Bicarbonate in extracellular fluid, haemoglobin in blood, protein and phosphate in cells, bone in chronic acidosis
Mnemonic
“Bicarbonate outside, protein and phosphate inside, bone for the long term”:
- Bicarbonate and carbonic acid - the main extracellular buffer, and the most important because it is an open system: the lungs remove carbon dioxide and the kidneys regenerate bicarbonate
- Haemoglobin - the main buffer in blood, and particularly effective because deoxygenated haemoglobin is a better proton acceptor, which underlies the Haldane effect
- Protein and phosphate - the main intracellular buffers
- Bone carbonate - a large reservoir mobilised in chronic acidosis, which is why chronic kidney disease causes bone disease
The Henderson-Hasselbalch equation ties it together: pH = 6.1 + log([HCO3] / 0.03 x PaCO2), so pH depends on the ratio of a renally controlled numerator to a respiratory denominator, not on either alone.
Bicarbonate is a poor buffer on paper because its pKa of 6.1 is far from 7.4, but it is by far the most important in practice precisely because both ends are physiologically regulated.
Expansion
| Buffer | Location | Notes |
|---|---|---|
| Bicarbonate | Extracellular fluid | Most important; open system with carbon dioxide removed by the lung |
| Haemoglobin | Red cells | The main blood buffer; better when deoxygenated (the basis of the Haldane effect) |
| Protein | Intracellular | Large total capacity |
| Phosphate | Intracellular and urine | Forms titratable acid |
| Bone | Skeleton | Slow but very large capacity in chronic acidosis |
The isohydric principle states that all buffers in a solution are in equilibrium with the same hydrogen ion concentration, so measuring one system, conveniently bicarbonate and carbon dioxide, tells you about all of them.
Bicarbonate seems a poor buffer, since its pKa of 6.1 is well away from physiological pH. It is effective because the system is open: carbon dioxide is continuously excreted, so the reaction is pulled away from acid and the effective capacity far exceeds what the pKa predicts.
Bone buffering matters clinically: chronic acidosis in renal failure or distal renal tubular acidosis releases calcium carbonate from bone, contributing to renal osteodystrophy and to stone formation, and this is one reason chronic acidosis is corrected with oral bicarbonate.