Haemoglobinopathies

Question 1

Hb A subunits

Answer 1

2xA and 2xB

Question 2

Hb F subunits

Answer 2

2x A and 2xY

Question 3

Hb A2 subunits

Answer 3

2xA and 2xD

Question 4

Structure of haemoglobin

Answer 4

• Binding site is Fe sitting below a porphyrin ring in haem centre which is bound to one axial histidine and to a further histidine residue
• Upon coordinatin of O2, Fe moves into plane of porphyrin and O2 H-bonds to distal histidine
• Hb moves from T state to R state
• Cooperative effect: binding/dissociation of O2 in Hb subunit results in conformational change which alters other subunit’s O2 affinities

Question 5

Bohr effect

Answer 5

Bohr effect: CO2 reduces Hb O2 affinity

Carbonic anhydrase catalyses reaction from Co2 and H2O to HCO3- and H+

Too much CO2 makes acidic environment

H+ stabilises T state through interprotein interactions

Results in release of O2

Question 6

Foetal Hb

Answer 6

• 2x A and 2xY
• Fetal Hb has higher O2 affinity at all partial pressures of O2 on dissociation curve
• It is able to remove O2 from adult Hb when the two bloods run next to eachother in placenta

Question 7

Globin pathologies

Answer 7

• Sickle cell anaemia - abnormal globin synthesis

- Thalassaemia - reduced globin synthesis

Question 8

Why is it advantageous to have sickle cell haemoglobin?

Answer 8

• Heterozygous amounts of sickle-cell haemoglobin results in lower parasite densities and hence malaria symptoms
• In areas of high malaria rates, sickle-cell allele confers advantage

Question 9

Sickle cell anaemia

Answer 9

Abnormal Hb aggregates and distorts shape of erythrocyte

Question 10

Sickle cell anaemia homozygous and heterozygous

Answer 10

• In homozygous individuals all Hb is affected, co-dominant alleles mean heterozygous people have both normal and abnormal Hb = sickle-cell trait
• Heterozygous people are usually healthy but may suffer some symptoms when O2 is reduced

Question 11

Sickle cell anaemia sx

Answer 11

physical weakness, pain, organ damage and stroke/paralysis

Question 12

Investigating sickle cell anaemia

Answer 12

• FBC HB between 6 and 9, low reticulocytes
• Blood film - sickle cells seen on blood film + Howell-Jolly bodies
• Hb electrophoresis

Question 13

Treatment for sickle cell anaemia

Answer 13

• Hydration
• Warmth
• Erythrocyte replacement
• Treat infection
• Analgesia
• Vaccinations
• Folic acid
• Penicillin
• Hydration, anoxia, infections, haemostasis, skin cooling

Question 14

A thalassaemia

Answer 14

A globin is deficient - 4 genes, 2 on each chromosome 16, 2 from each parent

Question 15

B thalassaemia

Answer 15

B globin is defective - 2 genes, 1 on each chromosome, 1 from each parent

Question 16

B thalassemia sx

Answer 16

• Anaemia
• Hepatomegaly
• Splenomegaly
• Haematopoesis
• Thalassaemia face
• Infections
• Osteoporosis
• Iron overload

Question 17

Investigating b thalassemia

Answer 17

• FBC
• Blood film - low Hb, low MCV, low MCH
• Electrophoresis
• Genetic testing
• Iron studies
• Radiology

Question 18

Treatment thalassemia

Answer 18

• Blood transfusion
• Immunisation
• Folic acid
• Iron chelation, splenectomy, endocrine therapy, vit D supplement