The importance of renal ammonia metabolism to whole body acid-base balance: a reanalysis of the pathophysiology of renal tubular acidosis.

Traditionally, the renal collecting duct has been assigned the dual role of (1) secreting protons derived from dietary metabolism to form luminal NH4+ and titratable acid and (2) generating new HCO3-. This view has recently been challenged. According to current concepts, whole body proton balance is maintained predominantly by the lungs which excrete protons derived from dietary metabolism as the acid anhydride CO2. In the process of excreting CO2, HCO3- is also lost from the body. It is the function of the kidney to generate new HCO3- to replenish this loss. The major site of new HCO3- generation is the proximal tubule rather than the collecting duct. New HCO3- is generated predominantly via the metabolism of organic anions, i.e. alpha-ketoglutarate, citrate, lactate, fatty acids. In the process of generating alpha-ketoglutarate from glutamine, NH4+ is formed. Under normal acid-base conditions, 50% of the NH4+ produced is excreted in the urine, and the remaining 50% is delivered to the renal veins. NH4+ delivered to the renal veins consumes HCO3- during ureagenesis. In the discussion which follows, these new concepts are reviewed and applied to an analysis of the pathophysiology of renal tubular acidosis.