6. Red Cells Flashcards
What is anaemia?
Reduction in red cells or their haemoglobin content
What causes anaemia?
Blood loss
Increased destruction
Lack of production
Defective production
How are red cells produced?
Come from hemopoetic stem cell
Develop into proerthybolsast
Then early and late erythroblasts
Finally normoblasts and reticulocyte and erthyrocyte
What do you need for red cell production
Iron, cobalt, manganese
Vitamins B12, folic acid, thiamine, Vit B6, C, E
Amino acids
Erythropoietin, GM-CSF, androgens, thyroxine
How do red cells breakdown?
Normal red cell lasts for 120 days It is recycled Globin—> utilised Iron—> recycled into heamoglobin Haem—> bilirubin gives colour to bile. Bound to albumin in the plasma and becomes unconjugated
What shape is a red blood cell?
Bi concave, depression in middle
What is a red cell?
Membrane
Enzymes
Haemoglobin
What happens if you have a genetic condition and make a rubbish red blood cell?
Heamolysis, don’t last as long and are killed
Describe the structure of the red blood cell membrane
Phosphate bi-lipid layer plus proteins
Spectrin and Ankrin link cells to floor
Defects in skeletal proteins lead to abnormalities
What is the most common red cell membrane deformity
Hereditary spherocytosis
Most common forms autosomal dominant
Defects in 5 different structural proteins:
Ankyrin Alpha spectrin Beta Spectrin Band 3 Protein 4.2 Red cells become spherical. Removed from circulation by the reticuloendothelial system (spleen, liver, bone marrow)
What is the clinical presentation of hereditary spherocytosis?
Anaemia Jaundice Splenomegaly Pigment gallstones Potential increased bilirubin
(Very common presentation with anyone with haemolytic anaemia)
What is the treatment of heriditary spherocytosis?
Folic acid
Blood transfusions (if red cell breakdown is very fast)
Splenectomy is severe anaemia
What are other rare membrane disorders?
Hereditary elliptocytsosis- cells form eliptocytes instead of spheres due to different proteins affected.
Hereditary pyropoikilocytosis- red cells look like they’re on fire
South East Asian ovalocytosis- benign
What are the two main enzyme pathways of the red blood cells?
Embden meyerhof glycolysis pathway- glycolysis pathway. Two important enzymes are glucose 6 phosphatase dehydrogenase. Protects the cell against oxidative damage
Pyruvate kinase is the other one
What is G6PD?
Commonest disease causing enzymolathy in the world. Many genetic variants. Cells vulnerable to oxidative damage
Confers protection against malaria
X linked- affects males, female carriers
What is the clinical presentation of GD6P
Bite and blister cells Variable degrees of anaemia Neonatal jaundice Splenomegaly Pigment gallstones
Can be precipitated by drugs, broad beans, infection.
Leads to intravaculae haemolysis
Heamoglobinuria - heamoglobin in urine
What is PKA deficiency?
Pyruvate kinase deficiency which leads to reduced ATP, rigid cells. Clinically this leads to various types
Anaemia
Jaundice
Gallstones
What is haemoglobin?
Heam” (iron) molecules surrounded by four globin chains- 2 alpha and 2 beta chains
Binds oxygen and release it throughout the body.
Gives you oxygen when you need oxygen. Oxygen dissociation curve shifts to the right in high demand oxygen situations.
How do you inherit the chains of heamoglobin?
2 alpha chains from mother
2 alpha chains from dad
1 beta chain from dad
1 beta chain from mum
Also possess suppressed levels of heamoglobin A2 and fetal heamoglobin
What are heamoglobinopathies?
Inherited abnormalities of haemoglobin synthesis
Reduced or absent globin chain production- thalassaemia- alpha or beta, produced normal chains but less of them
Point mutations leading to abnormal globin chains- sickle cell disease. Point mutation that leads to abnormal globin
People who have heamoglobinopathies are less likely to have malaria, does this apply to people who are only carriers?
Yes
What is sickle cell anaemia?
Haemoglobin forms crystals in low oxygen situations within the red blood cells and they “sickle”
This leads to haemolysis. This leads to inflammations, coagulation, endothelial damage, vasospamsm and in the end vaso-occlusion
How does sickle cell disease present?
Stroke- screen with cranial Doppler
Pulmonary infarcts
Cardiomegaly
Bone marrow hyperplasia (very common, present with crisis)
Renal impairment
Increased risk of gallstones
Sickling in spleen- auto infarction of the spleen.
Aplastic crisis- infection with erythrovirus causing no formation of RBC, leads to severe anaemia and requires transfusions
What is a sickle cell crisis?
Severe bone pain requiring opiods to treat. Keep hydrated and oxygenated
Children present in peripheries
Old people present in back, hips, axial bones
Triggered by infection, stress on the body
How do you manage sickle cell disease
Vaccination
Penicillin
Folic acid
Chronic blood transfusion blood transfusion or bone marrow for particular difficult disease
Disease modifying drug- hydroxycarbimide, prevents haemoglobin from sickling
What is thalassaemia?
Reduced or absent chain production.
Can be alpha thalassaemia- reduced alpha chain causes anemia, no alpha chains aren’t compatable with life
Beta thalassaemia- is always compatible with life, causes anaemia and haemolysis. Severe disease leads to transfusion dependent anaemia
What is thalassaemia minor?
Reduced red cell size as they’re a carrier of thalassaemia. Doesn’t effect life.
What occurs in beta thalassaemia major
Severe anaemia at 3-6 moths of age Expansion of ineffective bone marrow (hair on end appearance) Bony deformities Splenomegaly Growth retardation
How do you treat beta thalassaemia major?
Chronic transfusion support
Normal growth and development
Iron overloading- death in 2nd or 3rd decades to to heart/ liver/ endocrine disorders. Treated with iron chelation.
What is iron chelation?
Giving drugs desfererrioxamine infusions (desferal) Oral deferasirox (exjade)
Good adherence to chelation makes life expectancy near normal for those who suffers with beta thalassaemia. They must have regular ferritin monitoring and MRI scans
What are the rare gene defect in haem synthesis?
ALA synthesise mutations
Hereditary
Acquired
