Iron in Health and Disease Flashcards
how is the porphyrin ring made?
precursors form porphobilinogen which forms protoporphyrin
how does iron get back to the plasma?
taken up by macrophages which release it back into the plasma to be bound again to transferrin so it is recycled
iron absorption occurs where?
duodenum
what dietary substances increase iron absorption? why?
ascorbic acid
alcohol
reduce it to Fe2+ form which is more easily binded to
what dietary substances decrease iron absorption? why?
tea
cereal/nuts/seeds
calcium and dairy
bind to it and make it less available
what substance reduces Fe3+ to Fe2+
duodenal cytochrome B
what does DMT-1 do?
transports non-haem Fe2+ into the duodenal enterocyte
what does ferroportin do?
facilitates release of iron from the enterocyte to macrophages then gives it to transferrin
what is the major negative regulator of iron uptake?
hepcidin
how does hepcidin work? what effect does it have on iron?
binds to ferroportin and degrades it so that Fe2+ can’t escape from the duodenal cells/macrophages
how do non-haem iron and haem iron get into the duodenal enterocytes?
haem iron - via haem transporter
non-haem iron - via DMT-1
a tissue needs to have alot of ___ receptors for iron to be deposited there
transferrin
difference between holo and apotransferrin?
holotransferrin = iron bound transferrin apotransferrin = unbound transferrin
problem with serum ferritin?
is an acute phase protein so goes up with infection/malignancy
what happens to the body when iron is low? name the 4 steps of progression
- exhausted iron stores
- erythropoesis
- microcytic anaemia
- epithelial changes eg koilonychia/angular stomatitis
2 things needed to confirm iron deficiency
low Hb iron
reduced storage iron
what blood loss equivalates to 4.5mg iron?
9ml (this isnt much!!)
REMEMBER TO DOUBLE THE IRON LEVEL
globin is broken into what during recycling?
amino acids
what happens to iron in anaemia of chronic disease?
iron is stuck in the macrophage due to inc ferritin and hepcidin stimulated by inflammatory cytokines from the chronic disease so cant be released
cause of primary iron overload
hereditary haemochromatosis
secondary cause of iron overload
transfusional!
iron loading anaemia
where does iron accumulate in primary iron overload? how does this differ from anaemia of chronic disease?
parenchymal tissues
in ACD iron is in macrophages
pathophysiology of hereditary haemochromatosis?
mutation in HFE gene causes decreased hepcidinsynthesis = inc iron absorption
clinical features of haemochromatosis
middle age ++ asymptomatic! weakness fatigue joint pain impotence arthritis cirrhosis diabetes cardiomyopathy basically end organ failure
iron overload is iron levels >_g
5
Ix haemochromatosis and why
transferrin (>50% high)
ferritin (>300ug/l men or >200ug/l women)
liver biopsy for cirrhosis
genetic testing
Tx haemochromatosis
weekly venesection to get rid of Hb (450-500ml)
what are you doing to the ferritin by venesecting in haemochromatosis?
get ferritin down to <20 initially
thereafter keep ferritin <50
screening programme for HHaemo?
screen 1st degree relatives for gene and look at their iron stores
how can you stop iron overload in a patient who keeps getting transfusions?
give a chelating agent eg desferrioxamine or deferiprone
