Iron deficiency anaemia and anaemia of chronic disease Flashcards
What is required for normal red cell production?
- Drive for erythropoiesis by erythropoietin produced by the kidney
- the required globin genes for erythropoiesis
- Iron, folate, B12 and other minerals
- Functioning bone marrow
- No increased loss or destruction of red cells
What are the major roles of the red blood cells?
- CO2 removal
* O2 delivery from lungs to the tissues
Explain the shape of red blood cells
- Max surface area for gas exchange
* allows deformability so they can squeeze through capillaries
What structures are involved in the removal of CO2?
- Red blood cells
- Renal tubules
- Lungs
Describe the removal of CO2 by red blood cells
- CO2 diffuses into the red blood cell and reacts with H2O to form H+ and HCO3- (catalysed by carbonic anhydrase)
- H+ is buffered
- HCO3- is removed from the cell
- Chloride shift occurs to account for any change in charge
What is one molecule of Hb made of?
4 globin chains (2 alpha and 2 beta) and 4 haem groups (1 per globin chain)
Where is iron in the body?
- The total body count is 4 grams
- The bone marrow and red blood cells contain 3 grams
- Macrophages in reticular endothelial system: 200-300mg
- Enzymes contain 100mg
What are the enzymes that contain iron
- Cytochromes
- peroxidases
- xanthine oxidase
- catalases
- RNA reductase
Describe the transport of iron in the plasma
- bound to the glycoprotein transferrin
- Each transferrin has 2 iron binding domains
- 30% are saturated with Fe
- Transferrin delivers the iron to all the tissues, erythroblasts, hepatocytes and muscle
Where is transferrin synthesised?
In the hepatocytes
What is the effect on transferrin if there is low iron?
Increased production of transferrin
Explain erythroblast iron
- Transferrin bound to iron binds to a transferrin receptor on the erythroblast surface
- endocytosis
- the Fe is stored as erythroblast ferritin or is converted to haem by the mitochondria via the ALA-S2 enzyme
Explain macrophage iron
- phagocytose red blood cells
- globin is converted to amino acids
- haem is converted to iron and stored as ferritin or haemosiderin or the haem is converted to bilirubin
Explain the use of serum ferritin to estimate iron stores in the body
- Serum ferritin in proportional to reticular endothelial system
- 1 mmol/l of serum ferritin = 8mg of reticular endothelial iron
- The problem however is that ferritin is an acute phase protein so if there is inflammation or infection it will be inappropriately higher than what is in the stores
What is the daily iron need?
1-2mg a day (2 for women)
Hereditary haemochromatosis
- Absorb too much iron
- Iron overload
- Lose hepcidin
Describe iron absorption from the gut
- Haem (from red meat) enters the enterocyte as haem oxygenase
- Non-haem iron (white meat, cereals) =Fe 3+, is converted to Fe2+ via DCytb and is transported into cell via SMT1
- Both enter the labile iron pool
What happens to the labile iron pool within mature enterocytes?
- Converted to ferritin, sent to mitochondria
* Or is transported out of the cell via FPN (requires hepcidin) then is converted to Fe3+ via Hp, transferrin in plasma
What is the average lifespan of red blood cells?
120 days
What removes effete red blood cells?
The reticuloendothelial system
how is reticuloendothelial iron stored?
In ferritin or haemosiderin
What does hepcidin do?
- It reduces the levels of iron in the plasma
- It does this by reducing the amount absorbed by binding to ferroportin and degrading it and decreasing iron release from the RES
Where is hepcidin synthesised?
In the liver (requires the expression of HFE)
Describe the blood film of iron deficiency anaemia
Pale, hypo chromic and microcytic cells
What are the causes of hypo chromic, microcytic RBCs?
- Iron deficiency anaemia (not enough haem)
- Thalassaemia (not enough globin)
- Anaemia of chronic disease
- Sideroblastic anaemia (can’t form haem)
What is the normal saturation percentage of transferrin?
approx 30%
What is the saturation of transferrin in iron deficiency anaemia?
Less than 15%
Describe the development of iron deficiency anaemia in terms of serum ferritin, RES iron stores and Hb
- All normal
- Latent iron deficiency in which there is compensation: serum ferritin and RES iron stores are decreased but Hb is normal
- IDA: all decreased
In what cases can serum ferritin be increased/ normal even if there is an iron deficiency anaemia?
- In presence of tissue inflammation
- Rheumatoid arthritis (blood loss from NSAIDs)
- IBD
List the clinical signs of iron deficiency anaemia
- Koilonychia (spooning of the nails)
- Atrophic glossitis (painless, lose papillae)
- Angular stomatitis
What are the causes of iron deficiency anaemia?
- Dietary: especially in premature neonates and adolescent females (as periods develop/dieting)
- Malabsorption
- Blood loss
What is the most likely cause of iron deficiency anaemia in males and post menopausal women?
GI blood loss
What is the most common cause of iron deficiency anaemia in young women?
menstrual blood loss or pregnancy
only investigate GI causes if blood in the stool or GI symptoms
Caecal carcinoma
Often asymptomatic, grow as a cauliflower, faecal matter fluid so can get past
Symptoms of stricture in rectum
Apple core effect
•Obstruction
•Bleeding
•abdo pain
Symptoms of diverticular disease
- Bowel habit change
- Blood in stool
- Abdominal pain
What is the treatment of iron deficiency anaemia?
- Iron replacement
- Ferrous sulphate
- Ferrous gluconate (contains less elemental iron, better tolerated if experience GI symptoms from iron)
- IV iron can be given if worried about compliance but it is no more effective than oral iron
- Discover the cause of the anaemia
What are the main uses of IV iron?
- Intolerant of oral iron
- Compliance
- Renal anaemia and Epo (erythropoietin) replacement
What are the causes of anaemia of chronic disease?
- Infection
- Inflammation
- Neoplasia
Why does anaemia of chronic disease happen?
- Failure of iron utilisation
- Iron trapped in reticular endothelial system
- Raised levels of hepcidin
- Reduced epo response by erythroblasts in the bone marrow
- Depressed marrow activity, cytokine marrow depression
What is the result of anaemia of chronic renal failure?
Anaemia of chronic disease and decreased Epo
What are the lab values in anaemia of chronic disease?
- MCV/MCH normal or decreased
- ESR is increased
- Ferritin is normal or increased
- Iron is decreased
- Total iron binding capacity (TIBC) decreased
RBC rouleaux
Stack of coins appearance on a blood film - anaemia of chronic disaease
What is the treatment of anaemia of chronic disease?
Treat the underlying cause
