Red Cells 1 Flashcards
What is the mnemonic for remembering the causes of microcytic anaemia?
TAILS:
- Thalassaemia
- Anaemia of chronic disease
- Iron deficiency anaemia
- Lead poisoning
- Sideroblastic anaemia
Anaemia of chronic disease often occurs with…
chronic kidney disease due to reduced production of erythropoietin by the kidneys, the hormone responsible for stimylating red blood cell production.
Treatment is with Erythropoietin.
There are 3 As and 2 Hs for normocytic anaemia:
- Acute blood loss
- Anaemia of chronic disease
- Aplastic anaemia
- Haemolytic anaemia
- Hypothyroidism
What are the two types of macrocytic anaemia?
- megaloblastic: results from impaired DNA synthesis, preventing cells from dividing normally. Rather than dividing, they grow into large, abnormal cells.
- normoblastic.
megaloblastic macrocytic anaemia is caused by:
B12 deficiency
Folate deficiency
normoblastic macrocytic anaemia is caused by:
- alcohol
- reticulocytosis (usually from haemolytic anaemia or blood loss), refers to an increased concentration of immature blood cells (reticulocytes).
- hypothyroidism
- liver disease
- drugs, such as azathioprine, methotrexate
what are some symptoms and signs specific to iron deficiency anaemia?
Symptoms:
- Pica (dietary cravings for abnormal things, such as dirt or soil)
- Hair loss
Signs:
- koilonychia (spoon-shaped nails)
- angular cheilitis
- atrophic glossitis (smooth tongue)
- brittle hair and nails
jaundice could indicate which type of anaemia?
haemolytic
bone deformities can indicate which type of anaemia?
thalassaemia
which substances are required for red cell production?
- Metals: iron, copper, cobalt, manganese
- Vitamins: B12, folic acid, thiamine, Vit B6, C, E
- Amino acids
- Hormones: erythropoietin, GM-CSF, - androgens, thyroxine
what is the normal life span of red blood cells?
120 days
Why could jaundice indicate haemolytic anaemia? Talk about breakdown
Hemolysis: When red blood cells break down, it’s called hemolysis.
Bilirubin release: When red blood cells break down, they release hemoglobin, which is then converted into bilirubin.
Liver function: The liver normally processes and removes bilirubin from the blood.
Jaundice presentation: If the rate of red blood cell destruction is too high for the liver to handle, bilirubin levels rise in the blood, causing jaundice.
Describe hereditary spherocytosis and its presentation
- most commonly autosomal dominant
- defects in 5 different structural proteins of red blood cell: ankyrin, alpha spectrin, beta spectrin, band 3, protein 4.2.
- red cells are spherical
- removed from circulation by the RE system (extravascular)
Clinical presentation:
- anaemia
- jaundice (neonatal)
- splenomegaly
- pigment gallstones
Hereditary spherocytosis treatment
- folic acid (increased requirements)
- transfusion
- splenectomy if anaemia very severe
what is the role of Glucose 6 Phosphate Dehydrogenase (G6DP) in red cell glucose metabolism?
Protects red cell proteins (haemoglobin) from oxidative damage:
- produces NADPH - vital for reduction of glutathione
- reduced glutathione scavenges and detoxifies reactive oxygen species
Describe G6PD deficiency and its clinical presentation
- commonest disease causing enzymopathy in the world, many genetic variants
- cells vulnerable to oxidative damage, however confer protection against malaria
- X-linked > affects males, female carries
Clinical presentation, variable:
- variable degrees of anaemia from mild to severe
- neonatal jaundice
- splenomegaly
- pigment gallstones
Haemolysis is triggered by oxidative stress.
What are some triggers to haemolysis in G6PD deficiency?
Caused by oxidative stress
- infection: acute illness e.g. DKA, broad (Fava) beans
- Drugs: antimalarials, sulphonamides and sulphones, antibacterials: nitrofurantoin, analgesics: aspirin, antihelminthics, vitamin K analogues.
normal adult haemoglobin structure
Composed of haem molecule and:
- 2 alpha chains
- 4 alpha genes (Chr16)
- 2 beta chains
- 2 beta genes (Chr11)
What are some inherited abnormalities of haemoglobin synthesis?
Reduced or absent globin chain production:
- Thalassaemia (alpha, beta, delta, gamma)
Mutations leading to structurally abnormal globin chain:
- HbS (sickle cell), HbC, HbD, HbE, HbO Arab…
describe the structure of sickle cell haemoglobin (HbS)
Composed of haem molecule and:
- 2 alpha chains
- 2 beta (sickle) chains, caused by point mutation
how is sickle cell inherited?
Sickle cell anaemia is an autosomal recessive condition affecting the gene for beta-globin on chromosome 11. One abnormal copy of the gene results in sickle-cell trait. Patients with sickle-cell trait are usually asymptomatic. They are carriers of the condition. Two abnormal copies result in sickle-cell disease.
What are the steps in the pathophysiology of sickle cell disease?
- Haemoglobin S polymerisation
- vaso-occlusion
- endothelial dysfunction
- sterile inflammation
what are some triggers for a sickle cell crisis?
- infection
- hypoxia
- dehydration
- cold
- stress
What does sickle cell crisis refer to?
A spectrum of acute exacerbations caused by sickle cell disease. These range from mild to lige-threatening:
- vaso-occlusive crisis
- splenic sequestration crisis
- aplastic crisis
- acute chest syndrome
sickle cell disease clinical presentations
- painful vaso-occlusive crises: bone
- chest crisis
- stroke
- increased infection risk > hyposplenism
- chronic haemolytic anaemia: gallstones, aplastic crisis
- sequestration crises: spleen and liver
what is the management for a painful sickle cell crisis?
- often requires opiates
- hydration
- oxygen
- consider antibiotics
general management of sickle cells disease
- Avoid triggers for crises, such as dehydration
- Up-to-date vaccinations
- Antibiotic prophylaxis to protect against infection, typically with penicillin V (phenoxymethylpenicillin)
- Hydroxycarbamide (stimulates HbF)
- Crizanlizumab
- Blood transfusions for severe anaemia
- Bone marrow transplant can be curative
what causes thalassaemia?
A genetic defect in the protein chains that make up haemoglobin.
- defects in alpha-globin chains lead to alpha thalassaemia
- defects in beta-globin chains lead to beta thalassaemia
- both conditions are autosomal recessive
Describe beta-thalassaemia major.
Patients with beta thalassaemia major are homozygous for the deletion genes. They have no functioning beta-globin genes. This is the most severe form and usually presents with severe anaemia and failure to thrive in early childhood.
Beta-thalassaemia major clinical features
- severe anaemia
- present at 3-6 months of age
- expansion of ineffective bone marrow
- bony deformities
- splenomegaly
- growth retardation
- life expectancy untreated or with irregular transfusions < 10 years.
Beta-thalassaemia major treatment
- chronic transfusion support 4-6 weekly, but can cause iron overloading
- iron chelation therapy
- good adherence to chelation > life expectancy near normal, requires regular monitoring, ferritin and MRI scans
- bone marrow transplantation can be curative
- gene therapy
defects in the mitochondrial steps of haem synthesis result in?
sideroblastic anaemia
defects in cytoplasmic steps result in?
porphyrias
