I spoke about the urine anion gap with the @curbsiders but I want to emphasize what is oing on here:
In metabolic acidosis the kidneys try to excrete excess acid as ammonium NH4+. This is essential because even at a pH of 4.4, the hydrogen concentration is
In metabolic acidosis the kidneys try to excrete excess acid as ammonium NH4+. This is essential because even at a pH of 4.4, the hydrogen concentration is
The right answer is 0.04 mmol/L. To get rid of even a modest daily acid load of 50 mmol would require:
50 mmol of H+/ 0.04 mmol/L = 1,250 liters of urine
50 mmol of H+/ 0.04 mmol/L = 1,250 liters of urine
So the protons must be smuggled out and there are two choices: phosphate and ammonium. The trouble with phosphate is it cannot be ramped up. The amount of phosphate available to secrete is limited by dietary phosphorus intake.
The way to ramp up hydrogen excretion is to increase ammonia-genesis. The kidney responds to metabolic acidosis by increasing NH3 production. The NH3 is then converted to NH4+ which allows the kidney smuggle hydrogen into the urine without lowering the pH.
So detecting ammonium in the urine is a clue to a healthy kidney response to metabolic acidosis.
The easiest way to do this would be to directly measure urine NH4+ but...
The easiest way to do this would be to directly measure urine NH4+ but...
My understanding is that ammonium could be run on the same set up used to measure serum ammonia but it would require recalibration and labs don't want to do that for a low volume test.
The solution was to infer it’s presence by looking for the presence of an unmeasured cation by finding excess urine chloride.
Excess chloride = NH4+
No excess chloride = No NH4+
Excess chloride = NH4+
No excess chloride = No NH4+
This formula is an obvious over simplification. Chloride is not the only anion of note. We know that sulfates and phosphates are both anions. Calcium is another cation (but at low concentration).
And the CJASN article shows that it is laughably inaccurate
But even before there was empiric data, physicians found situations where the equation failed. There are disease states with excess pathologic anions in the urine. Ketones (specifically beta hydroxybutyrate if you must know) and hippurate.
Increased urinary hippurate happens with toluene exposure. Think glue sniffers and paint huffers.
Hippurte and beta-hydroxybutyrate are anions excreted in significant amounts so (Na + K) - Cl misses these unmeasured anions. The equation presumes that the only unmeasured ion is ammonium. These unmeasured anions blow-up the assumptions and the whole equation fails.
The equation will indicate an RTA when there is no RTA.
My equation skipped the contribution of glucose. If the patient has glucosuria, that will contribute to the urine osmolality and needs to be accounted for in the calculated osmolality. Add urinary glucose mg/dL divided by 18.
But what I really think you should do is use your brain and:
1. Correct the serum glucose so it is below 200
2. Recheck U/A
3. If the patient still has glucosuria realize that the patient has proximal tubule dysfunction and that the metabolic acidosis is proximal RTA (type 2)
1. Correct the serum glucose so it is below 200
2. Recheck U/A
3. If the patient still has glucosuria realize that the patient has proximal tubule dysfunction and that the metabolic acidosis is proximal RTA (type 2)
So that's it. What do you think?
Bonus question: Has anyone ever seen urine osmolar gap on a board exam? Please explain in replies
