Metabolic acidosis laboratory findings
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EditorInChief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)inChief: Rim Halaby, M.D. [2]
Overview
Metabolic acidosis is present when the blood bicarbonate concentration is decreased (<24 meq/L). The most important step in the evaluation of metabolic acidosis is to calculate the anion gap. Several laboratory measurements are useful in metabolic acidosis, such as arterial blood gas sampling, electrolytes, serum lactate and ketone concentrations, as well as toxicological screening (salicylate level, methanol, or ethylene glycol). The analysis of the urine electrolytes concentration might be useful in normal anion gap metabolic acidosis.
Laboratory Findings
Metabolic acidosis is present when the blood bicarbonate concentration is decreased (<24 meq/L). The evaluation of metabolic acidosis should target the following:
 Determine whether this is normal anion gap or high anion gap metabolic acidosis
 Determine whether metabolic acidosis is an isolated or combined process
 Determine whether respiratory compensation is appropriate or not
 Determine the underlying etiology of the metabolic acidosis
Laboratory tests include:
 Electrolytes plasma concentration to calculate the plasma anion gap:
 Plasma bicarbonate
 Plasma Na+
 Plasma Cl
 PCO2
 Arterial pH
 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^{}  HCO_{3}^{}) ❑ Consider measurement of albumin, Ca^{2+}, K^{+}, and Mg^{2+}  
High anion gap ❑ Screen for ketonuria (dipstick acetoactetae or plasma beta hydoxybutarate) ❑ Renal function ❑ Lactate concentration ❑ Toxin screen ❑ Osmolal gap  Normallow anion gap ❑ Urinary anion gap (Na^{+} + K^{+}  Cl^{})  
Note that, in case of ketonuria, urine acetoacetate might be initially absent.
Anion Gap
Calculation of Anion Gap
The anion gap can be calculated as follows:
Anion gap = Na^{+}  (Cl^{} + HCO3^{}) 
Note the following:
 If plasma glucose is elevated, use the measured Na^{+} concentration rather than the corrected one.
 The estimated anion gap is approximately 2.5 x the concentration of albumin.
 There is a decrease of the AG by 2.5 for every 1 g/dL decrease in plasma albumin.
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.
Anion gap  Interpretation 
High 

Low 

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 NH_{4}^{+}.
Urinary anion gap  Interpretation 
U (AG) < 0  Increased NH_{4}^{+} 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 
Plasma Osmolal Gap
Calculation of Plasma Osmolal Gap
The plasma osmolal gap can be useful in high anion gap metabolic acidosis. The plasma osmolal gap can be calculated as follows:
Plasma osmolal gap = plasma calculated osmolal gap  plasma measured osmolal gap Plasma osmolality= (2 x Na^{+}) + (Glucose/18) + (BUN/2.8) 
Interpretation of Plasma Osmolal Gap
The plasma osmolal gap is considered high if >10. A high osmolal gap represents an increase in unmeasured osmoles, such as in the cases of ingestion. The osmolal gap is also elevated in ketoacidosis and lactic acidosis.
Shown below is a table depicting the anion gap and osmolal gap in different types of ingestion.
Ingestion  Anion gap  Osmolal gap 
Ethanol  ↑  ↑ 
Methanol  ↑  ↑ 
Ethylene glycol  ↑  ↑ 
Formaldehyde  ↑  ↑ 
Ethylene glycol  ↑  ↑ 
Propylene glycol  ↑  ↑ 
Isopropyl alcohol  ↔  ↑ 
Acetaminophen  ↑  ↔ 
Salicylates  ↑  ↔ 
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 acidbase 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 PaCO_{2} = 1.2 [1 to 1.5] x Δ HCO_{3}^{} 
Note that compensation increases the pH but does not bring it to normal. If bicarbonate concentration is low and the pH is normal, this suggests a combined acidbase abnormality.
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  ↓  ↔  ↓ 
Δ Anion gap/Δ HCO3^{}
Calculation of Δ Anion gap/Δ HCO3^{}
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 Anion gap (AG)/ Δ HCO3^{} = (calculated AG  expected AG)/(calculated HCO3^{} expected HCO3^{}) 
Interpretation of Δ Anion gap/Δ HCO3^{}
Δ AG/ Δ HCO3^{}  Interpretation 
12  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 
Associated Potassium Disorders
Metabolic acidosis is commonly associated with hyperkalemia. As the H+ is low, K+ moves from inside the cell to the blood to ensure electrical neutrality.