Transport of oxygen and carbon dioxide

1. Overview

Oxygen and carbon dioxide are carried between the lungs and respiring tissues by the blood, and the two journeys are closely linked inside the red blood cell.

• Oxygen is carried almost entirely bound to haemoglobin, forming oxyhaemoglobin.
• Carbon dioxide is carried in three forms: mostly as hydrogencarbonate ions in the plasma, some as carbaminohaemoglobin, and a small amount dissolved directly in the plasma.

How haemoglobin loads and unloads oxygen is summarised by the oxygen dissociation curve, while the Bohr shift shows how haemoglobin automatically releases more oxygen wherever carbon dioxide levels are high. Reactions inside the red blood cell, driven by the enzyme carbonic anhydrase, together with the chloride shift that balances charge, are what tie oxygen and carbon dioxide transport together.

Key Definitions

• Haemoglobin: a red, globular protein in red blood cells with four polypeptide chains, each holding an iron-containing haem group that can bind one oxygen molecule.
• Partial pressure of oxygen (pO2): the contribution that oxygen makes to the total pressure of a gas mixture, used as a measure of how much oxygen is available.
• Oxygen dissociation curve: a graph showing the percentage saturation of haemoglobin with oxygen plotted against the partial pressure of oxygen.
• Cooperative binding: the way the binding of the first oxygen molecule changes the shape of haemoglobin so that further oxygen molecules bind more easily.
• Affinity (for oxygen): the tendency of haemoglobin to bind and hold on to oxygen; high affinity means oxygen binds readily, low affinity means oxygen is released more easily.
• Carbonic anhydrase: an enzyme in red blood cells that catalyses the reaction between carbon dioxide and water to form carbonic acid.
• Haemoglobinic acid: the compound formed when haemoglobin accepts hydrogen ions, which buffers the blood and helps release oxygen.
• Carbaminohaemoglobin: the compound formed when carbon dioxide binds directly to the amino groups of haemoglobin.
• Chloride shift: the movement of chloride ions into red blood cells to balance the charge as hydrogencarbonate ions move out into the plasma.
• Bohr shift: the shift of the oxygen dissociation curve to the right at higher carbon dioxide levels, so haemoglobin releases oxygen more readily in respiring tissues.

Content

Red blood cells and oxygen transport

Each haemoglobin molecule has four polypeptide chains, and each chain holds one haem group containing an iron(II) ion. Because each haem can bind one oxygen molecule ($O_2$), one haemoglobin molecule can carry a maximum of four oxygen molecules, forming oxyhaemoglobin:

$$Hb + 4O_2 \rightleftharpoons Hb(O_2)_4$$

In the lungs the partial pressure of oxygen is high, so oxygen binds to haemoglobin (loading or association). In respiring tissues the partial pressure of oxygen is low, so oxyhaemoglobin releases its oxygen (unloading or dissociation) for the cells to use in aerobic respiration.

Red blood cells are well suited to this role:

• they are packed with haemoglobin;
• they have a biconcave shape, giving a large surface area for gas exchange;
• they lack a nucleus and most organelles, leaving more room for haemoglobin.

Carbon dioxide transport and carbonic anhydrase

Carbon dioxide produced by respiring tissues is carried in the blood in three forms:

Form of transport	Approximate proportion
Hydrogencarbonate ions ($HCO_3^-$) in the plasma	about 85%
Carbaminohaemoglobin (CO₂ bound to the amino groups of haemoglobin)	about 10%
Dissolved directly in the plasma	about 5%

The hydrogencarbonate route depends on the enzyme carbonic anhydrase, found inside red blood cells. Carbon dioxide diffuses into the red blood cell, where carbonic anhydrase speeds up its reaction with water to form carbonic acid, which then dissociates:

$$CO_2 + H_2O \rightleftharpoons H_2CO_3 \rightleftharpoons H^+ + HCO_3^-$$

The hydrogencarbonate ions diffuse out of the red blood cell into the plasma, where most carbon dioxide is transported.

Haemoglobinic acid and the role of plasma

The hydrogen ions ($H^+$) released when carbonic acid dissociates would make the cell contents far too acidic. To prevent this, haemoglobin acts as a buffer: it accepts the hydrogen ions to form haemoglobinic acid (HHb). Importantly, taking up $H^+$ also causes haemoglobin to release its oxygen, supplying oxygen exactly where carbon dioxide (and therefore respiration) is highest.

The plasma mainly transports carbon dioxide as the hydrogencarbonate ions that move out of the red blood cells, plus the small fraction of carbon dioxide that is simply dissolved.

The chloride shift

As negatively charged hydrogencarbonate ions leave the red blood cell, the inside of the cell would become positively charged relative to the outside. To keep the charge balanced, chloride ions ($Cl^-$) move from the plasma into the red blood cell through a transport protein in the membrane. This movement is the chloride shift.

Its importance is that it keeps the charge balanced across the membrane, allowing hydrogencarbonate ions to keep diffusing out so that large amounts of carbon dioxide can be carried efficiently.

The oxygen dissociation curve

The oxygen dissociation curve plots the percentage saturation of haemoglobin (y-axis) against the partial pressure of oxygen, pO2 (x-axis). For adult haemoglobin the curve is an S-shape (sigmoid), as the solid curve in the figure below shows. This shape is explained by cooperative binding:

• The first oxygen molecule binds with difficulty, so at low pO2 the curve is shallow.
• Binding the first oxygen changes the shape of the haemoglobin molecule, making it easier for the second and third oxygen molecules to bind, so the curve rises steeply in the middle.
• As haemoglobin approaches full saturation it becomes harder to bind the last oxygen, so the curve flattens at high pO2.

