Determination of appropriate compensatory changes in the HCO₃– is useful to sort out the presence of an associated metabolic disorder (see above under Mixed Acid-Base Disorders). As in respiratory acidosis, the changes in HCO₃– values are greater if the respiratory alkalosis is chronic. In acute respiratory alkalosis, HCO₃– decreases 2 meq/L for every 10 mm Hg fall in PCO2. In chronic respiratory alkalosis, there is a compensatory decrease in renal acid excretion. Serum HCO3– decreases by 5 meq/L for every 10 mm Hg drop in PCO₂. While serum HCO₃– is frequently below 15 meq/L in metabolic acidosis, it is unusual to see such a low level in respiratory alkalosis, and its presence would imply a superimposed (noncompensatory) metabolic acidosis.

A. Symptoms and Signs: In acute cases (hyperventilation), there is light-headedness, anxiety, paresthesias, numbness about the mouth, and a tingling sensation in the hands and feet. Tetany occurs in more severe alkalosis from a fall in ionized calcium. In chronic cases, symptomatic findings are those of the primary disease.

B. Laboratory Findings: Arterial blood pH is elevated, and PCO₂ is low. Serum bicarbonate is decreased in chronic respiratory alkalosis.

Treatment is directed toward the underlying cause. In acute hyperventilation syndrome from anxiety, rebreathing into a paper bag will increase the PCO₂. Sedation may be necessary if the maneuver does not terminate the attack. Rapid correction of chronic respiratory alkalosis may result in metabolic acidosis as PCO₂ is increased in the setting of previous compensatory decrease in HCO₃–.

The major unmeasured cations are calcium (5 meq/L), magnesium (2 meq/L), gamma globulins, and potassium (4 meq/L). The major unmeasured anions are negatively charged albumin (2 meq/L per g/dL), phosphate (2 meq/L), sulfate (1 meq/L), lactate (1–2 meq/L), and other organic anions (3–4 meq/L). Traditionally, the normal anion gap has been 12 ± 4 meq/L. With the new generation of autoanalyzers (Bechman ASTRA analyzer), the reference range may be lower (6 ± 1 meq/L), primarily from an increase in Cl– values. Despite its usefulness, the serum anion gap can be misleading. Non-acid-base disorders that may contribute to an error in anion gap interpretation include hypoalbuminemia (see below), antibiotic administration (eg, carbenicillin is an unmeasured anion; polymyxin is an unmeasured cation), hypernatremia, or hyponatremia.

A decreased anion gap can occur because of a reduction in unmeasured anions or an increase in unmeasured cations.

A. Decreased Unmeasured Anions: If the sodium concentration remains normal but HCO₃– and Cl– increase, the anion gap will decrease. This is seen when there are decreased unmeasured anions, especially in hypoalbuminemia. For every 1 g/dL decline in serum albumin, a 2 meq/L decrease in anion gap will occur. The new reference range for anion gap diminishes the usefulness of a low anion gap categorization except to detect an increased anion gap acidosis mimicking a normal anion gap acidosis.

B. Increased Unmeasured Cations: If the sodium concentration falls because of addition of unmeasured cations but HCO₃– and Cl– remain unchanged, the anion gap will decrease. This is seen in severe hypercalcemia, hypermagnesemia, or hyperkalemia; IgG myeloma, where the immunoglobulin is cationic in 70% of cases; and lithium toxicity.