Three respiratory gases and the red cell: oxygen, carbon dioxide and nitric oxide

Abstract

Three vital gases – oxygen, carbon dioxide and nitrogen – intersect at the level of the human red blood cell. The delivery of oxygen to all tissues by red cells is essential to human life. Evolution has created a complex molecule, haemoglobin, designed for efficient uptake and off‐loading of oxygen. Iron rests at the centre of the haeme moiety and is critical for oxygen exchange. Although studied for over a century, some details of oxygen transport by the red cell remain uncertain. Recent research has focused on the interaction of haemoglobin with a complex of cell‐membrane proteins centred on band 3. In addition, there is renewed interest in the question of whether or not stored red cells deliver oxygen to tissues as well as fresh red cells. The interactions of CO2 with the red cell have drawn far less research attention. Plasma CO2 released by tissues serves as an essential trigger for oxygen release by haemoglobin via the Bohr effect. CO2 transport depends on conversion of CO2 to bicarbonate via red cell carbonic anhydrase in conjunction with chloride exchange across the red cell membrane. There is very little research on the effect of blood storage on CO2 excretion although this aspect of respiratory physiology is every bit as important as oxygen delivery. Nitric oxide (NO) physiology is directly related to oxygen delivery by the red cell. NO serves a local vasodilator to increase blood flow to hypoxic tissue beds. NO binds strongly to haemoglobin which serves as an NO sink. Under normal conditions, plasma NO synthesized by endothelial cells is not consumed by red cell haemoglobin because of a diffusion blockade across the red cell membrane that results from membrane structures not fully identified. Under conditions of red cell lysis, free haemoglobin scavenges NO reducing local vasodilation. Scavenging of NO is now recognized as an important component of the physiologic response to chronic haemolysis and is very likely to play an important role in the renal lesion of acute haemolysis. The three RBC gases are also the three principal gases of the Earth’s atmosphere. While CO2 is the least abundant of the three by far, it is also likely to be the most critical to the future survival of life on Earth – because small further increases in the concentration of CO2 will result in continued climate change, and large increases will be deadly. Thus, the management of three vital gases by the collection of red cells found within us has broad similarities to the collective management of our atmosphere. Just as the survival of individual tissue cells depends upon proper balance of these three respiratory gases, so too will their proper balance be the key to survival of life on Earth.