**2.1.1 Counter-current multiplier mechanism in the loop of Henle**  The countercurrent mechanism in the loop of Henle is illustrated in figure 2: Na+ H2O

Fig. 2. Countercurrent multiplier process in the loop of Henle, in creating osmotic gradient and urine concentration (adapted from [1]). Note Na+ absorption from the ascending limb, and passive diffusion of H2O from the descending limb.

For the loop of Henle shown in figure 2, as a start, it is assumed that the loop of Henle is filled with a fluid with a concentration of 300 mOsm/L. First, the sodium transport from the lumen of the ascending limb to the interstitium, which instantaneously equilibrates with the descending limb. The osmolality in the ascending limb decreases. Because of the higher osmolar interstitium, the fluid in the descending limb increases in osmolality as water is shifted out by passive osmosis. However, the hair-pin structure causes the flow of hyperosmolar fluid in the descending limb to enter the ascending limb. The steps are repeated over and over, with the effect that the process gradually traps sodium in the medulla and multiplies the concentration gradient until the osmolality of the fluid in the loop of Henle and the interstitium reaches 1200 to 1400 mOsm/L.

### **2.1.2 Concentration of urine in the medullary interstitium**

As discussed, tubular fluid entering descending loop of Henle is iso-osmotic to plasma. This tubular fluid becomes progressively concentrated towards the bend. In the ascending loop, it becomes less concentrated as it rises to the cortex (decreasing from over 1000 to 100).

Within the medullary interstitium, other mechanisms co-operate to concentrate the urine. Under the influence of ADH (anti-diuretic hormone) blood flow through the vasa recta is decreased, and osmotic equilibration of blood in the vasa recta with medullary interstitium is enhanced. Solutes such as sodium, chloride and urea enter the descending blood vessels as they pass through the progressively higher osmolality of the interstitium and H2O leaves the vessels. In the ascending limb, the opposite events take place and H2O is reabsorbed into the blood vessels.

In brief, the anatomical configuration of the vasa recta minimises but does not prevent solute loss from the medulla via the blood supply. Because of diffusion of H2O from the tubular lumen into the interstitium, there is equilibrium between fluid in the collecting tubule and that in the interstitium. The withdrawal of H2O from the collecting tubule leads to increase in the concentration of urea in the collecting tubule causing a high gradient across the duct membrane, which favours diffusion of urea from the collecting duct into the interstitium. From there, urea diffuses into the descending limb of the loop of Henle and is recirculated into the ascending limb and back into the collecting duct, contributing to the high urea concentration in the medulla in the concentrating kidney.

Fig. 3. Schematic diagram showing both the countercurrent multiplier process in the loop of Henle and the vasa recta producing the osmotic gradient. Depicted in the figure are: (i) the passive and active exchanges of water and ions, (ii) concentrations of tubular urine and peritubular fluid in millimetres per litre, (iii) percentages of glomerular filtrate within the tubule at various levels.

In summary (please refer to figure 3),

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repeated over and over, with the effect that the process gradually traps sodium in the medulla and multiplies the concentration gradient until the osmolality of the fluid in the

As discussed, tubular fluid entering descending loop of Henle is iso-osmotic to plasma. This tubular fluid becomes progressively concentrated towards the bend. In the ascending loop, it becomes less concentrated as it rises to the cortex (decreasing from over 1000 to 100). Within the medullary interstitium, other mechanisms co-operate to concentrate the urine. Under the influence of ADH (anti-diuretic hormone) blood flow through the vasa recta is decreased, and osmotic equilibration of blood in the vasa recta with medullary interstitium is enhanced. Solutes such as sodium, chloride and urea enter the descending blood vessels as they pass through the progressively higher osmolality of the interstitium and H2O leaves the vessels. In the ascending limb, the opposite events take place and H2O is reabsorbed into

In brief, the anatomical configuration of the vasa recta minimises but does not prevent solute loss from the medulla via the blood supply. Because of diffusion of H2O from the tubular lumen into the interstitium, there is equilibrium between fluid in the collecting tubule and that in the interstitium. The withdrawal of H2O from the collecting tubule leads to increase in the concentration of urea in the collecting tubule causing a high gradient across the duct membrane, which favours diffusion of urea from the collecting duct into the interstitium. From there, urea diffuses into the descending limb of the loop of Henle and is recirculated into the ascending limb and back into the collecting duct, contributing to the

Fig. 3. Schematic diagram showing both the countercurrent multiplier process in the loop of Henle and the vasa recta producing the osmotic gradient. Depicted in the figure are: (i) the passive and active exchanges of water and ions, (ii) concentrations of tubular urine and peritubular fluid in millimetres per litre, (iii) percentages of glomerular filtrate within the

loop of Henle and the interstitium reaches 1200 to 1400 mOsm/L.

high urea concentration in the medulla in the concentrating kidney.

**2.1.2 Concentration of urine in the medullary interstitium** 

the blood vessels.

tubule at various levels.

