FIGURE 4.

Overall model of renal epithelial ammonia transport under basal conditions. Numbers in blue show ammonia amounts relative to total urinary ammonia (100%). Under basal conditions, relatively little urinary ammonia derives from glomerular filtration. The proximal tubule generates ammonia. This occurs primarily via metabolism of glutamine, with generation of 2 NH₄⁺ and 2 HCO₃⁻ from each glutamine completely metabolized. NH₄⁺ is secreted preferentially into the luminal fluid through a mechanism that appears to involve NHE3-mediated Na⁺/NH₄⁺ exchange. Between the end of the proximal tubule that is accessible to micropuncture and the bend of the loop of Henle, there is ammonia secretion; this likely involves components of secretion in the proximal tubule straight tubule and in the thin descending limb of the loop of Henle. There is sufficient ammonia secretion such that ammonia delivery to the bend of the loop of Henle averages 160% of total urinary ammonia. In the ascending limb of the loop of Henle, there is ammonia reabsorption; this primarily occurs in the thick ascending limb of the loop of Henle via NKCC2-mediated NH₄⁺ uptake. At the early distal tubule, luminal ammonia accounts for only 20–40% of urinary ammonia excretion. The collecting duct, and possibly the DCT and the CNT, secrete ammonia, and account for the remaining 60–80% of urinary ammonia. Collecting duct ammonia secretion involves parallel H⁺ and NH₃ transport, with no measureable transepithelial NH₄⁺ permeability. Interstitial sulfatides (represented by the molecule encircled in green area) reversibly bind ammonia, limiting ionized interstitial ammonia concentrations.