2. The normal concentrations of ammonia and other nitrogenous compounds in blood and other body fluids - Concentration of ammonia

It is important to acknowledge that the available reference values for plasma ammonia have only been validated in small numbers of probands. Therefore, the existing reference values should rather be regarded as “decision limits for use in clinical practice”.

Ideally, free flowing (central in neonates and infants) venous or even arterial blood should be used. In particular, capillary blood is not suited for ammonia determination because tissue fluid and disrupted cells will lead to artificial elevations. However, some hospitals use capillary blood in their emergency room for the exclusion of hyperammonaemia; the convenience of this approach is obviously the use of a bedside test.

In consequence, capillary blood can be used for the exclusion of hyperammonaemia, but a high value in capillary blood must be confirmed by appropriate testing. Ammonia is present in blood in a remarkably low – micromolar – concentration which will depend on the age of the patient.

Table 2 provides the SI unit first (in μmol/l); in addition, the table provides the conventional unit (in µg/dl) which is probably used less frequently. For conversion, you need to calculate: µg/dl x 0.5872 = μmol/l.

Please make sure, whenever you are dealing with a patient with hyperammonaemia, that you know which unit you and your lab are using. Otherwise, fatal miscommunication and misinterpretation might occur.

Any elevation of plasma ammonia needs to be taken seriously. Quite often, a slight increase is caused by pre-analytical problems so you should always seek a clear understanding of the situation and always immediately repeat the analysis if ammonia is elevated and immediately initiate therapy in symptomatic patients.

Urine ammonia is not a relevant method of testing for patients with hyperammonaemia because it mainly reflects the renal capacity for acid excretion.

Ammonia can also be measured in the cerebrospinal fluid (CSF) and concentrations are similar to those in plasma because ammonia, being a small water soluble molecule, can easily cross the blood-brain-barrier.

Concentrations of ammonia in tissues and within cells are higher and ammonia is particularly trapped as ammonium in compartments with a low pH (such as in lysosomes and in renal tubule cells). This is of clinical relevance because sample haemolysis will directly lead to an increase in ammonia concentrations.

Please remember: ammonia determination is an emergency procedure in any patient with unexplained loss of consciousness or any unexplained change of consciousness. This is true for any age group, especially as inherited disorders can present at any age.