Arterial blood gas (ABG) and serum electrolyte values help clinicians diagnose and treat acid-base imbalances in critically ill patients. Calculated from results of a serum electrolyte panel, the anion gap helps clinicians assess and treat metabolic acidosis.

Eye on ions

Electrolytes in the body are ions, meaning that they have either a positive or negative charge. Those with a positive charge are cations; those with a negative charge are anions.

Sodium and potassium are positively charged, which is why they're represented as Na⁺ and K⁺. These are the main cations measured in the blood. The main anions measured in blood are chloride (Cl^-) and bicarbonate (HCO₃^-). For the body to maintain electrochemical balance and normal bodily functions, the number of anions should equal the number of cations. However, not all serum cations and anions are routinely measured, so we need to account for the unmeasured cations and unmeasured anions when we interpret ABGs. This concept is represented by the following equation: (Na⁺ + K⁺ + unmeasured cations) must equal (Cl^- + HCO₃^- + unmeasured anions).

Unmeasured cations (~7 mmol/L) include calcium, magnesium, and most other minerals. Unmeasured anions (~24 mmol/L) include proteins such as albumin and compounds such as phosphates, sulfates, and organic acids.

Where's the gap?

Normally, unmeasured anions exceed unmeasured cations. This is referred to as the anion gap, or AG. Because unmeasured anions always exceed unmeasured cations, the anion-gap equation- (Na⁺)-(Cl^- + HCO₃^-) -always produces a value greater than zero. The normal anion gap is 8 to 12 mEq/L.1

Metabolic acidosis is generally associated with either a normal anion gap (non-anion-gap metabolic acidosis) or a high anion gap (high-anion-gap metabolic acidosis).

High-anion-gap metabolic acidosis

An increase in the anion gap is caused by an increase in unmeasured anions or, less commonly, a decrease in unmeasured cations.2 Clinically, a high-anion-gap metabolic acidosis may reflect:

* ketoacidosis (diabetic, alcoholic, or starvation). Because of fatty acid metabolism, organic acids and ketones accumulate.

* lactic acidosis. Inadequate oxygen delivery to tissues, as in shock or cardiac arrest, triggers anaerobic metabolism.1

* renal failure (acute and chronic). The compromised kidneys can't excrete acids (sulfate and phosphate).

* toxicities involving salicylates, methanol, and ethylene glycol.2

Non-anion-gap metabolic acidosis

Metabolic acidosis associated with a normal anion gap can occur from the loss of bicarbonate and the retention of the chloride ion (hyperchloremic metabolic acidosis). Clinically, non-anion-gap acidosis is associated with diarrhea, renal failure, parenteral nutrition, and ureterosigmoidostomy.

A reduced anion-gap value is rare and usually indicates a lab error.3 Other possible causes include:

* an increase in unmeasured cations

* the addition to the blood of abnormal cations, as in lithium toxicity

* a reduction in concentration of albumin, a major unmeasured plasma anion, as in nephrotic syndrome

* hyperviscosity and severe hyperlipidemia.2

The following two case studies demonstrate how to calculate the anion gap and use the results to guide treatment decisions. The first example describes a normal anion-gap result and the second describes an abnormal result.

A 50-year-old woman is admitted with a 2-day history of acute severe diarrhea. These are her lab values:

* Na⁺, 134 mEq/L

* K⁺, 2.9 mEq/L

* Cl^-, 108 mEq/L

* HCO₃^-, 16 mEq/L

* Blood urea nitrogen (BUN), 31 mg/dL

* Creatinine, 1.5 mg/dL

Calculate the anion gap as follows: Na⁺-(Cl^- + HCO₃-) = 134 - (108 + 16) = 10. Because the gap is between 8 and 12 mEq/L, it's normal. Treatment for this patient includes fluid and electrolyte replacement and treating the cause of diarrhea.

A 22-year-old man with type 1 diabetes mellitus has a 1-day history of nausea, vomiting, polyuria, polydypsia, and vague abdominal pain. Physical exam reveals labored respirations, tachypnea, orthostatic hypotension, dry mucous membranes, dry skin, and decreased skin turgor. Here are his lab values:

* Na⁺, 132 mEq/L

* K⁺, 6.0 mEq/L

* Cl^-, 93 mEq/L

* HCO₃^-, 11 mEq/L

* Glucose, 720 mg/dL

* BUN, 38 mg/dL

* Creatinine, 2.6 mg/dL

Calculate his anion gap as follows: Na⁺-(Cl^- + HCO₃^-) = 132 - (93 + 11) = 28. Because the anion gap is greater than 12, it's abnormally high. Treatment for this patient in diabetic ketoacidosis includes volume replacement and normalization of glucose levels with insulin.

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