What is the most common cause of metabolic alkalosis?

From the Guidelines

The most common cause of metabolic alkalosis is diuretic therapy, particularly with loop and thiazide diuretics, as these medications increase urinary excretion of chloride and potassium while retaining bicarbonate, leading to an alkaline environment in the blood. This occurs because the diuretics inhibit the sodium-chloride transporter in the distal tubule, resulting in increased sodium delivery to the cortical collecting duct and consequent increased uptake by the sodium epithelial channel ENaC, leading to increased potassium excretion via the channel ROMK2 to maintain electrical neutrality 1. Additionally, the diuretic-induced natriuresis causes upregulation of ENaC, which is aldosterone-sensitive, and enhanced ENaC activity also increases cortical collecting tubule acid secretion, which can cause metabolic alkalosis 1. Other causes of metabolic alkalosis include vomiting or nasogastric suction, severe hypokalemia, excessive alkali ingestion, severe hypovolemia, and certain endocrine disorders like Cushing's syndrome or primary hyperaldosteronism. Some key points to consider when evaluating the cause of metabolic alkalosis include:

• The role of diuretic therapy in causing metabolic alkalosis, particularly with loop and thiazide diuretics 2, 1
• The importance of addressing the underlying cause of metabolic alkalosis, such as replacing fluid and electrolyte losses, and in severe cases, administering chloride-containing solutions to help correct the alkalosis
• The potential for severe hypokalemia to maintain metabolic alkalosis as the kidneys attempt to conserve potassium by excreting hydrogen ions instead 1
• The need for periodic monitoring of serum electrolytes in patients treated with chronic diuretic therapy to prevent and treat metabolic alkalosis 2

From the FDA Drug Label

Potassium depletion due to these causes is usually accompanied by a concomitant loss of chloride and is manifested by hypokalemia and metabolic alkalosis

• The most common cause of metabolic alkalosis is potassium depletion due to: + Therapy with diuretics + Primary or secondary hyperaldosteronism + Diabetic ketoacidosis + Inadequate replacement of potassium in patients on prolonged parenteral nutrition + Severe diarrhea, especially if associated with vomiting 3

From the Research

Metabolic Alkalosis Causes

• The most common cause of metabolic alkalosis is diuretic therapy, which leads to activation of the renin-angiotensin system, chloride depletion, increased distal sodium delivery, hypokalemia, and increased urine acidification, all of which contribute to bicarbonate retention 4.
• Diuretics, particularly loop and thiazide diuretics, can cause hypokalaemia, hyperuricaemia, hypomagnesaemia, and alterations to lipid and glucose metabolism, which can contribute to the development of metabolic alkalosis 5, 6.
• The disease state itself, such as congestive heart failure, can result in neurohormonal activation (renin-angiotensin system, sympathetic nervous system, and endothelin) that further amplifies the tendency toward alkalosis 4.
• Other factors, such as high daily salt intake, hyponatremia or hypokalemic, hypochloremic metabolic alkalosis, and reflex activation of the renal nerves, can also contribute to diuretic resistance and metabolic alkalosis 7.

Diuretic-Induced Metabolic Alkalosis

• Diuretic-induced metabolic alkalosis is a common complication in patients with heart failure, and treatment with acetazolamide can be effective in correcting the alkalosis 8.
• The use of diuretics can lead to a range of metabolic complications, including electrolyte and acid-base disorders, glucose and lipid abnormalities, and diuretic resistance 5, 6, 7.