Transport of oxygen and carbon dioxide

1Why does blood give up oxygen exactly where it is needed?

Blood leaving the lungs is about 97 % saturated with oxygen. At rest, the blood returning to the heart is still about 70 % saturated: the body took only a quarter. Yet in a sprinting leg muscle, blood can give up most of its oxygen within a second. The same haemoglobin behaves differently in different places, and the reason is written in the shape of one graph: the oxygen dissociation curve.

2The S-shaped curve

Table 1 gives the percentage saturation of haemoglobin at different partial pressures of oxygen, calculated from the Hill equation with typical values for human blood, at low carbon dioxide (as in the lungs) and at high carbon dioxide (as in active muscle). Figure 1 plots them.

Table 1: Percentage saturation of haemoglobin

Figure 1: Oxygen dissociation curves of human haemoglobin at low and high CO₂, plotted from Table 1 (Hill-equation values). Dashed vertical lines: typical pO₂ in the lungs, resting tissue and active muscle.

Why S-shaped? The first ${\mathrm{O}}_2\backslash mathrm\{O\_2\}$ molecule binds with difficulty. Once it binds, the shape of the haemoglobin molecule changes (a conformational change), making it easier for the second and third to bind: cooperative binding. So the curve is shallow at very low $p{\mathrm{O}}_{2}p\backslash mathrm\{O\_2\}$, then steep, then flattens as haemoglobin approaches full saturation.

Why the shape matters:

• At the top, the curve is flat. In the lungs, even if $p{\mathrm{O}}_{2}p\backslash mathrm\{O\_2\}$ falls a little (at altitude, or in mild lung disease), haemoglobin still loads almost fully.
• In the middle, the curve is steep. A small fall in $p{\mathrm{O}}_{2}p\backslash mathrm\{O\_2\}$ in the tissues releases a large amount of oxygen, exactly where cells are using it fastest.

3The Bohr shift

Respiring tissues produce carbon dioxide. In red blood cells it forms carbonic acid, which releases H⁺ ions. The H⁺ ions bind to haemoglobin and change its shape, lowering its affinity for oxygen. The curve moves to the right: at the same $p{\mathrm{O}}_{2}p\backslash mathrm\{O\_2\}$, haemoglobin is less saturated, so it releases more oxygen. The harder a muscle works, the more CO₂ it makes and the more oxygen it receives. In the lungs, where CO₂ diffuses out, the curve shifts back to the left and haemoglobin loads fully.

4Other oxygen-carrying pigments

Figure 2: Dissociation curves of myoglobin, fetal haemoglobin and adult haemoglobin (Hill-equation values). Dashed line: typical pO₂ in the placenta.

• Fetal haemoglobin has a curve to the left of adult haemoglobin: a higher affinity for oxygen. In the placenta, at about 4 kPa, fetal haemoglobin is about 76 % saturated when the mother's is about 59 %, so oxygen passes from the mother's blood to the fetus's.
• Myoglobin, in muscle cells, has one chain and one haem, so no cooperative binding: its curve is hyperbolic and far to the left. It stays saturated until $p{\mathrm{O}}_{2}p\backslash mathrm\{O\_2\}$ in the muscle falls very low, during hard exercise, and then releases its oxygen: an oxygen store.
• Animals living where oxygen is scarce, such as the llama at high altitude or the lugworm in mud burrows, have haemoglobin with curves to the left of ours.

5Carrying carbon dioxide

Figure 3: Carbon dioxide transport and the chloride shift in a red blood cell in a respiring tissue.

Carbon dioxide is carried in three ways, in typical proportions:

• about 85 % as hydrogencarbonate ions in the plasma. In red blood cells, the enzyme carbonic anhydrase rapidly combines CO₂ with water to form carbonic acid, which dissociates to H⁺ and $\mathrm{H}\mathrm{C}{\mathrm{O}}_3^{-}\backslash mathrm\{HCO\_3^-\}$. The $\mathrm{H}\mathrm{C}{\mathrm{O}}_3^{-}\backslash mathrm\{HCO\_3^-\}$ diffuses out into the plasma, and chloride ions diffuse in to keep the charge balanced: the chloride shift. The H⁺ ions are taken up by haemoglobin, forming haemoglobinic acid (HHb); this buffers the blood and releases oxygen (the Bohr effect);
• about 10 % combined with haemoglobin as carbaminohaemoglobin;
• about 5 % dissolved in the plasma.

In the lungs, all these reactions run in reverse, and CO₂ diffuses out into the alveoli.

6At altitude

Much of Rwanda is high: the Northern Province rises to the Virunga volcanoes, and Mount Karisimbi reaches about 4 500 m. As you climb, air pressure falls, so the $p{\mathrm{O}}_{2}p\backslash mathrm\{O\_2\}$ of the air falls too. A climber on Karisimbi breathes faster and her heart beats faster at first. People who live at altitude for weeks or longer make more red blood cells (stimulated by the hormone erythropoietin), so each litre of blood carries more oxygen. Because the top of the dissociation curve is flat, haemoglobin still loads reasonably well at moderately reduced $p{\mathrm{O}}_{2}p\backslash mathrm\{O\_2\}$.