Glomerular Filtration

The high hydrostatic pressure of the blood in the glomerular capillaries is responsible for a net driving force favoring ultrafiltration from the glomerular capillaries. In the young male adult, the glomerular filtration rate (GFR) averages about 130 mL/min, which amounts to a whopping 187 L/day. The high rate of glomerular filtration means that as plasma flows through the kidneys at a rate of 670 mL/min, 130 mL/min, or ~20%, is filtered. This 20% represents what is referred to as the filtration fraction (FF). The FF is calculated as the ratio of the GFR to the RPF:

As discussed later, the filtration fraction, which is usually given as a percent rather than a fraction, determines the effect of the renal blood flow on the GFR.

The GFR, as with most extensive parameters of body function, is proportional to body size and is correspondingly lower in females. Thus, reported values of the normal GFR vary over a wide range, but for the purposes of the following discussion, we will consider the average GFR to be 130 mL/min, or an average of ~180 L/day. This should be regarded as the optimal value that would be found in a young adult with healthy kidneys. GFR declines with age and in renal disease because of a decrease in the number of functioning glomeruli. Therefore, measurement of the GFR is an important index of renal function and the progression or amelioration of renal disease. The following section considers the individual driving forces that determine the net force for glomerular filtration and how those forces are modified by physiologic or pathologic mechanisms.

Forces Driving and Opposing Glomerular Ultrafiltration

As in all capillaries, the movement of fluid into or out of the glomerular and peritubular capillaries is

Cool Microscopy Leaf

FIGURE 2 Scanning electron micrograph of a fractured glomerulus revealing the beginning of the proximal tubule (PT) at the urinary pole (lower edge). The cross-sectional plane of the fracture has exposed the lumens of several glomerular capillaries. These capillaries have attenuated endothelial cells. In addition, one can see the visceral epithelium (VE) that covers the capillary loops, and the parietal epithelium (PE) that forms the outer wall of Bowman's space. Red blood cells (arrow) can be seen in some of the capillary loops. (Electron micrograph courtesy of Dr. Andrew P. Evan, Indiana University Medical Center, Indianapolis, IN.)

FIGURE 2 Scanning electron micrograph of a fractured glomerulus revealing the beginning of the proximal tubule (PT) at the urinary pole (lower edge). The cross-sectional plane of the fracture has exposed the lumens of several glomerular capillaries. These capillaries have attenuated endothelial cells. In addition, one can see the visceral epithelium (VE) that covers the capillary loops, and the parietal epithelium (PE) that forms the outer wall of Bowman's space. Red blood cells (arrow) can be seen in some of the capillary loops. (Electron micrograph courtesy of Dr. Andrew P. Evan, Indiana University Medical Center, Indianapolis, IN.)

governed by the balance of the so-called Starling forces (see Chapter 16), that is, the hydrostatic and osmotic pressure differences between the capillary lumen and the region surrounding the capillary. In the case of the peritubular capillaries, this region is the interstitial fluid, whereas the glomerular capillaries are surrounded by Bowman's space, as shown in Fig. 2. According to the Starling Law, the rate of fluid movement (Jv) will be determined by the following equation:

where Lp is the hydraulic conductivity of the capillary wall, A is its area, AP is the difference in hydrostatic pressure, and An is the difference in osmotic pressure across the capillary wall. The osmotic pressure is produced only by macromolecules because both the peritubular and glomerular capillaries are virtually impermeable to plasma proteins, but they are quite permeable to smaller solute molecules. In other words, the reflection coefficients of solutes smaller than proteins are zero (see Chapter 3). Therefore, the relevant osmotic pressure difference is the difference in COP.

In the case of the glomerular capillary, because plasma proteins normally appear in the glomerular ultrafiltrate only in extremely low concentrations, the COP of Bowman's space can be regarded to be zero. However, in diseases affecting the glomeruli, the permeability of the filtration barrier to proteins may rise and their concentration in Bowman's space can become appreciable, thus reducing the difference in COP between the plasma and the space.

It is difficult to estimate accurately the area of most capillary beds including the glomerular capillary network; consequently a parameter referred to as the ultrafiltration coefficient (Kf) is used to represent the product of the hydraulic conductivity and the area. Taking all of the preceding factors into consideration, Eq. [2] can be modified to give the rate of fluid movement (Jv), which in this case represents the GFR, as follows:

where Pc is the average glomerular capillary pressure, Pb is the pressure in Bowman's space, and ^cis the average CoP of the blood along the glomerular capillaries. As discussed later, CoP rises in the glomerular capillaries because of the fluid lost during filtration.

