Sickle Cell and Thalassaemia (OSMOSIS) Flashcards
Because Barbara's lectures are so awful
What is sickle cell anaemia?
Homozygous for HbS
What is sickle cell trait?
Heterozygous for HbS
What is the benefit of sickle cell trait?
Protects against malaria (P falciparum)
What is normal HbA made up of?
2 alpha and 2 beta chains
Each chain carries a heme molecule
How is HbS transmitted vertically?
Autosomal RECESSIVE
What does the mutation in sickle cell anaemia comprise of?
Substitution with VALINE
instead of glutamic acid
Valine is hydrophobic and mutates the beta globin chain
What is HbS made up of?
2 alpha + 2 mutated beta globin chains (+ heme)
What happens when HbS is de-oxygenated?
It changes shape, so it agglutinates with other HbS > forms long polymers that transform RBC got sickle
What is the process that leads to RBC destruction in SCD?
Repeated sickling > weakened RBC membrane > premature RBC destruction with intravascular haemolusis
What are consequences of intravascular haemolysis?
Consequences of intravascular haemolysis:
- anaemia
- decreased free haptoglobin > unconjugated bilirubin > jaundice
What are symptoms of sickle cell disease
Sickle cells stuck in capillaries
- dactillitis
- pain crisis, avascular necrosis
- renal necrosis
- acute chest syndrome
- stroke
- splenic infarct, sequestration > hyposplenism
What occurs as a consequence to hyposplenism in SCD?
Patients become susceptible to encapsulated bacteria e.g. strep pneumoniae, H influenza, N meningitides, Salmonella
What are typical blood cells visible on smear for sickle?
HOWELL JOLLY BODIES
What is alpha thalassaemia?
Deficiency in production of alpha globin chains of HbA
How are alpha chain mutations transmitted vertically?
Autosomal RECESSIVE
What is the disease that occurs with 2 defective alpha genes?
ALPHA thalassaemia MINOR
What is the disease that occurs with 3 defective alpha genes?
Haemoglobin H disease (excess beta chains form tetramers)
What is the disease that occurs with 4 defective alpha genes?
Hb Barts hydrops foetalis
Which Alpha thalassaemia is incompatible with life?
Hb Barts
How does thalassaemia show up on FBC?
Low Hb, low MCV, low MCH
How does thalassaemia show up on blood smear
microcytic hypo chromic anaemia with Target cells
What is alpha thalassaemia?
Deficiency/defect in production of beta globin chains of HbA
What chromosomes are beta globin genes found on?
Chr 11
What can the mutations for beta globin be?
low beta globin production (beta+)
NO beta globin productgion (beta0)
What are the two types of homozygous beta thalassaemi?
beta thalassaemia intermedia: beta + beta+
beta thalassamia major: beta0 beta0
How does beta thalassaemia major cause disease?
free alpha chains cause clumping > damage the RBC membrane > haemolysis in BM, extravascular haemolusis in spleen
What are sx of beta thalassaemia?
anaemia
jaundice
hepatosplenomeg
haemochromatosis
