3.4: The Urinary Anion Gap
- Page ID
- 10880
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The cations normally present in urine are Na+, K+, NH4+, Ca2+ and Mg2+. The anions normally present are Cl-, HCO3-, sulfate, phosphate and some organic anions. Only Na+, K+ and Cl- are commonly measured in urine so the other charged species are the unmeasured anions (UA) and cations (UC). Because of the requirement for macroscopic electroneutrality, total anion charge always equals total cation charge, so:
\[ Cl^{-} + UA = Na^{+} + K^{+} + UC \]
Rearranging:
\[ \text {Urinary Anion Gap} = (UA-UC) = [Na^{+}] + [K^{+}] - [Cl^{-}] \]
Clinical Use
Key Fact: The urinary anion gap can help to differentiate between GIT and renal causes of a hyperchloraemic metabolic acidosis.
It has been found experimentally that the Urinary Anion Gap (UAG) provides a rough index of urinary ammonium excretion. Ammonium is positively charged so a rise in its urinary concentration (ie increased unmeasured cations) will cause a fall in UAG as can be appreciated by inspection of the formula above.
How is this useful? Consider the following:
Step ONE: Metabolic acidosis can be divided into two groups based on the anion gap (AG):
- High anion gap acidosis
- Normal anion gap (or hyperchloraemic) acidosis.
It is easy to calculate the anion gap so this differentiation is easy and indeed clinically useful.
Step Two: Consider the hyperchloraemic group for further analysis. Hyperchloraemic acidosis can be caused by:
- Loss of base via the kidney (eg renal tubular acidosis)
- Loss of base via the bowel (eg diarrhoea).
- Gain of mineral acid (eg HCl infusion).
Step Three: Bowel or kidney as the cause?
Diagnosis between the above 3 groups of causes is usually clinically obvious, but occasionally it may be useful to have an extra aid to help in deciding between a loss of base via the kidneys or the bowel.
- If the acidosis is due to loss of base via the bowel then the kidneys can response appropriately by increasing ammonium excretion to cause a net loss of H+ from the body. The UAG would tend to be decreased, That is: increased NH4+ (with presumably increased Cl-) => increased UC =>decreased UAG.
- If the acidosis is due to loss of base via the kidney, then as the problem is with the kidney it is not able to increase ammonium excretion and the UAG will not be increased.
Does this work?
Experimentally, it has been found that patients with diarrhoea severe enough to cause hyperchloraemic acidosis have a negative UAG (average value -27 +/- 10 mmol/l) and patients with acidosis due to altered urinary acidification had a positive UAG. In many cases, the cause (gut or kidney) will be obvious, but occasionally calculation of the urinary anion gap can be useful.
Conclusion
In a patient with a hyperchloraemic metabolic acidosis:
- A negative UAG suggests GIT loss of bicarbonate (eg diarrhoea)
- A positive UAG suggests impaired renal distal acidification (ie renal tubular acidosis).
As a memory aid, remember neGUTive - negative UAG in bowel causes. For more details of the use of the UAG in differentiating causes of distal urinary acidification, see Batlle et al (1989).
Remember that is most cases the diagnosis may be clinically obvious (eg severe diarrhoea is hard to miss) and consideration of the urinary anion gap is not necessary.