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First published online May 13, 2004
Journal of Experimental Biology 207, 1985-1991 (2004)
Published by The Company of Biologists 2004
doi: 10.1242/jeb.01019

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Dogmas and controversies in the handling of nitrogenous wastes: Excretion of nitrogenous wastes in human subjects

Kamel S. Kamel, Surinder Cheema-Dhadli, Mohammad A. Shafiee and Mitchell L. Halperin^*

Renal Division, St Michael's Hospital, University of Toronto, Toronto, Ontario, M5B 1A6 Canada

View larger version (20K): [in a new window]   Fig. 1. Urea excretion and the avoidance of oliguria in a subject with a normal protein intake and a deficit of Na+, Cl– and water. The barrel-shaped structure represents the inner MCD; AQP-2 is shown as a clear oval and the urea transporter is shown as a shaded oval in its luminal membrane. The issues in the conundrum are shown to the left of the vertical broken line and features for its resolution are shown to the right of this line. To resolve the conundrum, the hypothesis is that urea can become an effective urine osmole in urine with a low ionic strength. This view is supported by the fact that the concentration of urea is higher in the luminal urine than the interstitial compartment (papilla; Table 2). VP, vasopressin; MCD, medullary collecting duct.

View larger version (16K): [in a new window]   Fig. 2. Urine pH and the risk of kidney stone formation. A urine pH that is close to 6.0 minimizes the risk of forming certain kidney stones. The urine pH that is most dangerous with respect to the formation of uric acid stones, is a value significantly lower than 6.0. In contrast, a urine pH significantly greater than 6.0 must also be avoided to minimize the risk of calcium phosphate (CaHPO4) stone formation.

View larger version (13K): [in a new window]   Fig. 3. Physiology of NH4+ excretion and acid–base balance. There are two major steps as shown on the left. First, NH4+ + HCO3– are produced when glutamine is metabolized in the proximal convoluted tubule (PCT). Second, NH4+ is transferred via the medullary interstitial compartment to the lumen of the medullary collecting duct (MCD) because of a high medullary concentration of NH3 and a low luminal NH3 concentration, the result of distal H+ secretion. Sajo et al. (1981), however, demonstrated that most of the NH4+ destined for urinary excretion was added before entering the MCD in rats with chronic metabolic acidosis. This conundrum could be resolved if the major function of events in the inner medulla could be to adjust the urine pH to 6.0 without compromising the excretion of NH4+ (see Fig. 4).

View larger version (14K): [in a new window]   Fig. 4. Transfer of NH4+ from the loop of Henle (LOH) to the medullary collecting duct (MCD). The medullary thick ascending limb (mTAL) of the LOH is shown on the far left and the MCD is shown on the right side of the figure. Reabsorption of NH4+ from the mTAL adds NH3 to the interstitial compartment (the H+ to convert it to NH4+ arrives at site 4). Recycling of NH4+ in the LOH raise the concentration of NH4+ in the medullary interstitium (site 1). NH4+ diffuses through the renal medullary interstitial compartment because its concentration is high and that of NH3 is too low for rapid rates of diffusion (site 2). NH4+ crosses the cell membranes of the MCD using two different NH4+/H+ exchangers, one on each of these cells (sites 3 and 4). The combination of NH4+ entry into and H+ exit from the lumen of the MCD (site 4) adjusts the urine pH upward (towards 6.0) despite continuing H+ secretion by the H+-ATPase (site 5). The net result is a final urine pH that is close to 6.0 and a somewhat higher rate of NH4+ excretion.