Human Physiology, 14th edition (2016)

Physiology of the Kidneys 599

It follows that if a substance in the plasma is filtered (enters

the filtrate in Bowman’s capsule) but is neither reabsorbed nor

secreted, its excretion rate must equal its filtration rate. This

fact is used to measure the volume of blood plasma filtered per

minute by the kidneys, called the glomerular filtration rate

(GFR). Measurement of the GFR is very important in assess-

ing the health of the kidneys.

Tubular Secretion of Drugs

Many molecules foreign to the body—known generally as xeno-

biotics and including toxins and drugs—are eliminated in the

urine more rapidly than would be possible by just glomerular

filtration. This implies that they are secreted by membrane car-

riers that somehow recognize them as foreign to the body. Con-

sidering that membrane carriers are specific and that there are so

many possible xenobiotic molecules, how is this accomplished?

Scientists have discovered that there is a large number of

transporters whose primary function is the elimination of xenobi-

otics. The major group of transport proteins involved in this elim-

ination is the organic anion transporter (OAT) family. These

carriers mediate a sodium-independent transport that secretes

some endogenous compounds—such as steroids and bile acids—

as well as numerous xenobiotics, including many therapeutic and

abused drugs. Relatively small xenobiotic molecules (including

penicillin and PAH, discussed shortly) are eliminated by the type

of OAT in the kidneys. These transporters are located in the baso-

lateral membrane of the proximal tubule and function to secrete

their transported molecules into the filtrate of the proximal tubule.

Larger xenobiotics are eliminated by the type of OATs produced

in the liver that transport xenobiotics into the bile (chapter 18,

section 18.5).

There are also organic cation transporters (OCTs) that

secrete particular xenobiotics such as metformin, a drug used to

treat type 2 diabetes mellitus (chapter 19, section 19.4). Genetic

studies indicate that OCT carriers vary significantly between

people, suggesting that these can contribute to individual vari-

ability in the elimination of this drug—and thereby cause differ-

ences in the responsiveness to the drug.

substances in the blood leaving the kidneys (in the renal vein)
is lower than their concentrations in the blood entering the kid-
neys (in the renal artery).

Transport Process Affecting

Renal Clearance

Renal clearance refers to the ability of the kidneys to remove
molecules from the blood plasma by excreting them in the
urine. Molecules and ions dissolved in the plasma can be
filtered through the glomerular capillaries and enter the glo-
merular capsules. Then, those that are not reabsorbed will
be eliminated in the urine; they will be “cleared” from the
blood.
The process of filtration, a type of bulk transport through cap-
illaries, promotes renal clearance. The process of reabsorption—
involving membrane transport by means of carrier proteins—moves
particular molecules and ions from the filtrate into the blood, and
thus reduces the renal clearance of these molecules from the blood.
There is another process that affects renal clearance, a mem-
brane transport process called secretion ( fig. 17.21 ). In terms of its
direction of transport, secretion is the opposite of reabsorption—
secreted molecules and ions move out of the peritubular capillaries
into the interstitial fluid, and then are transported across the baso-
lateral membrane of the tubular epithelial cells and into the lumen
of the nephron tubule. Molecules that are both filtered and secreted
are thus eliminated in the urine more rapidly (are cleared from the
blood more rapidly) than molecules that are not secreted. In sum-
mary, the process of reabsorption decreases renal clearance, while
the process of secretion increases renal clearance.
By examining figure  17.21 , you can see that the rate at
which a substance in the plasma is excreted in the urine is
equal to the rate at which it enters the filtrate (by filtration and
secretion) minus the rate at which it is reabsorbed from the
filtrate. This is shown in the following equation:

Excretion rate 5 (filtration rate 1 secretion rate) 2

reabsorption rate

Figure 17.21 Secretion is the reverse of reabsorption. The term secretion refers to the active transport of substances
from the peritubular capillaries into the tubular fluid. This transport is opposite in direction to that which occurs in reabsorption. In
the actual nephron, most of the reabsorption and secretion occurs across the walls of the proximal tubule, although some important
transport processes occur in later regions of the nephron tubule.

Secretion Reabsorption Filtration

Excretion