Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Haematology > The Haemoglobin Molecule and Thalassemia > Flashcards

The Haemoglobin Molecule and Thalassemia Flashcards

1
Q

What are the different types of globin proteins?

A

Alpha, Beta, Gamma, Delta (and embryonic)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

State the three different haemoglobins that are present in the human body.

A

HbA – alpha + beta = 95%
HbA2 – alpha + delta = 1-3.5%
HbF – alpha + gamma = trace

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Describe how affinity of haemoglobin changes with oxygen binding and how this helps its role of oxygen transport.

A

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)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What effect does 2,3-DPG have on oxygen delivery?

A

It facilitates oxygen delivery by making the haemoglobin molecule less flexible and pushing out the oxygen.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

State 3 factors that can shift the oxygen dissociation curve to the right.

A

Increase in 2,3-DPG
Increase in [H+]
CO2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What effect do HbS and HbF have on the oxygen dissociation curve?

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is special about alpha globin genes?

A

There are TWO alpha globin genes from each parent so there are FOUR alpha globin genes in total.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Which globin chains are present in early embryonic life but are switched off after about 3 months gestation?

A

Zeta and epsilon

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Which globins are present in foetal haemoglobin?

A

Alpha

Gamma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

When are the genes coding for the globin in foetal haemoglobin switched off?

A

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.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Which globin chains are present in HbA2?

A

Alpha

Delta

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

On which chromosomes are the two globin gene clusters and which genes are present in each cluster?

A 
Chromosome 16 – ALPHA cluster 
 TWO alpha genes  
 Zeta gene  
Chromosome 11 – BETA cluster 
 Beta gene  
 Gamma gene 
 Delta gene  
 Epsilon gene
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is thalassemia?

A

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 well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the two clinical variations of thalassemia?

A

Thalassemia trait = common variant with little clinical significance
Thalassemia Major- transfusion dependent = fatal without transfusion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the outcome of alpha thalassemia major?

A

Fatal in utero because alpha globin is needed to make HbF (alpha + gamma)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is the treatment outcome of beta thalassemia major?

A

Regular transfusions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is the name given to the loss of function of three alpha globin genes?

A

Haemoglobin H

Need life-long transfusions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is the name given to the loss of function of four alpha globin genes?

A

Haemoglobin Barts

Fatal in utero because alpha globin is needed to make HbF

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is beta thalassemia major? Describe how the disease progresses.

A

Two abnormal copies of Beta-globin gene
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
Present at 4 months
Severe anaemia
They will need life-long transfusions from this point onwards.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

State some features of thalassemia trait.

A 
Carrier state of thalassemia. 
Mildly anaemic can also be asymptomatic.
Hypochromic microcytic blood cells
LOW MCV 
LOW MCH
21
Q

What can be used to distinguish between alpha thalassemia trait and beta thalassemia trait?

A

Haemoglobin electrophoresis can be used to measure the relative proportions of HbA2
Beta Thalassemia = raised HbA2 and HbF (> 3.5%)
Alpha Thalassemia = normal HbA2 and HbF

22
Q

What types of mutation cause alpha thalassemia and beta thalassemia?

A

Alpha thalassemia – Deletion

Beta thalassemia – Point mutation

23
Q

What is alpha + thalassemia?

A

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

24
Q

What is alpha 0 thalassemia?

A

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

25
Q

How can you distinguish between alpha + and alpha 0 thalassemia?

A

Most people with alpha 0 thalassemia have a MCH < 25 pg

26
Q

What could be the potentially devastating consequences for someone with mild anaemia caused by alpha 0 thalassemia?

A

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).

27
Q

Which ethnic groups have a high prevalence of thalassemia?

A 
Chinese 
South-east Asian 
Greek 
Turkish 
Cypriot
28
Q

What is beta + thalassemia?

A

There is a reduction in beta globin output but there is still some residual beta globin gene expression

29
Q

What is beta 0 thalassemia?

A

There is NO output of beta globin

30
Q

What is the main cause of the pathophysiology of beta thalassemia?

