High anion gap acidosis (organic acidosis)

High AG metabolic acidosis is explained by eight mechanisms MUDPILES as shown in the table.  High anion gap in these conditions is due to consumption of bicarbonate in buffering excess acid.

Determination of osmolal gap in the presence of high anion gap acidosis, will help in determining the source of unmeasured anion.Methanol: It is metabolized by liver to formaldehyde and formic acid. Accumulation of this acid leads to metabolic acidosis with high anion gap and clinical symptoms of blindness. Methanol as well as other alcohol will also increase the plasma osmolality.

Urea of renal failure: Due the loss of renal tubular mass there is decreased ammonia formation, decreased hydrogen ion excretion and bicarbonate reabsorption.

Diabetes or ketoacidosis: These ketoacids accumulate and represent unmeasured anions. Accumulation of these ketone bodies cause decreased in bicarbonate, a normal or low Cl^- and high AG.

Isoniazid, Iron, or Ischemia (three I’s): These all lead to lactic acidosis. Isoniazid and Iron are hepatotoxic and lead to impaired lactate clearance. Ischemia lead to anaerobic glycolysis producing lactate.

Lactic acidosis: Physiologically it exists as lactate and is mainly produced by muscle cells (mainly during exercise) and erythrocytes during anaerobic glycolysis or any other conditions that lead to hypoxia. It is normally metabolized by the liver. Increase in lactate >2 mmol/L with associated increase in H⁺ is considered lactic acidosis. Alcoholism can also cause lactic acidosis as it prevents gluconeogenesis from lactate in liver, because oxidation of ethanol to acetaldehyde competes for the NAD⁺ that is necessary for conversion of lactate to pyruvate.