Diagnostic evaluation of primary metabolic acidosis in children

BUN: blood urea nitrogen; Na: sodium concentration in mEq/L or mmol/L; Cl: chloride concentration mEq/L; HCO₃: serum bicarbonate concentration in mEq/L; K: potassium concentration in mEq/L; UAG: urine anion gap.

* Serum bicarbonate concentrations are lower in neonates and young infants, as discussed in the UpToDate topic on the approach to metabolic acidosis in children.

¶ Blood gas measurement can be performed either with an arterial or venous blood gas sample. The blood gas pH differentiates primary metabolic acidosis (pH <7.35) from compensated respiratory alkalosis with low bicarbonate.

Δ In some cases, there may be more than 1 cause of metabolic acidosis (mixed metabolic acidosis). As an example, a child with severe diarrhea may have normal anion gap due to intestinal bicarbonate loss along with high anion gap acidosis due to hypovolemia leading to impaired renal acid excretion. In this setting, the delta anion gap may be useful to confirm mixed metabolic acidosis when both high and normal anion gap causes coexist. Its use in pediatric metabolic acidosis is discussed in the UpToDate topic on the approach to metabolic acidosis in children.

• Delta anion gap ratio is defined as the change in anion gap (from a normal of 12 mmol/L) divided by the change in bicarbonate (from normal of 24 mmol/L)

◊ For most patients with metabolic acidosis, a basic metabolic panel has already been obtained, which includes serum electrolytes. Serum anion gap is calculated based on serum electrolyte values and is noted in many laboratory results when a basic metabolic panel is obtained. The following formula is typically used in the United States. The normal anion gap varies from 4 to 12 mEq/L and a high anion gap is defined as >12 mEq/L using this formula:

• Serum anion gap = Na – (Cl + HCO₃)

In some countries, K is also included in the formula. High anion gap is defined as >16 mEq/L if serum K is included.

• Serum anion gap = (Na + K) – (Cl + HCO₃)

§ For most patients with metabolic acidosis, a basic metabolic panel has already been obtained. Based on the history, physical findings, and results from initial testing, additional testing is performed and may include serum creatinine, lactic acid, urinary ketones, blood cultures, and serum osmolality.

¥ Osmol gap is the difference between the measured and calculated osmolality. The calculated osmolality is based on the osmol level of normal solutes that circulate in the serum/plasma. Osmol gap >10 to 15 mosm/L suggests the presence of an additional solute.

• Osmol gap = Measured osmolality – Calculated osmolality mmol/L
• Calculated osmolality = 2 × Na + [Glucose concentration (mg/dL)/18] + [BUN concentration (mg/dL)/2.8]

The serum sodium is multiplied by 2 to account for the osmolal contributions of the accompanying anions (chloride and bicarbonate), and the divisors 18 and 2.8 convert units of mg/dL to mmol/kg for glucose and BUN, respectively.

‡ UAG is calculated based on urine electrolyte values using the following formula. A positive value indicates reduction in urinary ammonia excretion due to limited renal acidification, as observed in patients with distal renal tubular acidosis. A negative result indicates intact ability of the kidney to excrete acid, as seen in patients with gastrointestinal loss of bicarbonate and proximal renal tubular acidosis.

• UAG (in mEq/L or mmol/L) = Urine (Na + K – Cl)