Lecture 19: The Medullary Osmotic Gradient, Urine Formation and Acid-Base Balance
1. The Medullary Osmotic Gradient
1a. Formation of the Gradient: The Loop of Henle
The medullary osmotic gradient is the osmotic gradient that exists in the peritubular fluid from
the outer regions of the kidney (i.e., the border between the renal medulla and the renal cortex)
into the inner regions of the renal medulla. The osmolarity of the peritubular fluid at the
cortex/medulla boundary is 300 mOsm (milliosmoles). It steadily increases from 300 mOsm to
1400 mOsm in the inner core of the kidney. This osmotic gradient is what allows the kidney to
produce a concentrated urine (i.e., to produce a urine with an osmolarity that is greater than 300
mOsm; which is the osmolarity of blood).
The medullary osmotic gradient is established by the Loop of Henle which has different
permeability to water and ions between the ascending and descending sections of the loop. The
descending limb is permeable to H O, but impermeable to various ions (such as Na+, K+ or Cl-).
The ascending limb is the opposite; permeable to ions and impermeable to water.
The seven-step series of slides at the beginning of this lecture illustrate a scheme in which the
osmotic gradient is formed. Note that this gradient is formed during development and is
maintained by the same mechanisms throughout life. The scenario starts with a kidney without
an osmotic gradient: so, in both limbs, and in the peritubular fluid, the osmolarity is 300 mOsm
(the osmolarity of the blood plasma). The slides go through a series of steps in which ions are
pumped out of the ascending loop and water moves out of the descending loop. Fluid flows into
the loop of Henle from the proximal tubule (always with an osmolarity of 300 mOsm) and leaves
the loop of Henle, entering the distal tubule with an osmolarity of 100 mOsm. 2
The various steps in this scheme are not important from the point-of-view of exam questions.
This scheme was for illustrative purposes. The key points to note about the medullary osmotic
1) The osmolarity in the descending limb of the Loop of Henle is always the same as the
osmolarity in the peritubular fluid.
2) The osmolarity in the descending limb of the Loop of Henle and that in the peritubular fluid
are always 200 mOsm greater than the osmolarity in the ascending limb of the Loop of Henle.
3) Fluid enters the Loop of Henle with an osmolarity of 300 mOsm.
4) Fluid leaves the Loop of Henle and enters the distal tubule with an osmolarity of 100 mOsm
(i.e., it is hypo-osmotic to the peritubular fluid) surrounding the distal tubule.
5) The medullary osmotic gradient (i.e., the osmolarity in the peritubular fluid) goes from 300
mOsm at the “top” (the border of the cortex and medulla) to 1400 mOsm at the “bottom” (the
inner core of the kidney).
At any given level in the kidney (as you proceed from the outer regions to the inner core) there is
a difference of 200 mOsm between the fluid in the descending and ascending limbs of the Loop
of Henle. However, there is an 1100 mOsm difference in the osmolarity between the fluid at the
top (the border of the cortex and medulla) and the bottom (the inner core). The Loop of Henle is
called a countercurrent multiplier because it has converted this “horizontal” difference of 200
mOsm between the ascending and descending limbs into a 1100 mOsm difference in the
peritubular fluid between the outer and inner regions of the kidney.
1b. Maintenance of the Gradient: The Vasa Recta
The vasa recta is the capillary network that surrounds the Loop of Henle. Although it is a
capillary bed, it is conceptually easiest to think of it as a vessel that flows down into the core of
the kidney and then back up again (in the same way that the Loop of Henle does). The vasa recta
functions as a countercurrent exchanger. It helps to maintain the medullary osmotic gradient. It
removes some of the fluid and solutes that were transported across the Loop of Henle. This
prevents water and solutes from pooling in the peritubular fluid. 3
Blood enters the vasa recta with the regular osmolarity of blood plasma, 300 mOsm. As it moves
downward it gains solutes and loses water (due to the surrounding increase in osmolarity). By the
time the blood has reached the lowest part of the vasa recta it has an osmolarity of 1375 mOsm.
As blood moves upward (toward the outer regions of the kidney) it gains water and loses solutes
(again as a consequence of the upward lowering of the osmolarity of the peritubular fluid).
However, the osmolarity of the blood in the vasa recta does not fall back to the original 300
mOsm (the osmolarity that it entered with). Rather, blood leaves the vasa recta with an
osmolarity of 325-350 mOsm. There are several reasons for this. First, ions are being reabsorbed
as blood flows downward in the vasa recta. Second, urea is reabsorbed. Third, the presence of
plasma proteins means there is a colloid osmotic pressure. The vasa recta has functioned to
remove water (and solutes and urea) that were filtered in the kidney tubules and moved from the
Loop of Henle into the peritubular fluid. The gain of solutes and urea (coupled with the colloid
osmotic pressure of the plasma proteins) serves as the driving force to move water into the vasa
recta by osmosis. This prevents water from pooling in the peritubular fluid and allows it to return
to the circulatory system in general. 4
1c. Urea Handling
As fluid moves down the descending limb of the Loop of Henle urea moves into the tubular
fluid. As fluid moves up the ascending limb there is no movement of urea out of the Loop of
Henle. There is also no movement of urea out of the distal tubule or collecting tube. However,
once fluid flows down the collecting duct there is the movement of urea out of the collecting
duct into the peritubular fluid. This is drive by a concentration gradient as urea is concentrated in
the collecting duct as fluid is reabsorbed. Urea then moves into the vasa recta (driven by a
concentration gradient) as blood flows downward in the vasa recta. As blood flows up through
the vasa recta some of the urea moves back out into the peritubular fluid (it is in essence
recycled) while some of the urea is returned from the vasa recta back to the general circulation.
The presence of this urea in the vasa recta helps (as mentioned above) to serve as a driving force
for the osmotic movement of water from the peritubular fluid into the vasa recta. 5
2. Urine Formation
As hypo-osmotic fluid (100 mOsm) leaves the Loop of Henle and enters the distal tubule, the
water within this fluid can be reabsorbed by the distal tubule and the collecting duct. However,
this can only occur if they are permeable to water, and this permeability is hormonally regulated.
If the collecting duct is not permeable to water, the resulting urine will be very dilute (low
osmolarity) and of relatively high volume. If the collecting duct is permeable to water then the
resulting urine will be more concentrated (higher osmolarity) and the volume