Brainscape's Knowledge GenomeTM

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


See full index

CARDIO-RESPIRATORY 2 > Haemoglobinopathies > Flashcards

Haemoglobinopathies Flashcards

1
Q

Describe the structure of adult haemoglobin (Hb A)

A

There are 4 global subunits (two alpha and two beta) which an iron-containing haem group

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

Describe the alpha globin gene cluster for haemoglobin

A

On chromosome 16 there are two genes that code for the alpha subunit of haemoglobin (Therefore there are 4 copies in total, 2 maternal and 2 paternal) but there is also a zeta gene that can produce the zeta subunit instead of the alpha subunit

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

Describe the beta globin gene cluster for haemoglobin

A

On chromosome 11 there is a gene that codes for the beta globin chain, but also the epsilon gene, delta gene and two gamma genes that can produce these subunits instead of the beta subunit

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

Where is the gene for the zeta globin subunit found?

A

Chromosome 16

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

Where is the gene for the alpha globin subunit found?

A

Two copies on chromosome 16

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

What is the structure of haemoglobin Gower 1 (embryonic haemoglobin)?

A

Consist of two zeta and two epsilon subunits

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

What is the advantage of Hb Gower 1 in the first stages of embryonic development?

A

It has a very high affinity for oxygen which allows greater uptake from the placenta

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

Where is embryonic haemoglobin (Hb Gower 1) produced?

A

Embryonic yolk sac until about 6 weeks gestation

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

What is the structure of foetal haemoglobin (Hb F)?

A

There are two alpha subunits and two gamma subunits

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

Where is foetal haemoglobin (Hb F) produced?

A

Spleen and liver

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

What is the advantage of haemoglobin F for the foetus?

A

It has a greater affinity for oxygen than maternal haemoglobin which allows it to take up oxygen from placental blood

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

What is the structure of adult haemoglobin (Hb A)?

A

Two alpha and two beta subunits

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is the structure of adult haemoglobin 2 (Hb A2)?

A

Two delta subunits and two alpha subunits

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

What is meant by thalassaemia?

A

A condition that is caused by inadequate quantities of one or other of the subunits that make up adult haemoglobin

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

What is alpha thalassaemia?

A

This occurs when one or more of the alpha genes on chromosome 16 are defective or faulty

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

What is beta thalassaemia?

A

This occurs when there is a point mutation on chromosome 11 which interferes with beta subunit production by varying amounts

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

What does the severity of alpha thalassaemia depend on?

A

The number of gene allies that are defective or missing

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

What are the four kinds of alpha thalassaemia?

A

> Alpha thalassaemia minima (1 defective gene)
Alpha thalassaemia minor (2 defective genes)
Haemoglobin H disease (3 defective genes)
Hydrops fetalis/alpha thalassaemia major (4 defective genes)

19
Q

Describe alpha thalassaemia minima

A

This is where there is a defect in one alpha gene on chromosome 16, as there are 3 other functional genes this has minimal effect on Hb synthesis so there are no clinical symptoms (may have a slightly lower MCV)

20
Q

Describe alpha thalassaemia minor

A

There is a defect in two alpha genes on chromosome 16 but there are still 2 functional genes left, therefore there is normal RBC production, but they may have mild microcytic hypo chromic anaemia

21
Q

Describe haemoglobin H disease

A

This is where there is a defect in 3 alpha genes on chromosome 16 and this causes the production of two unstable haemoglobin’s into the blood: haemoglobin parts (has 4 gamma subunits) and haemoglobin H (has 4 beta subunits) which have a higher oxygen affinity than normal so least to poor oxygen release in tissues. There is microcytic, hypochromic anaemia in these individuals.

22
Q

What is the structure of haemoglobin Barts?

A

Has four gamma subunits and is unstable

23
Q

What is the structure of haemoglobin H?

A

Has four beta subunits and is unstable

24
Q

Describe hydrops fetalis (alpha thalassaemia major)

A

They have little circulating haemoglobin, and that they do have is haemoglobin Barts; this leads the infant to be oedematous and this condition is incompatible with life so the foetus cannot live outside of the uterus and may not survive gestation, if it does it will die shortly after birth.

