Reduced anion gap solves clinical puzzle - a case history

The anion gap (AG) is a calculated parameter derived from measured plasma electrolyte concentrations that is most frequently used to elucidate acid-base disturbances in the critically ill. It is defined as the difference between measured anions and cations in blood plasma and is calculated by subtracting the sum of chloride and bicarbonate concentration from plasma sodium concentration. 

In healthy individuals this difference is between 7 and 10 mmol/L. Increased AG, which is far more common than reduced AG, is a feature of most cases of metabolic acidosis; in some cases of metabolic acidosis however, AG remains within the normal range. So AG has proven helpful in the differential diagnosis of metabolic acidosis. 

Conditions associated with reduced AG are relatively few and individually rare but the finding of reduced AG can, like increased AG, be diagnostically useful as a recently published case history demonstrates.  The case concerns a 50 year old African American gentleman with sickle cell disease and chronic kidney disease who was admitted to hospital because of his deteriorating condition. 

This was assumed to be due to a sickle cell crisis evidenced by severe anaemia and increasing bone pain.  The anemia did not however appear to be haemolytic in nature as would be expected in sickle cell crisis, and despite blood transfusion, grew worse. After four days in hospital his condition further deteriorated with change in mental status (drowsiness, disorientation and slurred speech) that progressed to stupor.  

There was concern that this man was dying.  Laboratory testing at this time revealed plasma sodium 131 mmol/L, plasma chloride 112 mmol/L and plasma bicarbonate 19 mmol/L allowing a calculated AG of 0. Review of patient notes revealed he had a persistently reduced AG over the previous six months. 

Attending physicians focused on this ‘surprising’ rare finding and began considering the causes of reduced AG that might explain the patient’s condition.  This finally led to a diagnosis of multiple myeloma, a malignancy of the bone marrow characterised by anemia and bone pain. The patient’s condition improved after 14 days myeloma treatment, by which time he had returned to his condition prior to hospital admission. 

This case history is instructive in that it reminds that the clinical utility of AG is not confined to investigation of acid base-disturbance. It also confirms that myeloma can cause reduced AG, and that AG is dependent as much on unmeasured anions and cations as on those that are measured. In myeloma it is the marked increased in cationic protein (IgG paraprotein) in plasma that causes the reduced AG. 

In discussion of the case history the authors expand on the link between myeloma and reduced AG  and consider other causes of reduced AG.