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.
Table 21–14.Hyperchloremic, normal anion gap metabolic acidoses. ||Download (.pdf) Table 21–14. Hyperchloremic, normal anion gap metabolic acidoses.
|Renal Defect ||Serum [K+] ||Distal H+ Secretion ||Urinary Anion Gap ||Treatment |
|Urine pH ||Titratable Acid |
|Gastrointestinal HCO3– loss ||None ||↓ ||< 5.5 ||↑↑ ||Negative ||Na+, K+, and HCO3– as required |
|Renal tubular acidosis |
| I. Distal ||Distal H+ secretion ||↓ ||> 5.3 ||↓ ||Positive ||NaHCO3 (1–3 mEq/kg/day) |
| II. Proximal ||Proximal HCO3– reabsorption ||↓ ||Variable ||Normal ||Positive ||NaHCO3 or KHCO3 (10–15 mEq/kg/day), thiazide |
| IV. Hyporeninemic hypoaldosteronism ||Distal Na+ reabsorption, K+ secretion, and H+ secretion ||↑ ||Variable ||↓ ||Positive ||Fludrocortisone (0.1–0.5 mg/day), dietary K+ restriction, furosemide (40–160 mg/day), NaHCO3 (1–3 mEq/kg/day) |
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 ...