The GFR is determined by (1) the sum of the hydrostatic and colloid osmotic forces across the glomerular mem brane, which gives the net filtration pressure, and (2) the glomerular Kf. Expressed mathematically, the GFR equals the product of Kf and the net filtration pressure:

GFR= Kf × Net filtration pressure

The net filtration pressure represents the sum of the hydrostatic and colloid osmotic forces that either favor or oppose filtration across the glomerular capillaries (Figure 27-4). These forces include (1) hydrostatic pressure inside the glomerular capillaries (glomerular hydrostatic pressure, PG), which promotes filtration; (2) the hydrostatic pressure in Bowman’s capsule (PB) outside the capillaries, which opposes filtration; (3) the colloid osmotic pressure of the glomerular capillary plasma proteins (πG), which opposes filtration; and (4) the colloid osmotic pressure of the proteins in Bowman’s capsule (πB), which promotes filtration. (Under normal conditions, the concentration of protein in the glomerular filtrate is so low that the colloid osmotic pressure of the Bowman’s capsule fluid is considered to be zero.)

The GFR can therefore be expressed as

Although the normal values for the determinants of GFR have not been measured directly in humans, they have been estimated in animals such as dogs and rats. Based on the results in animals, the approximate normal forces favoring and opposing glomerular filtration in humans are believed to be as follows (see Figure 1):

Fig1. Summary of forces causing filtration by the glomerular  capillaries. The values shown are estimates for healthy humans. 

Some of these values can change markedly under different physiological conditions, whereas others are altered mainly in disease states, as discussed later.

INCREASED GLOMERULAR CAPILLARY FILTRATION COEFFICIENT INCREASES GFR

The Kf is a measure of the product of the hydraulic conductivity and surface area of the glomerular capillaries. The Kf cannot be measured directly, but it is estimated experimentally by dividing the rate of glomerular filtration by net filtration pressure:

Kf = GFR / Net filtration pressure

Because the total GFR for both kidneys is about 125 ml/min and the net filtration pressure is 10 mm Hg, the normal Kf is calculated to be about 12.5 ml/min/ mm Hg of filtration pressure. When Kf is expressed per 100 grams of kidney weight, it averages about 4.2 ml/min/ mm Hg, a value about 400 times as high as the Kf of most other capillary systems of the body; the average Kf of many other tissues in the body is only about 0.01 ml/ min/mm Hg per 100 grams. This high Kf for the glomerular capillaries contributes to their rapid rate of fluid filtration.

Although increased Kf raises GFR and decreased Kf reduces GFR, changes in Kf probably do not provide a primary mechanism for the normal day today regulation of GFR. Some diseases, however, lower Kf by reducing the number of functional glomerular capillaries (thereby reducing the surface area for filtration) or by increasing the thickness of the glomerular capillary membrane and reducing its hydraulic conductivity. For example, chronic, uncontrolled hypertension and diabetes mellitus gradually reduce Kf by increasing the thickness of the glomerular capillary basement membrane and, eventually, by damaging the capillaries so severely that there is loss of capillary function.

INCREASED BOWMAN’S CAPSULE HYDROSTATIC PRESSURE DECREASES GFR

 Direct measurements, using micropipettes, of hydrostatic pressure in Bowman’s capsule and at different points in the proximal tubule in experimental animals suggest that a reasonable estimate for Bowman’s capsule pressure in humans is about 18 mm Hg under normal conditions. Increasing the hydrostatic pressure in Bowman’s capsule reduces GFR, whereas decreasing this pressure raises GFR. However, changes in Bowman’s capsule pressure normally do not serve as a primary means for regulating GFR.

In certain pathological states associated with obstruction of the urinary tract, Bowman’s capsule pressure can increase markedly, causing serious reduction of GFR. For example, precipitation of calcium or of uric acid may lead to “stones” that lodge in the urinary tract, often in the ureter, thereby obstructing outflow of the urinary tract and raising Bowman’s capsule pressure. This situation reduces GFR and eventually can cause hydronephrosis (distention and dilation of the renal pelvis and calyces) and can damage or even destroy the kidney unless the obstruction is relieved.

INCREASED GLOMERULAR CAPILLARY COLLOID OSMOTIC PRESSURE DECREASES GFR

 As blood passes from the afferent arteriole through the glomerular capillaries to the efferent arterioles, the plasma protein concentration increases about 20 percent (Figure 2). The reason for this increase is that about one fifth of the fluid in the capillaries filters into Bowman’s capsule, thereby concentrating the glomerular plasma proteins that are not filtered. Assuming that the normal colloid osmotic pressure of plasma entering the glomerular capillaries is 28 mm Hg, this value usually rises to about 36 mm Hg by the time the blood reaches the efferent end of the capillaries. Therefore, the average colloid osmotic pressure of the glomerular capillary plasma proteins is midway between 28 and 36 mm Hg, or about 32 mm Hg.

