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Anion Gap

OVERVIEW

Anion Gap = Na+ – (Cl- + HCO3-)

  • The Anion Gap (AG) is a derived variable primarily used for the evaluation of metabolic acidosis to determine the presence of unmeasured anions
  • The normal anion gap depends on serum phosphate and serum albumin concentrations
  • An elevated anion gap strongly suggests the presence of a metabolic acidosis
  • The normal anion gap varies with different assays, but is typically 4 to 12mmol/L (if measured by ion selective electrode; 8 to 16 if measured by older technique of flame photometry)
  • If AG > 30 mmol/L then metabolic acidosis invariably present
  • If AG 20-29mmol/L then 1/3 will not have a metabolic acidosis
  • K can be added to Na+, but in practice offers little advantage

ALBUMIN AND PHOSPHATE

  • the normal anion gap depends on serum phosphate and serum albumin
  • the normal AG = 0.2 x [albumin] (g/L) + 1.5 x [phosphate] (mmol/L)
  • albumin is the major unmeasured anion and contributes almost the whole of the value of the anion gap.
  • every 1g/L decrease in albumin will decrease anion gap by 0.25 mmoles
  • a normally high anion gap acidosis in a patient with hypoalbuminaemia may appear as a normal anion gap acidosis.
  • this is particularly relevant in ICU patients where lower albumin levels are common

HIGH ANION GAP METABOLIC ACIDOSIS (HAGMA)

HAGMA results from accumulation of organic acids or impaired H+ excretion

Causes (LTKR)

  • Lactate
  • Toxins
  • Ketones
  • Renal

Causes (CATMUDPILES)

  • CO, CN
  • Alcoholic ketoacidosis and starvation ketoacidosis
  • Toluene
  • Metformin, Methanol
  • Uremia
  • DKA
  • Pyroglutamic acidosis, paracetamol, phenformin, propylene glycol, paraladehyde
  • Iron, Isoniazid
  • Lactic acidosis
  • Ethylene glycol
  • Salicylates

Effects of albumin

  • Anion gap may be underesitmated in hypoalbuminaemia, because if albumin decreased by 1g/L then the anion gap decreases by 0.25 mmol
  • To overcome the effects of the hypoalbuminaemia on the AG, the corrected AG can be used which is AG + (0.25 X (40-albumin) expressed in g/L

Lab tests to consider include:

  • lactate, glucose, creatinine and urea, urinary ketones, serum levels of methanol, ethanol, paracetamol, salicylates and ethylene glycol

NORMAL ANION GAP METABOLIC ACIDOSIS (NAGMA)

NAGMA results from loss of HCO3- from ECF

Causes (CAGE)

  • Chloride excess
  • Acetazolamide/Addisons
  • GI causes – diarrhea/vomiting, fistulae (pancreatic, ureters, billary, small bowel, ileostomy)
  • Extra – RTA

Causes (ABCD)

  • Addisons (adrenal insufficiency)
  • Bicarbonate loss (GI or Renal)
  • Chloride excess
  • Diuretics (Acetazolamide)

Calculate the urinary anion gap to differentiate between a GI and renal cause of a normal anion gap acidosis

  • urinary anion gap = (Na+ + K+) – Cl-
  • The remaining significant unmeasured ions are NH4+ and HCO3-
    • renal causes increased urinary HCO3- excretion thus increased urinary AG
    • GI causes increased NH4+ excretion thus decreased urinary AG

LOW ANION GAP

Causes

  • Non random analytical errors (increased Na+, increased viscosity, iodide ingestion, increased lipids)
  • Decrease in unmeasured anions (albumin, dilution)
  • Increase in unmeasured cations (multimyeloma (cationic IgG paraprotein), hypercalcaemia, hypermagnesaemia, lithium OD, polymixin B)
  • bromide OD (causes falsely elevated chloride measurements)

ADVANTAGES AND DISADVANTAGES OF THE ANION GAP

Advantages

  • simple to measure and evaluate acid-base disturbance
  • can be done at bed side

Disadvantages

  • reduced anions (ie hypoalbuminaemia) which is common in critical illness will reduce AG and may mask an elevated AG
  • unmeasured cations such as lithium and hyperglobulinaemia will reduce AG
  • hypercalcaemia and hypermagnesemia will reduce the AG
  • calculation of AG involves the measurement of electrolyte therefore is depends on the accuracy of measurement process.

References and Links

LITFL

Journal articles

FOAM and web resources


CCC 700 6

Critical Care

Compendium

Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also a Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of three amazing children.

On Twitter, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

3 Comments

  1. To overcome the effects of the hypoalbuminaemia on the AG, the corrected AG can be used which is AG + (0.25 X (40-albumin) expressed in g/L

    • Not done routinely in my institution, but it is listed above in the post:
      AG = 0.2 x [albumin] (g/L) + 1.5 x [phosphate] (mmol/L)

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