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).