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Anion gap

ISSN 2398-2993

Synonym(s): Cations, anions


  • Anion gap is a calculated value.
  • The formulae rests on the principle that electroneutrality is essential in the body.
  • AG = measured cations - measured anions
    = (Na+ + K+) - (HCO3- + CL-)
    = or (Na+ + K+) - (TCO2- + CL-) since HCO3- is the major contributor to TCO2, and changes in TCO2 concentration are interpreted as changes in HCO3- (small amounts of TCO2 come from dissolved H2CO3 and carbamino acids) .
  • Anion gap is an indirect measurement of changes in the unmeasured cations or anions (compartments).
  • Clinically significant changes in unmeasured compartment (AG) are usually restricted to changes in unmeasured anions, since large changes in unmeasured cations are usually not compatible with life, eg hypercalcemia Calcium: overview and hypermagnesemia Magnesium: overview.
  • Changes in unmeasured compartment (AG) impact on circulating levels of measured ions.



  • Detect presence of unidentified anions, which can effect the concentration of measured ions.
  • One of the methods to suggest a metabolic acidosis on a chemistry panel without a blood gas.
    • AG increase results in metabolic acidosis.
    • TCO 2 = HCO 3-, thus a decrease in HCO 3- can also result in a metabolic acidosis.
  • Can help distinguish between titrational and secretory acidosis. Distinction between the two mechanisms is important to help characterize and localize a disease process.
  • Secretory acidosis - occurs due to a loss of HCO 3- from the body.
  • Titrational acidosis - occurs due to consumption of HCO 3- with increased amounts of acid .
  • Titrational acidosis: AG increase, HCO3- decrease, CL unchanged relative to Na.
  • Secretory acidosis: AG =Normal , HCO3- decrease, CL increase relative to Na.


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HCO3- / TCO2

  • HCO3- is calculated from the pH and PCO2 by the Henderson- Hasselbalch equation, if blood gases are available.
  • Automated method (does not require blood gases):
    • Acidifying: CO 2 in plasma to gaseous CO 2 by dilution with acid buffer. Then measure CO 2 by indirect ISE.
    • Alkalinizing: CO 2 and carbonic acid to bicarbonate (HCO 3- ), HCO 3- is then measured by an enzymatic reaction, eg Olympus: a 2 step enzymatic indirect measurement of HCO3- by the change in absorbance of UV light, proportional to the amount of NADH that is oxidized.
  • Point Of Care Testing (POCT), use miniaturized direct ISE undiluted whole blood with disposable microelectrodes.
  • Electrolytes(sodium, potassium, chloride, bicarbonate)
  • ISE (ion specific electrode) by undiluted and diluted sample.
  • Flame photometry, diluted sample (Na+, K+).
  • Coulombmetric techniques, colorimetric methods (CL-).


  • Sodium, Potassium and Chloride:
    • Widespread, most commercial and University laboratories, but TCO2 and HCO3- are limited due to time constraints within which sample must be measured (contact local hospital if laboratory is geographically to far away).
  • POCT
    • I STAT from Heska.
    • VetScan from QCR&TRIO diagnostics Ltd.
    • VetLyte Electrolyte analyser from Idexx VetLab.


Predictive value

  • POCT are reported to provide sufficient reliability, precision and accuracy for clinical use.

Technique intrinsic limitations

  • Intrinsic
    • Need to change the membrane periodically if use ISE method, because it becomes contaminated by ions that compete or react with the selected ion or protein coats the membrane resulting in errors.
    • Lack selectivity: Chloride electrodes (ISE) and the colorimetric methods lack selectivity against other halide ions. Thus when bromide is used as an anti epileptic therapy or in bromide toxicity the chloride will be elevated (Coulombmetric methods are selective and thus not effected).
    • POCT: not yet established a method to detect drifts or shifts in quality control, since many use disposable electrode cartridges
  • Extrinsic
    • In patients with hypoproteinemia, the magnitude of the base deficit due to organic anions may be underestimated when AG is used to detect UA and protein is not considered.
      (The ANION GAP is a WEAK tool in the presence of HYPOPROTEINEMIA).
    • Point of Care Testing: quality control must include assessment of operator competency, instrument function and reagent performance.

Result Data

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Further Reading


Refereed Papers

Other sources of information

  • Tietz Fundamentals of Clinical Biochemistry. 5th edn. Eds: Burtis C A & Ashwood E R. ISBN 0-72168634-6. pp 118, 494 - 516.
  • Clinical Biochemistry of Domestic Animals. 5th edn. Eds: Kaneko J J, Harvey J W & Bruss M L. ISBN 0-12-396305-2. pp 490 - 499.
  • Biochemical Profiling in the Dog and Cat (1999) Ralston Purina Company, Published by The Gloyd Group, Inc. Wilmington, Delaware.
  • Veterinary Laboratory Medicine. In: Clinical Pathology. Eds: Duncan J R, Prasse K W & Mahaffey E A. 3rd edn. ISBN 0-8138-1917-2. pp 96-101.
  • Small Animal Clinical Diagnosis by Laboratory Methods. 2nd edn. Willard, Tvedten, Turnwald. ISBN 0-5202-6. pp 105-113.
  • Di Bartola (1992) Fluid Therapy in Small Animal Practice. W B Saunders Company, ISBN 0-7216-3182-7. pp 207-209.