Pathogenesis

The pathogenesis of metabolic alkalosis requires two processes: (1) generation and (2) maintenance. Generation occurs by net gain of bicarbonate ions [ ] or net loss of nonvolatile acid (usually HCl by vomiting) from the extracellular fluid. Although the kidneys have an impressive capacity to excrete under normal circumstances, in the maintenance stage of metabolic alkalosis, the kidneys fail to excrete , with retained because of volume contraction, a low glomerular filtration rate (GFR), or depletion of chloride (Cl ⁻ ) or potassium (K ⁺ ). Maintenance of metabolic alkalosis, therefore, represents a failure of the kidneys to eliminate in the usual manner. Retention, rather than excretion, of excess alkali by the kidney is promoted when (1) volume depletion, Cl ⁻ , and K ⁺ deficiency exist in combination with a reduced GFR, or (2) hypokalemia prevails because of autonomous hyperaldosteronism. In the first example, alkalosis is typically corrected by administration of NaCl and KCl, whereas, in the latter example, it is necessary to address the alkalosis by pharmacologic or surgical intervention rather than saline administration.

In assessing a patient with metabolic alkalosis, two questions should be considered: First, what is the source of alkali gain (or acid loss) that generated the alkalosis? Second, what mechanisms are operating to prevent excretion of excess , thereby maintaining, rather than correcting, the alkalosis?

Differential Diagnosis

To establish the cause of metabolic alkalosis ( Box 14.1 ), it is necessary to assess the extracellular fluid volume (ECV) status, the recumbent and upright blood pressure, and the serum potassium concentration ([K ⁺ ]). In hypertensive patients with chronic hypokalemia, it is also helpful to evaluate the renin-angiotensin system. For example, the presence of chronic hypertension and chronic hypokalemia in an alkalemic patient suggests either mineralocorticoid excess or a hypertensive patient receiving diuretics. Low plasma renin activity and urine [Na ⁺ ] and [Cl ⁻ ] values greater than 20 mEq/L in a hypertensive patient not taking diuretics are consistent with primary mineralocorticoid excess.

The combination of hypokalemia and alkalosis in a nonedematous patient with a low or normal BP can pose a challenging diagnostic problem. Possible causes include Bartter or Gitelman syndromes, magnesium deficiency, vomiting, exogenous alkali, and diuretic ingestion. Determination of urine electrolytes (especially [Cl ⁻ ]) and screening of the urine for diuretics may be helpful. When the urine chloride concentration is measured ( Table 14.1 ), it should be considered in context with assessment of the ECV status of the patient. A low urine [Cl ⁻ ] (i.e., <10 mEq/L) indicates avid Cl ⁻ retention by the kidney and denotes ECV depletion, even if the urine Na ⁺ is high (i.e., >20 mEq/L), whereas a high urine [Cl ⁻ ] in the absence of concurrent diuretic use suggests inappropriate chloride loss resulting from a renal tubular defect or mineralocorticoid excess. If the urine is alkaline with an elevated urine [Na ⁺ ] and [K ⁺ ], but the urine [Cl ⁻ ] is lower than 10 mEq/L, the diagnosis is usually either vomiting (overt or surreptitious) or alkali ingestion. If the urine is relatively acidic and has low concentrations of Na ⁺ , K ⁺ , and Cl ⁻ , the most likely possibilities are previous vomiting, the posthypercapnic state, or previous diuretic ingestion. If, on the other hand, neither the urine [Na ⁺ ], [K ⁺ ], nor [Cl ⁻ ] is depressed, magnesium deficiency, Bartter or Gitelman syndromes, or active diuretic use should be considered. Gitelman syndrome is distinguished from Bartter syndrome by the presence of hypocalciuria. In addition, hypomagnesemia may be present in both but is more common in Gitelman syndrome.

Metabolic Alkalosis Due to Exogenous Bicarbonate Loads