URINE CONCENTRATION AND DILUTION AND
OVERVIEW OF WATER HANDLING
In normal kidneys
more than 180 liters of fluid are filtered into the nephrons each day, but nearly
all of it is reabsorbed into the peritubular circulation.
Tight junctions form a watertight seal between tubular epithelial cells
throughout most of the nephron. Thus, water reabsorption occurs primarily
through a transcellular route, requiring specialized channels known as
aquaporins (AQPs) in both the apical and basolateral compartments of the plasma
membrane.
Because aquaporins are channels, and not pumps, the reabsorption of water
is a passive process, dependent on osmotic pressure from solutes concentrated
in the sur-rounding interstitium.
In each tubular segment, the reabsorption of water can be greater than,
less than, or equal to the reabsorption of solutes. As a result, urine becomes
more concentrated as it passes through some segments and more diluted as it
passes through others. The final concentration of excreted urine is determined
in the collecting duct, which reflects not only the fact that this segment is
located at the end of the nephron, but also that it reabsorbs water at a
variable rate based on hormonal input.
Proximal Tubule. The proximal tubule reabsorbs two thirds
of the filtered water. There is a large gradient for water reabsorption from
this segment because of the high rate of solute reabsorption. As solute begins
to accumulate in the interstitium, water crosses from the tubular lumen to the
interstitium through AQP-1 channels in both the apical and basolateral plasma
membranes.
Because water reabsorption from the proximal tubule is directly dependent
on the rate of solute reabsorption, and because AQP-1 channels are always
present, the filtrate remains iso-osmotic to plasma as it passes through this
segment.
Descending Thin Limb. The descending thin limb reabsorbs an
additional fraction of the filtered water. There is a large gradient for water
reabsorption from this segment even though it reabsorbs only a small amount of
solute. This gradient reflects the high rates of reabsorption from the thick
ascending limb, which is adjacent to the ascending thin limb and adds solute to
its surrounding interstitium. As in the proximal tubule, water crosses the
tubular epithelium through AQP-1 channels.
As described on Plate 1-24, the descending thin limbs of short-looped
(cortical) and long-looped (juxtamedullary) nephrons differ not only in length
but also in cellular composition. In short-looped nephrons, the descending thin
limb consists of type I cells, whereas in long-looped nephrons, it consists of
type II cells in the outer medulla and type III cells in the inner medulla.
Type I and II cells are more permeable to water than type III cells. Thus, in
long-looped nephrons, water reabsorption from the descending thin limb
decreases near the inner medulla.
Because water reabsorption exceeds solute reabsorption in the descending
thin limb, tubular fluid becomes more concentrated. This process, however, is
not under tight control. As a result, the descending thin limb does not have a
major role in determining the final concentration of excreted urine.
Ascending Thin Limb and Thick Ascending Limb. The ascending
thin limb (found only in long-looped nephrons) and thick ascending limb do not
contain aquaporin
channels and are therefore impermeable to water. The extensive reabsorption of
solutes from these segments, however, dilutes tubular fluid and establishes a
concentration gradient for water reabsorption from adjacent segments, such as
the descending thin limb and collecting duct.
Because the dilution process in the ascending limb is not under tight
control, this segment does not have a major role in determining the final
concentration of excreted urine.
Distal Convoluted Tubule. Like the thick ascending limb,
the distal convoluted tubule reabsorbs solutes but is impermeable to water.
Therefore, this segment dilutes tubular fluid but, for the same reasons as the
thick ascending limb, does not have a major role in determining the final
concentration of excreted urine. Connecting Tubule and Collecting Duct. The
connecting tubule and collecting duct reabsorb a variable volume of filtered
water, which determines the final concentration of excreted urine.
By reabsorbing more or less free water from the urine, these segments can
dilute or concentrate plasma, helping to offset the changes in osmolality that
result from inconsistent intake of water and salt over the course of each day.
The hormone that controls water reabsorption is known as antidiuretic hormone
(ADH, or vasopressin).
In response to increases in plasma osmolality, ADH is released from the
posterior pituitary. In the connecting tubule and collecting duct this hormone
causes vesicles containing AQP-2 channels to fuse with the apical plasma membrane
of principal cells. Since AQP-4 channels are always present in the basolateral
plasma membrane of these cells, the insertion of AQP-2 channels is sufficient to
cause a dramatic increase in water reabsorption.
Because of the countercurrent multiplier system, there is a strong
gradient for water reabsorption from the collecting duct that increases in
strength toward the papillae. Because water reabsorption is a passive process,
the maximum achievable urine concentration is equal to the peak osmolality in
the medullary interstitium, about 1200 mOsm/kg H2O. Such
concentrations are only achievable in long-looped nephrons, however, because
short-looped nephrons do not reach the inner medulla.
In addition to its direct effects on aquaporin channels, ADH has several
actions that enhance the countercurrent system and thus increase the gradient
for water reabsorption. In particular, this hormone increases solute
reabsorption from the thick ascending limb, constricts vasa recta capillaries
to reduce solute washout, and increases urea reabsorption from the inner
medullary collecting duct. Some of the urea that drifts toward the cortex is
secreted back into more proximal segments of the renal tubules so that it can
be deposited again in the inner medulla.
In response to decreases in plasma osmolality, ADH release is inhibited,
and AQP-2 channels are consequently endocytosed. The lack of water reabsorption
from the collecting duct, coupled with the ongoing reabsorption of sodium from
this segment, dilutes the urine to a minimum osmolality of 50 mOsm/kg H2O.
Over the course of several hours, variable input from the ADH system
leads to accumulation of urine in the bladder that has an osmolality between 50
and 1200 mOsm/kg H2O. In patients with abnormal serum sodium
concentrations, measurement of the urine osmolality can indicate whether the
defect lies in the urine concentration process or elsewhere.
