Learning Objectives

Describe and explain the oxygen dissociation curve for haemoglobin.

Describe and explain the effects of raised carbon dioxide concentrations on the haemoglobin dissociation curve

Describe and explain the differences between oxygen dissociation curves for haemoglobin, fetal haemoglobin and myoglobin, and explain the significance of these differences.

Describe and explain the increase in red blood cell count at high altitude.

The haemoglobin dissociation curve.

A molecule whose function is to transport oxygen from one part of the body to another must be able not only to pick up oxygen at the lungs, but also to release oxygen within the respiring tissues. Haemoglobin performs this task brilliantly.

To investigate how haemoglobin behaves, samples are extracted from blood and exposed to different concentrations, or partial pressures of oxygen.

The amount of oxygen which combines with each sample of haemoglobin is then measured.

The haemoglobin dissociation curve.

The maximum amount of oxygen with which a sample can possibly combine is given a value of 100%. A sample of haemoglobin which has combined with this maximum amount of oxygen is said to be saturated.

The amounts with which identical samples combine at lower oxygen partial pressures are then expressed as a percentage of this maximum value.

The percentage saturation of each sample can be plotted against the partial pressure of oxygen to obtain a dissociation curve.

The haemoglobin dissociation curve.

The S shaped curve.

The shape of the haemoglobin dissociation curve can be explained by the behaviour of a haemoglobin molecule as it combines with or loses oxygen molecules.

Oxygen molecules combine with the iron atoms in the haem groups of a haemoglobin molecule.

Each haemoglobin molecule has 4 haem groups . When an oxygen molecule combines with one haem group, the whole haemoglobin molecule is slightly distorted. The distortion makes it easier for a second oxygen molecule to combine with a second haem group

The S shaped curve.

This in turn makes it easier for a third oxygen molecule to combine with a third haem group. It is then a little harder for the fourth and final oxygen molecule to combine.

The shape of the curve reflects this behaviour.

The Bohr Shift

The behaviour of haemoglobin in picking up oxygen at the lungs, and readily releasing it when in conditions of low oxygen partial pressure, is exactly what’s needed.

It is even better at this than is shown by the dissociation curve. This is because the amount of oxygen it carries is affected not only by the partial pressure of oxygen, but also by the partial pressure of carbon dioxide.

The Bohr Shift Carbon dioxide is continually produced by respiring cells. It

diffuses from the cells and into blood plasma, from where some of it diffuses into the red blood cells.

In the cytoplasm of red blood cells there is an enzyme, carbonic anhydrase. This enzyme catalyses the following reaction:

CO2 + H2O -------------> H2CO3

Carbon dioxide Water Carbonic acid

The carbonic acid dissociates:

H2CO3 ----- H+ + HCO3-

Carbonic acid Hydrogen ions Hydrogencarbonate ions

The Bohr Shift

Haemoglobin readily combines with these hydrogen ions, forming haemoglobin acid, HHb. In so doing, it releases the oxygen which it is carrying .

The net result is 2 fold:

1) The haemoglobin ‘mops up’ the hydrogen ions which are formed when carbon dioxide dissolves and dissociates. A high concentration of hydrogen ions means a low pH; if the hydrogen ions were left in solution the blood would be very acidic. By removing the hydrogen ions from solution, haemoglobin helps to maintain the pH of the blood close to neutral. It is acting as a buffer.

The Bohr Shift

2) The presence of a high partial pressure of carbon dioxide causes haemoglobin to release oxygen. This is called the Bohr effect, after Christian Bohr who discovered it. High concentrations of carbon dioxide are found in actively respiring tissues, which need oxygen; these high carbon dioxide concentrations cause haemoglobin to release its oxygen even more readily than it would otherwise do.

Fetal haemoglobin

A developing foetus obtains its oxygen not from its own lungs, but from its mother’s blood. In the placenta, the mother’s blood is brought very close to that of the foetus, allowing diffusion of various substances from mother to foetus or vice versa.

Oxygen arrives at the placenta in combination with haemoglobin, inside the mother’s red blood cells. The partial pressure of oxygen in the blood vessels in the placenta is relatively low, because the foetus is respiring.

Fetal haemoglobin

The mother’s haemoglobin therefore releases some of its oxygen, which diffuses from her blood into the foetus’ blood.

The partial pressure of oxygen in the foetus’ blood is only a little lower than that in its mother’s blood. However, the haemoglobin of the foetus is different from its mother’s haemoglobin. Fetal haemoglobin combines more readily with oxygen than adult haemoglobin does, thus the fetal haemoglobin will pick up oxygen which the adult haemoglobin has dropped.

Myoglobin

Myoglobin is a red pigment which combines reversibly with oxygen. It is not found in the blood, but inside cells in some tissues of the body, especially in muscle cells. The red colour of meat is largely caused by myoglobin.

It has just one haem group, and can combine with just one oxygen molecule. However, once combined, the oxymyoglobin molecule is very stable, and will not release its oxygen unless the partial pressure of oxygen around it is very low indeed. Myoglobin acts an oxygen store.

Problems with oxygen transport

Carbon monoxide

One property of haemoglobin which can prove to be very dangerous is that it combines readily and irreversibly with carbon monoxide.

When fumes are inhaled the CO readily diffuses across the walls of the alveoli, into blood, and into red blood cells. Here it combines with the haem groups in the haemoglobin molecules, forming carboxyhaemoglobin.

Carbon monoxide

Haemoglobin combines with carbon monoxide 250 times more readily than it does with oxygen. Carboxyhaemoglobin is very stable and remains combines with the haemoglobin for a long time.

The result of this is that even relatively low concentrations of carbon monoxide can cause death by asphyxiation. The victim looks very bright red, the colour of Carboxyhaemoglobin.

Treatment of carbon monoxide poisoning involves administration of a mixture of pure oxygen and carbon dioxide – oxygen to combine with the haemoglobin and carbon dioxide to stimulate an increase in breathing rate.

High Altitude

We obtain our oxygen from the air around us. The further up we go e.g. if a person climbs a mountain, the lower the pressure is. This means the that the haemoglobin will become only 70% saturated in the lungs. Less oxygen will be carried around the body and the person may begin to feel breathless and ill.

If a person climbs steadily from sea level to a high altitude over just a few days, the body does not have enough time to adjust to this drop in oxygen availability, and the person may suffer from altitude sickness.

High Altitude

The symptoms frequently begin with an increase in the rate and depth of breathing, and a general feeling of dizziness and weakness.

These symptoms can easily be reversed by going down to a lower altitude.

Some people can become very ill. The arterioles in their brain dilate, increasing the amount of blood flowing into the capillaries, so that fluid begins to leak from them into the brain tissues. This can cause disorientation and fluid leaks in the lungs.