Blood buffers: The viewpoint of a biochemist.

Mammalian blood is a very complex system whose multiple physiological roles require that its pH is maintained constant, in spite of the necessity of carrying over 15 moles of CO₂ a day from the tissues to the lungs. The blood pH is maintained constant by several buffers, whose interplay is complex. The study of blood buffers is over a century old and has crossed major reinterpretations of the nature of acids and bases, from Arrhenius to Bronsted and Lowry, as well as an enormous evolution of our knowledge of protein structure, proteins being the most relevant among blood buffers. As a consequence, several theories have been developed to explain the physiological and pathological fluctuations of blood pH. This review compares the three main theories currently used: that based on the Strong Ions Difference (SID), due to Stewart and his followers; that based on the Base Excess, due to the Copenhagen school of respiration physiology; and the physiological one, due to the Boston school. These theories are not alternative but complementary and can be reconciled with each other, provided that some erroneous assumptions are corrected, and all three are expressed using the definitions proposed by Bronsted and Lowry.