Metabolic alkalosis is primary increase in bicarbonate (HCO₃⁻) with or without compensatory increase in carbon dioxide partial pressure (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 arterial blood gas and serum electrolyte measurement. The underlying condition is treated; oral or IV acetazolamide or hydrochloric acid is sometimes indicated.

(See also Acid-Base Regulation and Acid-Base Disorders.)

Metabolic alkalosis is bicarbonate (HCO₃⁻) accumulation due to

Acid loss
Alkali administration
Intracellular shift of hydrogen ion (H⁺—as occurs in hypokalemia)
Renal 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 sodium [Na] reabsorption and potassium [K] and hydrogen ion [H⁺] excretion) can elevate HCO₃⁻. Thus, hypokalemia is both a cause and a frequent consequence of metabolic alkalosis.

The most common causes of metabolic alkalosis are

Volume depletion (particularly when involving loss of gastric acid and chloride [Cl] due to recurrent vomiting or nasogastric suction)
Diuretic use

Among other causes of metabolic alkalosis are disorders that cause

Renal acid loss
Bicarbonate excess

Causes of Metabolic Alkalosis

Cause	Comments
Gastrointestinal acid loss*
Congenital chloridorrhea	Fecal Cl loss and HCO₃ retention
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
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, 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 calcium carbonate antacids provides Ca and HCO₃ load; hypercalcemia lowers PTH, increasing HCO₃ reabsorption
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
* Chloride-responsive.
† Chloride-unresponsive.
‡ May be either chloride-responsive or chloride-unresponsive.
Ca = calcium; Cl = chloride; H = hydrogen; HCl = hydrochloric acid; HCO₃ = bicarbonate; K = potassium; Mg = magnesium; NaCl = sodium chloride; NaHCO₃ = sodium bicarbonate; PTH = parathyroid hormone.

Metabolic alkalosis can be

Chloride (Cl)-responsive: Involves loss or excess secretion of Cl; it typically corrects with IV administration of NaCl-containing fluid.
Chloride-unresponsive: Does not correct with NaCl-containing fluids, and typically involves severe magnesium (Mg) and/or potassium deficiency or mineralocorticoid excess.

The 2 forms can coexist, eg, in patients with volume overload made hypokalemic by high-dose diuretics.

Symptoms and signs of mild alkalemia are usually related to the underlying disorder. More severe alkalemia increases protein binding of ionized calcium (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.

Arterial blood gas (ABG) and serum electrolyte measurements
Diagnosis of cause (usually clinical)
Sometimes measurement of urinary Cl⁻ and K⁺

Recognition of metabolic alkalosis and appropriate respiratory compensation is discussed in Diagnosis of Acid-Base Disorders and requires measurement of ABG and 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 (< 20 mmol/L) indicates significant renal Cl⁻ reabsorption and hence a Cl-responsive cause (see table Causes of Metabolic Alkalosis)
Urinary Cl > 20 mEq/L (> 20 mmol/L) suggests a chloride-unresponsive form.

Urinary K and the presence or absence of hypertension help differentiate the chloride-unresponsive alkaloses.

Urinary K < 30 mEq/day (< 30 mmol/day) signifies hypokalemia or laxative misuse.
Urinary K > 30 mEq/day (> 30 mmol/day) in a patient without hypertension suggests diuretic abuse or Bartter syndrome or Gitelman syndrome.
Urinary K > 30 mEq/day (> 30 mmol/day) in a patient with hypertension requires evaluation for hyperaldosteronism, mineralocorticoid excess, and renovascular disease.

Tests in patients with hypertension typically include plasma renin activity and aldosterone and cortisol levels (see Diagnosis of Cushing Syndrome and Diagnosis of Primary Aldosteronism).

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

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

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

Patients with chloride-unresponsive metabolic alkalosis rarely benefit from rehydration alone.

Patients with severe metabolic alkalosis (eg, pH > 7.6) sometimes require more urgent correction of blood pH. Hemofiltration or hemodialysis is an option, particularly if volume overload and renal dysfunction are present. Acetazolamide 250 to 375 mg orally or IV once or twice a day 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.

In patients with severe metabolic alkalosis (pH > 7.6) and kidney failure who otherwise cannot or should not undergo dialysis, 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/hour. Frequent monitoring of ABGs and electrolytes is needed.

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

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