The directions and usual magnitudes of these three forces—the glomerular capillary pressure, the hydrostatic pressure of Bowman's space, and the capillary CoP—are shown diagrammatically in Fig. 3. The values

FIGURE 3 Balance of hydrostatic and osmotic pressures governing glomerular filtration. The hydrostatic pressure in the glomerular capillaries is considerably higher than in other systemic capillaries and falls only modestly along the length of the glomerular capillary. on the other hand, the plasma CoP rises along the glomerular capillary because of the filtration of fluid into Bowman's space. The pressure in Bowman's space is about 20 mm Hg; and this pressure is required to propel the urine along the nephron. The net filtration pressure is given as the difference between the capillary hydrostatic pressure and the sum of the capillary CoP and the hydrostatic pressure in Bowman's space.

FIGURE 3 Balance of hydrostatic and osmotic pressures governing glomerular filtration. The hydrostatic pressure in the glomerular capillaries is considerably higher than in other systemic capillaries and falls only modestly along the length of the glomerular capillary. on the other hand, the plasma CoP rises along the glomerular capillary because of the filtration of fluid into Bowman's space. The pressure in Bowman's space is about 20 mm Hg; and this pressure is required to propel the urine along the nephron. The net filtration pressure is given as the difference between the capillary hydrostatic pressure and the sum of the capillary CoP and the hydrostatic pressure in Bowman's space.

presented in this figure are not known directly in the human, but have been extrapolated from measured values in experimental animals. These estimates are used to illustrate the relative magnitudes of the driving forces producing glomerular filtration. Under normal conditions, the glomerular capillary hydrostatic pressure averages 60 mm Hg and falls little along the length of a capillary loop because of the large cross-sectional area available for flow. The hydrostatic pressure in Bowman's space, which is estimated to be 20 mm Hg, opposes this hydrostatic pressure. The colloid osmotic pressure of the plasma rises along the glomerular capillary because as the protein-free fluid is filtered, the protein concentration in the plasma remaining in the capillaries rises. Thus, the average COP in the glomerular capillaries is higher than that of systemic plasma, and is estimated to be about 28 mm Hg. As shown in Fig. 3, the net filtration pressure is the algebraic sum of these three separate forces and is approximately 12 mm Hg. The factors that influence each of these individual forces, and thus govern the net filtration pressure, are considered in the following sections.

Glomerular Capillary Pressure

As discussed earlier, the relative resistances of the afferent and efferent arterioles determine glomerular capillary pressure. These resistances are in turn determined by hormonal and neural input to the smooth muscles of these arterioles. As illustrated by Fig. 4, when the resistance of the afferent arteriole is greater than that of the efferent arteriole, a greater fraction of the total arteriovenous pressure drop occurs across the afferent arteriole, and thus the glomerular capillary pressure is lower. Conversely, when the efferent arter-iolar resistance is greater than that of the afferent, the glomerular capillary pressure is higher than normal. In some circumstances, the changes in the two resistances are offsetting so that glomerular pressure remains constant while blood flow decreases, as they do whenever the afferent and efferent arteriolar resistances increase about equally. It might be expected that when glomerular pressure rises due to an increase in the resistance of the efferent arteriole (as shown in the third panel of Fig. 4) the GFR would increase, but the increased resistance also decreases RPF. The decreased flow rate causes the FF and thus the glomerular capillary COP to rise. In other words, ultrafiltration from the smaller blood flow produces a larger increase in the concentration of the remaining proteins. As discussed later, the rise in COP may result in a lower net effective filtration pressure, despite the increased capillary hydrostatic pressure.

Afferent Efferent Rpf Gfr

FIGURE 4 Effects of changes in the relative resistances of the afferent and efferent arteriolar resistances. For simplicity, it is assumed that the total resistance of the two arterioles together is constant in the three situations. Thus, in each panel, the total pressure drop from the renal artery (90 mm Hg) to the peritubular capillaries (30 mm Hg) and the RBF remains constant. When afferent and efferent arteriolar resistances are nearly equal (upper panel), the pressure drop across each arteriole is 30 mm Hg. If the afferent arteriolar resistance is greater (middle panel), the glomerular capillary pressure is lower. If the efferent arteriolar resistance is greater (lower panel), the glomerular capillary pressure is increased.

FIGURE 4 Effects of changes in the relative resistances of the afferent and efferent arteriolar resistances. For simplicity, it is assumed that the total resistance of the two arterioles together is constant in the three situations. Thus, in each panel, the total pressure drop from the renal artery (90 mm Hg) to the peritubular capillaries (30 mm Hg) and the RBF remains constant. When afferent and efferent arteriolar resistances are nearly equal (upper panel), the pressure drop across each arteriole is 30 mm Hg. If the afferent arteriolar resistance is greater (middle panel), the glomerular capillary pressure is lower. If the efferent arteriolar resistance is greater (lower panel), the glomerular capillary pressure is increased.

