21-19: Normal Anion Gap Acidosis

The two major causes are gastrointestinal HCO₃^– loss and defects in renal acidification (renal tubular acidosis) (Table 21–14). The urinary anion gap can differentiate between these causes.

A. Gastrointestinal HCO₃^– Loss

The gastrointestinal tract secretes bicarbonate at multiple sites. Small bowel and pancreatic secretions contain large amounts of HCO₃^–; massive diarrhea or pancreatic drainage results in stool HCO₃^– loss. Hyperchloremia occurs because the ileum and colon secrete HCO₃^– in exchange for Cl^– by countertransport. The resultant volume contraction causes increased Cl^– retention by the kidney in the setting of decreased HCO₃^–. Patients with ureterosigmoidostomies can develop hyperchloremic metabolic acidosis because the colon secretes HCO₃^– in the urine in exchange for Cl^–.

B. Renal Tubular Acidosis

Hyperchloremic acidosis with a normal anion gap and normal (or near normal) GFR, in the absence of diarrhea, defines RTA. The defect is either an inability to excrete H⁺ as ammonium (inadequate generation of new HCO₃^–) or inadequate reabsorption of filtered HCO₃^–. Three major types can be differentiated by the clinical setting, urinary pH, urinary anion gap, and serum K⁺ level. The pathophysiologic mechanisms of RTA have been elucidated by identifying the responsible molecules and gene mutations.

1. Classic distal RTA (type I)

This disorder is characterized by selective deficiency in H⁺ secretion by alpha intercalated cells in the collecting tubule. Despite acidosis, the urine cannot be fully acidified (urine pH > 5.5), which retards the binding of H⁺ to phosphate (H⁺ + HPO₄ ^2– → H₂PO₄) and inhibits titratable acid excretion. Furthermore, urinary excretion of NH₄Cl is decreased, and the urinary anion gap is inappropriately positive. Enhanced K⁺ excretion occurs probably due to less competition from H⁺ in the distal nephron ...