Understanding Metabolic Alkalosis
Metabolic alkalosis is a common acid-base disturbance characterized by an elevated blood pH (>7.45) due to a primary increase in serum bicarbonate (HCO3−) concentration [1.9.1, 1.9.3, 1.9.5]. Persistence of this condition signals that the kidneys are reabsorbing more bicarbonate than normal, failing to excrete the excess alkali [1.9.1, 1.9.4]. This disorder is the most frequent acid-base imbalance seen in hospitalized patients [1.8.3, 1.9.3]. The mortality rate increases significantly with rising pH, from about 45% at a pH of 7.55 to 80% at a pH of 7.65 [1.8.1, 1.8.2].
Common Causes and Pathophysiology
The development of metabolic alkalosis requires two factors: an initial event that generates the alkalosis and a secondary process that maintains it by preventing the kidneys from excreting the excess bicarbonate [1.9.3, 1.9.4].
**Generation Phase (Causes):
- Loss of Gastric Acid: Prolonged vomiting or nasogastric suction removes highly acidic stomach fluids, leading to a relative increase in bicarbonate in the blood [1.9.1, 1.9.2].
- Diuretic Use: Thiazide and loop diuretics can cause volume depletion and increased excretion of chloride and potassium, which stimulates the kidneys to retain bicarbonate [1.9.1, 1.9.4].
- Hypokalemia (Low Potassium): Low potassium levels cause a shift where hydrogen ions move into cells, raising the extracellular pH and promoting alkalosis [1.9.1, 1.9.2].
- Excess Alkali Administration: This can occur through overuse of bicarbonate-containing antacids (milk-alkali syndrome) or intravenous administration of bicarbonate or citrate (found in blood transfusions) [1.9.1, 1.9.2].
Maintenance Phase: The kidneys' failure to excrete bicarbonate is often driven by volume depletion (contraction alkalosis) and hypokalemia, which are powerful stimuli for bicarbonate reabsorption [1.9.1, 1.9.4].
Initial Treatment: Addressing the Cause
The cornerstone of managing metabolic alkalosis is treating the underlying cause and correcting any fluid and electrolyte imbalances [1.2.4, 1.9.1]. For many patients, especially those with chloride-responsive alkalosis (often from vomiting or diuretics), treatment involves an intravenous infusion of isotonic sodium chloride and potassium chloride to restore volume and correct hypokalemia [1.2.2, 1.9.1]. If a patient is on diuretics, the dosage may be reduced or the medication stopped [1.2.2].
Pharmacological Interventions
When addressing the underlying cause is insufficient or in more severe cases, specific medications are used to correct the pH imbalance. The choice of medication depends on the specific cause, the patient's volume status, and the severity of the alkalosis [1.2.1].
Carbonic Anhydrase Inhibitors (Acetazolamide)
Acetazolamide is a primary medication used, especially for diuretic-induced metabolic alkalosis or in patients with volume overload (e.g., congestive heart failure) who cannot tolerate saline infusions [1.2.1, 1.2.4].
- Mechanism of Action: It works by inhibiting the enzyme carbonic anhydrase in the proximal tubule of the kidney. This action reduces the reabsorption of sodium bicarbonate (NaHCO3), promoting its excretion in the urine along with sodium, water, and potassium. The result is a decrease in serum bicarbonate and a lowering of blood pH [1.2.1, 1.3.1].
- Considerations: A common side effect is hypokalemia (low potassium), which must be monitored carefully as it can worsen alkalosis [1.2.3]. Other side effects include drowsiness, paresthesias (tingling), and the potential for developing metabolic acidosis with long-term use [1.3.2, 1.3.3]. It is contraindicated in patients with significant renal or hepatic dysfunction [1.3.1].
Potassium-Sparing Diuretics
These medications are particularly useful in chloride-resistant metabolic alkalosis, such as conditions involving hyperaldosteronism [1.2.2].
- Spironolactone: This drug is an aldosterone antagonist. It works by competitively blocking aldosterone receptors in the distal renal tubules, which increases sodium and water excretion while conserving potassium and hydrogen ions needed to restore acid-base balance [1.2.1, 1.4.1]. It is effective for alkalosis caused by primary hyperaldosteronism but has a slow onset of action (24-48 hours), limiting its use in acute situations [1.4.1, 1.4.4].
- Amiloride and Triamterene: These drugs act by inhibiting sodium channels in the distal tubule, which also helps to retain potassium [1.2.1, 1.5.3]. Amiloride is effective in correcting diuretic-induced hypokalemia and metabolic alkalosis and can be used to treat Liddle syndrome, a condition where spironolactone is ineffective [1.5.1, 1.5.3].
Intravenous Acids
For severe metabolic alkalosis (pH > 7.55), or in cases where saline administration is contraindicated due to volume overload or renal failure, intravenous acids may be required [1.6.2, 1.6.3]. This therapy is reserved for critical situations like cardiac arrhythmias or hepatic encephalopathy and requires administration through a central venous line under close supervision, often by a nephrologist [1.2.3, 1.6.3].
- Hydrochloric Acid (HCl): Dilute solutions of HCl (0.1 N or 0.2 N) can be infused to directly neutralize excess bicarbonate [1.6.2].
- Arginine Hydrochloride: This is another acidifying agent that can be used to correct metabolic alkalosis and hypochloremia [1.7.1, 1.7.3]. It works by providing a chloride load, which helps the kidneys excrete bicarbonate [1.7.4].
Medication Comparison Table
| Medication Class | Example(s) | Mechanism of Action | Primary Indication(s) | Key Side Effects |
|---|---|---|---|---|
| Carbonic Anhydrase Inhibitors | Acetazolamide | Inhibits renal carbonic anhydrase, promoting bicarbonate excretion [1.3.1]. | Diuretic-induced alkalosis, volume overload states [1.2.2]. | Hypokalemia, metabolic acidosis, drowsiness [1.3.2, 1.3.3]. |
| Potassium-Sparing Diuretics | Spironolactone, Amiloride | Blocks aldosterone effects or sodium channels to retain K+ and H+ [1.2.1, 1.5.3]. | Chloride-resistant alkalosis (e.g., hyperaldosteronism) [1.4.1]. | Hyperkalemia, gynecomastia (spironolactone) [1.4.2]. |
| Intravenous Acids | Hydrochloric Acid, Arginine HCl | Directly titrates excess bicarbonate, provides chloride [1.6.2, 1.7.1]. | Severe metabolic alkalosis (pH >7.55), renal failure, volume overload [1.6.3]. | Hemolysis, requires central line, potential for over-correction [1.2.3]. |
Conclusion
The treatment of metabolic alkalosis is multifaceted, beginning with addressing the root cause and replenishing fluid and electrolytes. When pharmacological intervention is necessary, the choice of medication hinges on the specific etiology of the alkalosis. Acetazolamide is a frontline choice for common causes like diuretic use, while potassium-sparing diuretics are key for mineralocorticoid-driven states. In life-threatening situations, carefully administered intravenous acids provide a rapid but high-risk solution. Effective management requires a clear understanding of the patient's clinical status and the specific properties of each therapeutic agent.
For more in-depth information, you can refer to the Metabolic Alkalosis article on the StatPearls bookshelf from the National Center for Biotechnology Information.
