Hereditary anaemias (Red cells 1) Flashcards
what substances are required for red cell production?
metals: - iron - copper - cobalt - manganese vitamins; - vita B12 - folic acid - thiamine - vit B6, C and E amino acids erythropoietin, GM CSF, androgens, thyroxine
what its he reticuloendothelial system ?
various cells found throughout the body whose primary function is to remove damaged or dead cells
where does red cell breakdown occur?
reticuloendothelial system
what are red cells broken own into?
haem - iron and bilirubin
globin - amino acids
what is responsible for maintaing red cell shape and deformability?
skeletal proteins
what is responsible for hereditary spherocytosis?
defects in a structural proteins
defect in cell membrane
are common forms of hereditary spherocytosis autosomal dominant or recessive?
autosomal dominant
what is the condition inn which the red cells are spherical?
hereditary spherocytosis
what is the clinical presentation of hereditary spherocytosis?
anaemia
jaundice (neonatal)
splenomagely
pigment gallstones
what is the treatment for hereditary spherocytosis?
folic acid
tranfusion
splenectomy if anaemia very severe
what is G6PD deficiency?
deficiency in glucose 6 phosphate dehydrogenase which is required to protect red cell proteins (haemoglobin) from oxidative stress
red cells are then vulnerable o oxidative stress
what does G6PD deficiency confer protection against?
malaria
what is the clinical presentation of 6GPD deficiency?
neonatal jaundice splenomegaly pigment gallstones drug, broad bean or infection precipitated jaundice and anaemia - intravascular haemolysis - haemoglobinuria
what can trigger haemolysis in G6PD deficiency?
infection acute illness i.e. DKA drugs; - antimalarials - sulphonamides and sulphides - Nitrofurantoin - Aspirin - Antihelminthics i.e. B-naphthol - vitamin K analogues - probenecid - methylene blue
what is the bohr effect?
oxyhemoglobin saturation increases when patients PH increase, temp decreases
oxyhemoglobin saturation decreases when a patients PH decreases, temp and C02 increases
haemoglobin gives up oxygen (decreasing oxyhemoglobin saturation) depending on tissues needs
what is the normal Hg range for male and females?
male: 135-170 g/L
female: 120-160 g/L
what is the defect in thalassaemia?
reduced or absence of globin chain production resulting in abnormalities of haemoglobin synthesis
what is the defect in sickle cell disease?
mutations leading to structurally abnormal globin chain resulting in abnormalities of haemoglobin synthesis
are haemoglobinopathies autosomal dominant or recessive?
all recessive
what are the clinical presentations of sickle cell disease?
painful vaso-occlusive crises - bone chest crisis - pulmonary infarcts = pneumonia stroke increased infection risk - hyposplenism chronic haemolytic anaemia - gallstones - aplastic crisis sequestration crisis - spleen - liver
how can chronic haemolysis cause gallstones?
chronic haemolysis leads to an increase in billirubin excreted into the billiard tract which in turn can cause gallstones
how do you manage painful crisis in sickle cell?
give analgesia within 30 mins of presentation
hydration
oxygen
consider antibiotics
what life long prophylaxis should people with sickle cell be given?
vaccination
penicillin and malarial prophylaxis
folic acid
what are the management options for sickle cells disease?
blood transfusion
bone marrow transplant
disease modifying drugs e.g. hydroxycarbamide
gene therapy
what type of thalassaemia is transfusion dependent?
beta thalassaemia major
when does beta thalasaemia major present in life?
3-6 months of age
what is the presentation of beta thalassaemia major?
bone deformities
splenomegaly
growth retardation
(expansion of ineffective bone marrow)
what is the treatment for beta thalassaemia major?
iron chelation therapy
bone marrow transplantation
chronic transfusion
what defect causes porphyrias?
defect in cytoplasmic steps in haem synthesis
what defect causes sideroblastic anaemia?
defect in mitochondrial steps of haem synthesis
what is anaemia?
reduction in red blood cells or their haemoglobin content
what are the 3 main contents of the mature red cells (erythrocytes) ?
membrane
enzymes
haemoglobin
are majority of hereditary anaemia autosomal dominant or recessive?
recessive
in the average adult, what type of chains is the majority of haemoglobin composed of?
2 alpha and 2 beta chains
being a carrier of thalassaemia or sickle cell protects you from what?
malaria
