Case 2 - Sickle Cell Anaemia Flashcards
What is the structure of adult haemoglobin HbA?
- 2 alpha chain
- 2 beta chain
- 4 haem groups (bind O2)
How are the chains in HbA arranged and work?
Tetrahedrally
Allosteric - co-operative binding
What genetic pattern does Sickle cell disease show?
Autosomal recessive
What is the difference between sickle cell disease and trait?
Disease - 2 HbS gene
Trait - 1 HbS 1 HbA
How is the Hb gene mutated to form HbS gene?
Valine (neutral) replaces Glutamate (-ve charge) at the 6th amino acid position of the Beta-chain
What sort of mutation is HbA to HbS?
Substitutional mutation
When is the HbS structure most harmful?
In a deoxygenated state because the beta-chain changes to sickle shape and polymerise in more acidic (low pH) state - Acidosis [reduced blood flow]
Leads to occlusion of the vessel and infarction
Why does HbS polymerise?
Acidosis causes presence of a hydrophobic site - creating a point of contact between two nearby Hb molecules and leads to HbS polymerization
How does electrophoresis separate HbA and HbS?
It separates them by charge and mass. HbS is less negative than HbA so it moves less to positive
What do we see in the electrophoresis of sickle cell trait?
2 bands because it is heterozygous with both HbA and HbS
What are the 4 cell types we see on a blood film for Sickle Cell Anaemia?
- Reticulocyte (young RBC)
- Target cell
- Sickle cell
- Normal RBC
Why is there a higher reticulocyte count in Sickle Cell Anaemia?
Bone marrow produce more to compensate for defective sickle cell (which are being turned over rapidly)
What is splenomegaly?
Enlarged spleen from micro-infarction due to accumulated sickled cells
What is the function of the spleen?
Filters blood
What are the symptoms of Sickle cell disease?
Vision loss
Stroke
Bone crises
How is vision loss caused?
Sickle cell accumulate in microvessel of retina
- increase in pressure hence damage vessel
- Cause ischaemia leading to chemokine release
- Angiogenesis occurs and collateral is formed
- Collateral is easily damaged and also grows across area of vision
What is angiogenesis?
Formation of new blood vessel from spitting of old one
What is ischaemia?
Reduction of blood supply from blockage
What causes/type of strokes are there?
- Ischaemia (cerebral artery block/ silent stroke)
- Haemorrhagic stroke
- Block of major cerebral arteries
What is a silent stroke?
It is asymptomatic and only blocks smaller arteries
How does cerebral artery block induce stroke?
O2 deficiency to brain hence tissue death and infarction
What is a haemorrhagic stroke?
Due to angiogenesis where more collaterals are produced and gets damaged leading to haemorrhage
How does the blockage of a major cerebral arteries lead to stroke in sickle cell disease?
It is major symptomatic stroke where selectins are released and binds to sickle cell invoking inflammatory response hence blocking arteries
What happens in a bone crises?
Microvascular occulsion reducing flow to bone marrow
- in a prolonged ischaemia hence promoting sickle formation
