Anion Gap Formula
Measured cations + unmeasured cations = Measured anions + unmeasured anions.
Na+ + unmeasured cations = (Cl– + HCO3–) + unmeasured anions.
Anion gap (AG) = Na+ – (Cl– + HCO3–) = unmeasured anions – unmeasured cations.
The AG measures anions that are not normally included in routine electrolyte studies such as sulfates, phosphates, lactic acid, ketones, and other organic acids. Elevated AG acidosis occurs with organic acidosis, lactic acidosis, and DKA. Causes of normal AG acidosis include hyperchloremic acidosis, renal tubular acidosis, and acidosis secondary to bicarbonate wasting from the biliary tract and diarrhea.M
A normal anion gap is 8-12. Some sources say 8-14 but check with your lab as well.
The normal anion gap is 12 and it is made up mostly of albumin. See correction of AG for the level of albumin below.
NB: if there is hyperglycemia, use the measured, not correct sodium concentration to calculate the AG. Use the corrected sodium concentration to estimate the severity of dehydration in severe hyperglycemia.c
NB: Potassium has not included in the measured cations in this equation. Some providers include K+ so that the AG=(Na++ K+) – (Cl– + HCO3–). When this version is used, the normal value shifts by about 4 to account for the K+ that is included.
Two ways that Bicarb can be Lost to Produce AG vs Non-AG metabolic acidosis
**There are two ways to lose bicarb. One way is to combine it with an H+ from an acid leaving behind its conjugate base.
HCO3– + H+A– ↔ H2CO3 + A– ↔ CO2 +H2O + A–
The conjugate base (A–) then increases the measured anion gap. The causes of a high anion gap metabolic acidosis cause bicarb to be lost in this way.
The second to lose bicarb is to simply lose it as in diarrhea. You get a non-anion gap metabolic acidosis. Think of the causes of non-anion gap metabolic acidosis. That is what happens.
Albumin and the AG
A normal AG reflects the concentration of non-bicarbonate anion buffers such as albumin, phosphate, sulfate, and other organic acids.T Albumin (which has a net negative charge) is the single largest contributor to the AGU. Because of that, the AG must be adjusted downward in patients with hypoalbuminemia and upwards in patients with hyperalbuminemia.
Expected AG = [Abumin] x 2.5
The expected AG = 4 x 2.5 = 10 if the albumin is 4.
The reason for the above formula is that the expected AG decreases by approximately 2.5 mEq/L for every 1 g/dL decrease in the serum albumin concentration and also increases by the same 2.5 mEq/L for every 1 g/dL increase in serum albumin concentration.x
Normal values for albumin are 3.5 to 5.5 g/dL with 4 g/dL as the average.
A high AG necessitates delta gap or Delta ratio calculation to screen for additional acid-based disorders
“Elevated AG usually represents an abnormal accumulation of either endogenous or exogenous unmeasured anions and indicates a primary disorder (a metabolic acidosis), regardless of the pH or the serum bicarbonate (HCO3–). The substantial increase in unmeasured anions–which make the AG– will be accompanied by an equimolar decrease in bicarbonate unless the bicarbonate level is altered by another concomitant metabolic acid-base disturbance. Therefore, when AG metabolic acidosis is diagnosed, it is imperative to screen for the presence of additional acid-base abnormalities (called mixed metabolic acid-base disorders).”T
See how to calculate delta-delta or delta gap.
References / Notes
C. Cleveland Clinic Journal of Medicine. 2001 August;68(8):673-674. Should the actual or the corrected serum sodium be used to calculate the anion gap in diabetic ketoacidosis? Author: Laurence H. Beck, MD
U. https://www.uptodate.com/contents/the-delta-anion-gap-delta-hco3-ratio-in-patients-with-a-high-anion-gap-metabolic-acidosis
X. J Lab Clin Med. 2005 Dec;146(6):317-20. Influence of hypoalbuminemia or hyperalbuminemia on the serum anion gap. https://www.ncbi.nlm.nih.gov/pubmed/16310513
M. https://www.mdedge.com/jfponline/quiz/5857/nephrology/fluids-and-electrolytes
T. Tsapenko MV. Modified delta gap equation for quick evaluation of mixed metabolic Acid-base disorders. Oman Med J. 2013;28(1):73–74. doi:10.5001/omj.2013.18