Intro to SCD

Question 1

What leads to the formation of sickle cell Hb?

Answer 1

Missense mutation at codon 6 of the beta globin chain.

Glutamic acid replaced by valine.

Question 2

How does the glutamic acid to valine alter the properties of the Hb?

Answer 2

Valine makes the HbS insoluble.

Question 3

Is deoxyHb soluble or insoluble?

Answer 3

Insoluble

Question 4

What is the inheritance pattern for sickle cell disease?

Answer 4

Autosomal recessive:
HbSS - SCA
HbAS - Sickle trait (usually asymptomatic)

Question 5

What % of Africans (sub-Saharan) and Caribbeans carry HbS gene?

Answer 5

25% Africans

10% Caribbean

Question 6

What doe we mean by SCD?

Answer 6

SCDincorporates:
SCA (HbSS)
A number of compound heterozygous states that lead to a disease syndrome due to sickling
e.g. HbSC, HbS beta thalassaemia

Question 7

Outline SCD pathogenesis due to haemolysis of sickled RBCs.

Answer 7

Haemolysis (breakdown) of sickled red blood cells:
Shortened red cell lifespan to 20 days
Anaemia: baseline Hb concentration in HbSS is ~60-80 g/l (cf 125-160 for HbA)
Gall Stones (increased red cell breakdown products)
Aplastic Crisis (Parvovirus B19 where bone marrow erythropoiesis has been shut down)

Question 8

How does blockage to microvascular circulation (vasoconstriction-occlusion lead to SCD?

Answer 8

Tissue damage and necrosis (Infarction)
Pain
Dysfunction

Question 9

What is the effect of HbS on the oxygen-Hb curve?

Answer 9

Lower + right shift

The baseline Hb concentration in individuals with HbSS is lower than for Hb ~60-80 g/l (cf 125-160)
However this does not result in symptoms of anaemia. This can be partly explained by the Oxygen-Hb dissociation curve.

Question 10

What can SCD leading to haemolysis lead to?

Answer 10

Anaemia
Jaundice
Gallstones

Question 11

Which organs does SCD leading to vasodilator-occlusion lead to?

Answer 11

Bone
Kidney
Cerebral
Retina
Lung 
Spleen