Metabolic alkalosis is due to a primary increase in serum [HCO₃⁻], distinguished from chronic respiratory acidosis—with a compensatory increase in renal HCO₃⁻ reabsorption—by the associated increase in arterial pH (normal or decreased in chronic respiratory acidosis). Administered, exogenous alkali (HCO₃⁻, acetate, citrate, or lactate) may cause alkalosis if the normal capacity to excrete HCO₃⁻ is reduced or if renal HCO₃⁻ reabsorption is enhanced. A recently resurgent problem is “milk alkali syndrome,” a triad of hypercalcemia, metabolic alkalosis, and acute renal failure due to ingested calcium carbonate, typically taken for the treatment or prevention of osteoporosis or for symptomatic relief of peptic ulcer disease.

Metabolic alkalosis is primarily caused by renal retention of HCO₃⁻ and is due to a variety of underlying mechanisms. Pts are typically separated into two major subtypes: Cl⁻-responsive and Cl⁻-resistant. Measurement of urine Cl⁻ affords this separation in the clinical setting (Fig. 2-2). The quintessential causes of Cl⁻-responsive alkalosis are GI induced from vomiting or gastric aspiration through a nasogastric tube, and renal induced from diuretic therapy. Hypovolemia, chloride deficiency, activation of the RAA axis, and hypokalemia play interrelated roles in the maintenance of this hypochloremic or “contraction” alkalosis. The various syndromes of true or apparent mineralocorticoid excess cause Cl⁻-resistant metabolic alkalosis (Fig. 2-2); most of these pts are hypokalemic, volume expanded, and/or hypertensive.

FIGURE 2-2

The diagnostic approach to metabolic alkalosis. See text for details. GRA, glucocorticoid-remediable aldosteronism; HTN, hypertension; JGA, juxtaglomerular apparatus. (Modified from Dubose TD. Disorders of acid-base balance. In: Brenner and Rector’s The Kidney, 8th ed, Brenner BM [ed]. Philadelphia, Saunders, 2008 with permission.)

Common forms of metabolic alkalosis are generally diagnosed from the history, physical examination, and/or basic laboratory tests. ABGs will help determine whether an elevated [HCO₃⁻] is reflective of metabolic alkalosis or chronic respiratory acidosis; ABGs are required for the diagnosis of mixed acid-base disorders. Measurement of urinary electrolytes will aid in separating Cl⁻-responsive and Cl⁻-resistant forms. Urinary [Na⁺] may thus be >20 meq/L in Cl⁻-responsive alkalosis despite the presence of hypovolemia; however, urinary [Cl⁻] will typically be very low, except in pts with severe hypokalemia. Notably, urinary [Cl⁻] may be variable in pts with diuretic-associated alkalosis, depending on the temporal relationship to diuretic administration. Other diagnostic tests—e.g., plasma renin, aldosterone, cortisol—may be appropriate in Cl⁻-resistant forms with high urinary [Cl⁻] (Fig. 2-2).