rate of kidney blood flow, as well as the special properties of the glomerular capillary membranes. In this chapter we discuss the physical forces that determine the glomerular filtration rate (GFR), as well as the physiological mechanisms that regulate GFR and renal blood flow.

COMPOSITION OF THE GLOMERULAR FILTRATE

Like most capillaries, the glomerular capillaries are relatively impermeable to proteins, so the filtered fluid (called the glomerular 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. For example, 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.

GFR IS ABOUT 20 PERCENT OF RENAL PLASMA FLOW

 The GFR is determined by (1) the balance of hydrostatic and colloid osmotic forces acting across the capillary membrane and (2) the capillary filtration coefficient (Kf), the product of the permeability 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, which means that about 20 percent of the plasma flowing through the kidney is filtered through the glomerular capillaries (Figure 1). The filtration fraction is calculated as follows:

Filtration fraction = GFR/ Renal plasma flow

Fig1. Average values for total renal plasma flow (RPF), glomerular filtration rate (GFR), tubular reabsorption (REAB), and urine  f low rate. RPF is equal to renal blood flow × (1 – Hematocrit). Note  that GFR averages about 20% of the RPF, while urine flow rate is  less than 1% of the GFR. Therefore, more than 99% of the fluid  filtered is normally reabsorbed. The filtration fraction is the GFR/RPF. 

GLOMERULAR CAPILLARY MEMBRANE

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 2). 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 filtration, the glomerular capillary mem brane normally prevents filtration of plasma proteins.

Fig2. A, Basic ultrastructure of the glomerular capillaries.  B, Cross section of the glomerular capillary membrane and its major  components: capillary endothelium, basement membrane, and epithelium (podocytes). 

Surrounding the endothelium is the basement mem brane, which consists of a meshwork of collagen and proteoglycan 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 2). 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 thicker than 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 1 lists the effect of molecular size on filter ability of different molecules. A filterability of 1.0 means that the substance is filtered as freely as water, whereas a filterability of 0.75 means that the substance is filtered only 75 percent as rapidly as water. Note that electrolytes such as sodium and small organic compounds such as glucose are freely filtered. As the molecular weight of the molecule approaches that of albumin, the filterability rapidly decreases, approaching zero.

Table1. Filterability of Substances by  Glomerular Capillaries Based on Molecular Weight

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 3 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 are negatively charged molecules. Neutral dextrans are also filtered more readily than are negatively charged dextrans of equal molecular weight. The reason for these differences in filterability is that the negative charges of the basement membrane and the podocytes provide an important means for restricting large negatively charged molecules, including the plasma proteins.

Fig3. Effect of molecular radius and electrical charge of  dextran on its filterability by the glomerular capillaries. A value of 1.0  indicates that the substance is filtered as freely as water, whereas a  value of 0 indicates that it is not filtered. Dextrans are polysaccharides  that can be manufactured as neutral molecules or with negative or  positive charges and with varying molecular weights. 

In certain kidney diseases, the negative charges on the basement membrane are lost even before there are notice able changes in kidney histology, a condition referred to as minimal change nephropathy. The cause for this loss of negative charges is still unclear but is believed to be related to an immunological response with abnormal Tcell secretion of cytokines that reduce anions in the glomerular capillary or podocyte proteins. 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. Minimal change nephropathy is most common in young children but can also occur in adults, especially in those who have autoimmune disorders.

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مواضيع ذات صلة

Physiological Control of Glomerular Filtration and Renal Blood Flow

Renal Blood Flow

Determinants of The GFR

Urine Formation Results From Glomerular Filtration, Tubular Reabsorption, and Tubular Secretion

Multiple Functions of The Kidneys

التنظيم الحمضي – القاعدي في الجسم Acid-Base Balance

حصى الكلية Urinary Caliculi

أمراض الجهاز البولي

آلية التبول

المثانة البولية

طرق قياس وظائف الكلية

هرمون مضاد إدرار البول Anti-diuretic Hormone , ADH