Red cells 1 - congenital anaemias Flashcards
What is anaemia?
reduction in red cells or Hb content
Main substances required for RBC synthesis
erythropoietin
Vit B 12 and folic acid
iron
life span of RBC
120 days
reticuloendothelial system
macropahges in spleen, liver, lung, LN etc
recycling of RBC
globin - amino acids
haem - iron and bilirubin
unconjugated bilirubin
bound to albumin in plasma
3 areas of problems in congenital anaemias of RBC
membrane
enzymes
haemoglobin
red cell membrane
skeletal proteins keep shape and deformity
red cell membrane proteins
ankyrin
beta and alpha spectrin
band 3
inheritance of hereditary spherocytosis
autosomal dominant
RBC in hereditary spherocytosis
defects in membrane proteins
RBC are spherical and removed by RE system
Clinical presentation of hereditary spherocytosis
anaemia
jaundice (neonatal)
pigment gallstones
splenomegaly
Treatment of hereditary spherocytosis
folic acid
transfusion
splenectomy
G6P-D
enzyme protecting from oxidative stress
NADPH reduce glutathione, detoxifies oxygen species
What does G6P-D deficiency confer an advantage for?
malaria
G6P-D deficiency inheritance
x-linked
affect males and female carriers
G6P-D deficiency blood film
blister and bite cells
clinical presentation of G6P-D deficiency
neonatal jaundice
Drugs, beans,infection precipitated
splenomegaly
pigment gallstones
precipitants of G6P-D deficiency
drugs eg anti-malarials,anti-bacterials
fava beans
structure of haemoglobin
iron containing haem with 4 globin chains - 2 alpha and 2 beta
haemoglobin oxygen binding
oxyhaemoglobin - relaxed binding
deoxyhaemoglobin - tight binding : 2,3-DPG
Oxygen dissociative curve
hyperthermia
acidosis
hypercapnia
HbA or HbF higher O2 affinity?
HbF
alpha and beta chains - how many genes?
2 alpha chains - 4 alpha genes
2 beta chains - 2 beta genes
Thalassaemia underlying problem
reduced or absent globin chain production
sickle cell underlying problem
severely abnormal globin chain
sickle cell inheritance
autosomal recessive
1 in 4 affected, 1 in 2 carrier
Defomity of sickle cell
haem + 2 alpha chains + 2 beta (sickle chains)
point mutation in beta chain
Consequences of sickle cell
haemolysis due to red cell injury
inflammation, vasomotor tone, endothelial activation
VASO-OCCLUSION
Clinical presentation of sickle cell
painful vaso-occlusive crisis (bone) stroke chest crisis increased infection due to hyposplenism sequestration crisis - spleen, liver chronic haemolytic anaemia
life expectancy with sickle cell
M=42, female = 48
due to child and perinatal mortality
Painful crisis treatment
opiates
oxygen
hydration
?antibiotic
chest crisis symptoms
increasing hypoxia, chest pain, fever, infiltrates on CXR
chest crisis treatment
resp support antibiotics IV fluids analgesia transfusion
life long prophylaxis for sickle cell
vaccination, penicillin (+malaria), folic acid
acute events management for sickle cell
hydration, oxygen, infection, analgesia
Other treatments for sickle cell
transfusion
disease modifying drugs - hydroxycarbamide
bone marrow transplant and gene therapy
4 types of thalassaemia
homozygous alpha zero - incompatible with life
beta thalassaemia major - life long transfusion
non transfusion dependent
thalassaemia minor
Thalassaemia symptoms
severe anaemia:3-6months old
expansion of ineffective bone marrow - hair on end
splenomegaly
growth retardation
Treating thalassaemia
chronic transfusion support (4-6weekly)
avoid iron overload - chelation
curative bone marrow transplant
outcome of iron overload
heart, endocrine, liver failure
