From the Guidelines
Metabolic alkalosis is primarily caused by excessive loss of hydrogen ions or gain of bicarbonate in the body, with key causes including genetic disorders like Bartter syndrome, as highlighted in recent studies 1, 2. The main causes of metabolic alkalosis can be broken down into several categories, including:
- Excessive loss of hydrogen ions, such as through vomiting or nasogastric suction, which directly removes stomach acid
- Gain of bicarbonate, such as through excessive alkali administration like sodium bicarbonate or antacids
- Certain endocrine disorders, including hyperaldosteronism and Cushing's syndrome
- Contraction alkalosis, which can occur with volume depletion as the kidneys retain sodium and bicarbonate
- Milk-alkali syndrome from excessive calcium and absorbable alkali intake
- Genetic disorders affecting renal tubular function, such as Bartter syndrome, which can lead to chronic metabolic alkalosis, as noted in a 2021 study published in Kidney International 1
- Other rare tubulopathies, as listed in Table 4 of a 2021 study 2, which can also exhibit metabolic alkalosis
Bartter syndrome, in particular, is a significant cause of metabolic alkalosis, characterized by hypokalemic and hypochloremic metabolic alkalosis secondary to watery diarrhea, as described in a 2021 study 2. It is essential to distinguish between renal and extrarenal salt losses, with urinary chloride excretion assessed by either fractional chloride excretion or urinary sodium/chloride ratio being helpful in this regard, as discussed in a 2021 study 2. Treatment of metabolic alkalosis should target the underlying cause, addressing fluid, electrolyte, and acid-base imbalances, while also considering the potential risks and benefits of diagnostic tests, such as diuretic tests, which are now largely obsolete due to the availability of genetic analysis, as noted in a 2021 study 2.
From the Research
Causes of Metabolic Alkalosis
The causes of metabolic alkalosis can be divided into several categories, including:
- Loss of fixed acid or a net accumulation of bicarbonate within the extracellular fluid 3
- Loss of acid via the gastrointestinal tract or the kidney 3, 4
- Sources of excess alkali may be via oral or parenteral alkali intake 3
- Volume contraction, low glomerular filtration rate, potassium deficiency, hypochloremia, aldosterone excess, and elevated arterial carbon dioxide can impair the ability of the kidney to eliminate excess bicarbonate, promoting the generation or impairing the correction of metabolic alkalosis 3
- Major clinical states associated with metabolic alkalosis, including: + Vomiting 3, 4, 5, 6 + Aldosterone or cortisol excess 3, 4, 5 + Licorice ingestion 3 + Chloruretic diuretics 3, 4 + Excess calcium alkali ingestion 3 + Genetic diseases such as Bartter syndrome, Gitelman syndrome, and cystic fibrosis 3
- Chloride depletion alkalosis, mineralocorticoid excess syndromes, apparent mineralocorticoid excess syndromes, and excess alkali administration are also common causes of metabolic alkalosis 7
Pathogenesis of Metabolic Alkalosis
The pathogenesis of metabolic alkalosis involves either a loss of fixed acid or a net accumulation of bicarbonate within the extracellular fluid 3. The kidney plays a crucial role in maintaining acid-base balance, and factors that interfere with its mechanisms can impair the ability to eliminate excess bicarbonate, promoting the generation or impairing the correction of metabolic alkalosis 3, 4.
Maintenance of Metabolic Alkalosis
Maintenance of metabolic alkalosis is possible only in patients with impaired renal base excretion, which is most often produced by hypochloremia 6. The evaluation of volemic status and measurement of urinary Cl- and plasma levels of renin and aldosterone are crucial to identify the cause(s) of metabolic alkalosis 4.