Oxygen Transport and the Oxyhaemoglobin Curve

Why most oxygen travels with haemoglobin

Blood plasma can dissolve oxygen, but the amount carried by solution alone is too small to supply most tissue needs at ordinary pressures. Red blood cells contain haemoglobin, a protein with iron-bearing haem groups that binds oxygen reversibly. The textbook's approximate accounting states that about ninety-seven per cent of transported oxygen is associated with red blood cells, largely as oxyhaemoglobin, and about three per cent is dissolved in plasma. These figures are representative and depend on physiological conditions.

Each normal adult haemoglobin molecule contains four globin subunits with four haem groups and can bind up to four O₂ molecules. Binding is reversible: oxygen attaches readily when its partial pressure is high and can be released where its partial pressure is lower. The iron in functional haemoglobin remains in the ferrous state during normal oxygen binding; oxygenation is not equivalent to permanently oxidising the haem iron. A red cell is an oxygen transporter, not the cellular site where body tissues receive their final energy from oxygen.

Why oxygen saturation produces an S-shaped curve

When oxygen partial pressure is low, relatively few haemoglobin binding sites are occupied. As oxygen binds, the protein changes conformation in a way that makes additional oxygen binding more favourable. This cooperative effect creates a sigmoid, or S-shaped, curve when the percentage saturation of haemoglobin is plotted against pO₂. At high pO₂, most available sites are occupied and the curve approaches a plateau, while at intermediate pressures it rises steeply.

The curve's shape has clear biological advantages. At the high oxygen partial pressures characteristic of functioning pulmonary alveoli, haemoglobin is near high saturation, and modest changes in pO₂ produce relatively small changes in percentage saturation. In tissues with lower pO₂, the steeper curve permits appreciable release of oxygen in response to a modest fall in local partial pressure. Cooperative binding therefore supports both efficient loading at the lungs and unloading at metabolically active tissues.

How lungs favour loading and tissues favour unloading

In alveoli, pO₂ is high while pCO₂ and H⁺ concentration are relatively lower, favouring the formation of oxyhaemoglobin. In working tissues, pO₂ is lower and pCO₂, H⁺ concentration and temperature can be higher, favouring oxygen release. This does not mean blood in veins carries no oxygen: venous blood retains appreciable oxygen saturation under ordinary resting conditions. A tissue can increase oxygen extraction as metabolism intensifies, especially when local conditions favour oxygen release.

Higher CO₂ and greater acidity reduce haemoglobin affinity for oxygen at a given pO₂, shifting the oxygen dissociation curve to the right. This is a major part of the Bohr effect. Increased temperature also generally favours unloading and shifts the curve right. Conversely lower CO₂, lower H⁺ concentration and cooler temperatures tend to favour loading, producing a relative left shift. The effect of 2,3-BPG within red cells is another physiological modifier, but the textbook focuses on pO₂, pCO₂, H⁺ and temperature.

What a right-shifted curve means

A right shift does not mean that oxygen must move from tissues into blood, or that the blood has become entirely empty of oxygen. It means that at the same pO₂ a smaller fraction of haemoglobin sites is occupied, so oxygen can be released more readily. A left shift means haemoglobin holds onto oxygen more strongly at the same pO₂, supporting loading but potentially hindering delivery to tissues. To answer curve questions, always state which variable is held constant and whether you are describing affinity, saturation or actual delivered oxygen.

How much oxygen is delivered in a typical sample of blood?

The source states that each 100 mL of oxygenated blood can deliver about 5 mL of O₂ to tissues under normal conditions. This is a representative arterio-venous oxygen-content difference, not the total volume of oxygen present in 100 mL of arterial blood. Under heavy exertion tissues can extract a greater amount, so the delivered value changes. Never confuse millilitres of gaseous O₂ equivalent delivered with the liquid blood volume that transported it.

Oxygen diffusion out of capillaries is driven by local partial-pressure gradients, but haemoglobin releases bound oxygen as dissolved oxygen is consumed. Thus the dissolved oxygen pool and bound oxygen pool remain linked through reversible binding. In a well-oxygenated lung, oxygen entering plasma binds readily to haemoglobin, while in tissues oxygen use keeps local pO₂ low enough to favour net unloading.

Quick Quiz

Model Answers

1. At high lung pO₂, haemoglobin approaches the plateau of cooperative saturation. At lower tissue pO₂, the steep curve permits release; high local CO₂, H⁺ and temperature further reduce affinity.

2. Raising pCO₂ or H⁺ reduces haemoglobin affinity and shifts the curve to the right, enabling greater O₂ unloading at a given tissue pO₂.

3. Binding is cooperative: oxygen occupation of one site promotes additional site occupancy, generating a steep middle and flatter high-pressure region.

4. It is an approximate normal difference between arterial and venous blood oxygen content across tissues, not the maximum oxygen storage or the entire volume of blood.

5. Most oxygen is bound reversibly to haemoglobin inside erythrocytes; a much smaller fraction is dissolved in plasma. Both exchange through the dissolved phase when loading/unloading.