Metabolic alkalosis is a derangement characterized by increased plasma bicarbonate (HCO3–), resulting in a pH > ~7.45. This can be a product of hydrogen ion (H+) loss (e.g., vomiting or renal losses), intracellular shifting of H+, or retention/creation of HCO3–.
Typically, the proximal convoluted tubule’s (PCT) ion channels reabsorb all filtered amino acids/glucose and almost all of the HCO3– back into the interstitium. By comparison, only ⅔ of the filtered water, sodium, potassium, and chloride (Cl–) are reabsorbed.
By ↓ the extracellular fluid (ECF) status with diuretics, the PCT tries to compensate by ↑ water and HCO3– reabsorption causing “contraction alkalosis.” It follows that volume administration should ↓ proximal HCO3– reabsorption delivering more HCO3– to the distal nephron. Since this portion of the nephron does not have as much capacity to reabsorb HCO3–, much of it gets excreted in the urine.
Data has shown that alkalosis with Cl– deficiency improves with Cl– repletion even without ECF expansion; however, volume resuscitation without Cl– does not improve the alkalosis. So why is Cl– necessary?
Enter pendrin – the luminal Cl–-HCO3– exchanger in the beta-intercalated cells of the nephron’s collecting ducts. This protein is enhanced by low distal nephron Cl– delivery and intracellular alkalosis; however, HCO3– elimination is limited due to less Cl– available for exchange.
By repleting Cl–, more is delivered to the distal nephron resulting in bicarbonaturia to correct alkalosis. As far as using medications like acetazolamide to “spill HCO3– in the urine,” data shows it also ↓ the serum strong ion difference by ↑ Cl–.