Sickle Cell Anaemia

Describe the structure of RBCs

• Biconcave discs, anucleate, essentially no organelles

• Diameters larger than some capillaries

• Filled with haemoglobin (Hb) for gas transport

• Major factor contributing to blood viscosity

• Life span 120 days

Describe the structure of haemoglobin

• 4 polypeptide subunits

• 2 α, 2 β

• Contains 1 haem group per chain

• Globular protein with quaternary structure

Describe the assembly of haemoglobin

- The α - and β -globin polypeptides are translated from their respective mRNAs

- Upon haem binding, the protein folds into its native three-dimensional structure.

- Alpha globin chain is on chromosome 16

- Beta globin chain in on chromosome 11

-Normally equal amounts of alpha and beta chains produced (1:1)

What is a haemoglobinopathy?

inherited disorders of globin, the protein component of haemoglobin

What are the two groups of haemoglobinopathies?

1. Mutation resulting in reduced rate of synthesis of either chain type - result in α- and β-thalassaemia

2. Changes in Hb structure as a result of the synthesis of abnormal haemoglobin with an altered amino acid sequence - HbS, HbE, HbC

Which cell variant occurs in sickle cell anaemia?

HbS (most common)

How does sickle cell anaemia occur?

Point mutation at the 6th position on the β-globin chain changing in an A to a T. Results in glutamic acid being replaced with valine

What type of genetic disease is sickle cell anaemia?

Autosomal recessive

What is the threat of sickle cells?

• Under well oxygenated conditions HbS is fully oxygenated and soluble

• When HbS is deoxygenated it loses its solubility and polymerises into long rigid chains that distort the red cell (sickle shape)

• Polymerisation of HbS is reversible and sickle cell may revert back to normal shape after re-oxygenation

• However, after numerous cycles of oxygenation and deoxygenation, red cell becomes irreversibly sickled

• Sickle cells can block blood vessels

• Sickle cells are eliminated in liver and spleen

What are the threats of haemolytic anaemia?

RBCs are destroyed faster than they can be made, and causes an excess of bilirubin (RBC breakdown product)