Metabolic alkalosis

Definition

Metabolic alkalosis is a primary increase in blood bicarbonate (HCO₃⁻), with or without a compensatory rise in Pco₂. The pH may be raised or nearly normal; alkalemia is present at a pH above 7.45. A bicarbonate above 28 mmol/L is suggestive. Persistent alkalosis requires increased renal retention of bicarbonate, as bicarbonate is normally freely filtered and excreted.

Classification

• Chloride-responsive alkalosis: loss or excess secretion of chloride; the kidney exchanges less chloride for bicarbonate. Urinary chloride is below 20 mmol/L. Examples are vomiting, nasogastric suction, saluretics, laxative abuse, sweat losses in cystic fibrosis and post-hypercapnic alkalosis.
• Chloride-unresponsive alkalosis: usually due to hyperaldosteronism with volume expansion and increased distal sodium reabsorption, often with marked potassium or magnesium deficiency. Urinary chloride is above 20 mmol/L.
• Both forms can coexist, for example in fluid overload with saluretic-induced hypokalemia.

Aetiopathogenesis

The basic mechanisms are acid loss, alkali intake, a shift of H⁺ ions into cells (as in hypokalemia) and renal retention of bicarbonate. Volume depletion and hypokalemia are the most common stimuli for increased reabsorption; any rise in aldosterone or hormones with similar action increases potassium and H⁺ excretion via sodium reabsorption. Hypokalemia is therefore both a cause and a frequent consequence.

• Most common causes: saluretics and volume depletion, especially with loss of gastric acid and chloride through recurrent vomiting or nasogastric suction.
• Base excess: milk-alkali syndrome (calcium and alkali from antacids), alkali intake and metabolism of lactate or ketoacids after an organic acidosis.
• Mineralocorticoid excess: primary and secondary hyperaldosteronism (volume depletion, heart failure, cirrhosis with ascites, nephrotic syndrome, renal artery stenosis, renin-secreting tumors), Cushing syndrome and glycyrrhizin from liquorice.
• Tubulopathies: Bartter syndrome (presenting in early childhood) and Gitelman syndrome (young adults, additionally hypomagnesemia and hypocalciuria).
• Other causes: carbohydrate intake after starvation, potassium and magnesium deficiency, congenital chloride diarrhea and villous adenoma.

Clinical features

In mild alkalemia the symptoms of the underlying disease predominate. More marked alkalemia increases protein binding of ionised calcium; the resulting hypocalcemia causes headache, lethargy and neuromuscular excitability, sometimes with delirium, tetany and seizures. Accompanying hypokalemia causes muscle weakness. The electrolyte disturbances also lower the threshold for angina and arrhythmias.

Diagnosis

• Blood gas analysis and serum electrolytes including calcium and magnesium.
• Compensation: Pco₂ rises by about 0.6 to 0.75 mmHg for every 1 mmol/L increase in bicarbonate, usually not above about 55 mmHg. A greater rise suggests an additional respiratory acidosis, a smaller rise a respiratory alkalosis.
• History and examination: usually already identify common causes such as vomiting or saluretics.
• Urinary chloride: below 20 mmol/L indicates a chloride-responsive form, above 20 mmol/L a chloride-unresponsive form; not interpretable in chronic kidney disease stage 4 to 5.
• Urinary potassium and blood pressure: below 30 mmol/day in hypokalemia or laxative abuse; above 30 mmol/day without hypertension in saluretic abuse, Bartter or Gitelman syndrome; above 30 mmol/day with hypertension in hyperaldosteronism, mineralocorticoid excess or renovascular disease.
• Hormone tests in hypertension: plasma renin activity, aldosterone and cortisol.

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Further reading (open access)

1. MSD Manual Professional: Metabolic Alkalosis
2. MSD Manual Professional: Acid-Base Disorders
3. StatPearls: Physiology, Metabolic Alkalosis

Cross-references