What is the diagnostic workup for metabolic alkalosis?

From the Guidelines

The workup for metabolic alkalosis should begin with a thorough history and physical examination, focusing on potential causes such as vomiting, diuretic use, or excessive alkali ingestion, and initial laboratory tests should include a comprehensive metabolic panel and urine electrolytes to distinguish between chloride-responsive and chloride-resistant alkalosis. The diagnosis and management of metabolic alkalosis can be complex, and it is essential to consider various causes, including Bartter syndrome, as discussed in the study by 1. The study highlights the importance of distinguishing between renal and extrarenal salt losses, and the use of urinary chloride excretion to make this distinction, with fractional chloride excretion usually elevated (>0.5%) in Bartter syndrome. Key characteristics of Bartter syndrome include polyuria, hypokalemia, hypochloremic metabolic alkalosis, and normotensive hyperreninemic hyperaldosteronism, as outlined in the study by 1. The primary molecular defect in all types of Bartter syndrome leads to impaired salt reabsorption in the thick ascending limb of the loop of Henle, resulting in renal tubular salt wasting with activation of the renin-angiotensin system and consequent hypokalemic and hypochloremic metabolic alkalosis. Some patients with Bartter syndrome may present with nephrocalcinosis and/or urolithiasis, and a young age at onset of kidney stone disease should raise the clinical suspicion of a specific underlying cause, including (incomplete) distal renal tubular acidosis, as mentioned in the study by 1. The use of K-sparing diuretics, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers can help ameliorate the electrolyte abnormalities in Bartter syndrome, as discussed in the study by 1. In terms of treatment, volume repletion with normal saline (0.9% NaCl) at 100-150 mL/hour until the alkalosis resolves, along with potassium replacement if hypokalemic, is recommended for chloride-responsive cases, while further evaluation for mineralocorticoid excess, Bartter syndrome, or Gitelman syndrome is warranted for chloride-resistant cases. Severe cases (pH >7.60) may require careful administration of acetazolamide 250-500 mg orally or dilute hydrochloric acid in critical situations, as outlined in the example answer. The underlying pathophysiology involves either hydrogen ion loss (vomiting, nasogastric suction), excessive bicarbonate retention, or potassium and chloride depletion, which disrupt the body's acid-base balance, and addressing the primary cause is essential for definitive treatment, as discussed in the studies by 1.

From the Research

Metabolic Alkalosis Workup

• Metabolic alkalosis is a common acid-base disturbance in critically ill patients, characterized by an increase in serum bicarbonate and arterial pH 2.
• The pathogenesis of metabolic alkalosis involves either a loss of fixed acid or a net accumulation of bicarbonate within the extracellular fluid 2.
• 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 persistence of metabolic alkalosis 2.

Causes of Metabolic Alkalosis

• Major clinical states associated with metabolic alkalosis include vomiting, aldosterone or cortisol excess, licorice ingestion, chloruretic diuretics, excess calcium alkali ingestion, and genetic diseases such as Bartter syndrome, Gitelman syndrome, and cystic fibrosis 2.
• Metabolic alkalosis can be divided into four categories: chloride depletion alkalosis, mineralocorticoid excess syndromes, apparent mineralocorticoid excess syndromes, and excess alkali administration 3.

Diagnosis and Treatment

• 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.
• Treatment is usually supportive and based on the cause of the alkalosis, with the cornerstone being the correction of existing depletions and the prevention of further losses 4.
• Acetazolamide, a carbonic anhydrase inhibitor, can be effective in treating metabolic alkalosis in critically ill patients, with a rapid onset and long duration of action 5, 6.
• The mechanism of action of acetazolamide involves decreasing the serum strong ion difference, which is explained by the increased renal excretion ratio of sodium to chloride, resulting in an increase in serum chloride 6.