Red Cells Flashcards
What substances are required for red cell production?
Metals - iron, copper, cobalt, manganese.
Vitamins - B12, Folic acid, thiamine, B6, C, E.
Amino acids
Hormones - Erythropoitin, GM-CSF, androgens, thyroxine.
Where does red cell breakdown occur?
Reticuloendothelial system.
Macrophages in spleen, liver, lymph nodes and lungs.
What is the normal lifespan of a RBC?
120 days
What are the products of RBC breakdown?
Globin - amino acids reutilised.
Haem - Iron recycled into haemoglobin. Haem - biliverdin - bilirubin.
Unconjugated bilirubin is then bound to albumin in plasma.
Where can genetic defects occur in congenital anaemias?
In red cell membrane
In red cell metabolic pathways
In haemoglobin.
Most result in haemolysis.
What is responsible for maintaining a red cell’s shape?
Skeletal proteins maintain shape and deformability.
What is Hereditary Spherocytosis?
Autosomal dominant normally.
Defect in 5 different structural proteins: Ankyrin, Alpha spectrin, beta spectrin, band 3, Protein 4.2.
Results in spherical red cells that are then removed a bit faster from the circulation by reticuloendothelial system.
What is the clinical presentation of Hereditary Spherocytosis?
Variable due to which proteins are affected.
Anaemia - due to fast breakdown
Jaundice (neonatal) - faster breakdown so more bilirubin.
Splenomegaly
Pigment gallstones
What is the treatment for Hereditary Spherocytosis?
Folic acid
Transfusion
Splenectomy if anaemia severe.
What are some other examples of membrane disorders?
Hereditary Elliptocytosis
Hereditary Pyropoikilocytosis (all different shapes and sizes)
South East Asian Ovalcytosis.
What is anaemia?
Reduction in red cells or their haemoglobin content.
Where is Erythropoietin made?
Kidneys
What are the 2 important enzyme pathways in RBCs?
Glycolysis to provide energy - G6PD. Pyruvate kinase
Pentose phosphate shunt to protect from oxidative damage. Glucose 6-phosphate dehydrogenase.
What is the function of Glucose 6 Phosphate Dehydrogenase?
Protects red cell proteins from oxidative damage:
- produces NADPH vital for reduction of glutathione.
- reduced glutathione scavenges and detoxifies reactive oxygen species.
What is G6PD Deficiency?
Commonest disease causing enzymopathy. Red cells become vulnerable to oxidative damage - blister and but shaped cells.
Most common in malarial areas and is X- linked so female carriers and affected males.
What is the clinical presentation of G6PD deficiency?
Anaemia
Neonatal jaundice
splenomegaly
Pigment gallstones.
What are some external factors that precipitate haemolysis in G6PD deficiency?
Drugs
Broad beans
infection
Results in intravascular haemolysis and haemoglobinuria - vessels burst resulting in free floating haem.
What is another example of an enzyme deficiency?
Pyruvate kinase deficiency.
Results in reduced ATP, increased 2,3-DPG and rigid cells.
Presents with variable severity of anaemia, jaundice, gallstones.
Rare.
What is the structure of an adult haemoglobin molecule?
4 molecules of haem
2 alpha chains
2 beta chains
Iron is found within the haem molecule.
How does haemoglobin take in and release oxygen?
Haemoglobin has a relaxed binding structure when oxygen is bound. Once 1 molecule is bound it is easier for others to bind - cooperation.
Undergoes conformational change to release oxygen resulting in a tight binding structure. 2,3-DPG stabilises this tight structure.
What are the different types of haemoglobin?
Adult (HbA) is 2 alpha chains and 2 beta chains.
Foetal (HbF) is 2 alpha and 2 gamma chains. has a higher affinity for oxygen.
HbA2 is 2 alpha and 2 delta chains - only small amount of this.
How is your haemoglobin affected by your parents genes?
Get 2 alpha genes from both mum and dad located in Chr16.
Get 1 beta gene from mum and dad located in Chr11.
What is Thalassaemia?
Reduced or absent globing chain production. Can be alpha, beta, gamma or delta.
What sort of inheritance do most haemoglobinopathies have?
Autosomal recessive
Usually carriers are asymptomatic.
What is Sickle cell disease?
Point mutation in beta gene which if get 2 copies leads to polymerisation of haemoglobin forming crystals that are irreversibly stuck together - causes sickle shape.
Oxygen transfer is okay as sickle haem has allowed affinity for oxygen.
What are the consequences of polymerisation in sickle cell disease?
Haemolysis which leads to endothelial activation, promotion of inflammation, coagulation activation, deregulation of vasomotor tone by vasodilator mediators leading to Vaso-occlusion.
How does sickle cell disease present?
Can affect whole body. Severe bone pain Stroke Pulmonary infarcts Increased infection risk Hyposplenism Chronic haemolytic anaemia Gallstones Aplastic crisis Sequestration crisis - liver and spleen.
