8 - Iron Metabolism Flashcards
What are the causes of microcytic anaemia?
Hypochromic and smaller than normal due to decrease Hb production
What is iron used for in the body?
- Oxygen Carriers (myo and haemoglobin)
- Cofactor in enzymes (krebs, CYP450, cytochromes in mitochondria, catalase)
What are the different states of iron?
Ferrous (Fe2+) and Ferric (Fe3+)
Have to be in ferrous form to be absorbed. Haem iron is ferrous but non-haem is mixture
What are sources of haem and non-haem iron?
Need 10-15mg/day
How is iron absorbed?
1. CytB Reductase using Vit C in chyme
- DMT1 (divalent metal transporter) on apical enterocyte
- Haem degraded in cytoplasm to form ferric iron to be stored as ferritin
- Remaining iron transported to bloodstream via ferroportin
- In blood iron bound to transferrin and transported to bone marrow or taken up by macrophages in RES for storage pool
- Iron absorption regulated by hepcidin
How does hepcidin regulare iron absorption?
- Peptide hormone released by liver when iron overload (stopped with high EPO levels)
- Binds to ferroportin causing it to be degraded
- Inhibits transcription of DMT1
What other factors affect iron absorption apart from hepcidin?
Regulated by dietary factors, body iron stores and erythropoiesis
Of all of the iron stores in the body, 3.4g, where are they all found?
Functional Iron: Haemoglobin, enzymes, myoglobin, transported iron
Stored Iron (1g): Ferritin or Haemosiderin
Where is the main store of iron in the body?
Macrophages, Liver, Spleen
How do cells requiring iron uptake iron from the blood stream?
- Fe3+ bound transferrin binds to transferrin receptor
- Receptor-mediated endocytosis
- Fe3+ reduced to Fe2+ by the acidic environment in the endosome
- The Fe2+ is transported to cytosol via DMT1
- Fe stored in ferratin, exported by ferroportin (FPN1) or used in cytochromes
How does iron recycling occur in the body?
- 80% requirement from this
- Old RBC’s engulfed by macrophages, mainly splenic and kupffer
- Macrophages metabolise haem
- Iron exported to the blood (transferrin) or returned to storage pool of ferratin in macrophage
What are some mechanisms of regulating iron absorption?
- Hepcidin
- Regulation of transportes and receptors (HFE protein that binds to transferrin receptors to stop transferrin uptake)
- Talk between epithelia and macrophages
How does anaemia of chronic disease cause an iron deficiency?
What are some causes of iron deficiency?
Which groups are at risk of iron deficiency?
- Infants from breast to formula milk
- Children
- Women of child-bearing age due to periods >80ml
- Geriatric age group
What are the signs and symptoms of iron deficiency?
- Anaemia effects (pallor, tired, cardiac issues, tachypneoa, headache)
- Pica
- Cold hands and feet
- Epithelial changes like spoon nails
What blood parameters and what blood film would you see with iron deficiency?
- Low MCV, Low MCHC
- Elevated platelet count
- Normal or elevated WBC
- Low serum ferritin
- Low CHr
How do you treat iron deficiency?-
- Diet advice
- Oral supplement of ferrous sulphate for 2-3 months. Low compliance due to GI side effects (should see increase of 20g/L in 3 weeks)
- IM and IV iron
- Blood transfusion in emergency where cardiac compromise likely
Why is free iron dangerous?
Produces hydroxyl and peroxydl free radicals in the Fenton reaction
What is transfusion associated haemosiderosis?
- Repeated blood tranfusions, e.g sickle cell, so accumulation of iron
- 400ml of blood = 200mg iron
- Desferrioxamine chelating agent can delay inevitable effects
What is heredirary haemochromatosis and what are some problems than can arise with it?
- Autosomal recessive HFE gene mutation
- HFE normally interacts with transferrin receptor, reducing it’s affinity for Fe-transferrin
- Negative influence on iron uptake lost so iron accumulates as haemosiderin in end organs
- Treat with regular venesection
