In Panel 4, steady state has been reached, meaning that no additional solute is being added to the system. Thus the incoming and outgoing fluid are iso-osmotic. The overall effect of this process has been to establish high longitudinal gradients, whereas the transmem-brane gradient is comparatively small.

In Panel 5, which represents the actual loop of Henle, these same events occur but with important differences. First, the limbs are separated by an interstitium, rather than a single membrane. The ascending limb is impermeable to water but reabsorbs solutes into the interstitium. The descending limb, in contrast, is permeable to water but not to solutes. As a result, the concentration of fluid in the descending limb rapidly equilibrates with the concentration in the interstitium. Another difference is that the fluid leaving the loop of Henle is hypo-osmotic to the fluid coming in, reflecting the fact that a small amount of solute is continuously lost from the interstitium, preventing a steady state from being reached.

In Panel 6, the collecting duct is added to the model and runs parallel to the loop of Henle. In the presence of ADH (see Plate 3-17), the collecting duct becomes permeable to water, which is reabsorbed from the collecting duct lumen into the interstitium. This process is entirely passive, depending on the osmotic pressure of the interstitium. Thus the maximum concentration in the medullary interstitium determines the maximum concentration of the final urine.

The addition of the collecting duct also illustrates how urea contributes to formation of the interstitial concentration gradient, especially in the inner medulla. In the presence of ADH, the inner medullary collecting duct becomes permeable to urea. As water is reabsorbed from the cortical and outer medullary collecting ducts, urea becomes highly concentrated within the tubular fluid. Once the inner medulla is reached, urea flows out of the collecting duct and accumulates in the interstitium, contributing to the concentration gradient. Thus, as further described on Plate 3-17, ADH not only promotes water reabsorption from the collecting duct, but it also activates mechanisms that strengthen the concentration gradient, thereby ensuring water reabsorption is maximal.