Metabolic Alkalosis Workup

Metabolic alkalosis is diagnosed by measuring serum electrolytes and arterial blood gases. If the etiology of metabolic alkalosis is not clear from the clinical history and physical examination, including drug use and the presence of hypertension, then a urine chloride ion concentration can be obtained. Metabolic alkalosis secondary to volume depletion is usually associated with a low urine chloride ion concentration (< 20 mEq/L).

For an algorithmic approach metabolic alkalosis, see the image below.

Calculation of the serum anion gap may help to differentiate between primary metabolic alkalosis and metabolic compensation for respiratory acidosis. The anion gap is frequently elevated to a modest degree in metabolic alkalosis because of the increase in the negative charge of albumin and the enhanced production of lactate.

Normal values for the anion gap vary in different laboratories and between individual patients, however, so it is important to know the range of normal for the particular clinical laboratory and the prevailing baseline value for a particular patient.^[4] In any event, the only definitive way to diagnose metabolic alkalosis is with a simultaneous blood gases analysis that shows elevation of both pH and PaCO₂ and increased calculated bicarbonate.

Serum bicarbonate concentration can be calculated from a blood gas sample using the Henderson-Hasselbalch equation, as follows:

pH = 6.10 + log (HCO₃^- ÷ 0.03 × PaCO₂)

Alternatively, HCO₃^- = 24 × PaCO₂ ÷ [H⁺]

Because pH and PaCO₂ are directly measured, bicarbonate can be calculated.

Another means of assessing serum bicarbonate concentration is with the total carbon dioxide content in serum, which is routinely measured with serum electrolytes obtained from venous blood. In this method, a strong acid is added to serum, which interacts with bicarbonate in the serum sample, forming carbonic acid. Carbonic acid dissociates to carbon dioxide and water; then, carbon dioxide is measured.

Note that the carbon dioxide measured includes bicarbonate and dissolved carbon dioxide. The contribution of dissolved carbon dioxide is quite small (0.03 × PaCO₂) and is usually ignored, although it accounts for a difference of 1-3 mEq/L between the measured total carbon dioxide content in venous blood and the calculated bicarbonate in arterial blood. Thus, at a PaCO₂ of 40, a total carbon dioxide content of 25 means a true bicarbonate concentration of 23.8 (ie, 25 - 0.03 × 40).

The Henderson-Hasselbalch equation may fail to account for acid-base findings in critically ill patients. An alternative method of acid-base analysis, known as the quantitative, or strong ion, approach,^[5] determines pH on the basis of the following 3 independent variables (see Metabolic Acidosis):

• Strong ion difference (SID): Ions almost completely dissociated at physiologic pH (the cations Na⁺, K⁺, Ca⁺, and Mg⁺, and the anions Cl^- and lactate)
• Total weak acid concentration: Ions that can be dissociated or associated at physiologic pH (albumin and phosphate)
• pCO₂ (mm Hg)

In a study that compared the conventional Henderson-Hasselbalch equation with the strong ion approach, carried out in 100 patients with trauma who were admitted to a surgical intensive care unit, the investigators concluded that the strong ion approach provides a more accurate means of diagnosing acid-base disorders, including metabolic alkalosis and tertiary disorders.^[6]

Measurement of urine sodium ion concentration is used in many conditions to determine volume status, especially in patients with oliguria. However, volume depletion in metabolic alkalosis may not lead to low urine sodium. In the first few days of vomiting, the loss of acidic gastric secretions leads to an increase in serum bicarbonate concentration. The kidneys try to excrete the excess bicarbonate as the sodium or potassium salt. Therefore, despite volume depletion, the urine sodium level may be inappropriately high.

Measuring the plasma renin activity and aldosterone level may help in finding the etiology of metabolic alkalosis, especially in patients with hypertension, hypokalemic metabolic alkalosis, and renal potassium wasting without diuretic use. Low renin activity and high plasma aldosterone levels are found in primary hyperaldosteronism, including glucocorticoid-remediable hyperaldosteronism.

Low plasma renin activity and aldosterone levels are found in the following circumstances:

• Cushing syndrome
• Exogenous steroid use
• Congenital adrenal hyperplasia (CAH)
• 11-beta-hydroxysteroid dehydrogenase (11B-HSD) deficiency
• deoxycorticosterone (DOC)-secreting tumors
• Liddle syndrome

High plasma renin activity and aldosterone levels are found in the following circumstances:

• Renal artery stenosis
• Diuretic use
• Renin-secreting tumors
• Bartter syndrome
• Gitelman syndrome

Measure aldosterone levels in a 24-hour urine collection after salt loading to diagnose primary hyperaldosteronism.

To test for Cushing syndrome, measure plasma cortisol at midnight during sleep or free cortisol in a 24-hour urine study, or perform a dexamethasone suppression test.

Measurement of urine cortisol metabolites is used to diagnose the syndrome of apparent mineralocorticoid excess (AME). In AME and other conditions of 11B-HSD deficiency, the proportion of cortisol to cortisone metabolites is increased (ie, ratio of tetrahydrocortisol and 5-alpha-tetrahydrocortisol to tetrahydrocortisone).

In 11-hydroxylase deficiency, plasma and urine levels of DOC and 11-deoxycortisol are high. In 17-hydroxylase deficiency, DOC is elevated while 11-deoxycortisol is low. Another important difference between the 2 conditions is the impaired adrenal androgen synthesis in the latter and enhanced synthesis in the former. Therefore, measuring plasma or urine adrenal androgens (eg, dehydroepiandrosterone [DHEA], testosterone) may help to differentiate between the 2 conditions.

Obtain a urine diuretics screen to exclude surreptitious diuretic use in patients having unexplained hypokalemic metabolic alkalosis.

Perform adrenal imaging studies (eg, CT scan, MRI) to find the etiology of primary hyperaldosteronism, Cushing syndrome, and DOC excess.

Renal Doppler ultrasound, captopril renogram, MRI, and renal angiography are helpful in diagnosing renovascular hypertension (ie, significant renal artery stenosis). The preferred imaging method is controversial. For more information, see Imaging in Renal Artery Stenosis/Renovascular Hypertension.

Gene analysis is helpful to diagnose inherited causes of hypokalemic alkalosis. Examples are Liddle syndrome, glucocorticoid-remediable hypertension, Bartter syndrome, Gitelman syndrome, syndrome of AME, and CAH.