A

The surplus of alpha globin chains form tetramers.
These alpha globin tetramers precipitate in the bone marrow, which leads to ineffective erythropoiesis and haemolysis in the peripheralcirculation.

31
Q

Describe the pathogenesis of beta thalassemia.

A

There is death of red cells in the marrow because of ineffective erythropoiesis
The removal of red cells by the spleen causes:
 Large spleen
 Anaemia
 Increased EPO
 Expansion of bone marrow

32
Q

What are the consequences of regular blood transfusions used to treat beta thalassemia major?

A

Iron Overload
 Iron can accumulate in the liver (cirrhosis), heart (cardiac failure), endocrine organs (hypopituitarism, hypothyroidism, diabetes) etc.
Potential viral transmission

33
Q

Name three drugs that can be used to treat iron overload. List any negative aspects of these drugs.

A

Started after 10-12 transfusions OR when serum ferritin is over 1000mcg/L
Desferrioxamine (DFO)
 Not orally active – must be given via subcutaneous infusion
 Expensive
Deferiprone
 Urinary excretion
 Risk of agranulocytosis (which can lead to life-threatening sepsis)
 Patients need to be monitored closely for neutropenia
Deferasirox
 Faecal excretion

34
Q

What are the key indicators used to monitor for iron overload?

A

Serum ferritin- greater than 2500 increased complications
Liver biopsy- RARE
Ferriscan
MRI T2 cardiac and hepatic

35
Q

What are the good aspects of stem cell transplantation?

A

No transfusions
No chelation
Growth is normal
Curative treatment

36
Q

What are the bad aspects of stem cell transplantation?

A

Transplant associated mortality is high over the age of 17 (30%)
Relatively few transplants done in adults
Infertility due to stem cell transplant
If the patient is iron overloaded at the time of transplantation there is a massively increased risk

37
Q

Normal Hb Parameters?

A

120-165 mcg/L

38
Q

What is the pathway of Haem synthesis?

A

Mainly in mitochondria
Transferrin transports ferrous to RBC OR ferrous is liberated from ferritin molecules.
Glycine, B6 and SuccinylCoA create delta-ALA which is modified outside mitochondria, passes back in as promo-porphyrin.
Proto-pophyrin becomes Haem which binds w globins

39
Q

Where/How are globins made?

A

In ribosomes with amino acids

40
Q

What other proteins contain Haem?

A

Myoglobin

Cytochromes

41
Q

What does Haem structurally consist of?

A

Proto-porphyrin ring with central ferrous =

Ferro-proto-porphyrin

42
Q

What would you expect on a blood film of someone with Beta thalassaemia?

A 
Anaemia
Irregularly contracted cells
Hyprochromia
Nucleated RBC's
Pappenheimer bodies
Alpha chain precipitates
43
Q

What are the complications of Beta thalassaemia?

A

Cholelithiasis
Biliary sepsis
Cardiac/Liver failure

44
Q

What is the largest cause of death of people with Beta thalassaemia major?

A

Cardiac failure

45
Q

What are the clinical features of someone with Beta thalassaemia?

A 
Chronic fatigues
Jaundice
Splenomegaly
Erythroid hyperplasia
Frontal and maxilla bossing due to extra-medullary haematopoiesis.
46
Q

What are most of the complications of Beta thalassaemia major due to and how are they achieved?

A

Iron overload:

  1. Non-transfusion dependant iron overload, ineffective erythropoiesis so iron excess is not utilised
  2. Transfusion iron overload
47
Q

What infections are people with a high iron content more prone to?

A

Yersinia and otter gram negative infections

48
Q

What are the co-inherited Beta thalassaemia’s?

A
  1. Sickle beta thalassaemia

2. HbE beta thalassaemia- very common in SE Asia

49
Q

What are the haemoglobin gene expression and switching patterns?

A

Alpha- high early and stays high throughout pregnancy
Beta- Equal and opposite to Gamma, dominant after birth
Gamma- Equal and opposite to Beta, dominant pre natal
Delta- Production begins mid-natal, remains low forever
Epsilon and Zeta- Equal and opposite to Alph, level falls to zero after 8 weeks

Haematology (11 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions