Oxygen Transport

Although O₂ is dissolved in plasma, the vast majority of O₂ transport is carrier-mediated by haemoglobin (Hb), a process that can become saturated. Haemoglobin is close to 100% saturated at an arterial O₂ partial pressure (PaO₂) of 10 kPa or more when O₂ content (total O₂ in blood) is around 200 mL/L. In anaemia, PaO₂ and Hb saturation can be normal, but the O₂ content of blood will be reduced, explaining many of the symptoms. Understanding the relationships between PaO₂, O₂ content and Hb saturation is important when interpreting disturbed O₂ transport.

The partial pressure of O₂ in blood (PaO₂) indicates the amount of blood dissolved in plasma. If you left plasma (i.e. having removed blood cells) in an open vessel it would equilibrate with room air and have a PO₂ of 21 kPa. How much O₂ is this though?

That’s about 0.5 mL dissolved in each 100 mL of plasma (O₂ content).   However, blood equilibrates with alveolar air, which has a lower fraction of O₂ (PAO₂ = 14 kPa usually) and this is reflected in the lower PaO₂ of around 12-14 kPa.  So, the amount usually dissolved in plasma is about 0.3 mL O₂/100 mL.  By contrast, the usual O₂ content of whole blood is around 19 mL/100 mL (see below).  This huge difference illustrates the importance of the haemoglobin (Hb) in red blood cells as a carrier for oxygen transport.

The relationship between PaO₂ and O₂ content is fairly predictable, if the number of red cells and their content of haemoglobin are in the usual range (see below).  So, a PaO₂ reading tells us what the O₂ content should be under normal circumstances, but if something goes awry, the PaO₂ can look normal when everything else doesn’t.  Anaemia is the classical example of this, where a given volume of blood doesn’t contain the usual number of red cells, and hence haemoglobin.

There should be about 14 g of Hb per 100 mL of blood (this is a number worth remembering and it’s a bit lower in females than males) and each gram binds 1.34 ml of O₂.  What would happen if this level was halved?  We’ll assume that the usual 0.3 mL of dissolved O₂ is present, and that there’s adequate ventilation to saturate Hb:

In this example the PaO2 and O₂ saturation could be identical in these patients; only the O₂ content will differ.

If we took a venous (deoxygenated) blood sample and bubbled pure O₂ though it we would soon occupy all the sites for O₂ and the haemoglobin would become saturated (14 x 1.34 = 18.8 mL per 100 mL).  If we measured the percentage Hb saturation (%), PaO₂ (kPa) and O₂ content (mL/L) of sample during this procedure we would find that different things happen to each variable, as the Hb dissociation curve is not a simple, straight line.  We’d also find that pure oxygen isn’t required for this experiment.  In fact there’s more than enough O₂ in room air (21% O₂) to saturate Hb; even 10% O₂ would suffice.

The oxyhaemoglobin dissociation curve

Oxygen binds to haemoglobin (to form oxyhaemoglobin) and unbinds from it (to form deoxyhaemoglobin) depending on the PO₂ of plasma.  The haemoglobin (Hb) dissociation curve has two features that are of clinical relevance.  Firstly, the curve is close to linear from a PaO₂ value of 10 kPa or more, meaning that in the typical arterial range (10-13 kPa), haemoglobin is close to fully saturated.  Secondly, between a typical partial pressure of O₂ in venous blood (PvO₂) of 5 kPa and the lower end of the PaO₂ the curve shows that a large drop in O₂ saturation occurs over a narrow PaO₂ range, allowing O₂ to be delivered to tissues.  As blood enters a tissue with low PO₂, Hb gives up O₂ more readily.

Figure 1: The oxygen-Hb dissociation curve, describing the O₂ content of normal blood. A typical PvO₂ and the normal range for PaO₂ are shown. Note that for a wide range of PaO₂, Hb is almost completely saturated. Below 10 kPa, Hb gives up O₂ more readily to supply O₂ to the tissues.

The shape of the dissociation curve is the product of the complex way that O₂ binds to Hb.  Each molecule of Hb can bind four molecules of O₂, but the kinetics of each binding event differ.  Binding of the first O₂ molecule is the hardest step; subsequently each O₂ molecule binds more readily.  The point is that four different chemical reactions account for O₂ binding to Hb.

Myoglobin

Myoglobin is an intracellular protein found in muscle cells and is the protein that gives meat its red colour.  It is an intracellular storage depot for O₂. If you place a breast of chicken next to the same cut of meat from a duck, the former will be pale pink, while the latter is a deep red.  This difference reflects the different way this muscle is used by these related animals.  A duck flies and requires very high performance muscles to do so, a chicken doesn’t.  Myoglobin doesn’t release O₂ into the blood, since it has a higher affinity for O₂ than Hb.  Furthermore, the PO₂ in mitochondria is much lower than blood (0.4 kPa), so that when myoglobin does give up its O₂, the concentration gradient favours delivery to mitochondria rather than blood.

2,3-Diphosphogylerate (2,3-DPG)

Red blood cells contain no mitochondria (leaving room for more haemoglobin) and rely on anaerobic metabolism. Hence, red blood cells do not consume the O₂ that they transport.  2-3-diphosphoglycerate is a product of such metabolism and has an important effect on the haemoglobin dissociation curve (see below). Chronic hypoxia (such as may be caused by moving to high altitude or a chronic respiratory diseases such as COPD) increase the concentration of 2,3-DPG in red blood cells. 

Cyanosis

The colour of blood through skin appears purple/blue when it is deoxygenated as deoxy-Hb has a different colour spectrum.  In fact, venous blood is just a darker red colour – the blue/purple phenomenon is due to light scattering in the skin.  Once blood contains about 5 g/100 mL deoxy-Hb the colour difference is noticeable.

Shifting the dissociation curve

The oxygen dissociation curve is influenced by temperature, pH, 2,3-DPG levels and PaO₂. By shifting the curve, what we really mean is changing the affinity of Hb for O₂. It’s pretty easy to remember how the location of the curve is affected by remembering that the curve shifts to meet increased oxygen delivery to organs with increased metabolism. It’s physiology that makes sense. Consider the heart during exercise: as its rate increases the myocardium will produce more CO₂ (and hence increase H⁺, decreasing pH). This shifts the curve to the right (this effect on the oxygen dissociation curve is called the Bohr effect) so that Hb gives up O₂ more readily. Similarly, the myocardium will become warmer as it converts more energy into contractions. This increase in temperature will also shift the curve to the right. Finally, increased temperature will increase red blood cell metabolism, causing an increase in 2,3-DPG, which also causes a rightward shift of the curve. As all of these changes result in the oxygen dissociation curve shifting to the right, at a given and PaO₂, Hb more readily releases oxygen for the myocardium to utilise (Figure 2).

Figure 2: The effect of changes in pH, 2,3-DPG concentrations and temperature on the oxyhaemoglobin dissociation curve. In tissues where metabolism is high, Hb will release more O₂ than usual as the curve is shifted to the right. The opposite changes in these variables will cause a leftward shift, meaning that for a given PaO₂, Hb retains more O₂ than usual.