An old gentleman with diabetes mellitus was admitted because of severe diarrhoea leading to acute renal impairment, metabolic acidosis, and a serum glucose of 18 mmol/L, with positive urinary ketones. Diabetic ketoacidosis was initially suspected, but the serum anion gap was persistently normal. The diabetes was easily under control and diarrhoea persisted for few days and then subsided. Last serum anion gap remained normal to slighltly raised even after correcting for a lowish albumin, and patient was hyperventilating due to persistent hyperchloremic acidosis. The urinary anion gap (UAG) was checked to distinguish between the loss of base via the kidney (eg renal tubular acidosis) or loss of base via the bowel. Which of the following is incorrect?
A. The cations normally present in urine are Na+, K+, NH4+, Ca++ and Mg++.
B. The anions normally present are Cl-, HCO3-, sulphate, phosphate and some organic anions.
C. Urinary Anion Gap = ( Unmeasured anions – Unmeasured cations ) = [Na+]+ [K+] – [Cl-]
D. Patients with diarrhoea severe enough to cause hyperchloraemic acidosis have a very positive UAG.
Answer: D
To maintain electroneutrality: Cl–, HCO3–, sulphate, phosphate and some organic anions = Na+, K+, NH4+, Ca++ and Mg++
But as we normally only measure Na, K and Cl: Cl + UA = Na, K + UC; where UA is unmeasured anions, UC = unmeasure cations including the ammonium anion, and so UAG = UA – UC = Na + K – Cl. Normal value is usually quoted as -10 to +10 mmol/L.
If the acidosis is due to bowel loss of base, the kidneys respond by increasing ammonium (part of UC, and excreted with Cl- ) excretion to cause a net loss of H+ from the body. The UAG would tend to be decreased. It has been found that patients with diarrhoea severe enough to cause hyperchloraemic acidosis have a negative UAG (average value -27 +/- 10 mmol/l).
In short, in a patient with a hyperchloremic metabolic acidosis:
– A negative UAG suggests GI loss of bicarbonate (eg diarrhea)
– A positive UAG suggests impaired renal acidification (ie renal tubular acidosis).
It is easy to remember the mnemonic, "neGUTive" – negative UAG from the GUT!
Reference
1. Acid-base physiology
2. DC Batlle, M Hizon, E Cohen, C Gutterman, and R Gupta. The use of the urinary anion gap in the diagnosis of hyperchloremic metabolic acidosis. NEJM. Volume 318:594-599 March 10, 1988 Number 10.
Abstract:
We evaluated the use of the urinary anion gap (sodium plus potassium minus chloride) in assessing hyperchloremic metabolic acidosis in 38 patients with altered distal urinary acidification and in 8 patients with diarrhea.
– In seven normal subjects given ammonium chloride for three days, the anion gap was negative (-27 +/- 9.8 mmol per liter) and the urinary pH under 5.3 (4.9 +/- 0.03).
– In the eight patients with diarrhea the anion gap was also negative (-20 +/- 5.7 mmol per liter), even though the urinary pH was above 5.3 (5.64 +/- 0.14).
– In contrast, the anion gap was positive in all patients with altered urinary acidification, who were classified as having classic renal tubular acidosis (23 +/- 4.1 mmol per liter, 11 patients), hyperkalemic distal renal tubular acidosis (30 +/- 4.2, 12 patients), or selective aldosterone deficiency (39 +/- 4.2, 15 patients).
When the data on all subjects studied were pooled, a negative correlation was found between the urinary ammonium level and the urinary anion gap.
We conclude that the use of the urinary anion gap, as a rough index of urinary ammonium, may be helpful in the initial evaluation of hyperchloremic metabolic acidosis. A negative anion gap suggests gastrointestinal loss of bicarbonate, whereas a positive anion gap suggests the presence of altered distal urinary acidification.