Glomerular Dynamics

Fluid exchange across the glomerular capillaries is a passive process driven by hemodynamic and oncotic forces which are controlled primarily by changes in vascular smooth muscle tone. As shown in the following equation, GFR is dependent on the net effective filtration pressure (EFP) across the glomerular capillary wall and the filtration coefficient (Kf). The filtration coefficient represents the product of the hydraulic conductivity of the filtering capillaries and the total surface area available for filtration:

The main determinants of the effective filtration pressure are the glomerular pressure (Pg), which is the principal driving force, the pressure in Bowman's space (PB), and the colloid osmotic pressure in the glomerular capillaries (7rg). Glomerular pressure is counteracted by PB and 7rg, thus leading to a relatively small effective filtration pressure compared to the glomerular pressure. As shown in Fig. 1, colloid osmotic pressure (7rg) within the glomerular capillaries increases progressively along the length of the capillaries as a consequence of the filtration of a protein free ultrafiltrate into Bowman's space. This causes a progressive decrease in effective filtration pressure along the length of the capillaries [1, 17, 23].

FIGURE 1. Description of forces governing filtration at glomerular capillaries and reabsorption into the peritubular capillaries and ways that diuretics can alter filtered load of sodium. Increases in filtered load: renal vasodilation, increases in glomerular pressure (Pg), decreases in colloid osmotic pressure (IIg), and increases in filtration coefficient (Kt). Decreases in filtered load: renal vasoconstriction, increases in proximal tubule pressure (PB), decreases in glomerular pressure (Pg), and decreases in filtration coefficient (Kf).

FIGURE 1. Description of forces governing filtration at glomerular capillaries and reabsorption into the peritubular capillaries and ways that diuretics can alter filtered load of sodium. Increases in filtered load: renal vasodilation, increases in glomerular pressure (Pg), decreases in colloid osmotic pressure (IIg), and increases in filtration coefficient (Kt). Decreases in filtered load: renal vasoconstriction, increases in proximal tubule pressure (PB), decreases in glomerular pressure (Pg), and decreases in filtration coefficient (Kf).

Indirect measurements from humans and data extrapolated from experimental animals suggest that glomerular pressure is 55 to 60 mm Hg and proximal tubular pressure is 18 to 22 mm Hg in the normal human kidney. Plasma colloid osmotic pressure in humans averages 25 mm Hg. The increase in colloid osmotic pressure along the glomerular capillaries depends primarily on the filtration fraction; for filtration fractions usually observed in humans (0.18 to 0.20), efferent arteriolar colloid osmotic pressure reaches values of 35 to 37 mm Hg. Accordingly, EFP varies from a high of 15 mm Hg at the afferent end of the glomerular capillaries to only a few mm Hg at the terminal end of the capillary network. When renal vascular tone is elevated substantially and the filtration fraction is high, the protein concentration may increase so much that the resulting colloid osmotic pressure at the terminal segments of the glomerular capillaries reaches a value sufficient to neutralize the transglomerular hydrostatic pressure gradient. If "filtration equilibrium" is achieved, no further filtration of fluid occurs in the more terminal segments of the glomerular capillaries.

Under these conditions, part of the glomerular filtering surface area is not used but may be recruited during increases in plasma flow [1, 17].

Vasopressin and other hormonal systems regulate plasma osmolality and sodium concentration within relatively narrow limits; therefore, increases in filtered sodium load occur primarily as a consequence of increases in GFR usually caused by increases in glomerular pressure which increase effective filtration pressure. In addition, the rate of rise in colloid osmotic pressure along the glomerular capillaries can be reduced by increases in blood flow which lead to reductions in filtration fraction. Although plasma protein concentration is reduced in some pathological processes such as the nephrotic syndrome, it is generally well regulated. Nevertheless, procedures that lead to reductions in plasma protein concentration such as volume expansion with protein free solutions can increase EFP markedly due to reductions in plasma colloid osmotic pressure.

Pressure in Bowman's space is determined by the filtered load, proximal reabsorption rate and tubular fluid flow out of the proximal tubular segment. Thus, inhibition of tubular reabsorption rate, in particular at the level of the proximal tubule or loop of Henle, causes substantial increases in proximal tubule pressure which reduces effective filtration pressure and GFR. Accordingly, diuretics that increase proximal tubule pressure may lower GFR even when there are no changes in renal vascular resistance. Indeed, changes in GFR are not a reliable reflection of changes in renal plasma flow when diuretics are administered because of the variable changes in pressure in Bowman's space.

Increases in Kf can also increase GFR; however, the effects of increases in Kf tend to be self-limiting because of the eventual achievement of filtration equilibrium. Kf is thought to be regulated, in part, by the vasoactive tone of the mesangial cells, and many agents have been shown to alter mesangial cell contractile activity. In particular, angiotensin II, endothelin, nitric oxide, and several arachidonic acid metabolites, such as thromboxane, exert powerful actions on mesangial cells and have been shown to reduce Kf. The exact means by which changes in mesangial cell contractility influence Kf has not been clearly delineated. Their effects on Kf not withstanding, most agents that increase GFR do so by either increasing glomerular pressure or increasing blood flow or both. These changes occur most effectively by vasodilation of the preglomerular vasculature. If there is also vasodilation of the efferent arterioles, renal blood flow will increase more than GFR, leading to reductions in the filtration fraction. It is important to emphasize that decreases in filtration fraction, such as are generally seen during treatment with angiotensin-converting enzyme (ACE) inhibitors and other vasodilator agents are caused by combined vasodilation of both preglomerular and postglomerular arterioles. Indeed, exclusive dilation of the efferent arterioles is rare and leads to profound decreases in glomerular pressure and near cessation of filtration [1].

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