A 32-year-old woman is brought to the emergency department due to weakness, tingling, and numbness in her extremities. She takes no medications. Blood pressure is 110/70 mm Hg, pulse is 90/min, and respirations are 14/min. Physical examination is unremarkable. Laboratory results are as follows:
| Serum chemistry | |
| Sodium | 135 mEq/L |
| Potassium | 2.9 mEq/L |
| Chloride | 88 mEq/L |
| Bicarbonate | 37 mEq/L |
| Blood urea nitrogen | 22 mg/dL |
| Creatinine | 0.9 mg/dL |
| pH | 7.56 |
| Urine electrolytes | |
| Chloride | 7 mEq/L (normal: >20) |
| Sodium | 16 mEq/L (normal: >40) |
Which of the following is the most likely cause of this patient's condition?
Show Explanatory Sources
This patient's pH >7.45 and serum HCO3- >24 mEq/L is consistent with primary metabolic alkalosis. Measurement of urine chloride can be helpful in the differential diagnosis of metabolic alkalosis because adequate Cl- delivery to the distal renal tubules is necessary for excretion of HCO3-, which means that total body chloride depletion often plays an important role in the initiation and maintenance of metabolic alkalosis.
Etiologies of metabolic alkalosis that involve total body chloride depletion are characterized by hypovolemia and will demonstrate low urine chloride (<20 mEq/L). These types of metabolic alkalosis are considered saline responsive because repletion of Cl- with normal saline will normalize renal HCO3- excretion and correct the alkalosis. Such etiologies include:
Nasogastric suctioning or severe vomiting, which involves loss of H+ and Cl- (ie, hydrochloric acid) from the stomach.
Loop or thiazide diuretic overuse, which involves loss of Cl- and retention of HCO3- by the kidneys, eventually leading to total body chloride depletion (as well as hypovolemia). Of note, although these patients are overall chloride depleted, urine chloride may be high in the setting of recent diuretic ingestion (eg, within several hours of measurement).
Etiologies of metabolic alkalosis in the absence of chloride depletion include conditions of mineralocorticoid excess, such as primary hyperaldosteronism (Choice C). These patients are typically hypervolemic, and the metabolic alkalosis is primarily driven by aldosterone-mediated H+ loss from the kidneys. High urine chloride (>20 mEq/L) is present, and the metabolic alkalosis does not correct with Cl- repletion (saline unresponsive).
Autosomal recessive renal tubular channelopathies represent a special case. Bartter syndrome mimics loop diuretic overuse and Gitelman syndrome mimics thiazide diuretic overuse. Although affected patients are chloride depleted, high urine chloride is present because the defect persistently impairs renal Cl- reabsorption. The metabolic alkalosis is saline unresponsive, and kidney transplantation is the only definitive treatment.
(Choice A) Chronic hypoventilation (eg, obesity hypoventilation syndrome) causes a chronic respiratory acidosis. Low pH <7.35 is expected with high PaCO2 and a compensatory elevation in HCO3-.
(Choices B and E) Persistent diarrhea and renal tubular acidosis are typical causes of nonanion gap metabolic acidosis. Low pH is expected with low HCO3- and a compensatory decrease in PaCO2.
Educational objective:
Chloride is essential for renal excretion of HCO3- and total body chloride depletion often plays an important role in metabolic alkalosis. Etiologies of metabolic alkalosis characterized by chloride depletion include severe vomiting and diuretic overuse. These etiologies demonstrate low urine chloride (<20 mEq/L), and the alkalosis corrects with Cl- repletion (saline responsive).