Iron Metabolism Flashcards
What is iron required for?
Oxygen carriers
- haemoglobin
- myoglobin
Co-factor
Can the body excrete iron?
No
What are the common states of iron?
Ferrous iron
Ferric iron
What is the formula of ferrous iron?
Fe2+
What is the formula of ferric iron?
Fe3+
Which is the reduced form?
Ferrous iron (Fe2+)
Which is the oxidised form?
Ferric iron (Fe3+)
Where is iron absorbed?
Duodenum
Jejunum
What are sources of haem iron?
Liver
Kidney
Beef
Chicken
What are sources of non-haem iron?
Fortified cereals Raisins Beans Oats Rice
How is dietary iron absorbed?
Fe3+ reduced to Fe2+ by reductase
Fe2+ absorbed into enterocyte by DMT1
Fe2+ travels through ferroportin into blood
Hephaestin converts Fe2+ into Fe3+
How is iron stored in enterocytes?
As Fe3+ with ferritin
What is the cofactor for reductase?
Vitamin C
How is iron transported in the blood?
Fe3+ bound to transferrin
What inhibits ferroportin?
Hepcidin
Where is hepcidin produced?
Liver
What can reduce absorption of non-haem iron?
Tannins (tea)
Fibre
Antacids
What can increase absorption of non-haem iron?
Vitamin C
Citrate
How is iron stored?
Ferritin (soluble)
Haemosiderin (insoluble)
What is ferritin?
Globular protein complex with hollow core that has pores that allow iron to enter/leave
What is haemosiderin?
Aggregates of clumped ferritin particles, denatured protein and lipids - accumulate in macrophages
Where is haemosiderin found?
Liver
Spleen
Marrow
How is iron taken up by cells?
- Fe3+ bound to transferrin binds to transferrin receptor and is taken in by receptor-mediated endocytosis
- Fe3+ released and reduced to Fe2+ by acidic environment in endosome
- Fe2+ released from endosome by DMT1
- Once in cytosol
- stored in ferritin
- exported by ferroportin
- taken up by mitochondria
How is iron recycled?
Old RBCs engulfed by macrophages (mainly splenic and Kupffer cells)
Macrophages catabolise haem from RBCs
Iron exported to blood or returned to ferritin
What is the main regulator of iron absorption?
Hepcidin
What increases hepcidin synthesis?
Iron overload
What decreases hepcidin synthesis?
High erythropoietic activity
How is excess iron stored?
Haemosiderin
What is the problem with excess iron?
Promotes free radical formation
What can cause iron excess?
Transfusion associated haemosiderosis
Hereditary haemochromatosis
What is transfusion associated haemosiderosis?
Gradual accumulations of iron from repeated blood transfusions
Where does iron tend to accumulate?
Liver
Heart
Endocrine organs
How much iron is in 400ml blood?
200mg
How can you delay transfusion associated haemosiderosis?
Desferrioxamine
What is the inheritance pattern of hereditary haemochromatosis?
Autosomal recessive
What is the gene effected by hereditary haemochromotosis?
HFE gene on chromosome 6
How does hereditary haemochromatosis cause iron overload?
HFE protein normally interacts with transferrin receptor - reduces affinity for iron bound transferrin
Mutated HFE cant bind to transferrin
Too much iron enters cells
How is hereditary haemochromatosis managed?
Venesection
