Sickkle Cell Anaemia Flashcards
What is the structure of HbA?
2 alpha chains + 2 beta chains —> arranges tetrahedrally
4 haem groups
What happens to haemoglobin once O2 bind to it?
Conformational change —> changes shape —> increases binding capacity to O2
What causes HbS?
Autosomal recessive mutation in the beta globin (HBB) gene
—> non-conservative missense mutation
—> 6th amino acid (glutamate) swapped w/ valine —> hydrophobic —> promotes binding of Hb molecules —> sickle shape
What happens to HbS when it is bound to O2?
Nothing, carries O2 as normal
What happens to HbS when it is deoxygenated?
Beta globin chains change shape —> Hb clumps together —> chain —> bends into a sickle shape
What factors can escalate the condition?
Acidosis
Low O2 conc.
Vessels w/ small radius
Hoe does acidosis escalate the condition?
Blood pH decreases —> increases sickling
E.g from exercise —> lactic acid build up in tissue
How does low O2 conc. escalate the condition?
When Hb deoxygenated —> changes shape —> clumps together —> sickle shape
How do vessels w/ small radius escalate the condition?
Sickle cells not as flexible as normal RBCs
Build up of sickle cells in blood vessels —> blockage of blood flow —> can’t deliver blood to tissues —> no O2 —> infarction
What is electrophoresis?
Technique (using electricity) to separate molecules based on their charge and mass
What are the charges of glutamate and valine?
Glutamate = negative
Valine = neutral
What is the charge of HbS compared to HbA?
HbS is less negative than HbA
—> valine is neutral
What would you see in electrophoresis of sickle cell anaemia, sickle cell trait and normal?
HbA moves furthest towards the positive
HbS moves less towards the positive
Sickle cell trait —> two bands (HbA/HbS) —> autosomal recessive
What cells would you find in a blood film analysis?
Reticulocyte
Target cells
Normal RBCs
Sickle cells
Why would you find a higher than normal reticulocyte count in a blood film analysis?
Defective cells can’t carry O2 as well
Bone marrow has to produce more RBCs
Reticulocytes are immature but can still carry O2 —> not as well
Why is it bad having a higher than normal count of reticulocytes?
Don’t have flexibility of RBCs + bigger than normal RBCs —> can get stuck or broken
Why are there target cells in the blood film?
Have layer of decreased density in middle —> Hb spread out to sides due to binding of Hb
What are some symptoms of sickle cell?
Vision loss
Stroke
Bone crisis
Splenomegaly
Why does sickle cell cause vision loss?
Sickle cells accumulate in microvasculature of the retina
Pressure increases
Blood vessels become damaged
Ischaemia causes chemokine release —> tells eyes to produce more blood vessels
Angiogenesis causes collateral formation
Collaterals are easily damaged and can grow across areas of vision
What 2 type of strokes are caused?
Ischaemic
Haemorrhagic
How does an ischaemic stroke occur?
Sickle cells block blood vessels
Lack of blood supply leading to ischaemia and infarction
Silent strokes are asymptomatic
How does an haemorrhagic stroke occur?
Occurs due to angiogenesis
Collaterals are easily broken
Causing blood to leak out into tissues
Why does sickle cell cause bone crisis?
Reduced blood flow to bone marrow due to microvascular occlusion
Prolonged ischaemia leads ro infarction
Ischaemia exacerbates sickling
How does sickle cell cause splenomagaly?
Spleen has a very good blood supply —> lots of blood coming in but tiny vessels —> lots of blockages —> lots of blood in spleen
—> enlarged spleen
