The Haemoglobin Molecule and Thalassemia Flashcards
What are the different types of globin proteins?
Alpha, Beta, Gamma, Delta (and embryonic- epsilon and zeta)
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+]
CO2 (hypercapnia)
Increase temperature
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?
Alpha
Gamma
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?
Alpha
Delta
On which chromosomes are the two globin gene clusters and which genes are present in each cluster?
Chromosome 16 – ALPHA cluster TWO alpha genes Zeta gene Chromosome 11 – BETA cluster Beta gene Gamma gene Delta gene Epsilon gene
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
How is thalassemia classified in terms of clinical severity?
Minor: Thalassemia trait = common variant with little clinical significance
Intermediate: Thalassemia intermedia
Major: 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)