IRON Flashcards
why is safe storage and transport of iron important
can cause inflammation and organ damage due to oxidative stress and free radical production
where does the majority of iron absorption occur
duodenum
what dietary factors enhance iron absorption
haem iron is more readily absorbable than non-haem iron (eg red meats)
ascorbic acid (vitamin C)
alcohol
what dietary factors inhibit iron absorption
tannins eg tea
phytates eg cereals, bran, nuts and seeds
calcium
in which state must iron ions exist in order to be absorbed
Fe2+
which enzyme is responsible for converting ferric to ferrous iron for absorption
duodenal cytochrome B
what is the function of DMT-1
transports ferrous iron into the duodenal enterocyte
what is the function of ferroportin
facilitates iron export from the enterocytes
which protein binds to iron for transport
transferrin
what is hepcidin
negative regulatory of iron uptake
how is iron absorption regulated
hepcidin binds to ferroportin causing its degradation
this prevents iron from leaving the cells so serum iron reduces
where is hepcidin produced
in the liver
what causes production of hepcidin
iron load and inflammation
in which form should iron be to bind to transferrin
fe3+
which enzyme is needed to convert Fe2+ to Fe3+ for transport
haphaestin
what are the 3 compartments assessed in iron status
functional iron (Hb) transport iron (% saturation of transferrin) storage iron (ferritin)
how many iron binding sites are there on transferrin molecules
2
which tissues are especially rich in transferrin receptors
erythroid marrow
what is a normal level of transferrin saturation
20-50%
what happens to transferrin saturation in iron overload
elevates
what happens to transferrin saturation in iron deficiency
decreases
how many iron ions can a ferritin molecule store
4000
what form of iron is stored in ferritin
Fe3+
in which cases, other than iron overload, might ferritin go up and why
it is an acute phase protein so may rise in infection, malignancy etc
how can iron deficiency be confirmed
combination of anaemia (decreased Hb iron) and reduced storage iron (low serum ferritin)
what are causes of iron deficiency
insufficient intake to meet physiological demand
losing too much
not absorbing enough
what are common causes of chronic blood loss
menorrhagia
GI bleeding (tumours, ulcers, parasitic infection)
haematuria
what causes anaemia of chronic disease
increased ferritin synthesis and increased plasma hepcidin promotes iron storage and prevents iron transport
what causes primary iron overload
haemochromatosis
why does haemochromatosis cause iron overload
decreases synthesis of hepcidin resulting in increased absorption of iron
clinical features of haemochromatosis
weakness/fatigue joint pains impotence arthritis cirrhosis diabetes cardiomyopathy
when does haemochromatosis usually present
middle age or later
when iron overload >5 g
mutations in which gene are usually the cause of haemochromotosis
HFE gene
2 different mutations
how is haemochromatosis usually diagnosed
transferrin saturation >50%
serum ferritin >300 ug/L (men) or >200 ug/L (pre-menopausal women)
liver biopsy/imaging for evidence of cirrhosis
what is the treatment for haemochromatosis
initial treatment with weekly venipuncture (450-500 ml) until ferritin <20 ug/L
thereafter maintenance to keep ferritin <50 ug/L
what is the most common cause of mortality in haemochromatosis
hepatoma/liver disease
why is it safe to wait to screen children with parents with haemochromatosis until they are adults
because iron overload is gradual and won’t become pathologic until they are middle aged
causes of secondary iron overload
repeated red cell transfusions
excessive iron absorption due to overactive erythropoiesis
which disorders are treated with repeated red cell transfusions, and therefore increase the risk of iron overload
Thalassaemia
siderblastic anaemia
red cell aplasia
myelodysplasia
how is secondary iron overload treated
iron chelating agents
desferrioxamine (SC/IV)
deferiprone/deferasirox (PO)
why is venesection not a suitable treatment for secondary iron overload
the patients are already anaemia