25
Q

Describe the genetic inheritance of beta thalassaemia

A

Beta thalassaemia is an autosomal recessive condition. Those who are heterozygous are said to have beta thalassaemia trait (or beta thalassaemia minor), whereas those with homozygous recessive beta genes have beta thalassaemia major

26
Q

How does beta thalassaemia lead to hypochromic microcytic anaemia?

A

Due to the reduced synthesis of beta globin subunits, excess alpha globin subunits are produced in the developing erythroblasts in the bone marrow, and the alpha tetramers formed are unstable and subsequently precipitate out onto the erythrocyte membrane. This precipitation leads to intra-medullary destruction of the developing erythroblasts which ultimately leads to erythroid hyperplasia and ineffective erythropoiesis.

27
Q

What are the complications of untreated beta thalassaemia major?

A

Hypochromic, microcytic anaemia, bone marrow expansion, splenomegaly, bone deformity, failure to thrive from 6 months of age (when there is a switch from foetal haemoglobin), heart failure and death by age 3-4

28
Q

What would blood tests for those who are carriers for beta thalassaemia indicate?

A 
> Reduced Hb levels
> Very low MCV (microcytic)
> Very low MCH
> Normal Hb A
> Elevated Hb A2
> Normal Hb F
29
Q

What would blood tests for those with beta thalassaemia major display?

A 
> Very low Hb levels
> Very low MCV (microcytic)
> Very low MCH
> Very low/absent Hb A
> Elevated Hb A2
> Elevated Hb F
30
Q

How is thalassaemia major treated (both alpha and beta)?

A

Regular transfusions (with iron chelators to reduce iron-overload), splenectomy, allogeneic bone marrow transplant

31
Q

What is the problem with administering regular blood transfusions in the treatment of thalassaemia major?

A

It can lead to iron overload as these individual’s aren’t iron deficient and the blood will contain more iron

32
Q

What is sickle cell disease?

A

This disease involves a mutant form of one of the beta subunits which causes the red cells to become ‘sickle shaped’

33
Q

What are the complications of sickle ell disease?

A

Sickle cells can obstruct capillaries and restrict blood flow to an organ which leads to ischaemia, pain and end-organ damage

34
Q

What are the clinical signs of sickle cell disease?

A

Haemolytic anaemia, microvascular occlusion and large vessel damage

35
Q

Explain the pathophysiology of sickle cell disease

A

There is a single amino acid substitution in the beta gene on chromosome 11 (GAG –> GTG) which leads to valine being presented instead of glutamic acid . This causes the production of beta chain S (haemoglobin S)

36
Q

How does sickle cell disease cause anaemia?

A

The haemoglobin S has a decreased survival time so there is less haemoglobin circulating at any one time, and this causes anaemia

37
Q

What are the potential consequences of sickle cell disease?

A

Anaemia, increased susceptibility to infection, vaso-occlusive crises and chronic tissue damage due to occlusion and ischaemia.

38
Q

How is sickle cell disease managed?

A

Infection prophylaxis, analgesia for painful crises, transfusions if there are complications, bone marrow transplantation and hydroxyurea prescription to treat painful crises

39
Q

Why may hydroxyurea be given to manage sickle cell disease?

A

It can increase Hb F production which may reduce a painful crises

40
Q

What type of screening is there for sickle cell disease?

A

Carrier screening in areas with a history and/or neonatal screening using a heel-prick or cord blood test

41
Q

What is haemoglobin C?

A

This is a autosomal recessive disorder where there is mutation in the beta gene leading to the production of HbC. If an individual is homozygous with the mutation, nearly all Hb is in the Hb C form –> mild haemolytic anaemia. If the individual is heterozygous they have 1/3 of Hb C in their circulation which doesn’t cause anaemia.

42
Q

What are the consequences of haemoglobin C?

A

Haemoglobin C is a mutation in which there is an abnormal beta subunit. This causes reduced plasticity and flexibility of the erythrocytes. This causes excess red cell destruction (haemolysis) which can cause anaemia.

43
Q

What is haemoglobin E?

A

Haemoglobin E (HbE) is an abnormal hemoglobin with a single point mutation in the β chain. Haemoglobin and it’s inheritance is autosomal recessive.

44
Q

What are the consequences of haemoglobin E?

A

Mild beta thalassaemia develops at around 6 months after birth when Hb F stops being available.

CARDIO-RESPIRATORY 2 (35 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions