Patients are typically asymptomatic. If symptoms are present, they are often due to the underlying condition causing alkalosis. Physical examination findings are also typically related to the underlying disease driving the metabolic derangements. In patients with cirrhosis and severe metabolic alkalosis, agitation, disorientation, seizures, and coma may be presenting symptoms.
The generation phase is due to a loss of hydrogen ions in the urine or gastrointestinal tract, movement of hydrogen ions into the cells, the administration of sodium or potassium bicarbonate, the administration of citrate that is metabolized to bicarbonate, or volume contraction with a relatively stable bicarbonate concentration. In the maintenance phase, bicarbonate remains elevated via a variety of mechanisms including volume contraction, reduced effective arterial volume as seen in cirrhosis or heart failure, hypokalemia, hypochloremia, or renal impairment. Patients may initially experience hypoventilation, which serves to elevate partial pressure of carbon dioxide (pCO2) levels and lower pH, but this effect is short lived, as elevations in pCO2 decrease renal excretion of bicarbonate.
Common causes include:
- External loss of hydrogen ions due to vomiting or nasogastric suctioning of gastric contents – Patients have low urine chloride concentrations.
- Diuretic use – Loop or thiazide diuretics; patients have both high and low urinary chloride concentrations as the drug effect waxes and wanes with serum drug concentrations.
- Primary aldosteronism – Hypertension, mild volume expansion, and high urinary chloride concentration.
- Cushing disease, ectopic adrenocorticotropic hormone production, exogenous mineralocorticoid production, and production of mineralocorticoid-like substances.
- Liddle syndrome – Hypertension, mild volume expansion, and high urinary chloride concentration.
- Bartter syndrome and Gitelman syndrome – Hypotension, volume contraction, and high urinary chloride concentration.
- Diarrhea secondary to laxative abuse or villous adenoma (of note, these processes might manifest as a metabolic alkalosis, metabolic acidosis, or both).
- Congenital chloridorrhea – Rare genetic syndrome causing watery, chloride-rich diarrhea, hypokalemia, and metabolic alkalosis.
- Alkali administration with reduced renal function (eg, calcium-alkali syndrome or bicarbonate ingestion / infusion with reduced renal excretion).