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.
Table 21–15.Metabolic alkalosis. ||Download (.pdf) Table 21–15. Metabolic alkalosis.
|Saline-Responsive (UCl < 20 mEq/L) ||Saline-Unresponsive (UCl > 40 mEq/L) |
Excessive body bicarbonate content
Diuretic therapy (after diuretic effect has ceased)
Poorly reabsorbable anion therapy: carbenicillin, penicillin, sulfate, phosphate
Loss of HCl from vomiting or nasogastric suction
Intestinal alkalosis: chloride diarrhea
NaHCO3 (baking soda)
Sodium citrate, lactate, gluconate, acetate
Normal body bicarbonate content
Excessive body bicarbonate content
Bartter syndrome (renal salt wasting and secondary hyperaldosteronism)
Severe potassium depletion
Hypercalcemia and hypoparathyroidism
Adrenal enzyme (11-beta-hydroxylase and 17-alpha-hydroxylase) deficiency
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
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.