606
U N I T 7
Kidney and Urinary Tract Function
In addition to
reabsorbing
solutes and water, cells
in the proximal tubule also
secrete
organic cations and
anions into the urine filtrate (see Figs. 24-6 and 24-8).
Many of these organic anions and cations are end prod-
ucts of metabolism (e.g., urate, oxalate) that circulate
in the plasma. The proximal tubule also secretes exog-
enous organic compounds such as penicillin, aspirin,
and morphine. Many of these compounds are bound to
plasma proteins and not freely filtered in the glomerulus.
Therefore, excretion by filtration alone eliminates only a
small portion of these potentially toxic substances from
the body.
Loop of Henle.
The loop of Henle plays an important
role in controlling the concentration of the urine. It does
this by establishing a high concentration of osmotically
active particles in the interstitium surrounding the med-
ullary collecting tubules where the antidiuretic hormone
exerts its effects.
The loop of Henle is divided into three segments: the
thin descending segment, the thin ascending segment,
and the thick ascending segment. Taken as a whole,
the loop of Henle always reabsorbs more sodium and
chloride than water. This is in contrast to the proximal
tubule, which reabsorbs sodium and water in equal pro-
portions. The thin descending limb is highly permeable
to water and moderately permeable to urea, sodium,
and other ions. As the urine filtrate moves down the
descending limb, water moves out of the filtrate into the
surrounding interstitium. Thus, the osmolality of the fil-
trate reaches its highest point at the elbow of the loop of
Henle. In contrast to the descending limb, the ascending
limb of the loop of Henle is impermeable to water. In
this segment, solutes move out, but water cannot fol-
low and remains in the filtrate. As a result, the tubular
filtrate becomes more and more dilute, often reaching
an osmolality of 100 mOsm/kg H
2
O as it enters the dis-
tal convoluted tubule, compared with the 285 mOsm/kg
H
2
O in plasma. This allows for elimination of free water
from the body. For this reason, the segment of the tubule
is often called the
diluting segment.
The thick segment of the loop of Henle begins in the
ascending limb where the epithelial cells become thick-
ened. As with the thin ascending limb, this segment is
impermeable to water. The thick segment contains a
Na
+
/K
+
/2Cl
–
cotransport system (Fig. 24-9). This system
involves the cotransport of positively charged Na
+
and K
+
accompanied by two negatively chargedCl
–
. The gradient
for the operation of this cotransport system is provided
by the basolateral membrane sodium–potassium ATPase
pump, which maintains a low intracellular sodium con-
centration. Approximately 20% to 25% of the filtered
load of sodium, potassium, and chloride is reabsorbed
in the thick loop of Henle. Movement of these ions out
of the tubule leads to the development of a transmem-
brane potential that favors the passive reabsorption
of small divalent cations such as calcium and magne-
sium. The thick ascending loop of Henle is the site of
the powerful “loop” diuretics (e.g., furosemide [Lasix]),
which exert their action by inhibiting the Na
+
/K
+
/2Cl
–
cotransporters.
Distal and Collecting Tubules.
Like the thick ascend-
ing loop of Henle, the distal convoluted tubule is
relatively impermeable to water, and reabsorption of
sodium chloride from this segment further dilutes the
tubular fluid. Sodium reabsorption occurs through a
Na
+
/Cl
–
cotransport mechanism. Approximately 5%
of filtered sodium chloride is reabsorbed in this sec-
tion of the tubule. Unlike the thick ascending loop of
Henle, neither Ca
++
nor Mg
++
is passively absorbed
in this segment of the tubule. Instead, Ca
++
is actively
reabsorbed in a process that is largely regulated by
parathyroid hormone and possibly by vitamin D. The
thiazide diuretics, which are widely used to treat disor-
ders such as hypertension, exert their action by block-
ing sodium reabsorption in this segment of the renal
tubules, while enhancing the active reabsorption of cal-
cium into the blood via the calcium-sodium exchange
transport mechanism. For this reason, thiazide diuretics
have proved useful in reducing the incidence of calcium
kidney stones in persons with hypercalciuria (discussed
in Chapter 25).
The late distal tubule and the cortical collecting
tubule constitute the site where aldosterone exerts its
action on sodium reabsorption and potassium secretion
and elimination. Although responsible for only 2% to
5% of sodium chloride reabsorption, this site is largely
responsible for determining the final sodium concentra-
tion of the urine. The late distal tubule with the cortical
collecting tubule also is the major site for regulation of
potassium excretion by the kidney. When the body is
confronted with a potassium excess, as occurs with a
diet high in potassium content, the amount of potassium
secreted into the urine filtrate at this site may exceed the
amount filtered in the glomerulus.
Interstitial
fluid
Blood
Peritubular
capillary
Tubular
lumen
Tubular
fluid
Na +
Na +
K +
K +
K +
ATP
Thick ascending loop
of Henle cell
2Cl –
Cl –
Luminal cell membrane
Basolateral
cell membrane
FIGURE 24-9.
Sodium, chloride, and potassium reabsorption
in the thick segment of the loop of Henle.
