Metabolic Alkalosis

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

• Diuretic use

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

Among other causes of metabolic alkalosis are disorders that cause

• Bicarbonate excess

• Renal acid loss

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 (K) 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 stage 4 or 5 chronic kidney disease).

• 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 hemodialysis₃⁻ 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.