Haemoglobinopathies Flashcards
What amino acid change occurs due to a single base mutation in sickle cell??
Glutamate–> valine
What nucleotide change happens in sickle cell?
Adenine–> thymine
Why would cold precipitate a sickle cell crisis?
In cold- vasoconstriction
Therefore capillaries narrow and RBC more likely to get stuck
Why would being ill precipitate a sickle cell crisis?
Increased number of WBC in blood
Blood becomes more viscous
TF increases chance of occlusion
How would dehydration precipitate a sickle cell crisis?
Less water in blood
Increase in blood viscosity
Increased chance of occlusion
What is the word describing when sickled RBC get stuck in blood vessels?
Occlusion
What is a sickle cell crisis?
Lack of perfusion to an area (lack of O2 delivered to an area)
Causes ischaemia and pain
Define ischaemia
Inadequate blood supply to an organ/area
In sickle cell, where does the mutation occur? What is it?
B sub unit of Hb
A–>T
Glutamate–> Valine
Why won’t infants show symptoms of sickle cell immediately?
Because they have fetal haemoglobin- 2alpha & 2gamma. As SC affects B sub unit (which they don’t have), they won’t show symptoms until enough HbF has been replaced by HbS for suckling to occur.
What are the opposing characteristics of glutamate and valine?
Glutamate is hydrophilic, Valine is hydrophobic
Which chromosome is affected in sickle cell?
Chromosome 11
Why won’t infants show symptoms of sickle cell immediately?
Because they have fetal haemoglobin- 2alpha & 2gamma. As SC affects B sub unit (which they don’t have), they won’t show symptoms until enough HbF has been replaced by HbS for suckling to occur.
What causes sickling of RBC?
Glu->Val. In T/deoxy state, change to T state exposes sticky hydrophobic pockets on β sub unit, Hb molecules polymerise, causing sickling of RBC.
What are the consequences of sickling RBC? In brief.
*Transition from R->T state less likely *Less O2 binds to Hb *More O2 released to tissues
In sickle cell, how do RBC become irreversibly sickles/damaged?
In oxygenated state, they’re normal/bi concave, in T/deoxy state they’re sickled. When they become oxygenated again they return to biconcave, continuous change reduces elasticity and so they stay sickled.
Lifespan of normal and sickled RBC?
Normal= 120 days, Sickled= 20 days
Why do sickled RBC have a much shorter lifespan?
As O2 can’t bind as well, O2 forms superoxide which destroys fatty acids in RBC membrane (more likely to lyse) and causes production of Heinz Bodies. Spleen removes RBC with Heinz bodies and macrophages phagocytose RBC with altered membrane.
Why do they get anaemia in sickle cell?
Superoxide alters membrane structure causing haemolysis. Bone marrow can’t replace RBC as fast as they are being destroyed.
Also, polymerised Hb can’t bind as much O2
How may sickle cell lead to jaundice?
Haemolytic anaemia. Lots of haem being broken down lots of bilirubin, build up of bilirubin causes jaundice. Pre-hepatic jaundice
What is a sickle cell crisis?
Due to their reduced flexibility, sickled RBC can’t bend through small capillaries and so get stuck. (Occlusion) causing lack of perfusion to tissues, and lack of O2 (ischaemia)–>causing cell death (infarction) and pain.
Which organs are most often affected in a sickle cell crisis? Causing what..?
Bone, chest (pleuritic pain, breathlessness), brain (fits)
List a few ways you would manage sickle cell
Avoiding factors that would precipitate a crisis eg keeping warm, hydrated (IV fluids), oxygen (to try and promote R state and binding of O2), antibiotics (to reduce infection), pain killers
How has sickle cell trait been favoured in inheritance?
Those who are carriers of SC, TF have 50:50 sickled:normal RBC, are protected against malaria. TF they often live longer than those without trait and so can reproduce and pass on their trait to offspring.