Importance of the curve in lungs and tissues

The shape matters because of where the body operates on the curve:

• In the lungs the pO2 is high, so haemoglobin sits on the flat upper part of the curve and becomes almost fully saturated (it loads oxygen).
• In respiring tissues the pO2 is low, placing haemoglobin on the steep part of the curve. Here a small fall in pO2 causes a large drop in saturation, so haemoglobin readily unloads a lot of oxygen to the cells.

This means oxygen is taken up efficiently in the lungs and delivered generously to the tissues that need it most.

The Bohr shift

When tissues respire faster they release more carbon dioxide, which (via carbonic anhydrase) produces more $H^+$ in the red blood cell. A higher carbon dioxide level lowers haemoglobin's affinity for oxygen, shifting the whole dissociation curve to the right — this is the Bohr shift, shown by the dashed curve in the figure above. At any given pO2 the haemoglobin is less saturated, so it releases more oxygen.

The importance of the Bohr shift is that active tissues, which produce the most carbon dioxide, automatically receive the most oxygen for respiration — exactly when and where it is needed.

Worked example

Exam-style question: A student measures the oxygen saturation of haemoglobin in blood leaving a resting muscle and in blood leaving the same muscle during vigorous exercise, at the same partial pressure of oxygen. The saturation is lower during exercise. Explain why. [3]

Model answer:

• During exercise the muscle respires more and releases more carbon dioxide, which raises the hydrogen ion concentration in the red blood cells.
• This causes the Bohr shift, lowering haemoglobin's affinity for oxygen so the dissociation curve moves to the right.
• At the same partial pressure of oxygen the haemoglobin is therefore less saturated, having unloaded more oxygen to supply the respiring muscle.

Worked example

Exam-style question: For adult haemoglobin, the percentage saturation is 98% at the partial pressure of oxygen in the lungs (about 12 kPa), 75% at the partial pressure of oxygen in a resting tissue (about 5 kPa), and 30% in the same tissue during exercise (about 2 kPa). Calculate the percentage of oxygen unloaded between the lungs and the tissue at rest, and between the lungs and the tissue during exercise. State what your answers show. [3]

Model answer:

• Oxygen unloaded at rest = saturation in lungs − saturation in tissue = $98\% - 75\% = \mathbf{23\%}$.
• Oxygen unloaded during exercise = $98\% - 30\% = \mathbf{68\%}$.
• This shows that at the lower partial pressure of oxygen in an exercising tissue, haemoglobin unloads far more oxygen, because the tissue lies on the steep part of the curve where a small fall in pO2 releases a large amount of oxygen.

Key Equations

This topic is mostly qualitative, but the central reaction inside the red blood cell is:

$$CO_2 + H_2O \rightleftharpoons H_2CO_3 \rightleftharpoons H^+ + HCO_3^-$$

The hydrogen ions are then buffered by haemoglobin:

$$Hb + H^+ \rightarrow HHb \;\;(\text{haemoglobinic acid})$$

Common Mistakes to Avoid

• Confusing carbaminohaemoglobin with carboxyhaemoglobin. Carbaminohaemoglobin is carbon dioxide bound to haemoglobin; carboxyhaemoglobin is the stable compound formed when carbon monoxide binds. Mixing these up loses easy marks.
• Saying carbon dioxide is carried "as carbonic acid in the plasma". Most carbon dioxide is transported in the plasma as hydrogencarbonate ions; carbonic acid is only a short-lived intermediate formed inside the red blood cell.
• Forgetting the purpose of the chloride shift. It is not random movement: chloride ions enter to keep the charge balanced as hydrogencarbonate ions leave.
• Describing the dissociation curve without explaining cooperative binding. State that binding the first oxygen changes haemoglobin's shape, making the next molecules bind more easily — this is why the curve is S-shaped, not a straight line.
• Saying the Bohr shift moves the curve "up" or "down". A higher carbon dioxide level shifts the curve to the right, lowering affinity so more oxygen is released.
• Confusing where oxygen loads and unloads. Haemoglobin loads (associates with) oxygen in the lungs where pO2 is high, and unloads (dissociates from) oxygen in respiring tissues where pO2 is low.

Exam Tips

• Use the precise terms partial pressure of oxygen (not just "oxygen level") and percentage saturation when describing the dissociation curve, and quote values with units when reading off a graph.
• When asked to "describe" a curve, state the trend (shallow, then steep, then plateau); when asked to "explain" it, link each part to cooperative binding and affinity.
• To compare two curves (e.g. "the curve has shifted right - explain"), read off both curves at one fixed pO2 and state which is less saturated there, rather than describing each curve in full.
• For the Bohr shift, always connect the chain: more carbon dioxide gives more $H^+$, which lowers affinity, shifting the curve right so more oxygen is released to active tissues.
• Learn the three forms of carbon dioxide transport and roughly which is the largest (hydrogencarbonate ions) so you can answer "in what forms" questions fully.
• Be precise with names: haemoglobinic acid (haemoglobin plus $H^+$) and carbaminohaemoglobin (haemoglobin plus carbon dioxide) are different compounds with different roles.
• In explanation questions, link oxygen unloading to respiration: tissues with the highest demand produce the most carbon dioxide and so receive the most oxygen.