Sickle cell disease
- Lesion
One amino acid change makes haemoglobin stack into rods when oxygen is low. Stiff sickled cells block small vessels and break early.
What it is
Sickle cell disease is an autosomal recessive haemoglobinopathy caused by a point mutation that replaces glutamate with valine at position six of β-globin. Deoxygenated HbS polymerizes into long fibres, distorting and stiffening the red cell. Repeated sickling damages the membrane and dehydrates cells, producing chronic haemolysis, while sticky cells, inflammation and nitric oxide depletion cause microvascular occlusion and ischaemic injury in almost every organ. Trait confers protection against falciparum malaria, which explains its frequency in people of African descent, including Afro-Colombian communities.
Structure
- Smear: irreversibly sickled cells, target cells and Howell–Jolly bodies.
- Marrow hyperplasia expands bones: crew-cut skull on radiographs, prominent cheekbones.
- Spleen: early congestion, thrombosis and infarcts; later a small fibrotic nubbin with haemosiderin (autosplenectomy).
- Infarcts and necrosis in bone, brain, kidney medulla, retina, lung and skin (leg ulcers).
Step by step
- Valine replaces glutamate on β-globin, creating a hydrophobic patch.
- When deoxygenated, HbS molecules bind each other and form long polymer fibres.
- Cells take a sickle shape; repeated cycles damage the membrane and dehydrate the cell.
- Irreversibly sickled, rigid cells are removed by macrophages: chronic extravascular haemolysis.
- Sticky cells adhere to activated endothelium and leukocytes; free haemoglobin consumes nitric oxide.
- Slow flow in microvessels lets more cells sickle: occlusion, ischaemia and infarction.
Markers
- HbS
- HbF level
- Irreversibly sickled cells
Clinical notes
- Hand-foot syndrome (dactylitis) is often the first sign in infants.
- Acute chest syndrome (fever, chest pain, cough, infiltrates) and stroke are leading causes of death.
- Hydroxyurea raises HbF and reduces crises; vaccination and early antibiotics prevent many deaths.
In the lab
- Haemoglobin electrophoresis or chromatography shows HbS; newborn screening detects it early.
- Trait carriers have about 40% HbS and are usually asymptomatic, except for renal concentrating defects.
Test yourself
Think of the answer, then tap the question to see it.
Why do infants with sickle cell disease have no symptoms in the first months?
Their red cells contain mostly fetal haemoglobin, which inhibits HbS polymerization; symptoms start as HbF falls.
What is autosplenectomy?
Progressive infarction and fibrosis of the spleen in sickle cell disease, leaving a small fibrotic remnant and functional asplenia.
Which factors favour sickling?
Low oxygen tension, acidosis, dehydration (higher HbS concentration) and slow transit through microvessels.
Elsewhere in DurgiPedia
Connections
Microorganisms2
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Sickle cell disease: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Sickle cell disease: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026).
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Representative model, for educational purposes only.