Murewa Abebi - Sickle Cell Disease Flashcards
How does sickle cell disease occur
Base substitution on beta chain of Hb of charged glutamic acid for uncharged valine
How do sickle RBCs become sickled
The exposed hydrophobic surface area caused by conformational change of the Hb causes Hb molecules to be associated with each other rather than water.
Fibres of Hb are formed, forming rigid polymers which distort the shape of the cell
Why is the reticulocyte count in sickle cells higher than in normal cells?
Elevated levels of haemopoiesis due to anaemia
Why is the mcv in sickle cells higher than in normal cells
Lots of reticulocytes which are larger
How does exercise exacerbate sickle cell?
Increased deoxygenation of Hb, results in conformational change triggering sickling and so vasoocclusion
How does cold weather exacerbate sickle cell?
Cold weather stimulates vasoconstriction which increases susceptibility of clotting due to sickled cells.
How does infection exacerbate sickle cell?
How does dehydration exacerbate sickle cell?
Reduces plasma volume and increases blood viscosity, which promotes and sustains the sickling process
What are the treatments for sickle cell?
- Blood transfusions (supply functioning erythrocytes)
- Treating crises (giving painkillers, IV fluids & antibiotics)
- Hydroxycarbamide (stimulates HbF synthesis to increase O2 transport)
- Bone marrow transplant (replace mutated HSCs with healthy ones)
- Gene therapy
- Folic acid supplements (increases haemopoiesis)
How can sickle cell cause vision loss?
Accumulation of sickle cells in micro vessels in retina damages the vessels
How can sickle cell cause jaundice?
Life cycle of sickle cells shorter than normal RBCs so die faster than the liver can filter the bilirubin the sickle cells are being broken down into. The build up of bilirubin causes jaundice.
How can sickle cell cause jaundice?
Life cycle of sickle cells shorter than normal RBCs so die faster than the liver can filter the bilirubin the sickle cells are being broken down into. The build up of bilirubin causes jaundice.
How can CRISPR be used to cure sickle cell
1) Repair faulty beta globin gene using Cas 9 enzyme so only normal RBCs produced
2) Cas 9 breaks BCL11A gene in order to stimulate HbF production therefore sickling prevented
What is an ischaemic stroke
Cerebral artery is blocked resulting in oxygen deficiency
