Friday, February 19, 2010


Which one of the following is not a cause of elevated serum anion gap?
A. respiratory or metabolic alkalosis   27%
B. hypophosphatemia   36%
C. Metabolic acidosis associated with overproduction or decreased excretion of acid   27%
D. lab error  9%

The correct answer is hypophosphatemia.  This stem arose from a case we saw recently 
of a triple acid base disorder that had metabolic and resp alkalosis and an anion gap met 
acidosis as well.  The ph was 7.89 and the question arose, what are the causes of anion
gap? Can severe alkalemia cause an anion gap? 
An elevated gap can be produced by an increase in unmeasured anions or by a REDUCTION in unmeasured cations Usually we see the first kind and rule out MUDPILES ( the known causes of anion gap met acidosis). This leads to overproduction or decreased excretion of acid
Other minor causes are severe hypokalemia, hypocalcemia, hyperphosphetemia and hypomagnesemia. Severe alkalosis can lead to mild elevation in gap as well from three main factors:- volume depletion leading to 
an elevated albumin, increase in number of negative charges as ph is very alkalotic and slight increase in lactate  production as a compensatory response. Lab error is always a possibility
Hence the correct answer is hypophosphetemia as its the opposite that causes an elevated anion gap. A good reference is linked from CJASN


  1. T-diddy speaks, and the crowd hears:

    great post. i'm glad you brought this topic up. there's a great article on serum anion gap from CJASN. You can click here to get it if you wanna.



  3. Very interesting! Triple acid-base disorders always fascinate me.

    We have been using either ‘MUD-PILES’ or ‘KUSMALE’ as mnemonics for causes of anion gap metabolic acidosis ever since we learned about the anion gap. It is like they were handed over to us by Mother Nature herself! It is only when clinicians come up with newer ideas that we realize that they were created by mortal beings in the first place.

    Dr. Ankit Mehta and Dr. Joshua Emmett proposed a new mnemonic GOLD MARK, keeping in view the commoner causes of anion gap acidosis and disregarding the rare ones, specifically paraldehyde, isoniazid and iron. It was published in the Lancet in September 2008.

    Dr. Topf, on his blog ‘Precious bodily fluids’, has also shared the story about how the mnemonic came into being. Interested? Here’s the link:


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