Haemoglobin

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Haemoglobin

• 4 globin chains each with 1 Haem
• 3 main haemoglobins
• Hb A Alpha2 Beta2
• Hb A2 Alpha2 delta2
• Hb F Alpha2 Gamma2
• Main purpose to carry O2 --- Haem part
• Amino acid sequence critical with variations
  leading to alterations in O2 carrying
• 
  solubility
• 
  integrity

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Haemoglobin 2

• Critical Locations
• Alpha1 beta2 contact --- O2 affinity
• Prox distal Histidine of Haem pocket ---
• Haem oxidation HbM
• Haem contact areas --- globin instability
• unstable
  HbS

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Haemoglobinopathies

• Quantitative --- normal chain def.
• Thalasaemias
• Qualitative ---- Abn chains (amino acids)
• Altered solubility HbS
• HbC
• Instability Unstable Hb
• Altered O2 Affinity Increased
• 
  Chesapeake
• 
  Kempsey
• Decreased
• 
  Seattle
• Cyanosis HbM

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Thalassaemias

• Deficiency / absence normal chain. No abnormal
  chain present
• Named by missing chain
• Alpha Thal Alpha chain missing
• Beta Thal Beta chain missing
• Autosomal dominant trait though heterozygotes
  have minimal difficulty
• RNA/DNA defect in regulator gene function with
  resultant def of messenger RNA

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Beta Thalassaemia

• Defective Beta chain formation, partial or
  complete
• Mechanism of anaemia
• Inneffective erythropoesis
• Decreased RBC survival (haemolysis)
• Defective Hb formation

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Beta Thalassaemias

• Clinical Types / features
• Thal minor Asymptomatic
• Hypochromic
  microcytic
• anaemia. Target
  cells
• Thal intermedia
• Thal Major Severe anaemia Tx dep.
• Spleen

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Beta Thalassaemia

• Haemoglobin studies
• Thal minor --- incr slight incr A2
• Thal major --- markedly incr F
• 
  30-90

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Sickle cell disease HbS

• Single amino acid substitution
• Beta 6 Glutamic Acid ? Valine
• (HbC is Beta 6 Glu ? Lycine)
• Change alters the solubility of HbS causing it
  to come out of solution in esp when deoxygenated

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Beta Thalassaemia

• Therapy / prognosis
• Blood
• Folic acid
• Iron chelation
• Splenectomy