Diseases of the Blood Pt 2

Question 1

What are the 3 types of defects that come under inherited haemolytic anaemia?

Answer 1

1. red blood cell cytoskeletal defects
2. red blood cell enzyme defects
3. haemoglobin defects

Question 2

What is hereditary spherocytosis as an example of a RBC cytoskeletal defect?

Answer 2

It is caused by mutations in a or b spectrin

spectrin is part of the cytoskeleton

this leads to small, compact, dense RBCs

Question 3

What is the most common RBC enzyme defect?

Answer 3

Deficiency of glucose-6-phosphate dehydrogenase (G6PD)

This is involved in NADPH metabolism

Question 4

What is the exact mutation that causes sickle cell disease?

Answer 4

A mutation in the beta globin gene of haemoglobin

A substitution at position 6 changes Glu for Val

Question 5

How does the Glu –> Val substitution affect the RBC?

Answer 5

It causes polymerisation of haemoglobin

This distorts the RBC and gives the sickle shape

Question 6

What other factor will influence the shape change of the RBC in sickle cell disease?

Answer 6

Sickle haemoglobin (Hb S) cannot absorb as much oxygen

Question 7

When does a sickle cell crisis occur?

How long does it last?

Answer 7

It occurs when a microvasculature is blocked

It can last for a few days or longer, depending on where in the body it is

Question 8

How does a microvasculature become blocked in a sickle cell crisis?

Answer 8

The sickle cell is wider than the RBC so gets stuck

Cells will also stack up and stick together, which causes them to increase in size so they cannot pass through capillaries

Question 9

Which part of the body is usually affected by a sickle cell crisis and why?

Answer 9

The joints and the bones as these contain the smallest blood vessels

Question 10

How does the spleen become more prone to infection in sickle cell disease?

Answer 10

Abnormal RBCs are degraded much more rapidly

This causes the spleen to become overworked

Question 11

What “benefit” has been seen in heterozygous individuals with sickle cell disease?

Answer 11

There is some resistance to malaria

Question 12

Where are the haemoglobin alpha and beta gene clusters found?

Answer 12

There are 2 alpha genes on chromosome 16

There is 1 beta gene on chromosome 11

Question 13

How many copies of the alpha and beta gene for haemoglobin are there?

Answer 13

Adults have 2 genes for the alpha subunits so have 4 copies in total

There is 1 gene for the beta subunit so 2 copies in total

Question 14

What can mutations in the alpha or beta subunits or haemoglobin lead to?

Answer 14

Inherited haemolytic anaemia

Question 15

What is thalassaemia?

Answer 15

When individuals produce no or too little haemoglobin so they cannot carry sufficient amounts of oxygen around the body

Question 16

What is the “benefit” of having heterozygous thalassaemia?

Answer 16

Thalassaemia is mild and may provide protection against malaria

Question 17

What is a-thalassaemia caused by?

Answer 17

Large deletions of the alpha-globin

There are 2 a-genes on chromosome 16

Question 18

What combinations lead to mild, severe and fatal a-thalassaemia?

Answer 18

Mild:
a-/aa and a-/a-

Severe:
a-/–

Fatal:
–/– and leads to stillbirth

Question 19

What is b-thalassaemia caused by?

Answer 19

Point mutations in the b-globin gene

Question 20

What happens if both copies of the beta globin gene are affected in b-thalassaemia?

Answer 20

The patient has foetal haemoglobin (Hb F) and b-thalassaemia major

Question 21

What happens if only one copy of the beta globin gene is affected in b-thalssaemia?

Answer 21

The patient has b-thalassaemia minor

Question 22

how does thalassaemia lead to anaemia?

Answer 22

The disorder results in large numbers of red blood cells being destroyed, which leads to anaemia