Sickle cell anaemia

Pathogenesis (mechanism)
In a normal person,
  • RBCs contain Hb molecules.
  • One Hb molecule contains 4 polypeptide chains.
  • 2 alpha & 2 beta chains.
  • A particular gene is responsible for the formation of 2 beta chains.
  • It is situated on the short limb of 11th chromosome.
  • In a particular beta chain, 6th amino acid is the hydrophilic glutamic acid.
  • Glutamic acid is responsible for the polarization of a particular oxygen molecule to bind with the Hb molecule.
  • The bound oxygen molecule is then transported in the RBC to supply the body cells.
 

In an anaemic patient,
  • Beta globin gene is affected (point mutation).
  • It is responsible for the formation of affected beta chains.
  • Normal 2 alpha chains & 1 beta chain combine with the affected beta chain to form an abnormal Hb molecule called sickle cell haemoglobin (Hbs).
  • So, 6th amino acid of the affected beta chain is not the glutamic acid but hydrophobic amino acid called valine.
  • The oxygen molecules cant bind with the valine.
  • Then the total number of oxygen molecules that can bind with a Hb molecule become less.
  • So, the body cells prone to ischemia. 
  • In low oxygen concentrations (ex – high altitude), absence of the polar amino acid at the 6th position of beta chain promotes non covalent polymerization of Hb molecules.
  • Hb molecules become aggregated.
  • Aggregated Hb molecules become precipitated.
  • Due to the precipitate, RBCs loss their membrane elasticity.
  • RBCs distort their shape due to loss of membrane elasticity.
  • This process is called sickling.
  • Sickle cells are rapidly removed from the circulation because they are non reversible with high oxygen concentrations.
 
Inheritance
  • Autosomal recessive disease.
  • Inherited by consanguineous marriages.
  • Both males & females are affected.
  • The trait is shown when both genes are recessive (homozygous).
  • Heterozygous females are carries.
  • They do not show the disease (asymptomatic).
  • But they transmit this gene to their children.
  • There is a 1-in-4 chance of their child developing the disease & 1-in-2 chance of their child is being just a carrier.
  • Heterozygous individuals are moderately resistant to the malarial infection.  
 
Complications

  • Splenomegaly
  • Jaundice
  • Severe anaemia
  • Tachycardia
  • Reticulocytopenia
  • Stroke
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