Clinical Case 74: Answers and Summary

True or False: The standard measurement of anion gap will miss lactic acidosis if the lactate level is <10

True	24 (72%)
False	9 (27%)

Anion gap will miss lactic acidosis if lactate <10.
misses 50% lactate 5-10,
misses 80% if Lactate 3-5

Interesting, many cases would be missed if we just relied on the anion gap. Interestingly, such an old study done in 1990s: probably worth re looking at this phenomenon and why?

Topic Discussion: Anion Gap

What are the limitations of the anion gap use? A recent article in CJASN has some key points.

A.Uses of anion gap
1. evaluate met acidosis
2. detect paraproteins
B. Classically AG has been using HCO3, Cl and Na for calculations. Should K be used? The rationale for not using K is because the absolute change in its concentration observed clinically is small. It might be useful if the K is too low or too high. So if K was 7meEg/L, it should be included in the calculation.
C. Based on the research done on what normal AG is, the span of population is from 8-10meq/L.

D. Figge equation: correction for albumin
So corrected AG= anion gap + 0.25 *( normal albumin- measured albumin (g/dl)
E. Interestingly the article points out from their review that the sensitivity of increased anion gap in detecting hyperlactatemia is very poor. Range is from 44% to 78%. If lactic acidosis is suspected, perhaps directly measuring that rather than relying on AG might be useful.
F. Baseline value for individuals AG to optimize the use of the calculation of AG in the detection of acidosis is what the authors suggest.

CLINICAL CASE 52: ANSWERS and SUMMARY

TRUE OR FALSE: SEVERE METABOLIC OR RESPIRATORY ALKALOSIS CAN LEAD TO AN ANION GAP METABOLIC ACIDOSIS.

True 60%

False 40%

Severe alkalemia can cause an increase in anion gap.  Alkalemia leads to glycolysis in the liver and a mild lactic acidosis. In severe volume contracted state, the anion gap can be seen with change in valence of circulating proteins to preserve extracellular volume.  

A prior post had discussed this as well. 

See the references below:

Emmett M, Narins R. Clinical use of the anion gap. Medicine 1977; 56:38–45.

Kraut J, Madias N. Serum anion gap: its uses and limitations in clinical medicine. Clin J Am Soc Nephrol 2007; 2: 162–174.

TOPIC DISCUSSION: Low or negative Anion gap!

 We often encounter positive anion gaps and know very well the causes of + anion gap.

In certain clinical settings,one can also see a low, zero or negative anion gap.
What are the causes that one has to consider in a low anion gap?
If one considers Na, K, Mg, Ca and immunoglobulins (IgG) as + cations and Cl, Bicarb, Phos, IgA and Phos as negative anions then the anion gap is the balance of these substances. Usually normal is 10-12.
So if one increases the + cations or decreases the - anions, you can have a negative or low anion gap.

Hence the causes are obvious
1. Hyperkalemia, Mg and Calcemia
2. elevated paraproteins( igG usually)-- one of the classic causes and whenever you see a low or negative anion gap, think paraproteinemias
3. decreased albumin or phosphorus
4. Lithium( increases the Cationic side)
5. Unmeasured cations like bromide or iodine or triglycerides can also do it
6. Lab error( most common cause)
7. Severe hypernatremia
8. Spurious elevation of HCo3 if cells are not separated from the sera
9. Over estimation of Cl ion

Out of these the ones to cause a negative anion gap more than low anion gap are lab errors, paraproteins, bromide and iodine intoxication.

Something to keep in mind while we walk the wards!
A nice review is here

http://www.ncbi.nlm.nih.gov/pubmed/17699401
http://www.pbfluids.com/2009/08/high-osmolar-gap-and-low-anion-gap.html