Red Cells 1 Flashcards
What are the causes of low Hg levels?
Blood loss
Increased destruction
Lack of/defective production
What are the key substances needed for red cell production?
Iron
B12
Folic acid
Erythropoietin
Where does red cell breakdown take place?
Reticuloendothelial system
Macrophages in spleen
(also Liver, lymph nodes, lungs)
What is the fate of globin in red cell breakdown?
Amino acids reused
What is the fate of Haem in red cell breakdown?
Iron - reused
Haem –> Biliverdin –> bilirubin
What is the normal life span of a RBC?
120 days
How does bilirubin travel in the blood?
Bound (unconjugated) to albumin in plasma
What is contained within a RBC?
Membrane
Enzymes
Haemoglobin
What are the causes of congenital anaemias?
Genetic defects described in membrane, enzymes or haemoglobin
Reduce red cell survival - (haemolysis)
What is the role of skeletal proteins in RBC?
Maintain cell shape and deformability
Defects in RBC skeletal proteins can lead to what?
Increased cell destruction
What is Hereditary Spherocytosis?
Autosomal dominant
Defect in 5 structural proteins of red cells
Leads to spherical RBC
Removed from circulation in RE system
Hereditary Spherocytosis results in defects in which structural proteins?
Ankyrin Alpha spectrin Beta spectrin Band 3 Protein 4.2
How does Hereditary Spherocytosis present?
Anaemia
Jaundice
Splenomegaly
Pigment gallstones
How is Hereditary Spherocytosis treated?
Folic acid
Transfusion
Splenectomy
What are the roles of enzymes in RBC?
Glycolysis (for energy)
Pentose Phosphate shunt (protect from oxidative damage)
What enzymes are key in RBC function?
G-6-P dehydrogenase (PP shunt)
Pyruvate kinase
What is the role of G-6-P Dehydrogenase?
Produce NADPH
Detoxifies reactive oxygen species
G6PD deficiency results in what?
Vulnerable to oxidative damage
Protection against malaria (more common in malarial areas)
How is G6PD deficiency transmitted?
X-linked, males more affected
How does G6PD deficiency present?
Neonatal jaundice
Drug/infection/broad bean precipitated jaundice and anaemia
Splenomegaly
Pigment gallstones
Pyruvate kinase deficiency causes what?
Anaemia
Jaundice
Gallstones
Rigid cells
What is the structure of Hemoglobin?
4 Heme (+ 4Fe)
2 a chains
2 b chains
Outline Oxygen binding to Haemoglobin?
1st is hard, 2nd 3rd and 4th is ‘easier’
What is the role of 2,3 DPG?
Forms tight haemoglobin structure
What causes ‘right’ Bohr shift?
Acidity
Increased DPG
Increased Temp
Increased CO2
What causes ‘left’ Bohr shift?
Alkalinity
Decreased DPG
Decreased Temp
Decreased CO2
Outline the inheritance of alpha globin chains?
2 from mother, 2 from father
What is the normal adult haemoglobin ratio?
Hb A (aaBB) - 97% Hb A2 (aadd) - 2% Hb F (aayy) - 1%
What are haemoglobinopathies?
Inherited abnormalities in haemoglobin synthesis
What is Thalassaemia?
Reduced or absent globin (a or B) chain production
Mutations/deletions
What is Sickle cell?
Point mutation leading to structurally abnormal (B) globin chains
(Glutamine replaced by Valine in Beta chains)
Where is sickle cell endemic?
West/central africa
North india
Where is Thalassaemia endemic?
Mediterranean
Baltics
India
Asia/North Oceania
What form of inheritance occurs in haemoglobulinaemias?
Autosomal recessive
How does ‘cell sickling’ take place?
Haemoglobin crystallises when deoxygenation and forms a Sickle
This process is irreversible when re-oxygenating
What are the consequences of HbS polymerisation?
Haemolysis Damaged endothelium Pro-inflammatory state Coagulation Vaso-occlusion
How does Sickle-cell disease present?
Painful vaso-occlusive crises in bones Stroke Increased Infection risk Chronic haemolytic anaemia Reduced life expectancy Renal impairment Splenic infarction - hyposplenic
How is sickle cell pain crisis managed?
Analgesia - opiates
Hydration
Oxygen
?Antibiotics
How is sickle cell disease managed?
Prophylaxis (as hyposplenic) Vaccination Penicillin Folic acid) Blood transfusion Hydroxycarbamide Bone marrow transplant
What is fetal hemoglobin?
alpha alpha gamma gamma
Outline ‘alpha’ thalassaemias
- a/aa
- -/aa (incompatible with life)
Outline ‘beta’ thalassaemias?
Reduced beta chains, more dependence on gamma and delta chains
Chronic haemolysis and anaemia
What is the spectrum of thalassaemia?
Homozygous alpha zero thalassaemia (no alpha chains, incompatible with life)
Beta thalassaemia major (transfusion dependent)
Non-transfusion dependent thalassaemia
Thalassaemia minor “trait”
How does Beta thalassaemia major present?
Severe anaemia from 3-6 months
Bone deformities (expansion of bone marrow)
Splenomegaly
Growth retardation
How is Beta thalassaemia major managed?
Chronic transfusion
Iron chelation therapy (to manage Iron overload)
Bone marrow transplantation
Defaults in mitochondrial steps of haem synthesis cause what?
Hereditary sideroblastic anaemia
