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Anion Gap


The Anion Gap is an approximate measurement of ions, that is molecules with a charge, either negative or positive. Sodium and potassium are positively charged and therefore called cations; this is why they are often represented as Na+ and K+ respectively. These two are the main cations measured in the blood. Negatively charged molecules are called anions, and the major anions measured in the blood are chloride (Cl) and bicarbonate (HCO3). You can tell those electrolytes in the blood because they are measured as mEq/L rather than in milligrams/dL. Because your body must remain neutral, or in other words having the same amount of positive ions as negative ions, the equation (Na+ + K+ + unmeasured cations) must = (Cl + HCO3 + unmeasured anions). Some of the unmeasured cations (~7Mmol/L) include calcium, magnesium, and most other minerals. Unmeasured anions (~24 Mmol/L) include proteins like albumin, and phosphates, sulfates, etc. There are always more unmeasured anions than cations, and thus the “anion gap” equation, (Na+ + K+) – (Cl + HCO3), is always greater than zero.

If your lab report does not include an anion gap, you can calculate it yourself by converting the CO2 result to HCO3 by subtracting 1 mEq/l from the CO2 content…

Optimum Value: 10 to 12 MMol/L depending on the method of calculation.

The Anion Gap is increased when there are excessive anions/acids in the blood. This is either from too much acid production or insufficient removal of acids (either through the lungs, stomach, or kidneys). Excess acids lead to a rapid respiratory rate (the body wants to blow off the extra CO2), an inability to hold your breath (the acid build up forces you to exhale), low blood pressure (due to vasodilation), fatigue, poor appetite, etc. The high anion gap indicates that the electrical charge of the fluids are too negative compared to the inside of the cell. Because the charge across cell membranes is required for many enzymes and energy production, a reduced charge may result in less energy production (oxidative phosphorylation and ATP). A high anion gap may also indicate a functional need for alkaline minerals.

The electrical potential between the inside of the cell and the outside of the cell is basis for nearly all transactions that occur with in the cell. Within the cell the chief cation is potassium and the chief anion is phosphorus. Outside the cell the sodium is balanced by chloride. The balance between the inside and the outside of the cell is maintained by a pump that sends potassium in and sends sodium out. When there is an insufficiency of these electrolytes, electricity can’t be generated – as a result energy production and cellular function is compromised.

Common causes of an elevated Anion Gap include:

  • 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

The Anion Gap is decreased by free radical pathology due to overproduction of alkaloids. Other causes that have been reported associated with a reduced anion gap are

  • Alkalosis for any reason
  • Hyperchloremic acidosis (excess chloride)
  • Multiple Myeloma
  • Hyponatremia (low blood sodium level; see appropriate lab finding webpage)
  • Hypoalbuminemia (see 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)
  • Polymyxin B

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