Sickle cell disease Flashcards
What causes sickle cell disease?
Mutation in the beta gene resulting in the production of HbS (2 alpha 2 sickle beta chains)
What and where is the mutation that causes sickle cell disease?
- single amino acid substitution on the beta globin gene at position 6 on chromosome 11
- Glutamine is substituted for valine
What does the rate of polymerisation of HbS depend on?
- Deoxygenation rate
- Hb concentration
- HbF
Why do the sickle cells cause problems?
- They are much bigger and more rigid than normal erythrocytes
- They can cause blockages
Describe the blood film in sickle cell disease
Lots of sickle red cells and some target cells
What is the clinical result of sickle cell disease?
- Anaemia due to reduced red cell survival because of haemolysis, also causes chronic endothelial dysfunction
- Vaso-occlusion: tissue hypoxia/ infarction, pain and tissue damage (often requiring strong pain killers)
- It is a multisystem disease
Brain - sickle cell
- Stroke (if untreated 10% children will have stroke)
* moya moya (in children with stroke, blood vessels try to grow around the blockage but fragile so risk of aneurysm
Lungs - sickle cell
- Acute chest syndrome
* Pulmonary hypertension
Bones - sickle cell
- Dactilytis in kids
* Osteonecrosis in adults
Spleen - sickle cell
Hyposplenic
Kidneys - sickle cell
- Loss of concentration in urine (kids will continue to bed wet later than peers)
- Infarction
Urogenital - sickle cell
•Chronic or acute priapism (long lasting painful erection)
Eyes - sickle cell
Vascular retinopathy
Placenta - sickle cell
Fetal loss / IUGR (intra uterine growth restriction)
What is an overview of the treatment of sickle cell anaemia?
- Prevention of crises
- Prompt management of crises
- Bone marrow transplant (few at present)
- Potential gene therapy soon
