Bicarbonate (HCO₃, HCO₃^-) is the major extracellular buffer in the blood; it functions with carbonic acid (H₂CO₃) in maintaining acid-base balance. Normally, the ratio of bicarbonate to dissolved carbon dioxide (CO₂), which derives from H₂CO₃, is 20:1. If this ratio is altered, acid-base imbalance occurs. Additional CO₂, for example, causes increased acidity (falling pH), whereas loss of CO₂ produces alkalinity (rising pH). Similarly, additional bicarbonate leads to alkalosis, whereas loss of bicarbonate produces acidosis.

The lungs control regulation of CO₂ levels. Bicarbonate levels are under renal control; the kidneys regulate both the generation of bicarbonate ions and their rate of urinary excretion. Bicarbonate also participates with chloride in the bicarbonate-chloride shift mechanism involving red blood cells.

Measurement of serum bicarbonate ion concentration may be made directly or indirectly by means of total CO₂ content, because more than 90 percent of blood CO₂ exists in the ionized bicarbonate form. Bicarbonate also is measured as part of blood gas determinations. Numerous disorders, especially those involving acid-base imbalance, and drugs are associated with altered serum bicarbonate levels (Table 5-25).