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Hydrogen carbonate formation in red blood cells

In the tissues, red cells keep converting carbon dioxide into hydrogen carbonate (bicarbonate) by removing the products: haemoglobin binds hydrogen ions; a membrane protein swaps hydrogen carbonate out for chloride.

Remember

In the tissues, haemoglobin soaks up the hydrogen ions and a membrane protein exports hydrogen carbonate from the cell, so neither product builds up and carbon dioxide keeps being converted.

Memory aid

haemoglobin is a sponge for hydrogen ions

Haemoglobin works like a sponge that soaks up the hydrogen ions, so the reaction does not get blocked.

In the tissues, carbon dioxide enters a red blood cell and combines with water, giving hydrogen ions and hydrogen carbonate ions (bicarbonate). Free hydrogen ions would make the cell more acidic if they accumulated. The enzyme carbonic anhydrase speeds this reaction up. A reaction like this slows and stops when its products pile up, so for it to carry on, the products have to be removed.

The hydrogen ions are dealt with by haemoglobin, which acts as a buffer (a molecule that soaks up hydrogen ions to keep the pH steady). It binds them inside the cell, particularly once it has given up its oxygen in the tissues. Haemoglobin is an especially good buffer because red cells contain so much of it.

The hydrogen carbonate leaves the cell into the plasma through the chloride-bicarbonate exchanger, a protein in the cell membrane that swaps one hydrogen carbonate ion out for one chloride ion in. This swap is called the chloride shift. Trading one negative ion for another keeps the electrical charge of the cell and blood unchanged.

With both products being removed, the reaction continues, and most carbon dioxide ends up as hydrogen carbonate in the plasma. Carbonic anhydrase speeds the reaction but does not itself remove either product, so it is the buffering and the export that keep the process going.

In the lungs the exchange runs the other way: hydrogen carbonate re-enters the red cells and is converted back to carbon dioxide.

Key facts

The reaction
carbon dioxide combines with water inside the red cell, giving hydrogen ions and hydrogen carbonate ions, and carbonic anhydrase speeds it up.
Hydrogen ions
haemoglobin binds them inside the cell, so they do not build up.
Hydrogen carbonate
in the tissues it leaves the red cell into the plasma through the chloride-bicarbonate exchanger, swapping places with chloride.
Why it keeps going
in the tissues, removing a product keeps the reaction moving forwards, so carbon dioxide keeps being converted to hydrogen carbonate.
Where the buffering sits
the hydrogen ions are buffered by amino acids in the globin chains (the globin part of haemoglobin), not by haem iron, which binds oxygen.
A separate route
carbon dioxide can also bind to haemoglobin as carbaminohaemoglobin (carbon dioxide attached to the globin part of haemoglobin), but this is a separate way of carrying it and does not remove the hydrogen ions.

Exam traps

  • Albumin acts as a buffer in plasma, outside the red cells, so it does not take up the hydrogen ions made inside them. Haemoglobin does that job.
  • Carbonic anhydrase cannot keep the reaction going on its own, because the enzyme speeds the reaction without removing either product.
  • In the tissues, moving hydrogen carbonate into a red cell through the exchanger would reverse the chloride shift and slow the conversion, because hydrogen carbonate must leave the cell.

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Based on 6 SimpleMed+ questions written and peer-reviewed by UK doctors.

Last updated 7 November 2026. For medical education only, not clinical advice.