Haemoglobin & Oxygen Delivery PDF

Haemoglobin & oxygen delivery GAVIN KNIGHT Learning Objectives On completion of this session, you should be able to: 1. Explain the structure of the oxygen dissociation curve 2. Explain the impact of 2,3 DPG on oxygen delivery 3. Consider the role of the Bohr effect in modifyi...

Haemoglobin & oxygen delivery GAVIN KNIGHT Learning Objectives On completion of this session, you should be able to: 1. Explain the structure of the oxygen dissociation curve 2. Explain the impact of 2,3 DPG on oxygen delivery 3. Consider the role of the Bohr effect in modifying oxygen affinity Haemoglobin Function Binds oxygen via Fe2+ Transport Nitric Oxide forming: iron nitrosyl Hb, Fe2+NO Hb Can form alphanitrosyl or betanitrosyl haemoglobin respectively via thiol (-SH) groups to form S-nitroshaemoglobin Transports CO2 - carbaminohaemoglobin Hb’s affinity for oxygen determines proportion of oxygen released to the tissues Can be demonstrated using oxygen dissociation curve When the curve is shifted to the right, affinity is decreased Shift to the left affinity is increased Oxygen Dissociation Curve p5 CO2 Acidity 0 2,3DPG Exercise Temperature Modelling the relationships between haemoglobin oxygen affinity and the oxygen cascade in humans The Journal of Physiology, Volume: 597, Issue: 16, Pages: 4193-4202, First published: 09 July 2019, DOI: (10.1113/JP277591) 2,3-DPG  The major regulator of O2 affinity  Intermediate product of glycolysis  2,3-DPG binds to deoxyhaemoglobin in a 1:1 ratio  Stabilises the quaternary structure of Hb via -chains  Changes Hb from an R to T state  2,3-DPG is released at high pO2 2,3 DPG Binding: HbA Relaxed Tense The Bohr Effect  Describes the effect of pH on Hb-oxygen affinity  Hb is an important buffer  Proton accepted when oxygen released  Lactic acid and CO2 increase [H+]  Raised [H+] causes reduced oxygen affinity for Hb, releasing more oxygen to tissues Link to Hb Carbonic anhydrase CO2 + H2O H2CO3 HCO3- + H+ dioxide plus water Carbon carbonic acid bicarbonate and hydrogen ion Link to chloride shift equilibrium by Nikhil from Noun Project (CC BY 3.0) Carbon dioxide transport Oxyhaemoglobi Carbaminohaemoglo n bin By Gladissk - marvin sketch, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php? curid=23728920 Oxygen Dissociation Curve At a pH of 7.4 and an pH 7.6 oxygen tension of 26mmHg, haemoglobin is pH 7.4 50% saturated. If the pH pH 7.2 increases to 7.6, the curve is shifted left – indicating increased oxygen affinity. Conversely, a decrease of pH to 7.2 shifts the curve to the right, decreasing the oxygen affinity of haemoglobin, making oxygen available to the tissues. Summary  The structure of the oxygen dissociation curve is based upon subunit interactions  The oxygen dissociation curve demonstrates the affinity of haemoglobin for oxygen  2,3-DPG and H+ are important facilitators of oxygen delivery  The oxygen dissociation curve is not static, it changes in line with individual physiological needs