Hydrostatic Pressure in Bowman's Space

The hydrostatic pressure of 20 mm Hg in Bowman's space is required to drive the flow of urine along the nephron against the resistance presented by the long, thin, tubular segments leading eventually to the ducts of Bellini. These ducts empty into the renal calyces, which are approximately at atmospheric pressure. Based on Poiseuille's law (see Chapter 10), the pressure in Bowman's space will be proportional to the resistance of the nephron and the rate of urine flow in the nephron. When urine flow is increased, for example, by diuretics, or when there is an obstruction of the lower urinary tract, the pressure in Bowman's space rises. This increase in pressure in Bowman's space decreases the net filtration pressure, and thus decreases the GFR.

The length and inside diameter of each nephron segment is relatively invariant and, therefore, its resistance to flow is constant. However, pathologic processes may affect the outflow resistance. This is frequently seen in elderly men with benign prostatic hypertrophy. The resulting urethral outflow resistance often leads to incomplete emptying of the bladder and to increased pressure in the bladder, which is transmitted up the urinary tract. This results in a higher pressure in the calyces and the necessity for a higher pressure in Bowman's space to drive urine flow. Partial or complete obstruction of the lower urinary tract by kidney stones or tumors also leads to increases in the pressure in Bowman's space. These conditions produce a decrease in the net filtration pressure and, thus, a decrease in GFR.

Colloid Osmotic Pressure in the Glomerular Capillaries

As protein-free fluid is filtered from the glomerular capillary plasma, the protein concentration of the remaining plasma rises, producing a corresponding rise in the CoP, as illustrated in Fig. 5. When RPF falls to a greater degree than the GFR, the CoP rises more rapidly along the glomerular capillaries. In the extreme, the COP rises sufficiently to reduce the net filtration pressure to zero in the distal end of the glomerular capillary, as shown in Fig. 5 (lower panel). The resulting balance of forces is referred to as filtration equilibrium, and it results in the loss of filtration in the distal portion of the capillary. The rise of CoP in the glomerular capillary is inversely related to the FF as shown in Fig. 6. Because in humans FF is normally about 20%, filtration equilibrium probably never occurs under physiologic conditions. However, if renal blood flow is reduced by proportional changes in the resistances of the afferent and efferent arterioles so that the net hydrostatic pressure driving force remains the same, FF rises. Figure 6 indicates that filtration equilibrium would be attained at any filtration fraction in excess of about 37%. It is for this reason that the RPF has an important influence on the net filtration pressure and hence on GFR.

Absorption of Fluid in Peritubular Capillaries

In the peritubular capillaries, the situation is much different. Because of the resistance of the efferent arteriole, the hydrostatic pressure in the peritubular capillaries is much lower than in other capillary networks in the body. Conversely, because of the filtration of protein-free fluid from the glomerular capillaries, the plasma entering the peritubular capillaries has a much higher CoP. Both the low hydrostatic pressure and the high CoP of the peritubular capillary plasma favor the reabsorption of fluid from the interstitial spaces surrounding the nephrons, which is the primary function of the peritubular capillary network.

Reabsorption by the peritubular capillaries can be altered by changes in either the hydrostatic or the CoP

FIGURE 5 Effect of glomerular capillary plasma flow on net filtration pressure. At normal flow rates (upper graph), the COP of the plasma in the glomerular capillaries rises as fluid is filtered from the capillaries. If the plasma flow rate is slowed (lower graph) by increased vascular resistance, the plasma COP in the capillaries rises more steeply and may become equal to the net hydrostatic pressure, which is the difference between the glomerular capillary pressure (Pc = 60 mm Hg) and the pressure in Bowman's space (Pb = 20 mm Hg). In this situation, called filtration equilibrium, the net filtration pressure becomes zero before the end of the glomerular capillary network, and no filtration occurs beyond that point.

FIGURE 5 Effect of glomerular capillary plasma flow on net filtration pressure. At normal flow rates (upper graph), the COP of the plasma in the glomerular capillaries rises as fluid is filtered from the capillaries. If the plasma flow rate is slowed (lower graph) by increased vascular resistance, the plasma COP in the capillaries rises more steeply and may become equal to the net hydrostatic pressure, which is the difference between the glomerular capillary pressure (Pc = 60 mm Hg) and the pressure in Bowman's space (Pb = 20 mm Hg). In this situation, called filtration equilibrium, the net filtration pressure becomes zero before the end of the glomerular capillary network, and no filtration occurs beyond that point.

across them. For example, if the COP of the peritubular capillary plasma is reduced because of a lower FF, fluid will not be reabsorbed from the interstitium as rapidly, and hydrostatic pressure will rise in the interstitium until it is sufficient to drive uptake into the capillaries at the same rate at which it is reabsorbed by the nephrons. However, this interstitial pressure increases only when the interstitial volume has increased. The absorption of fluid by peritubular capillaries is considered further in Chapters 26 and 29 in connection with the regulation of salt and water reabsorption by the proximal nephron.

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