Gas Transport and The Haldane Effect

By Chandan Sekhon - Medicine Student @ Peterhouse, Cambridge

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Oxygen (O2) and carbon dioxide (CO2) are respiratory gases which must be exchanged between the external environment and tissues. Oxygen is taken into the bloodstream via diffusion from the lungs at alveoli, by crossing the alveolar epithelium and capillary endothelium into the bloodstream. The blood then transports this oxygen to tissues to allow aerobic respiration to occur. CO2 diffuses into the bloodstream after being produced as a waste product of respiration from cells. This CO2 is transported via the bloodstream into alveoli at the lungs, where it is expelled from the body. This system helps maintain a steep concentration gradient of these gases for efficient diffusion.

Oxygen Transport:

Oxygen is transported via the bloodstream in two formats. The first is by being dissolved in the blood plasma. Only a very small proportion of the oxygen transported in the blood is carried by this method of transport. Most of the oxygen is transported attached to haemoglobin which is contained within red blood cells. There are two forms of haemoglobin found in humans: the foetal form and the adult form. There is also a third type – the sickle cell type which occurs as a result of an abnormality reducing the affinity for oxygen. Each chain in the molecule has an iron-containing porphyrin ring which oxygen binds to. The uptake of oxygen by haemoglobin is dependent upon the partial pressure of oxygen (PO2). If there is an abnormality with oxygen binding/oxygen transport, disorders can occur in the individual such as anaemic hypoxia (when the oxygen-carrying capacity of the blood is reduced) and hypoxic hypoxia (when there is low arterial PO2).

CO2 Transport:

CO2 is transported in the blood in three main ways. Similar to O2, CO2 can be dissolved in the blood plasma. Unlike O2, dissolved CO2 forms a larger proportion of the CO2 in the blood. Another way CO2 can be transported is via carbamino products. CO2 can bind to the amine groups of amino acids which form proteins found in the plasma. A similar proportion of CO2 is transported via this method as dissolved CO2. The reaction below shows the equilibrium which occurs in the formation/breakdown of carbamino compounds:

-NH2 + CO2 <———> -NHCOOH <———> -NHCOO- + H+

The largest proportion of CO2 is transported as bicarbonate (HCO3-). An equilibrium is established where bicarbonate is formed and broken down depending on the concentration of CO2, H2O and H+ ions. The formation and breakdown of H2CO3 from CO2 and H2O is catalysed by the enzyme carbonic anhydrase. This equilibrium is shown before:

Carbonic Anhydrase

H2O + CO2 <———> H2CO3 <———> HCO3- + H+

Haldane Effect:

The quantity of CO2 transported in the blood is dependent on the PO2 and the saturation of haemoglobin. It has been observed that more CO2 is transported by the blood if the blood has a lower PO2 and vice versa. This is because deoxygenated haemoglobin is a weaker acid than oxygenated haemoglobin, so it will bind a greater number of protons than oxygenated haemoglobin, which helps maintain the mass action chemical gradient for HCO3- production (therefore, deoxygenated haemoglobin binds more CO2). This is called the Haldane effect. The PO2 transport of the body is also partly depended on the PCO2. An increase in PCO2 decreases the affinity of haemoglobin for oxygen. This reduces the ability of haemoglobin to load oxygen but increases its ability to unload oxygen, helping increase the amount of oxygen available for diffusion to body tissues. A decrease in PCO2 has the reverse effect.

Further reading:

1. This is a very good article explaining both the Haldane effect and the Bohr effect, giving a great introduction to it: https://www.tandfonline.com/doi/pdf/10.3109/00365517309082411?casa_token=kJiEX5qom_AAAAAA%3AKBhlgoKoaGEnPL79tK3Gq4FNKWfeFL0ouOTWcElTg78liF1GgcXnSoOQldFu2v9LXwqhuMBU8pYpEg&

2. This article is great if you want to go further into the physiology behind oxygen transport: https://www.sciencedirect.com/science/article/pii/S0955388697000416?casa_token=rNy6YpaE-PIAAAAA:-Lc32GRY0kRhsnXptLiuYo2Ag60OehRTq3vGdgjb72QDZXt_Ns8bsXdXlTuj6n5W_pxWH9m0Op8

3. Quite a long article, but very detailed and interesting about CO2 transport: https://journals.physiology.org/doi/full/10.1152/physrev.2000.80.2.681

4. This is a very interesting article about sickle-cell disease and a lot about its epidemiology: https://www.sciencedirect.com/science/article/pii/S014067361061029X?casa_token=sCLEI-vWNFoAAAAA:3q-zRSnhi--GMhvsbWlMuZ3Pzeeb7HPbfKpWxGnsYe46RjaR2tN62ymnMCQ_F3stvhgJpo2NUco