Haemolytic anemia and haemoglobinopathies

Question 1

What do haemolytic anemias result from?

Answer 1

The haemolysis of red blood cells in vessels or the spleen

Question 2

Lifespan of erythrocytes

Answer 2

120 days

Question 3

Amount bone marrow can increase production by if necessary

Answer 3

5 to 6 times

Question 4

Ways of getting haemolytic anemia

Answer 4

Inherited it acquired

Question 5

Inherited causes of haemolytic anemia

Answer 5

Glycolysis defect- pyruvate kinase deficiency limits the production of ATP
Pentose-P Pathway- glucose-6-dehydrogenase deficiency leads to oxidative damage
Membrane protein- e.g hereditary spherocytosis
Haemoglobin defect- sickle cells

Question 6

Causes of acquired haemolytic anemia

Answer 6

Mechanical damage
Antibody damage
Exposure to chemicals or oxidants
Heat damage
Enzymatic damage e.g. snake venom

Question 7

Problems caused by haemolytic anemias

Answer 7

May decrease the life expectancy of erythrocytes to 20 to 30 days rather than 120 days

Question 8

Microangiopathic haemolytic anemias

Answer 8

Red cells are damaged by physical trauma . May be due to the red cells getting snagged as they pass through vessels with fibrin strands- e.g. DIC.
Red blood cells can be destroyed by shear stress caused by a faulty heart valve

Question 9

Causes of immune haemolytic amenias

Answer 9

Infections
Lymphprogenerative disorders e.g. leukaemia or lymphoma
Reactions to drugs e.g. cephalosporins

Question 10

Warm autoimmune haemolytic anemia

Answer 10

IgG antibodies attach the red cell membranes, may cause splenomegaly

Question 11

Cold autoimmune haemolytic anemia

Answer 11

IgM antibodies recognise the body’s epitopes

Question 12

Pyruvate kinase deficiency

Answer 12

An inherited metabolic disorder - it autosomal dominant and recessive

Question 13

Pyruvate kinase isoenzymes

Answer 13

Isoenzymes L and R coded for by the PKLR gene

Question 14

G6PDH deficiency

Answer 14

X linked recessive

It is a rate limiting step in the glucose phosphate pathway- only source of reduced glutathione

Question 15

Hereditary spherocytosis

Answer 15

Autosomal dominant disease in abnormalities in rbc cell membrane proteins

Question 16

4 membrane proteins involved in hereditary spherocytosis

Answer 16

Spectrin
Ankyrin
Band 3
Protein 4.2

Question 17

What does spectrin do?

Answer 17

Links the plasma membrane to the actin cytoskeleton

Question 18

What does ankyrin do?

Answer 18

Links membrane proteins to underlying spectrin and actin

Question 19

What does band 3 do?

Answer 19

Physically links plasma membrane to cytoskeleton

Question 20

What does protein 4.2 do?

Answer 20

Regulates the association of band three with ankyrin

Question 21

Haemoglobinopathies

Answer 21

Inherited disorders where the expression of one+ of the globin chains is abnormal

Question 22

Thalasaemia

Answer 22

Reduced or absent expression of normal alpha or beta globin chains.

Question 23

Abnormal haemoglobin variants

Answer 23

Result from mutations in genes or beta globin chains

Question 24

Normal haemoglobin structure

Answer 24

Tetromer of four globin chains- 2 alpha and two non aliphatic- beta delta or gamma, which have a haem group

Question 25

Three main normal types of haemoglobin

Answer 25

2 alpha and 2 Baga 2 alpha and two delta 2 aliphatic and two gamma

Question 26

HbS

Answer 26

The variant for sickle cell disease

Question 27

Why is sickle cell anemia so common?

Answer 27

Being heterozygous infers some protection from malaria so it is an evolutionary adavantage

Question 28

Consequences of sickle cell formation

Answer 28

Vasocclusive episodes- occlusion of small capillaries as sickle cells get trapped Anemia- as sickle cells will under go haemolysis reducing the erythrocytes lifespan to approx 30 days Jaundice- and gall stones from haemolysis Splenic atrophy

Question 29

Only cure for sickle cell anemia

Answer 29

Haematopoetic stem cell transplant- this rarely happens as it is rare to find a donor with a sufficient genetic match

Question 30

Thalassamia

Answer 30

A group of inherited disorders which result from decreased or absent alpha or beta globin chains, so an imbalance in the tetramer

Question 31

Beta thalassaemia

Answer 31

Occurs from a mutation in one or both of the beta globin genes leading to a reduction in the amount or the absence of the beta globin chain

Question 32

Alpha thalassaemia

Answer 32

Deflection or loss of function of one of four alpha chains

Question 33

There types of alpha thalasssaemia

Answer 33

Thalassaemia minor which requires no transfusion- they are a carrier Thalassaemia intermedia- requires transfusions intermittently Thalassaemia major- transfusion dependemnt.