Haemoglobin and Related Disorders Summary

Overview of Haemoglobin

  • Haemoglobin (Hb): A crucial protein in red blood cells responsible for transporting oxygen (O2) and carbon dioxide (CO2).
1. Structure of Haemoglobin
  • Composition:
    • Made of four chains: 2 alpha (α) and 2 beta (β) chains.
    • Each chain contains a haem group with an iron atom.
  • Function:
    • Oxygen binds reversibly to the iron in the haem group, which also contributes to the red color of blood.
2. Myoglobin vs Haemoglobin
  • Myoglobin (Mb):
    • Single subunit protein primarily found in muscles with high O2 affinity for storage.
  • Haemoglobin (Hb):
    • Allosteric protein with a cooperative binding mechanism, allows for effective O2 transport.
3. Oxygen Binding Mechanism
  • Cooperative Binding:
    • The binding of one O2 molecule enhances the likelihood of further O2 molecules binding to Hb.
    • Sigmoidal oxygen dissociation curve indicates increasing affinity with each O2 bound.
4. The Bohr Effect
  • Definition:
    • Hb's affinity for O2 decreases with increasing CO2 and decreasing pH (more acidic conditions).
  • Mechanism:
    • High [H+] leads to protonation of histidine residues, stabilizing the tense (T) state of Hb and reducing O2 affinity, promoting O2 release in active tissues.
5. Role of 2,3-BPG
  • Function:
    • 2,3-bisphosphoglycerate (BPG) decreases Hb's affinity for O2, enhancing O2 delivery under hypoxic conditions (ex. high altitude).
  • Mechanism:
    • BPG binds between beta chains, promoting the tense state of Hb.
6. Differences Between Adult (HbA) and Foetal Haemoglobin (HbF)
  • Composition:
    • HbA: 2α and 2β chains.
    • HbF: 2α and 2γ chains, which gives it a higher affinity for O2 than HbA.
  • Function in Development:
    • HbF allows a fetus to extract O2 more effectively from maternal blood.
7. Haemoglobinopathies
  • Definition: Genetic disorders affecting Hb synthesis and structure.
  • Examples:
    • Sickle cell anaemia (HbS): Caused by a mutation in the β-globin gene leading to a deformity in red blood cells, causing blockages in blood vessels. Symptoms include pain and potential organ damage.
    • Thalassemia: Characterized by reduced synthesis of α or β chains, leading to anemia and other complications.
8. Clinical Implications of Sickle Cell Traits
  • Sickle Cell Trait:
    • Carries a protective effect against malaria, particularly in regions where malaria is endemic.
  • Treatment:
    • Hydroxyurea and gene therapy are proposed to alleviate symptoms and promote HbF production.
9. Thalassemia

g - Classification:

  • B-thalassemia: Results from impaired β-globin chain production, with severity varying by genotype.
  • Complications include anemia and potential dependence on blood transfusions.
    • Epidemiology:
  • Prevalent in regions such as the Mediterranean, the Middle East, and parts of Africa and Asia.