Anion Gap and its Significance

The anion gap is the difference between unmeasured anions and unmeasured cations, and estimated as

plasma anion gap = (Na+) – (HCO3 ) – (Cl-)

Normal Values= 8-16mEq/L



• The most important cations are calcium, magnesium and potassium
• Major anions are albumin, phosphate, sulphate and other organic anions.
• The anion gap will increase if unmeasured anions increase or unmeasured cations fall

Use of Anion Gap


• In diagnosing different causes of metabolic acidosis
• Metabolic acidosis caused by excess nonvolatile acids (besides HCl), such as lactic acid or ketoacids, is associated with an increased plasma anion gap because the fall in [HCO3-] is not matched by equal increase in [Cl-].
• The metabolic acidosis associated with diarrhea or renal tubular acidosis has a normal anion gap because the decrease in [HCO3-] is matched by an increase in [Cl-].



Metabolic Acidosis Associated with Increased or Normal Anion Gap
Increased Anion Gap
• Diabetic Ketoacidosis
• Lactic Acidosis
• Chronic Renal Failure
• Aspirin Poisoning
• Methanol Poisoning
• Ethylene Glycol Poisoning
• Starvation
Normal Anion Gap (Hyperchloremia)
• Diarrhea
• Renal Tubular Acidosis
• Carbonic Anhydrase Inhibitors
• Addison Disease
• Acid Ingestion (HCl,NH4Cl)
• K+ -Sparing Diuretics
• Pancreatic fistula



Elevated Anion Gap
• Causes
• Ketoacid overproduction due to fat metabolism (diabetes, alcohol, starvation)
• Lactic Acid overproduction due to respiratory failure (the tissue has inadequate oxygen), genetic defects of enzymes of carbohydrate metabolism, nutritional deficiencies that impair the bodies ability to metabolize lactic acid (B vitamins, especially vitamin B1)
• Inability to excrete acids (sulfate and phosphate) due to renal disease (usually with an elevated BUN and creatinine).
• Dehydration.
• Medications such as salicylates causing a metabolic block.
• Toxins such as ethylene glycol, methanol, paraldehyde, propyl alcohol

Decreased Anion Gap


• Causes
• Alkalosis for any reason
• Hyperchloremic acidosis (excess chloride)
• Multiple Myeloma
• Hyponatremia (low blood sodium level;)
• Hypoalbuminemia (albumin can increase the amount of free blood calcium)
• Bromide Ingestion (displaces chloride)
• Uncalculated blood cations (calcium, magnesium)
• Lithium toxicity (can be due to effects on sodium)
• Primary hypothyroidism
• Kidney disease (due to the loss of the cations sodium and or potassium)