Metabolic alkalosis is primary increase in HCO₃⁻ with or without compensatory increase in Pco₂; pH may be high or nearly normal. Common causes include prolonged vomiting, hypovolemia, diuretic use, and hypokalemia. Renal impairment of HCO₃⁻ excretion must be present to sustain alkalosis. Symptoms and signs in severe cases include headache, lethargy, and tetany. Diagnosis is clinical and with ABG and serum electrolyte measurement. The underlying cause is treated; oral or IV acetazolamide or HCl is sometimes indicated.

Etiology

Metabolic alkalosis is HCO₃⁻ accumulation due to acid loss, alkali administration, intracellular shift of hydrogen ion (H⁺—as occurs in hypokalemia), or HCO₃⁻ retention. Regardless of initial cause, persistence of metabolic alkalosis indicates that the kidneys have increased their HCO₃⁻ reabsorption, because HCO₃⁻ is normally freely filtered by the kidneys and hence excreted. Volume depletion and hypokalemia are the most common stimuli for increased HCO₃⁻ reabsorption, but any condition that elevates aldosterone or mineralocorticoids (which enhance Na reabsorption and K and H⁺ excretion) can elevate HCO₃⁻. Thus, hypokalemia is both a cause and a frequent consequence of metabolic alkalosis. Causes are listed; the most common are volume depletion (particularly when involving loss of gastric acid and Cl from recurrent vomiting or nasogastric suction) and diuretic use (Table 4: Acid-Base Regulation and Disorders: Causes of Metabolic Alkalosis).

Table 4
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Causes of Metabolic Alkalosis Cause Comments GI acid loss* Gastric acid loss due to vomiting or nasogastric suction Loss of HCl and acid coupled with contraction alkalosis due to release of aldosterone and subsequent resorption of HCO3 Congenital chloridorrhea Fecal Cl loss and HCO3 retention Villous adenoma Probably secondary to K depletion Renal acid loss Primary hyperaldosteronism† Includes congenital adrenal hyperplasia Secondary hyperaldosteronism† Occurs with volume depletion, heart failure, cirrhosis with ascites, nephrotic syndrome, Cushing syndrome or disease, renal artery stenosis, or renin-secreting tumor Use of glycyrrhizin-containing compounds† (eg, licorice, chewing tobacco, carbenoxolone, Lydia Pinkham's vegetable compound) Glycyrrhizin inhibition of enzymatic conversion of cortisol to less active metabolites Bartter syndrome† Rare congenital disease causing hyperaldosteronism and hypokalemic metabolic alkalosis that manifests in early childhood with renal salt wasting and volume depletion Gitelman syndrome† Similar to Bartter syndrome Characterized in addition by hypomagnesemia and hypocalciuria Manifests in young adults Diuretics (thiazide and loop)‡ Multiple mechanisms: Secondary hyperaldosteronism due to volume depletion, Cl depletion, or contraction alkalosis; may be Cl-unresponsive because of concomitant K depletion Hypokalemia and hypomagnesemia† Stimulate K and Mg reabsorption and H excretion; alkalosis unresponsive to NaCl and volume replacement until deficiencies corrected; low K causing H to shift into cells and raising extracellular pH HCO3 excess Posthypercapnic* Persistent elevation of compensatory HCO3 levels, often with volume, K, and Cl depletion Postorganic acidosis Conversion of lactic acid or ketoacid to HCO3 worsened by HCO3 therapy for acidosis NaHCO3 loading Occurs with overzealous loading or with loading in patients who have hypokalemia; serum becomes more alkalotic as H shifts back into cells Milk-alkali syndrome Chronic ingestion of Ca carbonate antacids provides Ca and HCO3 load; hypercalcemia decreases and GFR prevents elimination of the excess HCO3 load Contraction alkalosis* Diuretics (all types) Sweat loss in cystic fibrosis NaCl loss concentrates a fixed amount of HCO3 in a smaller total body volume Other Carbohydrate refeeding after starvation Resolution of starvation ketosis or acidosis with improved cellular function Laxative abuse* Unclear mechanism Some antibiotics (eg, carbenicillin, penicillin, ticarcillin) Contain nonreabsorbable anion, which increases K and H excretion *Cl-responsive. †Cl-unresponsive. ‡May be either Cl-responsive or Cl-unresponsive. Causes of Metabolic Alkalosis Cause Comments GI acid loss* Gastric acid loss due to vomiting or nasogastric suction Loss of HCl and acid coupled with contraction alkalosis due to release of aldosterone and subsequent resorption of HCO3 Congenital chloridorrhea Fecal Cl loss and HCO3 retention Villous adenoma Probably secondary to K depletion Renal acid loss Primary hyperaldosteronism† Includes congenital adrenal hyperplasia Secondary hyperaldosteronism† Occurs with volume depletion, heart failure, cirrhosis with ascites, nephrotic syndrome, Cushing syndrome or disease, renal artery stenosis, or renin-secreting tumor Use of glycyrrhizin-containing compounds† (eg, licorice, chewing tobacco, carbenoxolone, Lydia Pinkham's vegetable compound) Glycyrrhizin inhibition of enzymatic conversion of cortisol to less active metabolites Bartter syndrome† Rare congenital disease causing hyperaldosteronism and hypokalemic metabolic alkalosis that manifests in early childhood with renal salt wasting and volume depletion Gitelman syndrome† Similar to Bartter syndrome Characterized in addition by hypomagnesemia and hypocalciuria Manifests in young adults Diuretics (thiazide and loop)‡ Multiple mechanisms: Secondary hyperaldosteronism due to volume depletion, Cl depletion, or contraction alkalosis; may be Cl-unresponsive because of concomitant K depletion Hypokalemia and hypomagnesemia† Stimulate K and Mg reabsorption and H excretion; alkalosis unresponsive to NaCl and volume replacement until deficiencies corrected; low K causing H to shift into cells and raising extracellular pH HCO3 excess Posthypercapnic* Persistent elevation of compensatory HCO3 levels, often with volume, K, and Cl depletion Postorganic acidosis Conversion of lactic acid or ketoacid to HCO3 worsened by HCO3 therapy for acidosis NaHCO3 loading Occurs with overzealous loading or with loading in patients who have hypokalemia; serum becomes more alkalotic as H shifts back into cells Milk-alkali syndrome Chronic ingestion of Ca carbonate antacids provides Ca and HCO3 load; hypercalcemia decreases and GFR prevents elimination of the excess HCO3 load Contraction alkalosis* Diuretics (all types) Sweat loss in cystic fibrosis NaCl loss concentrates a fixed amount of HCO3 in a smaller total body volume Other Carbohydrate refeeding after starvation Resolution of starvation ketosis or acidosis with improved cellular function Laxative abuse* Unclear mechanism Some antibiotics (eg, carbenicillin, penicillin, ticarcillin) Contain nonreabsorbable anion, which increases K and H excretion *Cl-responsive. †Cl-unresponsive. ‡May be either Cl-responsive or Cl-unresponsive.

