Red Cells - Part 1 Flashcards
What is anaemia?
Reduction in red cells or their haemoglobin content
Can be from blood loss, increased destruction, lack of production and defective production
What is the red cell in the blood called?
Reticulocyte and Erythrocyte (fully matured)
What are the substances required for red cell production?
Iron, copper cobalt and Mg
B12, folic acid, thiamine, B6, C and E
Amino acids
Erythropoietin
Where is erythropoietin produced?
In the kidney in response to hypoxia
Describe the lifespan of a red blood cell
120 days
Broken down in reticuloendothelial system - macrophages in spleen, liver, LNs and lungs
Globin - recycled amino acids
Haem - iron recycled back to haemoglobin and haem is broken down to bilirubin
What type of bilirubin does red cell breakdown cause?
Unconjugated bilirubin
Describe congenital anaemias
Genetic defects described in red cell membrane, metabolic pathways and haemoglobin
Most reduce red cell survival - haemolysis
Carrier states often silent and prevalence varies geographically
Describe the red cell membrane
Lipid bilayer
Skeletal proteins are responsible for maintaining red cell shape and deformability
Defects in skeletal proteins can lead to increased cell destruction
Describe hereditary spherocytosis
Most common forms autosomal dominant
Defects in 5 different structural proteins described
Red cells are spherical and removed from circulation by the RE system
What is the clinical presentation of hereditary spherocytosis?
Anaemia, jaundice (neonatal), splenomegaly and pigment gallstones
What is the treatment for hereditary spherocytosis?
Folic acid - increased requirements
Transfusion
Splenectomy if anaemia is severe
What are some other rare membrane disorders in red cells?
Hereditary elliptocytosis, hereditary pyropoikilocytosis and south east Asian ovalocytotic
What are the 2 main pathways for red cell survival?
Glycolysis - provides energy and 2,3 DPG is a biproduct
Pentose phosphate shunt - protects from oxidative damage
What is glucose 6 phosphate dehydrogenase (G6PD)?
Protects red cell proteins (haemoglobin) from oxidative damage
Produces NADPH which is vital for reduction of glutathione
Reduced glutathione scavenges and detoxifies reactive oxygen species
Describe G6PD deficiency
Commonest disease causing enzymopathy - many genetic variants
Cells venerable to oxidative damage
Confers protection against malaria
X linked - affects males and female carriers
Blister and bite cells seen
What is the clinical presentation of G6PD deficiency?
Variable degrees of anaemia - mild to severe, neonatal jaundice, splenomegaly and pigment gallstones
Haemolysis triggered by oxidative stress
What are the triggers to haemolysis in G6PD deficiency?
Infection, acute illness (DKA), broad beans and many drugs (antimalarials, antibacterial and aspirin)
Describe pyruvate kinase deficiency
Reduced ATP, increased 2,3 DPG and cells rigid
Variable severity of anaemia, jaundice and gallstones
Describe the structure of haemoglobin
2 alpha (encoded by 4 alpha genes) and 2 beta chains (encoded from 2 beta genes)
Haem - iron and protein structure
Carries O2 - tight bind structure when giving up O2
Hb A - 97%
A little bit of Hb A2 and Hb F
What are haemoglobinopathies?
Inherited abnormalities of haemoglobin synthesis
Reduced or absent globin chain production - thalassaemia (alpha, beta, delta and gamma)
Mutations leading to structurally abnormal globin chain - HbS (sickle cell)
Mainly all autosomal recessive
Describe sickle cell disease
Sickle haemoglobin (HbS) composed of haem molecule, 2 alpha chains and 2 beta (sickle) chains
Beta point mutation for beta S
Describe the pathophysiology of sickle cell
Haemoglobin S polymerisation
Vaso-occlusion
Endothelial dysfunction
Sterile inflammation
Intra-vascular haemolysis
What are the triggers for a sickle crisis?
Infection, hypoxia, dehydration, cold and stress
What are the clinical presentations for sickle cell anaemia?
Painful vaso-occlusion crisis - bone
Chest crisis
Stroke
Increased infection risk - hypo-splenism
Chronic haemolytic anaemia - gallstones and aplastic crisis
Sequestration crises - spleen and liver enlargement
What is the treatment for sickle cell painful crisis?
Severe pain and often required opiates
Hydration, oxygen and consider antibiotics
How is sickle cell disease managed?
Hydration, oxygenation, prompt treatment of infection, analgesia, blood transfusion and life long prophylaxis - vaccinations, penicillin and folic acid
Disease modifying drugs - hydroxycarbamide and Voxelator
Bone marrow transplantation, gene therapy and HbF
Describe thalassaemia
Reduced or absent globin chain production
Mutation or deletion in genes
Chain imbalance - chronic haemolysis and anaemia
What is the spectrum of clinical severity seen in thalassaemia?
Homozygous alpha zero thalassaemia - no alpha chains and hydrops fetalis which is incompatible with life
Homozygous beta thalassaemia (major)- no beta chains and transfusion dependant anaemia
Non transfusion dependant thalassaemia - range of genotypes
Thalassaemia minor (common) - carrier state which gives small red cells
What is beta thalassaemia major presentation?
Severe anaemia at 3-6 months of age
Expansion of ineffective bone marrow (hair on end appearance) and bony deformities
Splenomegaly
Growth retardation
If untreated then life expectancy is under 10 years
What is the treatment of beta thalassaemia major?
Chronic transfusion support 4-6 weekly
Normal growth and development
Iron loading needs to be treated with iron chelation therapy (desferal)
Bone marrow transplantation is curative
Describe defects in haem synthesis
Defects in mitochondrial steps of haem synthesis result in sideroblastic anaemia - ALA synthase mutations, hereditary and acquired
Defects in cytoplasmic steps result in porphyria
