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PH-HE03

Sickle cell disease

How a single change in the beta-globin gene makes haemoglobin polymerise when it gives up oxygen, how stiff sickled cells block small vessels and break down early, and how this explains pain crises, organ damage and infection risk.

By the end, you can

  • Describe the mutation that produces haemoglobin S and how sickle cell disease is inherited.
  • Explain how deoxygenated HbS polymerises and what makes sickling more likely.
  • Explain how sickled cells cause vaso-occlusion and ischaemic pain.
  • Relate chronic haemolysis to anaemia, jaundice and gallstones.
  • Explain why the spleen is damaged and why this raises the risk of serious infection.
  • Recognise the blood film, tissue changes, crises and tests of sickle cell disease, and explain how hydroxycarbamide, transfusion, infection prevention and curative treatments act on the mechanism.

What it is

Sickle cell disease is a group of inherited conditions in which red cells contain mainly haemoglobin S (HbS), which polymerises when deoxygenated and distorts the cells. The commonest and usually most severe form is sickle cell anaemia (HbSS, two copies of the sickle gene); others include HbSC disease and HbS/beta-thalassaemia. Carriers with one copy (sickle cell trait, HbAS) usually have no symptoms.

3 types to tell apart
Sickle cell anaemia (HbSS)
Two sickle genes; most haemoglobin is HbS. Usually the most severe form.
HbSC disease and HbS/beta-thalassaemia
One sickle gene with another abnormal beta gene; severity ranges from mild to as severe as HbSS.
Sickle cell trait (HbAS)
One sickle gene; about 60% of haemoglobin is normal HbA. Usually no symptoms, with rare complications under extreme conditions.

US spelling: haemoglobin → hemoglobin, anaemia → anemia, thalassaemia → thalassemia, haem → hem.

Normal function

Flexible red cells and the spleen

Adult haemoglobin (HbA) has two alpha and two beta globin chains, each holding an iron-containing haem. It stays dissolved inside the red cell whether it carries oxygen or not, so the cell remains a soft, flexible biconcave disc about 7–8 micrometres across.

That flexibility lets red cells fold to squeeze through capillaries narrower than themselves and through the narrow slits of the . They survive about 120 days.

The spleen filters the blood. Its macrophages remove old, stiff or damaged red cells and capture bacteria in the bloodstream, especially those with a sugar capsule, such as pneumococcus, which antibodies and macrophages in the spleen are particularly good at clearing.

Point to it on the model