- Overproduction or ingestion of fixed acid or loss of base produces an increase in arterial [H+] (acidemia)
- HCO3- is used to buffer the extra fixed acid.  As a result, the arterial [HCO3-] decreases.  This decrease is the primary disturbance.
- Acidemia causes hyperventilation (Kussmaul breathing), which is the respiratory compensation for metabolic acidosis.
- Renal correction of metabolic acidosis consists of increased excretion of the excess fixed H+ as titratable acid and NH4+, and increased reabsorption of "new" HCO3-, which replenishes the HCO3- used in buffering the added fixed H+.
- In chronic metabolic acidosis, an adaptive increase in NH3 synthesis aids in the excretion of excess H+.
- In metabolic acidosis, the serum [HCO3-] decreases as it is depleted in buffering fixed acid.