Red Cells 1 Flashcards
What is anaemia?
Reduction in red cells or their haemoglobin content
Substances required for red cell production
Metals:IRON, copper, cobalt, manganese
Vitamins: B12, FOLIC ACID, thiamine, vit B6
Amino acids
Hormones: ERYTHROPOIETIN, androgens, thyroxine
Describe red cell breakdown
Occurs in reticuloendothelial system
After 120 days rbc broke down into:
- Globin (amino acids reused)
- Haem (iron recycled into haemoglobin, haem converted into bilirubin)
What are the main components of a mature red blood cells
Membrane filled with enzymes and haemoglobin
Examples of congenital anaemia?
Hereditary Spherocytosis
G6PD deficiency
Thalassemia,
Sickle Cell disease
What type of inheritance is hereditary spherpcytosis
Autosomal dominant
What structural proteins in red cell membrane does hereditary spherocytosis affect
Ankyrin, Alpha spectrin, Beta specctrin, Band 3, Protein 4.2
What shape are hereditary spherocytosis red blood cells
Spherical
What is the reticuloendothelial system
removes immune complexes from the circulation
Includes: monocytes of the blood, macrophages in connective tissue, lymphoid organs, bone marrow, bone, liver, lung
Clinical presentation of hereditary spherocytosis
Anaemia,
Jaundice,
Splenmegaly,
Pigment gallstones
Treatment of hereditary spherocytosis
Folic acid,
Transfusion,
Splenectomy (if severe)
Examples of some rare genetic anaemia membrane disorders
Hereditary elliptocytosis,
Hereditary pyropoikilocytosis,
South East Asian ovalocytosis
What provides red cells with energy and protects from oxidative damage
Provides energy- glycolysis
Oxidative damage protection- pentose phosphate shunt (with G6PD enzyme)
How does Glucose 6 phosphate dehydrogenase protect red cell proteins from oxidative damage
Produces NADPH
Which reduces glutathione (which scavenges and detoxifies reactive oxygen species)
How is G6PD deficiency inherited
X-linked
Pro and Con of G6PD deficiency
Pro- protects against malaria
Con- cells vulnerable to oxidative damage
How do cells appear in G6PD deficiency
Blister cells
Bite cells
Clinical presentation of G6PD deficiency
Variable degrees of anaemia
Neonatal jaundice
Splenomegaly
Pigment gallstones
Triggers to haemolysis in G6PD deficiency
Infection,
Acute illness eg DKA
Broad (fava) beans
Drugs- antimalarials, sulphonamides and sulphones, antibacterials, analgesics (aspirin), antihelminthics (B-naphthol), miscellaneous (vitamin K analogues, probenecid, methylene blue)
What is Pyruvate kinase deficiency
Reduced ATP and increased 2,3-DPG
Causes anaemia, jaundice, gallstones
What is Haemoglobin made up of
2 alpha chains
2 beta chains
Iron,
Haem
Hb A (aaBB) Hb A2 (aadeltadelta) Hb F (aayy)
Function of haemoglobin function
Gas exchange:
-O2 to tissues,
CO2 to lungs
Oxygen dissociation curve:
- shifts as a compensatory mechanism
- “Bohr effects”
- acidosis
- hyperthermia
- hypercapnia
What are haemoglobinopathies
Inherited abnormalities of haemoglobin synthesis
Examples of haemoglobinopathies
Thalassaemia
Sickle cell
What is Thalassaemia
Reduced or absent globin chain production
can be alpha thalassaemia (mutation/ deletion in alpha gene)
Or beta thalassaemia (mutation/deletion in beta genes)
What is sickle cell disease
Mutations leading to structurally abnormal globin chain
Sickle haemoglobin composed of haem molecule and 2alpha chains, 2 beta (sickle) chains (due to point mutations)
What kind of inheritance is thalassemia
Autosomal recessive
Consequences of HbS polymerisation
Haemolysis leading to vaso-occlusion
Sickle cell disease clinical presentation
Cerebral infarcts Retinopathy Cardiomegaly Congestive heart failure Cholelithiasis Renal infarcts- haematuria Pulmonary infarcts- pneumonia Splenomegaly Infarcts of extremities Vaso-occlusion Ulcer of leg Aseptic bone necrosis- osteomyelitis Bone marrow hyperplasia
Complications of sickle cell disease
Painful vaso-occlusive crisis of bone
Chest crisis
Stroke
Increased infection risk due to hyposplenism
Chronic haemolytic anaemia (gallstones, aplastic crisis)
Sequestration crisis
Treatment of acute painful crisis
Opiates,
Hydration,
Oxygen,
Consider antibiotics
Management of sickle cell disease
Life long prophylaxis:
- vaccination,
- penicillin
- folic acid
Blood transfusion (alloimmunisation)
Bone marrow transplantation
Gene therapy
Prognosis of homozygous alpha zero thalassaemia
Incomparable with life
Known as hydrops fetalis and there will be no alpha chains
How severe is beta thalassaemia major
No beta chains present
Dependent on transfusion
What is non-transfusion dependent thalassaemia
Range of genotypes
Unlike beta thalassaemia major there is no dependence on transfusion
What is thalassaemia minor
“Trait” or carrier state
Hypochromic microcytic red cell indices
What is beta thalassaemia major
Severe anaemia Presents at 3-6 months Expansion of ineffective bone marrow Bony deformities Splenomegaly Growth retardation
What is the life expectancy of someone with beta thalassaemia major without regular transfusions
<10 years
Beta thalassaemia major treatment
Chronic transfusion support every 4-6 weeks
However this causes iron overloading so this needs treated
- iron chelation therapy (s/c desferrioxamine or oral deferasirox)
Bone marrow transplants
What is monitored in someone with beta thalassaemia major
Ferritin levels
MRI scans
To ensure normal life expectancy
