What is the role of ammonia (NH3) in the pathogenesis of metabolic acidosis?

Updated: Oct 10, 2018
  • Author: Christie P Thomas, MBBS, FRCP, FASN, FAHA; Chief Editor: Vecihi Batuman, MD, FASN  more...
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Answer

Ammonia is produced in the proximal tubule from the amino acid glutamine, and this reaction is enhanced by an acid load and by hypokalemia. Ammonia is converted to ammonium (NH4+) by intracellular H+ and is secreted into the proximal tubular lumen by the apical Na+/H+ (NH4+) antiporter.

The apical Na+/K+ (NH4+)/2Cl- cotransporter in the thick ascending limb of the loop of Henle then transports NH4+ into the medullary interstitium, where it dissociates back into NH3 and H+. The NH3 enters the collecting duct epithelial cells via the basolateral ammonia transporters, RhBG and RhCG, and then is transported into the lumen of the collecting duct via apical RhCG, where it is available to buffer H+ ions and becomes NH4+. NH4+ is trapped in the lumen and excreted as the Cl salt, and every H+ ion buffered is an HCO3- gained to the systemic circulation.

The increased secretion of H+ in the collecting duct shifts the equation to the right and decreases the NH3 concentration, facilitating continued diffusion of NH3 from the interstitium down its concentration gradient into the collecting duct lumen, allowing more H+ to be buffered. The kidneys can adjust the amount of NH3 synthesized to meet demand, making this a powerful system to buffer secreted H+ in the urine. [1]


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