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Urea Recycling

  • Urea is an osmotically active waste product of protein metabolism and during periods of urine concentration can contribute nearly half the osmoles of the corticopapillary osmotic gradient. Ultimately, the reason why concentrations of urea are higher in the renal medullary interstitium is that the highest levels of tubular urea resorption occur in the medullary sections of the collecting duct. However, the amount of urea resorption and thus the magnitude of urea's contribution to the corticopapillary osmotic gradient is regulated by Antidiuretic Hormone (ADH).
Tubular Urea Handling
  • General Features
    • Urea transport in the nephron is always driven by passive diffusion; however, different sections of the nephron display differential permeability to the molecule. Throughout the nephron more water is resorbed than urea and thus urea becomes progressively concentrated as it moves distally through the tubule. Thus, the highest concentrations of tubular urea are found in the most distal sections of the nephron.
  • Proximal Tubule
    • The proximal tubule is mildly permeable to urea and nearly half the filtered urea is resorbed in this segment. However, as mentioned, because more water is proportionally resorbed, tubular urea becomes concentrated.
  • Thin Henle
    • The thin Henle is relatively permeable to urea and as it dives into the renal papilla the concentration of urea in the surrounding interstitium is typically greater than within the tubule. Therefore, urea is generally secreted into the thin Henle. The amount of urea secretion depends on the size of the corticopapillary urea gradient. When the corticopapillary urea gradient is large, sizable amounts of urea secretion occur in the thin Henle. When the papillary interstitial urea concentration is low, urea secretion into the thin Henle is minimal.
  • Thick Henle and Distal Convoluted Tubule
    • These segments are highly impermeable to urea and given the large amounts of water resorption in these segments, urea becomes increasingly concentrated within the tubule.
  • Collecting Ducts
    • The medullary portion of the collecting ducts display the highest levels of permeability to urea. Ultimately, the reason why urea is more concentrated in the renal medulla, and thus contributes to the corticopapillary osmotic gradient, is two fold: 1) The distal portion of the collecting ducts is highly urea-permeable, 2) Tubular urea is the most concentrated in this segment and thus there is the largest driving force for passive urea resorption in the distal collecting ducts.
    • However, the permeability of the medullary collecting ducts can significantly increase in the presence of ADH. In the presence of ADH, specific urea transporters are placed on the tubular epithelial cell membrane in this segment, rendering it more urea-permeable.
Regulation of Urea Resorption
  • Overview
    • The primary locus at which urea transport is regulated is the medullary section of the collecting ducts. The ultimate amount of urea resorbed in the collecting ducts is dependent on the permeability and the tubular concentration of urea in this segment. Both of these factors are affected by the presence of ADH.
  • ADH Absent
    • When ADH is absent the volume of water in the tubule is relatively high in the distal collecting duct, thus diluting the concentration of tubular urea and making the driving force for passive resorption of urea low. In addition, in the absence of ADH the medullary collecting tubule permeability to urea is less. Together, these factors combine to reduce urea resorption in the distal collecting duct and lessen the contribution of urea to the corticopapillary osmotic gradient.
  • ADH Present
    • In the presence of ADH, water volume is avidly resorbed in the distal tubule and thus urea becomes highly concentrated, generating a large driving force passive urea resorption. As discussed above, the presence of ADH also renders the medullary collecting ducts highly permeable to urea. Together, these factors result in large amounts of urea being resorbed from the medullary collecting ducts and thus contributing to the corticopapillary osmotic gradient.
Urea Recycling
  • In order to increase the magnitude of the medullary urea gradient, the kidneys recirculate the urea within the renal interstitium. As the concentration of urea in the renal medulla increases, the driving force for passive urea secretion into the medullary sections of the thin Henle also rises. This serves to increase the urea concentration within downstream distal sections of the tubule, especially the medullary collecting ducts. Higher concentrations of urea in the distal collecting ducts simply increases the driving force for passive resorption of urea into the medullary renal interstitium. As urea cycles in this way, termed "Urea Recycling", its corticopapillary concentration gradient increases in size.