Flashcards in Pathophysiology of Anaemia Deck (19):
What are the requirements for normal RBC production?
- Drive (EPO)
- Recipe (genes)
- Ingredients (iron, B12, folate and minerals)
- Functional bone marrow
What is transferrin (Tf)?
- Glycoprotein synthesised in hepatocytes that has 2 iron binding domains and delivers iron to all tissues
What is Hepcidin?
- The 'low iron' hormone and reduces levels of iron in the plasma by binding to ferroportin and degrading it
- This reduces iron absorption and decreases iron release from the RES
It is synthesised in the liver and requires HFE for its production
What are the signs and symptoms of IDA?
- Atrophic glossitis
- Angular stomatitis
- Oesophageal web (Plummer Vinson Syndrome)
What are the causes of IDA?
- Blood loss
How is IDA diagnosed and treated?
- Low serum ferritin
- Hypochromic microcytic RBCs on blood film
- Replacement with ferrous sulphate, ferrous gluconate and IV iron - remember to discover cause
What is the pathophysiology of ACD?
- RES iron blockage/iron trapped in macrophages, reduced EPO response and depressed marrow activity/cytokine marrow depression
How is ACD diagnosed?
- N/↓ MCV/MCH
- ↓ Iron
- ↓ TIBC
- ↑ ESR
- ↑/N Ferritin
- Hypochromic mycrocytic or normochromic normocytic RBCs on blood film
Why does B12/folate deficiency cause anaemia?
- Disparity in rate of synthesis or precursors of DNA
- Ineffective erythropoiesis (death of mature cells whilst still in marrow)
How is B12/folate deficiency diagnosed?
- Megaloblastic anaemia on blood film
- Symptoms include tiredness, easy bruising, mild jaundice, atrophic glossitis and neurological problems
- Raised bilirubin
- Raised LDH
What is the most common cause of B12 deficiency?
- Pernicious anaemia
- Autoimmune disease where body attachs parietal cells
What is the most common cause of folate deficiency?
- Lack of dietary intake
What are haemoglobinopathies?
- Inherited conditions causing a relative lack of normal globin chains due to absent genes (thalassaemias) or variants (abnormal) globin chains (i.e. sickle cell disease)
What are problems with alpha globin chains?
- Most people have 4 alpha globin chains
- α+ thal trait (missing one)
- Homozygous α+ thal trait (missing two, one on each allele)
- α0 thal trait (missing two α, both on same allele)
- HbH disease (missing three)
- α thal major (missing four, incompatible with life in utero)
What are problems with beta globin chains?
- Beta thalassaemia (missing B genes – should have 2) trait isn’t pathogenic but leads to small red cells.
Beta thalassaemia major is an AR disorder where the body is unable to make adult haemoglobin (HbA) leading to significant dyserythropoeises.
Main problem with this is it leads to iron deficiency.
What is sickle cell disease?
- Leads to abnormal haemoglobin variants
- Due to a point mutation on the beta gene in chromosome 11 which makes blood cells rigid so they can't bend through blood vessels
- Clinical result is haemolysis and vaso-occlusion (hypoxia)
What types of acquired haemolytic anaemias are there?
- Autoimmune (warm type - IgG, cold type - IgM)
- Isoimmune (haemolytic disease of the new-born)
- Non-immune (fragmentation haemolysis)
How does the Direct Coombs Test work?
- Detect antibody on RBC surface
- RBCs coated with IgG autoantibodies
- Add antihuman Ig which forms lattice for RBCs agglutinate
- Positive in patients with haemolytic anaemia