Fig2. Increase in colloid osmotic pressure in plasma flowing  through the glomerular capillary. Normally, about one fifth of the  fluid in the glomerular capillaries filters into Bowman’s capsule,  thereby concentrating the plasma proteins that are not filtered.  Increases in the filtration fraction (glomerular filtration rate/renal  plasma flow) increase the rate at which the plasma colloid osmotic  pressure rises along the glomerular capillary; decreases in the filtration fraction have the opposite effect. 

Thus, two factors that influence the glomerular capillary colloid osmotic pressure are (1) the arterial plasma colloid osmotic pressure and (2) the fraction of plasma filtered by the glomerular capillaries (filtration fraction). Increasing the arterial plasma colloid osmotic pressure raises the glomerular capillary colloid osmotic pressure, which in turn decreases the GFR.

Increasing the filtration fraction also concentrates the plasma proteins and raises the glomerular colloid osmotic pressure (see Figure 2). Because the filtration fraction is defined as GFR/renal plasma flow, the filtration fraction can be increased either by raising the GFR or by reducing renal plasma flow. For example, a reduction in renal plasma flow with no initial change in GFR would tend to increase the filtration fraction, which would raise the glomerular capillary colloid osmotic pressure and tend to reduce the GFR. For this reason, changes in renal blood f low can influence GFR independently of changes in glomerular hydrostatic pressure.

With increasing renal blood flow, a lower fraction of the plasma is initially filtered out of the glomerular capillaries, causing a slower rise in the glomerular capillary colloid osmotic pressure and less inhibitory effect on the GFR. Consequently, even with a constant glomerular hydrostatic pressure, a greater rate of blood flow into the glomerulus tends to increase the GFR and a lower rate of blood flow into the glomerulus tends to decrease the GFR.

INCREASED GLOMERULAR CAPILLARY HYDROSTATIC PRESSURE INCREASES GFR

 The glomerular capillary hydrostatic pressure has been estimated to be about 60 mm Hg under normal conditions. Changes in glomerular hydrostatic pressure serve as the primary means for physiological regulation of GFR. Increases in glomerular hydrostatic pressure raise the GFR, whereas decreases in glomerular hydrostatic pressure reduce the GFR.

Glomerular hydrostatic pressure is determined by three variables, each of which is under physiological control: (1) arterial pressure, (2) afferent arteriolar resistance, and (3) efferent arteriolar resistance.

Increased arterial pressure tends to raise glomerular hydrostatic pressure and, therefore, to increase the GFR. (However, as discussed later, this effect is buffered by autoregulatory mechanisms that maintain a relatively constant glomerular pressure as blood pressure fluctuates.)

Increased resistance of afferent arterioles reduces glomerular hydrostatic pressure and decreases the GFR (Figure 3). Conversely, dilation of the afferent arterioles increases both glomerular hydrostatic pressure and GFR.

Fig3. Effect of increases in afferent arteriolar resistance (RA,  top panel) or efferent arteriolar resistance (RE, bottom panel) on renal  blood flow, glomerular hydrostatic pressure (PG), and glomerular filtration rate (GFR).

Constriction of the efferent arterioles increases the resistance to outflow from the glomerular capillaries. This mechanism raises glomerular hydrostatic pressure, and as long as the increase in efferent resistance does not reduce renal blood flow too much, GFR increases slightly (see Figure 3). However, because efferent arteriolar con striction also reduces renal blood flow, filtration fraction and glomerular colloid osmotic pressure increase as efferent arteriolar resistance increases. Therefore, if constriction of efferent arterioles is severe (more than about a threefold increase in efferent arteriolar resistance), the rise in colloid osmotic pressure exceeds the increase in glomerular capillary hydrostatic pressure caused by efferent arteriolar constriction. When this situation occurs, the net force for filtration actually decreases, causing a reduction in GFR.

Thus, efferent arteriolar constriction has a biphasic effect on GFR (Figure 4). At moderate levels of con striction, there is a slight increase in GFR, but with severe constriction, there is a decrease in GFR. The primary cause of the eventual decrease in GFR is as follows: As efferent constriction becomes severe and as plasma protein concentration increases, there is a rapid, nonlinear increase in colloid osmotic pressure caused by the Donnan effect; the higher the protein concentration, the more rapidly the colloid osmotic pressure rises because of the interaction of ions bound to the plasma proteins, which also exert an osmotic effect, as discussed in Chapter 16.   

Fig4. Effect of change in afferent arteriolar resistance or  efferent arteriolar resistance on glomerular filtration rate and renal  blood flow. 

To summarize, constriction of afferent arterioles reduces GFR. However, the effect of efferent arteriolar constriction depends on the severity of the constriction; modest efferent constriction raises GFR, but severe efferent constriction (more than a threefold increase in resistance) tends to reduce GFR.

Table 1 summarizes the factors that can de crease GFR.

Table1. Factors That Can Decrease the  Glomerular Filtration Rate

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مواضيع ذات صلة

Physiological Control of Glomerular Filtration and Renal Blood Flow

Renal Blood Flow

Glomerular Filtration—The First Step in Urine Formation

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