The kidney concentrates urine by driving water via osmosis from the tubule lumen into a hyperosmotic interstitium
The kidney generates dilute urine by pumping salts out of the lumen of tubule segments that are relatively impermeable to water. What is left behind is tubule fluid that is hypo-osmotic (dilute) with respect to the blood.
How does the kidney generate concentrated urine? One approach could be to pump water actively out of the tubule lumen. However, water pumps do not exist (see pp. 127–128). Instead, the kidney uses osmosis as the driving force to concentrate the contents of the tubule lumen. The kidney generates the osmotic gradient by creating a hyperosmotic interstitial fluid in a confined compartment, the renal medulla. The final step for making a hyperosmotic urine—controlled by regulated water permeability—is allowing the lumen of the medullary collecting duct (MCD) to equilibrate with the hyperosmotic interstitium, resulting in a concentrated urine.
Although net absorption of H2O occurs all along the nephron, not all segments alter the osmolality of the tubule fluid. The proximal tubule, regardless of the final osmolality of the urine, reabsorbs two thirds of the filtered fluid isosmotically (i.e., the fluid reabsorbed has nearly the same osmolality as plasma). The loop of Henle and the distal convoluted tubule (DCT) reabsorb salt in excess of water, so that the tubule fluid leaving the DCT is hypo-osmotic. Whether the final urine is dilute or concentrated depends on whether water reabsorption occurs in more distal segments: the initial and cortical collecting tubules (ICT and CCT) and the outer and inner medullary collecting ducts (OMCD and IMCD). Arginine vasopressin (AVP)—also called antidiuretic hormone (ADH)—regulates the variable fraction of water reabsorption in these four nephron segments. Figure 13-9 shows the structure of AVP.
Tubule fluid is isosmotic in the proximal tubule, becomes dilute in the loop of Henle, and then either remains dilute or becomes concentrated by the end of the collecting duct
Figure 38-1 shows two examples of how tubule-fluid osmolality (expressed as the ratio TFOsm/POsm) changes along the nephron. The first is a case of water restriction, in which the kidneys maximally concentrate the urine and excrete a minimal volume of water (antidiuresis). The second is a case of ingestion of excess water, in which the kidneys produce a large volume of dilute urine (water diuresis). In both cases, the tubule fluid does not change in osmolality along the proximal tubule, and it becomes hypotonic to plasma by the end of the thick ascending limb of the loop of Henle (TAL), also known as the diluting segment (see pp. 757–758). The fluid exiting the DCT is hypo-osmotic with respect to plasma, regardless of the final urine osmolality (see Fig. 38-1).
FIGURE 38-1 Relative osmolality of the tubule fluid along the nephron. Plotted on the y-axis is the ratio of the osmolality of the tubule fluid (TFOsm) to the osmolality of the plasma (POsm); plotted on the x-axis is a representation of distance along the nephron. The red record is the profile of relative osmolality (i.e., TFOsm/POsm) for water restriction, whereas the blue record is the profile for high water intake. (Data from Gottschalk CW: Micropuncture studies of tubular function in the mammalian kidney. Physiologist 4:33–55, 1961.)
Under conditions of restricted water intake or hydropenia, elevated levels of AVP increase the water permeability of the nephron from the ICT to the end of the IMCD. As a result, the osmolality of the tubule fluid increases along the ICT (see Fig. 38-1, red curve), achieving the osmolality of the cortical interstitium—which is the same as the osmolality of plasma (~290 mOsm)—by the end of this nephron segment (also the end of the classic distal tubule in Fig. 38-1). No additional increase in osmolality occurs along the CCT, because the tubule fluid is already in osmotic equilibrium with the surrounding cortical interstitium. However, in the MCDs, the luminal osmolality rises sharply as the tubule fluid equilibrates with the surrounding medullary interstitium, which becomes increasingly more hyperosmotic from the corticomedullary junction to the papillary tip. Eventually the tubule fluid reaches osmolalities that are as much as four times higher than the plasma. Thus, the MCDs are responsible for concentrating the final urine.
In summary, the two key elements in producing a concentrated urine are (1) the hyperosmotic medullary interstitium that provides the osmotic gradient, and (2) the AVP that raises the water permeability of the distal nephron. How the kidney generates this interstitial hyperosmolality is discussed in the next subchapter, and the role of AVP is discussed in the last subchapter.
Under conditions of water loading, depressed AVP levels cause the water permeability of the distal nephron to remain low. However, the continued reabsorption of NaCl along the distal nephron effectively separates salt from water and leaves a relatively hypo-osmotic fluid behind in the tubule lumen. Thus, the tubule fluid becomes increasingly hypo-osmotic from the DCT throughout the remainder of the nephron (see Fig. 38-1, blue curve).