Anion gap

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Priyamvada Singh, M.D. [2]

Overview

The anion gap is representative of the unmeasured anions in the plasma, and these anions are affected differently based on the type of metabolic acidosis. The anion gap is used to aid in the differential diagnosis of metabolic acidosis. Chloride and bicarbonate comprise 85% of the anions in the serum. The remaining anions are called the anion gap and is primarily formed by negative charges on plasma protein. Normal reference range AG is between 3 and 11 meq/L (average 6 meq/L)

Uses

The primary function of the anion gap measurement is to allow a clinician to narrow down the possible causes of a patient's metabolic acidosis. For example, if a patient presents with metabolic acidosis, but a normal anion gap, then conditions that cause a high anion gap can be ruled out as being the cause of the acidosis.

Calculation

It is calculated by subtracting the serum concentrations of chloride and bicarbonate (anions) from the concentrations of sodium plus potassium (cations):

• Serum AG = Measured cations - measured anions; Serum AG = Na - (Cl + HCO3)
• Serum AG = Unmeasured anions - unmeasured cations
• Anion Gap = ( [Na⁺]+[K⁺] ) - ( [Cl^-]+[HCO₃^-] )
• However, for daily practice, the potassium is frequently ignored, leaving the following equation:
• Anion Gap = ( [Na⁺] ) - ( [Cl^-]+[HCO₃^-] )

Interpretation

Anion gap can be classified as either high, normal or, in rare cases, low. A high anion gap indicates that there is loss of HCO₃^- without a subsequent increase in Cl^-. Electroneutrality is maintained by the increased production of anions like ketones, lactate, PO₄^-, and SO₄^-; these anions are not part of the anion-gap calculation and therefore a high anion gap results. In patients with a normal anion gap the drop in HCO₃^- is compensated for by an increase in Cl^- and hence is also known as hyperchloremic acidosis.

Complete Differential Diagnosis of the Causes of Anion gap

Low anion gap

A low anion gap is relatively rare but may occur from the presence of abnormal positively charged proteins, as in multiple myeloma, or in the setting of a low serum albumin level.

• Electrolyte abnormality - hypercalcemia, hypermagnesemia, hypernatremia, underestimation of serum sodium
• Hyperviscosity-multiple myeloma, paraproteinemia
• Hypoalbuminemia
• Lithium toxicity
• Pheochromocytoma
• Bromism
• Dilution

Normal anion gap (hyperchloremic acidosis)

Usually the HCO₃^- lost is replaced by a chloride anion, and thus there is a normal anion gap.

• Enteral causes
  • Diarrhea (note: vomiting causes hypochloraemic alkalosis)
  • Pancreatitis, Pancreatic fistula
  • Arginine and lysine during total parenteral nutrition
  • Ureteroenterostomy
  • Ileal stoma
• Ammonium chloride and Acetazolamide (Carbonic anhydrase inhibitors)
• Renal loss of HCO₃^- i.e. proximal renal tubular acidosis, renal failure, hypoaldosteronism, distal renal tubular acidosis
• Alcohol (such as ethanol) can effect anion gap by inducing alcohol dehydrogenase enzyme.
• Recovery from diabetic ketoacidosis

High anion gap

The bicarbonate lost is replaced by an unmeasured anion and thus you will see a high anion gap. The mnemonic "MUDPILES" is used to remember the causes of a high anion gap.

M - methanol/metformin
U - uremia
D - diabetic ketoacidosis
P - paraldehyde/propylene glycol
I - Infection/ischemia/isoniazid
L - lactate
E - ethylene glycol/ethanol
S - salicylates/starvation

Some people, especially those not in the emergency room, find the mnemonic KIL-U easier to remember and also more useful clinically:

K - Ketones
I - Ingestion
L - lactic acid
U - uremia

All of the components of "mudpiles" are also covered with the "KIL-U" device, with the bonus that these are things that can kill you.

Ketones: more straightforward than remembering diabetic ketosis and starvation ketosis, etc.

Ingestion: methanol, metformin, paraldehyde, propylene glycol, isoniazid, ethylene glycol, ethanol, and salicilates are covered by ingestion. These can be thought of as a single group: "ingestions" during the initial consideration, especially when not triaging a patient in the emergency room.

Lactate: including that caused by infection and shock

External links

• Clinical Physiology of Acid-Base and Electrolyte Disorders by Rose, Post
• Intensive Care Medicine by Irwin and Rippe
• The ICU Book by Marino
• Calculator at mcw.edu

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