What causes distal renal tubular acidosis (RTA) (type 1) in patients with non-anion gap (AG) (hyperchloremic) metabolic acidosis?

Updated: Dec 08, 2020
  • Author: Christie P Thomas, MBBS, FRCP, FASN, FAHA; Chief Editor: Vecihi Batuman, MD, FASN  more...
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Several different mechanisms are implicated in the development of distal RTA. These include a defect in 1 of the 2 proton pumps, H+ –ATPase or K+ -H+ –ATPase, that can be acquired or congenital. This may lead to loss of function (ie, secretory defect) or a reduction in the rate of H+ secretion (ie, rate-dependent defect).

Another mechanism is a defect in the basolateral Cl-/HCO3- exchanger, AE1, or the intracellular carbonic anhydrase that can be acquired or congenital. This also causes a secretory defect.

Back-diffusion of the H+ from the lumen via the paracellular or transcellular space is another mechanism; this occurs if the integrity of the tight junctions is lost or permeability of the apical membrane is increased (ie, permeability or gradient defect). With a urine pH of 5.0 and an interstitial fluid pH of 7.4, the concentration gradient facilitating back-diffusion of free H+, under conditions of increased permeability of the collecting duct epithelia, is approximately 250-fold.

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