Metabolic alkalosis involving loss or excess secretion of Cl is termed Cl-responsive, because it typically corrects with IV administration of NaCl-containing fluid. Cl-unresponsive metabolic alkalosis does not, and it typically involves severe Mg or K deficiency or mineralocorticoid excess. The 2 forms can coexist, eg, in patients with volume overload made hypokalemic from high-dose diuretics.

Symptoms and Signs

Symptoms and signs of mild alkalemia are usually related to the underlying disorder. More severe alkalemia increases protein binding of ionized Ca⁺⁺, leading to hypocalcemia and subsequent headache, lethargy, and neuromuscular excitability, sometimes with delirium, tetany, and seizures. Alkalemia also lowers threshold for anginal symptoms and arrhythmias. Concomitant hypokalemia may cause weakness.

Diagnosis

• ABG and serum electrolytes
• Diagnosis of cause usually clinical
• Sometimes measurement of urinary Cl⁻ and K⁺

Recognition of metabolic alkalosis and appropriate respiratory compensation is discussed in Acid-Base Regulation and Disorders: Diagnosis and requires ABG and measurement of serum electrolytes (including Ca and Mg).

Common causes can often be determined by history and physical examination. If history is unrevealing and renal function is normal, urinary Cl⁻ and K⁺ concentrations are measured (values are not diagnostic in renal insufficiency). Urinary Cl < 20 mEq/L indicates significant renal Cl⁻ reabsorption and hence a Cl-responsive cause (see Table 4: Acid-Base Regulation and Disorders: Causes of Metabolic Alkalosis). Urinary Cl > 20 mEq/L suggests a Cl-unresponsive form.

Urinary K and presence or absence of hypertension help differentiate Cl-unresponsive alkaloses. Urinary K < 30 mEq/day signifies hypokalemia or laxative misuse. Urinary K > 30 mEq/day without hypertension suggests diuretic abuse or Bartter or Gitelman syndrome. Urinary K > 30 mEq/day with hypertension requires evaluation for hyperaldosteronism, mineralocorticoid excess, and renovascular disease. Tests typically include plasma renin activity and aldosterone and cortisol levels (see Adrenal Disorders: Diagnosis and see Adrenal Disorders: Diagnosis).

Treatment

• Cause treated
• IV 0.9% saline solution for Cl-responsive metabolic alkalosis

Underlying conditions are treated, with particular attention paid to correction of hypovolemia and hypokalemia.

Patients with Cl-responsive metabolic alkalosis are given 0.9% saline solution IV; infusion rate is typically 50 to 100 mL/h greater than urinary and other sensible and insensible fluid losses until urinary Cl rises to > 25 mEq/L and urinary pH normalizes after an initial rise from bicarbonaturia. Patients with Cl-unresponsive metabolic alkalosis rarely benefit from rehydration alone.

Patients with severe metabolic alkalosis (eg, pH > 7.6) sometimes require more urgent correction of serum pH. Hemofiltration or hemodialysis is an option, particularly if volume overload and renal dysfunction are present. Acetazolamide 250 to 375 mg po or IV once/day or bid increases HCO₃⁻ excretion but may also accelerate urinary losses of K⁺ and phosphate (PO₄⁻); volume-overloaded patients with diuretic-induced metabolic alkalosis and those with posthypercapnic metabolic alkalosis may especially benefit.

Hydrochloric acid in a 0.1 to 0.2 normal solution IV is safe and effective but must be given through a central catheter because it is hyperosmotic and scleroses peripheral veins. Dosage is 0.1 to 0.2 mmol/kg/h. Frequent monitoring of ABG and electrolytes is needed.

Key Points

• Metabolic alkalosis is HCO₃⁻ accumulation due to acid loss, alkali administration, intracellular shift of hydrogen ion, or HCO₃⁻ retention.
• The most common causes are volume depletion (particularly when involving loss of gastric acid and Cl from recurrent vomiting or nasogastric suction) and diuretic use.
• Metabolic alkalosis involving loss or excess secretion of Cl is termed Cl-responsive
• Treat the cause and give patients with Cl-responsive metabolic alkalosis 0.9% saline IV.
• Cl-resistant metabolic alkalosis is due to increased aldosterone effect.
• Treatment of Cl-resistant metabolic alkalosis involves the correction of hyperaldosteronism.

Last full review/revision February 2013 by James L. Lewis, III, MD