Overview

Reference range≈130–175 g/L (men), ≈120–155 g/L (women)

O₂ binding capacity≈1.34 mL O₂ per g Hb

P50≈26–27 mmHg

Arterial O₂ content≈200 mL/L (20 mL/dL)

CO affinity vs O₂≈200–250×

Types of haemoglobin. In adults, HbA (α2β2) makes up about 97% of the total, and HbA2 (α2δ2) about 2–3.5%. HbF (α2γ2) is the main fetal haemoglobin and is less than 1% in adults. HbF binds 2,3-BPG poorly, so its affinity for oxygen is higher than HbA's. This helps oxygen pass from mother to fetus across the placenta.

Oxygen capacity. Each haem binds one O₂ molecule, so each haemoglobin carries up to four. One gram of haemoglobin binds about 1.34 mL of O₂. The oxygen content of arterial blood (CaO₂) is 1.34 × Hb (g/dL) × SaO₂ + 0.003 × PaO₂ (mmHg). Normally this is about 20 mL O₂ per dL of blood, almost all of it bound to haemoglobin.

Cooperative binding. Haemoglobin switches between a low-affinity T (tense) state and a high-affinity R (relaxed) state. Each O₂ that binds makes it easier for the next to bind. This gives the oxygen dissociation curve its S (sigmoid) shape. Haemoglobin is about 97–98% saturated at a PO₂ of 100 mmHg (arterial blood) and about 75% saturated at 40 mmHg (mixed venous blood). The P50, the PO₂ at which it is half saturated, is about 26–27 mmHg.

Shifts of the curve. The curve shifts to the right (lower affinity, easier unloading of O₂) with raised CO₂, raised H⁺ (the Bohr effect), raised 2,3-BPG and raised temperature, all of which occur in exercising muscle. It shifts to the left with the opposite changes, and with HbF, carbon monoxide and methaemoglobin.

CO₂ transport. About 70% of CO₂ travels as bicarbonate, about 20–23% as carbamino compounds (mostly with haemoglobin) and about 7–10% dissolved. Deoxygenated haemoglobin binds CO₂ and H⁺ better than oxygenated haemoglobin (the Haldane effect). This helps blood pick up CO₂ in the tissues and release it in the lungs.

Function

Binds and carries O₂, loading it in the lungs and unloading it in the tissues.
Carries part of the CO₂ (as carbamino-haemoglobin) and buffers H⁺.
Interacts with nitric oxide and may help regulate local blood flow.

Clinical significance

Carbon monoxide poisoning

CO binds haemoglobin about 200–250 times more avidly than O₂. It also shifts the curve to the left, so the oxygen that is carried is released less readily. Standard pulse oximeters read falsely normal, so CO-oximetry is needed. Treatment is 100% oxygen, and hyperbaric oxygen in selected cases.

Methaemoglobinaemia

In methaemoglobinaemia, haem iron is oxidised to Fe³⁺, which cannot carry oxygen. Causes include nitrites, dapsone and benzocaine. The blood looks chocolate-brown and the pulse oximeter reads around 85%. It is treated with methylene blue.

Haemoglobinopathies and HbA1c

Sickle cell disease is caused by HbS. Thalassaemias result from reduced production of α or β chains. In β-thalassaemia trait, HbA2 is raised. HbA1c is haemoglobin with glucose attached. Its level reflects average blood glucose over about the previous 2–3 months and is used to diagnose and monitor diabetes.

Mnemonics

Right shift

"CADET, face Right": CO₂, Acid, 2,3-DPG, Exercise and Temperature shift the curve to the right.

Test yourself

Which of the following shifts the oxygen–haemoglobin dissociation curve to the LEFT, increasing O₂ affinity?

Increased 2,3-BPG
Fever
Fetal haemoglobin (HbF)
Acidosis

Answer: Fetal haemoglobin (HbF)

HbF binds 2,3-BPG poorly, so it has a higher O₂ affinity than HbA. This lets the fetus extract O₂ from maternal blood. Raised CO₂, acid, 2,3-BPG and temperature all shift the curve to the right ("CADET, face Right").