Acid–base physiology

A lactic acidosis will be accompanied by a normal anion gap in the presence of which one of the following circumstances?

a) Concurrent diabetic ketoacidosis

b) Hypoalbuminaemia

c) Lithium poisoning

d) Intractable vomiting

e) Hypoaldosteronism

Answer: b

Explanation

The anion gap describes the apparent discrepancy between the summed concentrations

of the anions and cations that are commonly measured in the plasma. It is relevant when

considering the origin of a metabolic acidosis. It is, of course, an artefact of measurement

as laws of electrochemical neutrality dictate that the summed concentrations of the

anions and cations must be equal. It is the ‘unmeasured’ anions that account for the

gap. Commonlymeasured anions are Cl−, HCO3− and PO4 − while commonly measured cations are K+, Na+, Mg2+ and Ca2+. There are typically more unmeasured anions, and around 80% of these are the negatively charged molecule, albumin. Others include sulphate (SO4 2–), bromide (Br−), and other plasma proteins. Unmeasured cations consist

of some normal plasma proteins and notably the paraproteins found in multiple myeloma.

Although strictly one should sum all the cations measurable and compare to the sum of all the measurable anions, the anion gap is simplified to Na+ – (HCO3−+Cl−) with a reference range of 8 to 12mEq/L. Renal physicians often include potassium (K+) in the calculation, thus their range is a little higher. If acid is added to plasma, it will be buffered by HCO3 − whose concentration will fall. If the acid added is hydrochloric acid (H+Cl−) then the corresponding rise in Cl− concentration will render the anion gap unchanged. 

However, any other acid will decrease the HCO3 − level while adding unmeasured

anions to the plasma and the anion gap will increase. Typical examples of this include

ketoacids, lactic acid, urea, aspirin, ethylene glycol, methanol and ethanol. If HCO3

− is

lost from the plasma (e.g. diarrhoea, renal tubular acidosis, hypoaldosteronism) and

endogenous or exogenous Cl− restores electroneutrality then the anion gap is normal and

a hyperchloraemic acidosis has developed. Given that albumin accounts for the large

majority of ‘unmeasured’ anions, its significant influence on the anion gap should not be

overlooked. A fall in serum albumin concentration will cause a corresponding drop in

the anion gap, such that a hypoalbuminaemic patient with even a severe lactic acidosis

may have a normal anion gap.