SUMMARY
Two major nitrogenous waste products, urea and ammonium(NH4+), are produced in humans when proteins are oxidized, and in this manuscript their excretions are examined from two perspectives. First, the specific physiology of each nitrogenous waste is reviewed and the current dogmas summarized. Second, their excretions are considered in the context of integrative physiology, i.e. the need to ensure that the urine composition is appropriate to minimize the risk of kidney stone formation. After the latter analysis, weak links in our understanding of the overall physiology become apparent and a conundrum is defined. The conundrum for the excretion of urea focuses on the fact that urea is not an effective osmole in the medullary-collecting duct when vasopressin acts. As a result, it appears that urinary urea cannot prevent a large decline in the urine flow rate and thereby minimize the risk of forming kidney stones in electrolyte-poor urine. The conundrum for the excretion of NH4+ is: high rates of NH4+excretion require a low urine pH, yet a pH ∼6.0 must be maintained in order to reduce the risk of precipitating uric acid in the urine. Possible ways of resolving these conundrums require novel physiological interpretations.
