Metabolic acidosis laboratory findings

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Laboratory Findings

Metabolic acidosis is present when the blood bicarbonate concentration is decreased (<24 meq/L). In order to determine the underlying etiology of the metabolic acidosis, the following laboratory measurements are needed to specify whether metabolic acidosis is an isolated or combined process and to calculate the plasma anion gap:

• Plasma bicarbonate
• PCO2
• Arterial pH
• Plasma Na+
• Plasma Cl-

In normal anion gap metabolic acidosis, additional measurement of urinary Na+, K+, and Cl- is needed in order to calculate urinary anion gap.

In high anion gap metabolic acidosis, the osmolal gap needs to be calculated; and therefore, blood sodium concentration, blood glucose, and BUN are needed.

Shown below is an algorithm depicting the series of laboratory tests needed to evaluate metabolic acidosis.

❑ Anion Gap (Na+ - Cl- - HCO3-) ❑ Consider measurement of albumin, Ca2+, K+, and Mg2+)

High anion gap ❑ Screen for ketonuria (dipstick acetoactetae or plasma beta hydoxybutarate) ❑ Renal function ❑ Lactate concentration ❑ Toxin screen ❑ Osmolal gap

Normal-low anion gap ❑ Urinary anion gap (Na+ + K+ - Cl-)

Anion Gap

Calculation of Anion Gap

The anion gap can be calculated as follows:

Anion gap = Na+ - (Cl- + HCO3-)

Interpretation of Anion Gap

Anion gap (AG) is: unmeasured anions - unmeasured cations

• Unmeasured anions include plasma proteins
• Unmeasured cations include calcium, potassium, magnesium

When an anion decrease, another anion must increase as a compensation to keep the electrolyte balance. In metabolic acidosis, a decrease in the bicarbonate is associate with an increase in another anion. For example, when bicarbonate decreases, chloride might increase as a compensation. In that case the anion gap remains within normal limits. If chloride does not increase following the decrease of bicarbonate, another unmeasured anion must increase leading to an increase in the anion gap.

Shown below is a table that summarizes the interpretation of the anion gap results. Note that a change in the unmeasured cation might lead to a change in the anion gap without any alteration in the acid base status.

High	Increased in unmeasured anions, OR Decrease in unmeasured cations such as calcium, potassium, magnesium
Low	Laboratory mistake (the most common etiology) Low albumin level: There is a decrease of the AG by 2.5 for every 1 g/dL decrease in plasma albumin, OR Increase in unmeasured cations such as calcium, potassium, magnesium Elevated cationic paraprotein (immunoglubulin G gammopathy) Ingestion of pyridostigmine bromide (used to treat myasteniagravis)

Urinary Anion Gap

Calculation of Urinary Anion Gap

The urinary anion gap must be calculated in normal anion gap metabolic acidosis. The anion gap can be calculated as follows:

Urinary anion gap = (Na+ + K+)- (Cl-

Interpretation of Urinary Anion Gap

Urinary anion gap= Unmeasured anion- unmeasured cations

The major unmeasured cation is NH₄⁺.

• U (AG) < 0 : Increased NH₄⁺ production to accompany the increased Cl^- which reflects that the kidneys are not the cause of the metabolic acidosis
• U(AG) ≥ 0: Impaired NH4+ production as in the case of renal failure, renal tubular acidosis type 1, renal tubular acidosis type 4

Hypochloremia vs Hypercholremia

The following equation can be used to assess the variation in chloride concentration in response to the metabolic acidosis: Na⁺/ Cl^-

• If Na⁺/ Cl^- < 1.4: Hyperchloremia (usually associated with normal anion gap metabolic acidosis)

• If Na⁺/ Cl^- > 1.4: Hypochloremia

Respiratory Compensation

In metabolic acidosis, there is respiratory compensation that starts within a short period of the onset of the acid-base disturbance. Respiratory alkalosis (through hyperventilation) occurs in order to decraese PaCO2 and therefore compensate for the metabolic acidosis.

The expected change in PaCo2 is as follows:

Expected respiratory compensation: Δ PaCO2 = 1.2 [1 to 1.5] x Δ HCO3-

Pure vs Combined Metabolic Acidosis

Pure vs combined metabolic acidosis can be estimated using the following values: plasma HCO3^-, PCO2, and arterial pH. Shown below is a table summarizing the findings in the different scenarios.

Acid base status	Plasma bicarbonate (meq/L)	Arterial pH	PCO2 (mmHg)
Normal	24	7.4	40
Pure metabolic acidosis	↓	↓	↓
Combined metabolic and respiratory acidosis	↓	↓	↔
Combined metabolic and respiratory alkalosis	↓	↔	↓

Pure high anion gap metabolic acidosis can be differentiated from combined metabolic acidosis by using the following equation: Δ Anion gap (AG)/ Δ HCO3^-

Δ AG/ Δ HCO3-	Interpretation
1-2	Pure high anion gap metabolic acidosis
<1	High anion gap metabolic acidosis PLUS normal anion gap metabolic acidosis
>2	High anion gap metabolic acidosis PLUS metabolic alkalosis

The following laboratory studies should be considered:

• Anion gap
• Arterial blood gas sampling
• ECG (to assess for arrhythmias)
• Electrolytes basic metabolic panel), complete blood count.
• Imaging of the kidneys
• Serum lactate, ketone
• Toxicological screening, salicylate level (methanol or ethylene glycol)
• Urinalysis can reveal acidity, (salicylate poisoning) or alkalinity (renal tubular acidosis type I), and ketones in ketoacidosis.