21-20: Metabolic Alkalosis

Metabolic alkalosis is characterized by high HCO₃^–. Abnormalities that generate HCO₃^– are called “initiation factors,” whereas abnormalities that promote renal conservation of HCO₃^– are called “maintenance factors.” Thus, metabolic alkalosis may persist even after the initiation factors have resolved.

The causes of metabolic alkalosis are classified into two groups based on “saline responsiveness” using the urine Cl^– as a marker for volume status (Table 21–15). Saline-responsive metabolic alkalosis is a sign of extracellular volume contraction and is much more commonly encountered than saline-unresponsive alkalosis, which implies excessive total body bicarbonate with either euvolemia or hypervolemia. The compensatory increase in PCO₂ rarely exceeds 55 mm Hg; higher PCO₂ values imply a superimposed primary respiratory acidosis.

A. Saline-Responsive Metabolic Alkalosis

Saline-responsive alkalosis is characterized by normotensive extracellular volume contraction (contraction alkalosis) and hypokalemia. Hypotension and orthostasis may be seen. In vomiting or nasogastric suction, loss of acid (HCl) initiates the alkalosis, but volume contraction from Cl^– loss maintains the alkalosis (due to increased proximal reabsorption of NaHCO₃ and secondary hyperaldosteronsim). Renal Cl^– reabsorption is high, and urine Cl^– is low (less than 20 mEq/L). In alkalosis, bicarbonaturia may force Na⁺ excretion as the accompanying cation even if volume depletion is present, and urine Cl^– is preferred to urine Na⁺ as a measure of extracellular volume. Diuretics are a common cause of metabolic alkalosis, but in this setting, the utility of urine Cl^– to assess volume is limited.

Metabolic alkalosis is generally associated with hypokalemia due to the direct effect of alkalosis on renal potassium excretion and secondary hyperaldosteronism from volume depletion. Hypokalemia exacerbates the metabolic alkalosis by increasing bicarbonate reabsorption in the proximal tubule and hydrogen ion secretion in the distal tubule. Administration of KCl will correct the disorder.

B. Saline-Unresponsive Alkalosis

1. Hyperaldosteronism

Primary hyperaldosteronism causes extracellular volume expansion and hypertension by increasing distal sodium reabsorption. Aldosterone increases H⁺ and K⁺ excretion, producing metabolic alkalosis and hypokalemia. In an attempt to decrease extracellular volume, high levels of NaCl are excreted resulting in a high urine Cl^– (greater than 20 mEq/L). Therapy with saline (NaCl) in this setting will only increase volume expansion and hypertension and will not treat the underlying problem of mineralocorticoid excess.

2. Alkali administration with decreased GFR

The normal kidney has a substantial capacity for bicarbonate excretion, protecting against metabolic alkalosis even with large HCO₃^– intake. However, urinary excretion of bicarbonate is inadequate in CKD. If large amounts of HCO₃^– are consumed, as with intensive antacid therapy, metabolic alkalosis will occur. Lactate, citrate, and gluconate can also cause metabolic alkalosis because they are metabolized to bicarbonate. In milk-alkali syndrome, sustained heavy ingestion of absorbable antacids and milk causes hypercalcemic kidney injury and metabolic alkalosis. Volume contraction from renal hypercalcemic effects exacerbates the alkalosis.

A. Symptoms and Signs

There are no characteristic symptoms or signs. Orthostatic hypotension may be encountered. Concomitant hypokalemia may cause weakness and hyporeflexia. Tetany and neuromuscular irritability occur rarely.

B. Laboratory Findings

The arterial blood pH and bicarbonate are elevated. With respiratory compensation, the arterial PCO₂ is increased. Serum potassium and chloride are decreased. There may be an increased anion gap. The urine Cl^– can differentiate between saline-responsive (less than 25 mEq/L) and unresponsive (greater than 40 mEq/L) causes.

Mild alkalosis is generally well tolerated. Severe or symptomatic alkalosis (pH > 7.60) requires urgent treatment.

A. Saline-Responsive Metabolic Alkalosis

Therapy for saline-responsive metabolic alkalosis is correction of the extracellular volume deficit with isotonic saline. Diuretics should be discontinued. H₂-blockers or proton pump inhibitors may be helpful in patients with alkalosis from nasogastric suctioning. If pulmonary or cardiovascular disease prohibits adequate resuscitation, acetazolamide will increase renal bicarbonate excretion. Hypokalemia may develop because bicarbonate excretion may induce kaliuresis. Severe cases, especially those with reduced kidney function, may require dialysis with low-bicarbonate dialysate.

B. Saline-Unresponsive Metabolic Alkalosis

Therapy for saline-unresponsive metabolic alkalosis includes surgical removal of a mineralocorticoid-producing tumor or blockage of aldosterone effect a mineralocorticoid antagonist (see Chapter 26).