Tubular handling of water

1. Normally, 180 L of fluid is filtered through the glomeruli each day, while the average daily urine
volume is about 1 L. The same load of solute can be excreted per 24 h in a urine volume of 500 mL
with a concentration of 1400 mOsm/kg or in a volume of 23.3 L with a concentration of 30 mOsm/kg.
At least 87% of the filtered water is reabsorbed, even when the urine volume is 23 L; and the
reabsorption of the remainder of the filtered water can be varied without affecting total solute
excretion. Therefore, when the urine is concentrated, water is retained in excess of solute; and when it
is dilute, water is lost from the body in excess of solute. Both facts have great importance in the
regulation of the osmolality of the body fluids.
 A key regulator of water output is vasopressin (ADH) acting on the collecting ducts.
Gain or Loss
of Water in
Excess of
Solute (L/d)
Urine
Concentration
(mOsm/kg H2O)
Urine
Volume
(L/d)
Percentage of
Filtered Water
Reabsorbed
GFR
(mL/min
)
……2902.498.7125
Urine isotonic to
plasma
1.9 gain14000.599.7125
Vasopressin
(maximal
antidiuresis)
20.9 loss3023.387.1125
No vasopressin
("complete" diabetes
insipidus)

2. I. Proximal Convoluted Tubule
In the Proximal convoluted tubule, water reabsorption is always
linked to Na+ reabsorption, and the mechanism is described as
isosmotic.
 The routes of solute and water reabsorption are shown by the
following steps:
1. Na+ enters the cell across the luminal membrane. Because the luminal
membrane is very permeable to water, water follows the solute to maintain
isosmolarity.
2. Na+ is pumped out of the cell by the Na+-K+ ATPase, which is located in
the peritubular or basolateral membranes. ("Basal" refers to the cell
membranes facing the peritubular capillary [2a], and "lateral" refers to the
cell membranes facing the lateral intercellular spaces between cells [2b].)
As Na+ is pumped out of the cell, water again follows passively.
3. The lateral intercellular space is an important route for reabsorption of
solute and water. Isosmotic fluid accumulates in these spaces between the
proximal tubule cells, as described in step 2. (Electron micrographs show
the spaces actually widening when there is increased proximal tubule
reabsorption.) This isosmotic fluid in the spaces is then acted upon by
Starling forces in the peritubular capillary.
The major Starling force driving reabsorption is the high oncotic pressure
(πc) of peritubular capillary blood. Recall that glomerular filtration

3. • Important Notes:
 The entire proximal tubule reabsorbs 65% of the filtered water. The
tight coupling between Na+ and water reabsorption is called
isosmotic reabsorption.
 This bulk reabsorption of Na+ and water (the major constituents of
ECF) is critically important for maintaining ECF volume.
 The proximal tubule is the site of glomerulotubular balance, a
mechanism for coupling reabsorption to the GFR.
 Aquaporin-1 is localized to both the basolateral and apical
membrane of the proximal tubules and its presence allows water to
move rapidly out of the tubule along the osmotic gradients set up by
active transport of solutes, and isotonicity is maintained.

4.  Changes in ECF Volume
A. ECF volume expansion produces a decrease in fractional
reabsorption in the proximal tubule. When ECF volume is
increased (e.g., by infusion of isotonic NaCl), the plasma
protein concentration is decreased by dilution, and the
capillary hydrostatic pressure (Pc) is increased. For the
peritubular capillaries, these changes result in a decrease
in πc and an increase in Pc. Both of these changes in
Starling forces in the peritubular capillary produce a
decrease in fractional reabsorption of isosmotic fluid in
the proximal tubule. A portion of the fluid that would have
been reabsorbed instead leaks back into the lumen of the
tubule (across the tight junction) and is excreted. This
alteration of glomerulotubular balance is one of several
mechanisms that aids in the excretion of excess NaCl and
water when there is ECF volume expansion.
Glomerulotubular balance ensures that normally 65%
of the filtered Na+ and water is reabsorbed in the
proximal tubule. This balance is maintained because
the glomerulus communicates with the proximal
tubule via changes in the πc of peritubular capillary
blood. However, glomerulotubular balance can be
altered by changes in ECF volume. The mechanisms
underlying these changes can be explained by the
Starling forces in the peritubular capillaries
B. ECF volume contraction produces an increase in fractional
reabsorption in the proximal tubule . When ECF volume is
decreased (e.g., diarrhea or vomiting), the plasma protein
concentration increases (is concentrated) and the capillary
hydrostatic pressure decreases. As a result, there is an increase in
πc and a decrease in Pc of peritubular capillary blood. These
changes in Starling forces in the peritubular capillaries produce
an increase in fractional reabsorption of isosmotic fluid. This
alteration of glomerulotubular balance is a logical protective
mechanism, as the kidneys are trying to restore ECF volume by
reabsorbing more solute and water than usual.
In addition to the Starling forces, a second mechanism contributes to
the increased proximal tubule reabsorption that occurs in ECF volume
contraction. A decrease in ECF volume causes a decrease in blood
volume and arterial pressure that activates the renin-angiotensin-
aldosterone system. Angiotensin II stimulates Na+-H+ exchange in
the proximal tubule, and thereby stimulates reabsorption of Na+,
HCO3-, and water. Because the angiotensin II mechanism specifically

5. II. Loop of Henle
A. Thin Descending Limb and Thin Ascending Limb
The thin descending limb is permeable to water and small solutes such as NaCl and urea. In
countercurrent multiplication, water moves out of the thin descending limb, solutes move into the thin
descending limb, and the tubular fluid becomes progressively hyperosmotic as it flows down the
descending limb. The thin ascending limb also is permeable to NaCl, but it is impermeable to water.
During countercurrent multiplication, solute moves out of the thin ascending limb without water, and the
tubular fluid becomes progressively hyposmotic as it flows up the ascending limb.
B. Thick Ascending Limb
The cells of the thick ascending limb are impermeable to water, clearly an unusual characteristic since
virtually all other cell membranes are highly permeable to water. As a consequence of the water
impermeability, NaCl is reabsorbed by the thick ascending limb, but water is not reabsorbed along with it.
For this reason, the thick ascending limb also is called the diluting segment: Solute is reabsorbed, but
water remains behind, diluting the tubular fluid.
C. DISTAL TUBULE AND COLLECTING DUCT
The early distal tubule is impermeable to water. Thus, it reabsorbs solute but leaves water behind, which
then dilutes the tubular fluid. For this reason, the early distal tubule is called the cortical diluting segment
.
 A key regulator of water output in the distal tubule and the collecting duct is vasopressin (ADH) acting
on H2O channels
( aquaporine-2) present in Principal cells . This is called facultative water reabsorption.

6.  Summary Of Tubular Handling Of Water
Hormone ActionsCellular MechanismMajor FunctionSegment/Cell Type
...................Passive diffusion
Isosmotic reabsorption
of solute and water
Proximal Tubule
ADH stimulates Na+-
K+-2Cl- cotransport
Na+-K+-2Cl-
cotransport
Reabsorption of NaCl
without water
Dilution of tubular
fluid
Thick Ascending Limb
of The Loop of the
Henle
PTH stimulates Ca2+
reabsorption
Na+-Cl- cotransport
Reabsorption of NaCl
without water
Early Distal Tubule
ADH stimulates water
reabsorption
Water channels
( aquaporine-2)
Variable water
reabsorption
Late Distal Tubule and
Collecting Ducts (principal
cells)