Fig. 2
Gradient medullary concentration conceptual mechanism. Normal physiology: NaCl is actively reabsorbed across the thick ascending limb by the NKCC2 cotransporter. Water (H2O) is reabsorbed across the descending limb segment by AQP1 water channels. Water is reabsorbed across the collecting duct by AQP2 on the apical membrane in the presence of ADH, and AQP2,3,4 on the basolateral membrane. Urea (and other osmoles) are concentrated within the collecting duct lumen (by water reabsorption) until it reaches the terminal inner medulla segment, where urea is reabsorbed by the urea transporters (UTA1, UTA3). The inner medulla contains several urea recycling pathways that constantly contribute to maintain its high interstitial urea concentration (not show). Medullary Washout: In that absence of high interstitial urea concentration, the passive reabsorption of solutes and water despite the presence of ADH is limited, leading to high volume of iso-osmolar urine