Red Cells 1 Flashcards
What is anemia?
1 - Reduction in red cell number
2 - Reduction in haemoglobin content of red blood cells
What are the main causes of anaemia?
1 - Blood loss
2 - Increased destruction of RBC’s
3 - Decreased production of RBC’s
4 - Problems with production of RBC’s
What are the key metals required for RBC production?
Iron
Copper
Manganese
What are the key vitamins required for RBC production?
B12
Folic acid
Thiamine
B6
What are the key hormones required for RBC production?
Erythropoietin (produced in kidney)
What is the reticuloendothelial system?
Part of the Immune system that involves phagocytic cells in the Reticular connective tissue
Where does breakdown of RBC’s occur?
Gets eaten in the Reticuloendothelial system by macrophages:
- Spleen
- Liver
- Lymph nodes
How is bilirubin transported in the plasma?
Bound to albumin
Where is bilirubin processed?
Liver
What is unconjugated bilirubin?
A product of RBC breakdown following the removal of haem from haemoglobin
In what ways are RBC’s affected by genetic anaemias?
1 - RBC membrane
2 - Metabolic pathways (enzymes)
3 - Haemoglobin
In genetic anaemias, what happens to the RBC membrane that results in anaemia?
Genetic defects in skeletal proteins lead to increased cell destruction
What type of inheritance is most common in Hereditary Spherocytosis?
Autsosmal dominant
What are the 5 different structural proteins that are defected in hereditary spherocytosis?
Ankyrin
Alpha spectrin
Beta spectrin
Band 3
Protein 4.2
What is the clinical presentation of hereditary spherocytosis?
1 - Anaemia
2 - Jaundice (neonatal)
3 - Splenomegaly
4 - Pigment gallstones
What is the treatment of hereditary spherocytosis?
Folic acid
Transfusion
Splenectomy
What is the purpose of the pentose phosphate shunt pathway?
Protect RBC’s from oxidative damage
What are the most common red cell enzyme disorders?
G6PD
Pyruvate Kinase deficiency
What happens to RBC’s in someone with a G6PD deficiency?
RBC’s become vulnerable to oxidative damage
What is the clinical presentation of a G6PD deficiency?
1 - Neonatal Jaundice
2 - Drug induced anaemia or jaundice
3 - Broad beans or Infection
4 - Splenomegaly
5 - Pigment gallstones
What drugs can trigger haemolysis in G6PD deficiency?
Antimalarials
Antibacterials
Analgesics
What is the pathogenesis of pyruvate kinase deficiency?
1 - Reduced ATP
2 - Increased 2,3-DPG (diphosphoglycerate)
3 - RBC’s become rigid
What is the normal structure of haemoglobin?
4 globular proteins wrapped around Haem group (2 alpha chains, 2 beta chains)
Each globular protein is wrapped around a Iron containing heme group
What are the 2 states in which haemoglobin can exist?
Oxyhaemoglobin
Deoxyhaemoglobin
Does fetal hameoglobin (HbF) or adult haemoglobin (HbA) have a higher affinity for oxygen?
HbF
What is the most common adult haemoglobin?
Hb A (2alphas, 2betas)
What are haemoglobinopathies?
Inherited abnormalities of haemoglobin synthesis
What are the two forms of abnormalities of haemoglobin synthesis?
1 - Problems with globin chain production (e.g. alpha, beta chains)
2 - Structurally abnormal globin chains (sickle cell disease)
Which regions of the world have the highest rates of haemoglobinopathies?
Malaria prone areas
What mode of inheritance is sickle cell disease?
Autosomal Recessive
What is the haemoglobin structure in sickle cell disease?
Haem molecules with 2 alpha and 2 beta (sickle) chains
Do RBC’s become sickle shaped during oxygenation or deoxygenation?
Deoxygenation
What are the consequences of sickle cell haemoglobin (HbS)?
Haemolysis
What are the processes that occur within blood vessels as a result of sickle cell disease?
1 - Endothelial activation
2 - Inflammation
3 - Coagulation activation
4 - Dysregulation of vasomotor tone
5 - Vaso-occlusion
What are the clinical presentations of sickle cell disease?
1) Pain in Bone caused by vaso-occlusive crisis
2) Chest crisis (chest pain and fever)
3) Stroke
4) Sequestration crisis (vessels of spleen become blocked and spleen eventually infarcts)
5) Increased infection risk (hyposplenism)
How should sickle cell pain and chest crisis (acute sickle cell events) be managed?
1 - Analgesia
2 - Fluids
3 - Oxygen
4 - Antibiotics
How is sickle cell disease managed long-term?
Vaccination
Penicillin prophylaxis
Folic acid
Blood transfusion
Bone marrow transplantation
What disease modifying drug can be used for sickle cell disease?
Hydroxycarbamide
What are the Thalassaemia group of blood disorders?
Reduced or absent globin chain production
What haemoglobin chain is affected in sickle cell disease?
Beta
What globin chains are affected in thalasseamias disease?
alpha and beta
Which globin chains are affected in alpha thalassaemia?
Alpha globin chains
Which globin chains are affected in beta thalassaemia?
Beta globin chains
What are the different types of thalassaemias?
1 - Homozygous alpha zero
2 - Beta thalassaemia major
3 - Thalassaemia minor
What is the biggest problem faced by those with Beta Thalassaemia major?
Severe anaemia
What other clinical signs are common in beta thalassaemia major?
1 - Splenomegaly
2 - Growth retardation
3 - Bony deformities
4 - Expansion of ineffective bone marrow
What is the treatment for Beta Thalassaemia major?
4-6 weekly blood transfusion with Iron chelation therapy (remove excess Iron caused by transfusion)
What is the purpose of measuring direct and indirect bilirubin?
Indirect bilirubin (unconjugated bilirubin) - check Liver function
Direct bilirubin (conjugated bilirubin) - check for haemolytic anaemia
