Oxygen transport and the dissociation curve

The two ways oxygen travels

Oxygen moves in blood in two forms, and only one of them matters clinically.

Content of oxygen: CaO₂ = (1.34 × Hb × SaO₂) + (0.003 × PaO₂)

The dissolved fraction is roughly 1.5% of the total. That single fact explains why anaemia drops oxygen delivery even when the PaO₂ and the saturation are both perfect — and why the pulse oximeter looks reassuring in a patient who is bleeding to death.

Why the curve is sigmoid

Haemoglobin has four subunits. Binding of the first oxygen molecule changes the quaternary structure from the tense (T) to the relaxed (R) state, which raises the affinity of the remaining sites. This positive cooperativity produces the S shape, and the shape does two jobs:

• The flat upper part (PaO₂ 60–100 mmHg) protects loading. A fall in alveolar PO₂ from 100 to 60 mmHg costs only about 8% saturation, so moderate lung disease or altitude does not immediately desaturate the patient.
• The steep lower part (PaO₂ 20–40 mmHg) enables unloading. A small further fall in tissue PO₂ releases a large amount of oxygen.

The clinical corollary of the flat top: SpO₂ is an insensitive early marker of deteriorating gas exchange. By the time the saturation falls below 90%, PaO₂ is already near 60 mmHg and the patient is on the steep part of the curve, where further deterioration is rapid.

What shifts the curve

Right shift = reduced affinity = better unloading in tissue.

• ↑ PCO₂ and ↓ pH (the Bohr effect)
• ↑ Temperature
• ↑ 2,3-BPG (chronic hypoxia, anaemia, high altitude, stored blood loses it)

Left shift = increased affinity = poorer unloading.

• ↓ PCO₂, ↑ pH, ↓ temperature, ↓ 2,3-BPG
• Fetal haemoglobin (γ chains bind 2,3-BPG poorly, so HbF holds oxygen more tightly and can strip it from maternal blood across the placenta)
• Carboxyhaemoglobin — carbon monoxide both occupies binding sites and left-shifts the remaining ones, which is why CO poisoning is far worse than the equivalent degree of anaemia
• Methaemoglobin — Fe³⁺ cannot bind oxygen and left-shifts the remaining ferrous sites

CADET, face Right! — CO₂, Acid, 2,3-DPG, Exercise, Temperature.

Three traps

1. "SpO₂ 100%, so oxygenation is fine." In carbon monoxide poisoning a standard pulse oximeter reads carboxyhaemoglobin as oxyhaemoglobin and reports a falsely normal saturation. Measure co-oximetry.
2. "P50 tells you the saturation." P50 (normally ~26–27 mmHg) is the PO₂ at which haemoglobin is half saturated; a higher P50 means a right-shifted, lower-affinity curve.
3. "Cyanosis appears at a fixed saturation." Central cyanosis needs roughly 5 g/dL of deoxygenated haemoglobin. A polycythaemic patient looks cyanosed early; a profoundly anaemic patient may never look cyanosed despite dangerous hypoxaemia.

The one-line anchor

The curve's shape is a loading guarantee at the top and an unloading amplifier at the bottom; everything that shifts it is either a signal of metabolic activity (shifts right) or a specialised carrier that must hold on tighter (shifts left).