Case 2 - Sickle Cell

Question 1

Outline the base pathology of sickle cell disease

Answer 1

Base substitution usually occurs in the gene for the β-polypeptide chain of haemoglobin at codon no.6 (charged glutamic acid):
𝑮𝒍𝒖𝒕𝒂𝒕𝒎𝒊𝒄 𝒂𝒄𝒊𝒅 → 𝑼𝒏𝒄𝒉𝒂𝒓𝒈𝒆𝒅 𝑽𝒂𝒍𝒊𝒏𝒆

Question 2

Outline the structure of HbS

Answer 2

Haemoglobin consists of 2⍺ & 2β chains (tetramer), Haemoglobin S (HbS) occurs if the β-chains are altered. This is caused by the inheritance of one or two copies of an abnormal β globin gene are inherited. HbS is insoluble at low partial pressures (Deoxygenated form) – Crystalising out (Forms Sickle shape). Deformation of erythrocyte (red cell) causes vascular occlusion, leading to sickle cell anaemia.

Question 3

Outline the mechanism of HbS

Answer 3

During deoxygenation, the haemoglobin molecules undergo conformational change, whereby the amino acids interact through hydrophobic interactions. The exposed hydrophobic surface area causes the haemoglobin molecule to be associated with each other. HbS molecules polymerise into fibres, due to valine interlocking protrusion.

Question 4

Outline the process of sickling

Answer 4

This is the process by which fibre builds on pre-existing structure, with rigid polymers distorting the conformation of the cell, thereby changing its shape. Acidosis leads to a decrease in affinity to oxygen. Low-flow vessels also increase the deoxygenation time.