Approach
Systematic evaluation of acid-base status of the patient provides insight into the underlying medical problem. The differential diagnosis of the cause of metabolic alkalosis can be narrowed down by clinical evaluation and laboratory investigation.
Clinical evaluation
The evaluation of the patient with metabolic alkalosis begins with ascertaining whether there is volume depletion leading to chloride depletion.
A history of vomiting, nasogastric suction or drainage, diuretic use, cystic fibrosis, hypercapnia, or excessive bicarbonate (HCO₃) or alkali intake should be sought.
Patients may present with tingling, muscle cramps, weakness, cardiac arrhythmias, and/or seizures.[5][20][21] Some of these symptoms may be due to a decrease in circulating ionized calcium, which results from the greater binding to albumin when pH is high. It is important to note that patients may develop serious or even fatal arrhythmias and/or seizures without preceding symptoms.
There are no specific signs of metabolic alkalosis, but examination may provide clues to the underlying cause.
Occasionally, compensatory metabolic alkalosis is an incidental finding in patients with chronic respiratory acidosis.
Investigations
These clinical conditions with acid-base disorders can be effectively evaluated by a stepwise pathophysiologic approach.
Arterial blood gas (ABG) and urinary chloride concentration measurements should be requested and the data interpreted using the following steps:
Determine the disturbance in pH:
Arterial pH indicates the ongoing disturbance -- alkalosis versus acidosis.
At sea level the normal pH is 7.42±0.02.
Increase in arterial pH >7.45 suggests that the major ongoing disturbance is alkalosis.
Identify the primary disorder:
To determine the primary disorder, examine the directional changes of serum HCO₃ and arterial partial pressure of carbon dioxide (PaCO₂) from the normal and their relation with change in arterial pH.
If the pH is high and HCO₃ is high (>24 mEq/L), then the primary disorder is metabolic alkalosis.
Assess compensation in response to the primary disorder:
With simple metabolic alkalosis, the normal adaptive respiratory response increases the arterial PaCO₂ by 0.25 to 1 times the increase in serum HCO₃.
Determine the type of metabolic alkalosis:
In general, the urinary chloride concentration is >20 mEq/L in patients who do not respond to volume expansion with normal saline (chloride-resistant metabolic alkalosis), whereas it is <10 mEq/L in those who do respond to volume expansion (chloride-responsive metabolic alkalosis).[22]
Further investigations to determine the underlying cause of metabolic alkalosis are performed based on the history and examination findings.
Further investigation in chloride-resistant metabolic alkalosis
Serum potassium is a useful first test in some conditions, including primary hyperaldosteronism, apparent mineralocorticoid excess, Liddle syndrome, Bartter syndrome, Gitelman syndrome, profound potassium depletion, and licorice ingestion.
Serum aldosterone and serum renin activity should be measured in patients with hypertension and a history compatible with primary hyperaldosteronism, secondary hyperaldosteronism, renal artery stenosis, apparent mineralocorticoid excess, or Liddle syndrome.
Further investigations in hypertensive patients are indicated as follows:
If there are clinical features of Cushing syndrome, diagnosis is confirmed with 24-hour urinary free cortisol and a corticotropin-releasing hormone stimulation test with dexamethasone suppression test.[7]
24-hour urine aldosterone is measured in primary hyperaldosteronism.
24-hour urinary free cortisol to cortisone ratio is useful in conjunction with the history in confirming licorice ingestion.
Renal artery stenosis should be confirmed with duplex renal ultrasound.
In the absence of hypertension, but with features in the history or examination suggestive of Bartter syndrome or Gitelman syndrome, measurement of serum potassium, as well as urinary calcium and chloride, is indicated. Serum magnesium is low in Gitelman syndrome, differentiating it from Bartter syndrome.
Further tests in nonhypertensive patients are as follows:
Serum calcium and parathyroid hormone are indicated if hypercalcemia of nonhyperparathyroid etiology is a potential diagnosis.
Serum phosphate should be monitored in poststarvation refeeding syndrome.
A urinary drug screen would detect any current diuretic therapy if not evident from the history. It is not routinely done but can be performed if the cause of the alkalosis is not readily apparent.
Further investigation in chloride-responsive metabolic alkalosis
Urinary and fecal chloride should be measured in patients with excessive gastrointestinal secretion losses (vomiting, gastric drainage, villous adenoma of colon, congenital chloride diarrhea).
A sweat test and genetic testing are indicated if cystic fibrosis is suspected.
Diagnosis is clinical in cases of postdiuretic therapy, HCO₃ administration, and milk-alkali syndrome, and no further testing is required.
In the scenario of posthypercapnia, elevated PaCO₂ would have been detected on the ABG analysis.
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