Plate 3-2

CLEARANCE

Solutes that cannot be metabolized, such as sodium and potassium, enter the kidneys in arterial blood and then leave in venous blood and urine. At a steady state, such solutes are not retained within the kidneys. Thus the rate at which a non-metabolized solute x enters the kidneys is equal to the rate at which it leaves, as expressed in the following equation:

RPF = renal plasma flow

[RA]_x = concentration of x in renal arterial blood

[RV]_x = concentration of x in renal venous blood

= rate of urine production

[U]_x = concentration of x in urine

(Because RPF >>> both renal arterial and renal venous flow can be considered equal to RPF, even though the former is slightly greater than the latter.)

By rearrangement,

With this formulation, it is evident that the rate at which x is extracted from renal blood is equal to the rate at which it is excreted in urine.

The “clearance” of substance x, also known as C(x), is equal to the hypothetical subset of RPF from which x is completely removed (“cleared”) as it passes through the kidneys. For this subset, [RV]_x is equal to zero. Thus by substituting C(x) for RPF in the above equation:

Since [RA]_x is always equal to the systemic plasma concentration of x ([P]_x), one can make further substitutions and rearrange to solve for C(x):

It is often useful to compare clearances of different substances because these values offer basic information about how they are handled in the nephrons. Specifically, substances that undergo net secretion into the renal tubules will have higher clearance values than those substances that undergo only filtration, whereas those that undergo net reabsorption will have lower clearance values (see Plate 3-6).

RENAL PLASMA FLOW

The clearance principle can be used to determine the rate of renal plasma flow. As stated above,

If the entire RPF is “cleared” of x, meaning all of the x that enters the kidneys is excreted in urine, [RV]_x equals zero in the above equation, such that:

By simple substitution and rearrangement,

Nearly all of the paraaminohippurate (PAH) that enters the kidneys is transferred from blood to urine through a combination of filtration and secretion. Thus [RV]PAH is equal to almost zero under normal circumstances. As a result, C(PAH) approximates RPF. A small amount of PAH does reach the renal vein, however, because of the tiny fraction of blood that is shunted past the filtration and secretion apparatus. As a result, C(PAH) slightly underestimates RPF, with the discrepancy growing larger in conditions that increase the shunted volume.

Renal Blood Flow. Once RPF is known, a simple equation permits conversion to renal blood flow (RBF):

RPF = RBF×(1−hematocrit)

RBF is typically equal to about 20% to 25% of the total cardiac output, or about 1 to 1.5 L/min. Since the kidneys together account for less than 0.5% of total body weight, they are very richly perfused compared with other organs. Such perfusion, which far exceeds their metabolic needs, permits extensive filtration and fine-tuning of plasma contents. The overwhelming majority of blood flow is directed toward the cortex, which contains the glomerular capillaries.

The kidneys have numerous autoregulation mechanisms that maintain renal blood flow nearly constant over a wide range of systemic arterial pressures. These mechanisms operate by adjusting the renal vascular resistance, primarily in the cortical radiate (interlobular) arteries, afferent arterioles, efferent arterioles, and peritubular capillaries. These vessels are under the control of numerous hormones and sympathetic input, as described on Plate 3-18.