What is the cause of metabolic alkalosis due to excess aldosterone (a hormone)?

From the Guidelines

Aldosterone can cause metabolic alkalosis by increasing renal hydrogen ion excretion and sodium reabsorption, as evidenced by the most recent guidelines from the European Heart Journal in 2024 1. When aldosterone levels are elevated, it stimulates the sodium-potassium pump in the distal tubule and collecting ducts of the kidneys, leading to increased sodium reabsorption and potassium excretion. This process also promotes hydrogen ion secretion into the tubular lumen, resulting in increased bicarbonate reabsorption and alkalosis. Some key points to consider in the diagnosis and management of primary aldosteronism include:

• The aldosterone-to-renin ratio (ARR) is recommended for primary aldosteronism screening, as stated in the 2024 ESC guidelines for the management of elevated blood pressure and hypertension 1.
• The most accurate and reliable means of screening for primary aldosteronism is the aldosterone:renin activity ratio, according to the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults 1.
• Treatment focuses on addressing the underlying cause, which may include surgical removal of an aldosterone-producing adenoma, administration of aldosterone antagonists like spironolactone (50-400 mg daily) or eplerenone (25-100 mg daily), or correction of volume depletion, as recommended in the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline 1.
• Potassium replacement is often necessary, and in severe cases, acetazolamide (250-500 mg) may be used to promote bicarbonate excretion, as mentioned in the example answer.
• Monitoring of electrolytes, particularly potassium levels, is essential during treatment to prevent dangerous imbalances, as emphasized in the example answer. It is essential to note that the prevalence of primary aldosteronism is higher in patients with resistant hypertension, with a prevalence of approximately 20%, as reported in the study published in Hypertension in 2008 1. However, the most recent and highest quality study, the 2024 ESC guidelines, should be prioritized when making a definitive recommendation, and the aldosterone-to-renin ratio (ARR) is thus recommended for primary aldosteronism screening 1.

From the FDA Drug Label

5.3 Electrolyte and Metabolic Abnormalities In addition to causing hyperkalemia, spironolactone can cause hyponatremia, hypomagnesemia, hypocalcemia, hypochloremic alkalosis, and hyperglycemia.

The cause of metabolic alkalosis due to excess aldosterone is not directly stated in the provided drug labels. However, it can be inferred that excess aldosterone leads to increased sodium reabsorption and hydrogen ion excretion, resulting in metabolic alkalosis.

• Key points:
  • Excess aldosterone increases sodium reabsorption
  • Increased sodium reabsorption leads to increased hydrogen ion excretion
  • Hydrogen ion excretion results in metabolic alkalosis

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From the Research

Metabolic Alkalosis due to Excess Aldosterone

• Metabolic alkalosis is a condition characterized by an increase in blood pH due to excessive loss of hydrogen ions or gain of bicarbonate ions.
• Excess aldosterone, a hormone produced by the adrenal glands, can lead to metabolic alkalosis, as seen in primary hyperaldosteronism 3, 4, 5, 6.
• The mechanism by which excess aldosterone causes metabolic alkalosis is related to its effects on the kidneys, where it promotes sodium retention and potassium excretion, leading to hypokalemia and increased bicarbonate reabsorption 7.

Effects of Excess Aldosterone on the Body

• Excess aldosterone can lead to resistant hypertension, hypokalemia, and metabolic alkalosis, as well as heart failure with preserved ejection fraction 3.
• The biochemical evaluation of primary aldosteronism typically reveals elevated plasma aldosterone concentrations, low plasma renin activity, and metabolic alkalosis 3, 4.
• The distinction between adrenal hyperplasia and aldosterone-producing adenoma is essential for selecting the appropriate treatment, which may include surgical or pharmacological interventions 4.

Diagnosis and Treatment of Primary Aldosteronism

• The diagnosis of primary aldosteronism involves case detection, case confirmation, and subtype classification, using tests such as the aldosterone-to-renin ratio and imaging exams 4, 6.
• Treatment of primary aldosteronism aims to lower excess aldosterone levels, using medications such as aldosterone antagonists, and may lead to improved blood pressure control and resolution of symptoms 3, 4.