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 11^th chromosome.
• In a particular beta chain, 6^th 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, 6^th 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 6^th 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