Haemoglobin & Oxygen Delivery Concepts

Study Notes

Haemoglobin binds oxygen via iron(II) ions (Fe²⁺).
Haemoglobin also transports nitric oxide (NO). It can form iron nitrosyl haemoglobin (Fe²⁺NO Hb) or alpha- or beta-nitrosyl haemoglobin.
It also carries CO₂ as carbaminohaemoglobin.
Haemoglobin's oxygen affinity determines the amount of oxygen released to the tissues. This can be shown on an oxygen dissociation curve.
A rightward shift on the oxygen dissociation curve indicates a decreased affinity, while a leftward shift indicates an increased affinity.

Students should be able to explain the structure of the oxygen dissociation curve.
Students should be able to explain the effect of 2,3-DPG on oxygen delivery.
Students should be able to consider the role of the Bohr effect in modifying oxygen affinity.

Haemoglobin binds oxygen via Fe²⁺.
It transports nitric oxide, forming iron nitrosyl Hb (Fe²⁺NO Hb), and can form alpha or beta nitrosyl haemoglobin.
It transports CO₂ as carbaminohaemoglobin.
Haemoglobin's affinity for oxygen dictates how much oxygen is released to tissues.
The oxygen dissociation curve describes this affinity. A right-shifted curve means lower affinity, releasing more oxygen to tissues. A left-shifted curve indicates greater affinity, less oxygen released to the tissues.

The curve shows how the saturation of haemoglobin with oxygen changes with varying PO₂ (partial pressure of oxygen).
The graph shows control, high affinity and low affinity states with oxygen saturation levels and related partial oxygen pressures (P50).
Factors that affect the curve's position (affinity) include CO₂, acidity, and temperature, as well as 2,3-DPG.

2,3-DPG is a key regulator of oxygen affinity.
It's an intermediate product of glycolysis.
It binds to deoxyhaemoglobin in a 1:1 ratio.
2,3-DPG stabilises the quaternary structure of haemoglobin (Hb), specifically through the β-globin chains.
It shifts the oxygen dissociation curve to the right, decreasing oxygen affinity, making oxygen more readily available to the tissues.
2,3-DPG is released at high PO₂.

2,3-DPG binding changes haemoglobin's conformation.
When 2,3-DPG binds to deoxyhaemoglobin (lower oxygen), it causes a shift to the tense (T) state, decreasing the oxygen affinity.

The Bohr effect describes how pH affects haemoglobin's oxygen affinity.
Haemoglobin functions as a buffer, accepting protons when oxygen is released.
Increased acidity (lower pH) decreases oxygen affinity, releasing more oxygen to tissues.
This is caused by increased CO₂ and lactic acid production during metabolism.

CO₂ is transported in the blood in three forms: dissolved in plasma, bound to haemoglobin as carbaminohaemoglobin, and as bicarbonate ions (HCO₃⁻).
In the presence of carbonic anhydrase, CO₂ reacts with water to form carbonic acid (H₂CO₃). Carbonic acid then dissociates into bicarbonate ions and hydrogen ions (H⁺).
The chloride shift occurs to maintain ionic balance.

At a pH of 7.4 and an oxygen tension of 26 mmHg, hemoglobin is 50% saturated.
Increasing pH increases hemoglobin's oxygen affinity, shifting the curve to the left.
Decreasing pH decreases hemoglobin's oxygen affinity, shifting the curve to the right.

The oxygen dissociation curve's shape results from interactions between its subunits.
2,3-DPG and H⁺ significantly impact oxygen delivery.
The oxygen dissociation curve dynamically adjusts based on physiological needs.