A bicarbonate deficit can occur through the loss of excessive intestinal secretions such as diarrhea, suction, or fistulas. A loss of HCO₃ can also occur through the renal system. Such conditions have the potential to cause a metabolic acidosis.

Metabolic acidosis that results from increased acid levels can occur in situations involving an accumulation of lactic acid as in shock or cardiac
arrest when anaerobic metabolism occurs due to insufficient oxygenation. Ketoacidosis can also result in metabolic acidosis, particularly with uncontrolled diabetes mellitus but also with excessive alcohol consumption, starvation, or ketogenic weight loss diets. Ingestion of methanol, ethylene glycol, or acetylsalicylic acid can produce extreme situations of metabolic acidosis and possible death. Decreased renal function also leads to a metabolic acidosis due to an inability of the kidneys to secrete H⁺ into the urine or to conserve HCO₃^–. This frequently occurs in the elderly as renal function decreases and the kidneys cannot eliminate an increased amount of acid that has accumulated or been ingested.

Hyperchloremic acidosis occurs with overtreatment of chloride-type medications, intravenous and hyperalimentation solutions, or increased absorption by the kidneys. Because HCO₃^– and Cl^– are both anions, the HCO₃^– concentration decreases when an excess of Cl^– are available. Ammonium chloride breaks down into NH₄⁺ and Cl^–, allowing the ammonium ion to be converted to urea in the liver. This frees the Cl^–, allowing it to bind with available H⁺. The combination forms hydrochloric acid, resulting in a situation of bicarbonate deficit and increased acid.