The establishment of the medullary interstitial osmotic gradient in the current model occurs through a process called countercurrent multiplication. During this process, solute (primarily NaCl) is reabsorbed without water from the ascending limb of Henle’s loop into the surrounding medullary interstitium. This leads to a decrease in osmolality in the tubular fluid and an increase in osmolality in the interstitium at this point. The increased osmolality of the interstitium then causes water to be reabsorbed from the descending limb of Henle’s loop, thereby increasing the tubular fluid osmolality in this segment. Thus, at any point along the loop of Henle, the fluid in the ascending limb has a lower osmolality than the fluid in the adjacent descending limb. This osmotic difference is known as the single effect. Due to the countercurrent flow of tubular fluid in the descending and ascending limbs, this single effect can be multiplied, resulting in an osmotic gradient within the medullary interstitium. At the tip of the papilla, the osmolality is 1200 mOsm/kg H2O compared to 300 mOsm/kg H2O at the corticomedullary junction.

Figure 35.7 provides a schematic representation of the processes involved in excreting both dilute urine (water diuresis) and concentrated urine (antidiuresis). Three key concepts underlie these processes:

1. Dilute urine is achieved through the AVP-dependent reabsorption of water from the collecting duct.
2. NaCl reabsorption from the ascending limb of Henle’s loop dilutes the tubular fluid and simultaneously generates a high concentration of NaCl in the medullary interstitium (up to 600 mmol/L at the tip of the papilla). This high concentration drives water reabsorption from the collecting duct.
3. Urea accumulates in the medullary interstitium (up to 600 mmol/L), enabling the kidneys to excrete urine with a similarly high urea concentration. This facilitates the excretion of large amounts of urea with relatively little water.

Now, let's consider how the kidneys excrete dilute urine (water diuresis) when AVP levels are low or zero:

1. The fluid entering the descending thin limb of the loop of Henle from the proximal tubule is isosmotic with respect to plasma. This reflects the isosmotic nature of solute and water reabsorption in the proximal tubule.
2. Water is reabsorbed from the thin descending limb of Henle’s loop, with the majority of reabsorption occurring in the outer medulla. This limits the amount of water added to the deepest part of the inner medullary interstitial space, preserving the hyperosmolality of this region of the medulla.

(Source: Adapted from Sands JM et al. Urine concentration and dilution. In: Brenner and Rector’s The Kidney. 9th ed. Philadelphia: Saunders; 2012.)
In the current model the medullary interstitial osmotic gradient is established by a process termed countercurrent multiplication. By this process, solute (principally NaCl) is reabsorbed without water from the ascending limb of Henle’s loop into the surrounding medullary interstitium. This decreases the osmolality in the tubular fluid and raises the osmolality of the interstitium at this point. The increased osmolality of the interstitium then causes water to be reabsorbed from the descending limb of Henle’s loop, thus increasing the tubular fluid osmolality in this segment. Thus at any point along the loop of Henle the fluid in the ascending limb has an osmolality less than fluid in the adjacent descending limb. This osmotic difference was termed the single effect. Because of the countercurrent flow of tubular fluid in the descending (fluid flowing into the medulla) and ascending (fluid flow out of the medulla) limbs, this single effect could be multiplied, resulting in an osmotic gradient within the medullary interstitium, where the tip of the papilla has an osmolality of 1200 mOsm/kg H2O compared to 300 mOsm/kg H2O at the corticomedullary junction.
Fig. 35.7 schematically depicts the processes for excreting a dilute urine (water diuresis) as well as a concentrated urine (antidiuresis). Three key concepts underlie these processes: 1.
Urine is concentrated by AVP-dependent reabsorption of water from the collecting duct.
2.
Reabsorption of NaCl from the ascending limb of Henle’s loop dilutes the tubular fluid and at the same time generates a high [NaCl] in the medullary interstitium (up to 600 mmol/L at the tip of the papilla), which then drives water reabsorption from the collecting duct.
3.
Urea accumulates in the medullary interstitium (up to 600 mmol/L), which allows the kidneys to excrete urine with the same high urea concentration. This allows large amounts of urea to be excreted with relatively little water. First, how the kidneys excrete dilute urine (water diure sis) when AVP levels are low or zero is considered. The following numbers refer to those encircled in
Fig. 35.7A + AVP: 140 − AVP: 140 + AVP: 290 Cortex + AVP: 1200 + AVP: 1200 − AVP: 600 − AVP: 50 • Fig. 35.6 Tubular fluid osmolality along the nephron in the presence (+AVP) and in the absence (−AVP) of arginine vasopressin. See text for details. (Adapted from Sands JM et al. Urine concentration and dilution. In: Brenner and Rector’s The Kidney. 9th ed. Philadelphia: Saunders; 2012.) 1.
Fluid entering the descending thin limb of the loop of Henle from the proximal tubule is isosmotic with respect to plasma. This reflects the essentially isosmotic nature of solute and water reabsorption in the proximal tubule (see ). (NOTE: Water is reabsorbed from the segments of the proximal tubule via AQP1.) 2.
Water is reabsorbed from the thin descending limb of Henle’s loop. Most of this water is reabsorbed in the outer medulla, thereby limiting the amount of water added to the deepest part of the inner medullary interstitial space and thus preserving the hyperosmolality of this region of the medulla. (NOTE: Water is reabsorbed via AQP1.) 3.