Sickle cell disease

Question 1

What is HbS?

Answer 1

Results from a single point mutation whereby glutamate is replaced by valine at position six

Glutamine is polar (-ve and hydrophilic) whereas valine is non polar (uncharged and hydrophobic)

This makes deoxyhaemoglobin S insoluble

Question 2

What creates the sickled cell shape?

Answer 2

HbS polymerises to form tactoids that distort the red blood cells shape

Question 3

What type of inheritance patter does sickled cell anaemia show?

Answer 3

Autosomal recessive disorder

Question 4

Name the two pathogenesis of sickle cell disease?

Answer 4

Haemolysis - breakdown of sickled RBCs
Shortened red cell lifespan
Anaemia
Gall stones - due to increased rbc breakdown
aplastic crisis - bone marrow erythropoiesis shuts down

Blockage to microvascular circulation (vaso-occlusion)
Tissue damage and necrosis
Pain
Dysfunction

Question 5

Explain the pathophysiology of SCD

Answer 5

Hypoxia > polymerisation of HbS > sickling of RBCs

results in either haemolysis or vasoccclusion

Question 6

what is the early presentations of SCD?

Answer 6

Symptoms rare before 4-6 months as fetal hb is predominant

Dactylitis - inflammation of digits
Pooling of RBCs in spleen -splenic sequestration

Question 7

What is functional hyposplenism?

What does this increase susceptibility to?

Answer 7

Repeated vaso-occlusion (usually without symptoms) in HbSS leads to the spleen no longer working

Increases susceptibility to encapsulated bacterial infections

Question 8

What are the presentations of acute chest syndrome in SCD?

Answer 8

New pulmonary infiltrate on chest X-ray 
Fever 
cough 
chest pain 
Tachynpnoea

Question 9

What are some clinical/blood film features of SCD?

Answer 9

Low Hb
High reticulocyte count

Sickle cells
Boat cells
Target cells
Howell Jolly bodies - features of hyposplenism DNA remnants