Sickle Cell Anaemia

Question 1

Describe the gene for sickle cell

Answer 1

Missense mutation at codon 6 of the gene for B globin > glutamic acid replaced by valine (glu is polar and soluble but valine is non polar and insoluble). Doxyhaemoglobin S is insoluble and so HbS polymerises to form fines - tactoids

Question 2

Describe the effects of sickling and stages

Answer 2

1. Distortion - polymerisation initially reversible with formation of oxyHbs - subsequently irreversible
2. Dehydration
3. Increased adherence to endothelium

Cells are rigid, adherent and dehydrated

Question 3

Give the possible haemaglobinopathies

Answer 3

Sickle cell anaemia
Sickle cell carrier (Sc)
Sickle cell thalassaemia

Question 4

Pathogenesis of sickle cell

Answer 4

Overall: shortened red life span (haemolysis), results in anaemia, gallstones and aplastic crisis:

1. Anaemia: due to reduced erythropoietic drive, because HbS has low affinity, no hypoxia to stimulate erythropoietin
2. Gall stones: increased haemolysis - increased bilirubin and other red cell breakdown products = excreted through the gallbladder.
3. Aplastic crisis: parvovirus infects the developing red cells in bone marrow and blocks production
4. Blockage to microvascular circulation: tissue damage and necrosis (infarction) and pain and dysfunction

Consequence of tissue infarction = hyposplenism
Bones = dactylitis
Avascular necrosis, osteomyelitis and leg ulcers
Lungs - acute chest syndrome
Urinary tract
Brain
Eyes

Question 5

Describe the early presentation and emergency of sickle

Answer 5

Symptoms at 3-6 months as foetal Hb switches, early manifestations of dactylitis, splenic sequestration and infection-s pneumoniae

Sickle emergency STOPPED HERE SORRY