What is the optimal clinical approach to the patient with metabolic alkalosis?
A concise and clinically relevant approach to the patient with metabolic alkalosis. The first step is to rule out the common causes of metabolic alkalosis: vomiting and use of diuretics. Although this may be evident from the clinical history, some patients may deny the intake of diuretics or previous vomiting. Examining the urine electrolytes is particularly helpful for this diagnosis. The traditional classification distinguishes those with Cl − -responsive alkalosis from those with Cl − -unresponsive alkalosis, so begin with the concentration of Cl − in the urine (U Cl ). A very low U Cl is expected when there is a deficit of HCl and/or NaCl as in vomiting. The recent intake of diuretics will cause the urinary excretion of Na + and Cl − to be elevated. However, note that after diuretic action wears off, U Cl will be low, so that diuretics should be seen as causing Cl − -responsive alkalosis. The U Na may be high if there is a recent episode of vomiting, representing further generation of metabolic alkalosis, in which case bicarbonaturia and higher urine pH are expected. This increase in U Na during the generation of metabolic alkalosis is why the U Cl is considered the best test because it is low whether the patient is in the generation or maintenance phases.
Another state of Cl − -responsive metabolic alkalosis is posthypercapneic metabolic alkalosis. This occurs in patients with chronic respiratory acidosis whose metabolic compensation in response to increases in PCO 2 leads to increases in serum [HCO 3 − ]. If exacerbation of pulmonary disease leads to sudden intubation and some degree of hyperventilation with a decrease in PCO 2 , the bicarbonate is now high, the PCO 2 is near normal, and metabolic alkalosis is present. This posthypercapneic alkalosis is a state of Cl − depletion as the kidneys were responding to the respiratory acidosis by preferentially reabsorbing Na + in the PCT with HCO 3 − and excreting Cl − . Correction of the serum [HCO 3 − ] will occur only when Cl − is administered. Because giving Na + is often undesirable in such situations, when heart failure may be present and the goal is to keep the alveoli dry, KCl is usually the preferred therapy.
Cl − -unresponsive metabolic alkalosis is generally associated with syndromes that have increased mineralocorticoid activity. If the U Cl is not low, assessment of effective arterial blood volume and blood pressure will help diagnose patients with disorders of high primary mineralocorticoid activity (effective arterial blood volume is not low, hypertension is present). These patients may be separated from those with syndromes causing tubular dysfunction of normal Na + -reabsorptive processes. These patients resemble those taking diuretics because they have mutations in genes coding for Na + transporters. Patients with mutations in genes that lead to changes in the activity of the K-dependent sodium chloride transporter in the thick ascending limb of the loop of Henle have Bartter syndrome and have a phenotype similar to those taking loop diuretics. Those with mutations causing dysfunction in the sodium chloride cotransporter expressed in the distal tubule have Gitelman syndrome and appear as though they are taking thiazides. Both have low effective arterial blood volume with the absence of hypertension. Both have hypokalemia and metabolic alkalosis. However, the patients with Gitelman have low urine calcium, consistent with the effects of thiazides, whereas those with Bartter have increased urine calcium, consistent with the effect of loop diuretics. Another secret for distinguishing genetic abnormalities from surreptitious diuretic use is serial measurements of U Cl in spot urine samples. Patients with Bartter or Gitelman syndromes should have persistently high U Cl , whereas those with diuretic abuse will have intermittently high U Cl .
