Mind the Gap

As Nate mentioned in a previous post, the urinary anion gap is helpful in differentiating whether a non-gap acidosis is of renal or extra-renal origin.

Urinary Anion Gap = Na + K – Cl

Because the major cation in the urine is NH4, this gives you a rough estimate of the NH4 level. In the setting of a distal RTA, the urine NH4 should be low and therefore there should be a positive anion gap. The problem with this test is that if there is some other unmeasured anion (e.g. ketoacids or hippurate following glue-sniffing) or even if the patient’s diet leads to significant changes in PO4 or SO4 excretion, it can be very inaccurate. One alternative suggested by Mitch Halperin is to measure the urinary osmolar gap. This is more useful because it detects the NH4 excretion regardless of the anion that is excreted along with it.

Urine Osmolar Gap = measured Uosm – calculated Uosm

Calculated Uosm = 2(Na + K) + Urea (mmol) + Glucose (mmol)

Because the other major cation in the urine is NH4 and this must be matched by an accompanying anion, most of the gap is therefore made up of NH4, giving you this formula.

Urinary NH4 = Urinary Osmolar Gap/2

The osmolar gap must be divided by two in order to account for the anion being excreted with NH4. Of course, this would all be easier if we could measure the NH4 directly. In our hospital, the assay for measuring NH4 is an enzymatic method using glutamate dehydrogenase. The lab was not able to give me a specific answer as to why they could not use this test on urine but looking around the net, it appears that it is not useful for measuring large quantities of NH4. The normal value in the serum is <35 µmol/L while in the setting of a metabolic acidosis, urine levels should be >200 mmol/day, orders of magnitude higher. So it seems for the moment that we are stuck with the osmolar gap as the best estimate in many hospitals.

Ref: Fluid, Electrolyte and Acid-Base Physiology, Halperin 2010