The Kidneys and Regulation of Water and Inorganic Ions
gland and known as
Vasopressin stimulates the insertion into the luminal
membrane of a particular group of aquaporin water channels
made by the collecting duct cells. Thus, in the presence of a
high plasma concentration of vasopressin, the water permea-
bility of the collecting ducts increases dramatically. Therefore,
water reabsorption is maximal, and the ﬁ nal urine volume is
small—less than 1 percent of the ﬁ ltered water.
Without vasopressin, the water permeability of the col-
lecting ducts is extremely low, and very little water is reab-
sorbed from these sites. Therefore, a large volume of water
remains behind in the tubule to be excreted in the urine. This
increased urine excretion resulting from low vasopressin is
simply means a large urine
ﬂ ow from any cause. In a subsequent section, we will describe
the control of vasopressin secretion.
which is distinct from the
other kind of diabetes (diabetes mellitus, or “sugar diabetes”),
illustrates what happens when the vasopressin system malfunc-
tions. Diabetes insipidus is caused by the failure of the posterior
pituitary to release vasopressin
central diabetes insipidus
the inability of the kidney to respond to vasopressin
genic diabetes insipidus
Regardless of the type of diabetes
insipidus, the permeability to water of the collecting ducts is
low even if the patient is dehydrated. A constant water diuresis
is present that can be as much as 25 L/day.
Note that in water diuresis, there is an increased urine
ﬂ ow, but not an increased solute excretion. In all other cases
of diuresis, termed
the increased urine
ﬂ ow is the result of a primary increase in solute excretion. For
example, failure of normal sodium reabsorption causes both
increased sodium excretion and increased water excretion,
because, as we have seen, water reabsorption is dependent
on solute reabsorption. Another example of osmotic diuresis
occurs in people with uncontrolled
case, the glucose that escapes reabsorption because of the
huge ﬁ ltered load retains water in the lumen, causing it to be
excreted along with the glucose.
To summarize, any loss of solute in the urine must be
accompanied by water loss (osmotic diuresis), but the reverse
is not true. That is, water diuresis is not necessarily accompa-
nied by equivalent solute loss.
Urine Concentration: The Countercurrent
Before reading this section you should review, by looking
up in the glossary, several terms presented in Chapter 4—
In the section just concluded, we described how the kid-
neys produce a small volume of urine when the plasma con-
centration of vasopressin is high. Under these conditions, the
urine is concentrated (hyperosmotic) relative to plasma. This
section describes the mechanisms by which this hyperosmo-
larity is achieved.
The ability of the kidneys to produce hyperosmotic urine
is a major determinant of the ability to survive with limited
water intake. The human kidney can produce a maximal uri-
nary concentration of 1400 mOsmol/L, almost ﬁ ve times the
osmolarity of plasma, which is typically in the range of 285 to
300 mOsmol/L (rounded off to 300 mOsmol/L for conve-
nience). The typical daily excretion of urea, sulfate, phosphate,
other waste products, and ions amounts to approximately 600
mOsmol. Therefore, the minimal volume of urine water in
which this mass of solute can be dissolved equals
= 0.444 L/day
This volume of urine is known as the
obligatory water loss.
The loss of this minimal volume of urine contributes to dehy-
dration when water intake is zero.
Urinary concentration takes place as tubular ﬂ uid ﬂ ows
collecting ducts. The interstitial ﬂ
surrounding these ducts is very hyperosmotic. In the presence
of vasopressin, water diffuses out of the ducts into the inter-
stitial ﬂ uid of the medulla and then enters the blood vessels of
the medulla to be carried away.
The key question is: how does the medullary interstitial
ﬂ uid become hyperosmotic? The answer involves several inter-
related factors: 1. The countercurrent anatomy of the loop of
Henle of juxtamedullary nephrons; 2. Reabsorption of NaCl in
the ascending limbs of those loops of Henle; 3. Impermeability
of those ascending limbs to water; 4. Trapping of urea in the
medulla; and 5. Hairpin loops of vasa recta to minimize wash-
out of the hyperosmotic medulla. Recall that Henle’s loop
forms a hairpin-like loop between the proximal tubule and the
distal convoluted tubule (see Figure 14–2). The ﬂ
the loop from the proximal tubule ﬂ ows down the descending
limb, turns the corner, and then ﬂ ows up the ascending limb.
The opposing ﬂ ows in the two limbs is termed a countercur-
rent ﬂ ow, and the entire loop functions as a
to create a hyperosmotic medullary inter-
Because the proximal tubule always reabsorbs sodium and
water in the same proportions, the ﬂ uid entering the descend-
ing limb of the loop from the proximal tubule has the same
osmolarity as plasma—300 mOsmol/L. For the moment, let’s
skip the descending limb because the events in it can only be
understood in the context of what the
limb is doing.
Along the entire length of the ascending limb, sodium and
chloride are reabsorbed from the lumen into the medullary
). In the upper (thick) portion
of the ascending limb, this reabsorption is achieved by trans-
porters that actively cotransport sodium and chloride. Such
transporters are not present in the lower (thin) portion of the
ascending limb, so the reabsorption there is a passive process.
For simplicity in the explanation of the countercurrent mul-
tiplier, we shall treat the entire ascending limb as a homoge-
neous structure that actively reabsorbs sodium and chloride.
the ascending limb is relatively imper-
meable to water,
so that little water follows the salt. The net
result is that the interstitial ﬂ uid of the medulla becomes
hyperosmotic compared to the ﬂ uid in the ascending limb
because solute is reabsorbed without water.