Flashcards in The Haemoglobin Molecule and Thalassemia Deck (38)
What are the different types of globin proteins?
Alpha, Beta, Gamma, Delta (and embryonic)
State the three different haemoglobins that are present in the human body.
HbA – alpha + beta = 95%
HbA2 – alpha + delta = 1-3.5%
HbF – alpha + gamma = trace
Describe how affinity of haemoglobin changes with oxygen binding and how this helps its role of oxygen transport.
The more oxygen binds, the greater the affinity of the haemoglobin for oxygen.
This is good because if deoxyhaemoglobin has a low affinity for oxygen(as no oxygen is already bound), it will only pick up oxygen if the oxygen saturation is very high (i.e. in the lungs) so it will not take up oxygen in the metabolically active tissues where the oxygen saturation is low and where the tissues need oxygen.
Similarly, oxyhaemoglobin has a high affinity for oxygen so it will only give up oxygen in environments where the oxygen saturation is very low (i.e. respiring tissues that need oxygen)
What effect does 2,3-DPG have on oxygen delivery?
It facilitates oxygen delivery by making the haemoglobin molecule less flexible and pushing out the oxygen.
State 3 factors that can shift the oxygen dissociation curve to the right.
Increase in 2,3-DPG
Increase in [H+]
What effect do HbS and HbF have on the oxygen dissociation curve?
HbS has a lower affinity for oxygen than HbA so it shifts the ODC to the right
HbF has a higher affinity for oxygen than HbA so it shifts the ODC to the left
What is special about alpha globin genes?
There are TWO alpha globin genes from each parent so there are FOUR alpha globin genes in total.
Which globin chains are present in early embryonic life but are switched off after about 3 months gestation?
Zeta and epsilon
Which globins are present in foetal haemoglobin?
When are the genes coding for the globin in foetal haemoglobin switched off?
It is decreased towards birth and in the first year after birth.
After 1 year of life, the normal adult pattern of haemoglobin synthesis would have been established.
Which globin chains are present in HbA2?
On which chromosomes are the two globin gene clusters and which genes are present in each cluster?
Chromosome 16 – ALPHA cluster
TWO alpha genes
Chromosome 11 – BETA cluster
What is thalassemia?
Disorders in which there is a reduced production of one of the two types of globin chains in haemoglobin leading to imbalanced globin chain synthesis
What are the two clinical variations of thalassemia?
Thalassemia trait = common variant with little clinical significance
Transfusion dependent – Thalassemia Major = fatal without transfusion
What is the outcome of alpha thalassemia major?
Fatal in utero because alpha globin is needed to make HbF (alpha + gamma)
What is the outcome of beta thalassemia major?
Diagnosed and treated in early infancy with regular transfusions
What is the name given to the loss of function of three alpha globin genes?
Need life-long transfusions
What is the name given to the loss of function of four alpha globin genes?
Fatal in utero because alpha globin is needed to make HbF
What is beta thalassemia major? Describe how the disease progresses.
Severe defect in both beta globin chains
The foetus will have no problem in utero because they have normal functioning HbF (which doesn’t need beta globin)
At around 2-3 month after birth, you get a transition from HbF to HbA
At this time the baby will become profoundly anaemic.
They will need life-long transfusions from this point onwards.
State some features of thalassemia trait.
This the carrier state of thalassemia.
They may be mildly anaemic but they can also be normal.
Usually have a LOW MCH and LOW MCV
What can be used to distinguish between alpha thalassemia trait and beta thalassemia trait?
Haemoglobin electrophoresis can be used to measure the relative proportions of HbA2
Beta Thalassemia = raised HbA2 (> 3.5%)
Alpha Thalassemia = normal/low HbA2
What types of mutation cause alpha thalassemia and beta thalassemia?
Alpha thalassemia – deletion
Beta thalassemia – point mutation
What is alpha + thalassemia?
The situation in which one of the two globin genes on a chromosome are deleted (this can happen on one or both chromosomes)
Someone who is heterozygous for alpha+ thalassemia will still have 3 functioning alpha globin genes so they will only be mildly anaemic
What is alpha 0 thalassemia?
The situation in which both of the two globin genes on a chromosome are deleted (this can happen in one or both chromosomes)
In the heterozygous state there are still 2 functioning alpha globin genes so they will also only experience mild anaemia
How can you distinguish between alpha + and alpha 0 thalassemia?
Most people with alpha 0 thalassemia have a MCH < 25 pg
What could be the potentially devastating consequences for someone with mild anaemia caused by alpha 0 thalassemia?
Someone with alpha 0 thalassemia may not experience any symptoms themselves, but if they try and have a child with someone who also has alpha 0 thalassemia then there is a chance that their child may not have any functioning alpha genes (haemoglobin barts).
Which ethnic groups have a high prevalence of thalassemia?
What is beta + thalassemia?
There is a reduction in beta globin output but there is still some residual beta globin gene expression
What is beta 0 thalassemia?
There is NO output of beta globin