iron in health disease]] Flashcards
iron important in electron transport e.g.?
mitochondria production of ATP
ferric ?
fe3
ferrous
fe2
iron present in ? (3)
haemoglobin, myoglobin, enzymes eg cytochroms
why is iron dangerous?
it induces oxidative stress
assessment of iron status
functional - haemoglobin
transport (% saturation with transferrin)
storage (ferritin)
what transports iron from donor tissues to tissues expressing receptors ?
transferrin
ferritin - large intracellular protein - stores up to ?
4000 iro arims
tiny amount of serum ferritin reflects intracellular ferritin synthesis in response to iron - indirect measure of storage iron
y
how is iron absorption regulated?
intraluminal factors - solubility or iron, reduction of ferric to ferrous.
mucosal factors - DMT 1 and ferroportin at mucosal surface
hepcidin - major negative regulator of iron uptake.
where is hepcidin produced?
liver
what is it produced in response to?
iron load and inflammation
what facilitates iron export from the enterocyte?
ferroportin
what is iron passed on to to be transported elsewhere?
transferrin
what does hepcidin do?
down regulates ferroportin
normal amount of iron in the body?
4g
lack of iron?
angular stomatitis, koilonychia, skin changes
iron deficiency can be confirmed by?
combination of anaemia and low storage iron (ferritin)
causes of iron deficiency?
diet, bleeding, malabsorption
bleeding
menorrhagia, GI tumours, haematuria
GI bleeds can occurr without any symptoms
y
what is the maximum iron absorption of iron per day?
4-5mg
this can balance with GI blood loss i.e. no symptoms
y
anaemia of chronic disorders, what happens?
old red cell broken down. increased transcription of ferritin mRNA stimulated by inflammatory cytokines. get increased ferritin synthesis and increase in hepcidin, which blocks ferroportin mediated release of iron
results in?
impaired iron supply to marrow erythroblasts and eventually hypchromic red cells
primary iron overload?
long term excess iron absorption with parenchymal rather than macrophage iron loading and eventual organ damage
what is the parenchyma?
functional part of the organ
clinical features of hereditary haemocromatosis?
weakness, fatigue, joint pains, arthritis, cirrhosis, diabetes, cardiomyopathy, impotence
haemocromatosis can cause deposits anywhere
hypogonadism, cancer, cirrhosis, cardiomyopathy, diabetes, arthropathy
presentation usually in middle age or later
> 5g
mutations of HFE gene, in particular which mutations?
C282Y, H63D
main effect thought to be through?
reduced hepcidin synthesis
diagnosis: phenotype
transferrin saturdation >50%, serum ferritin >300 in men or >200 in pre menopausal women
why would you consider doing a liver biopsy?
can get cirrhosis in haemacromatosis
treatment of hereditary haemacromotosis?
weekly phlebotomy (400-500ml) 200-250mg iron
how much iron in 100ml blood?
50mg
initial aim to exhaust iron stores
ferritin below 20
thereafter keep ferritin below?
50
causes of death in hereditary haemocromotosis?
diabetes, infections, cardiac failure, hepatic failure, bleeding varies, hepatoma
first degree relatives: especially siblings risk 1/4
HFE genotype and iron status
why important to do family studies?
haemocromatosis may be asymptomatic until irreversible organ damage has occurred. this underlines the importance of family studies
secondary iron overload
repeated red cell transfusions, excessive iron absorption related to over active erythropoesis
regular blood transfusions
each unit of blood contains 200-250 mg iron
patients with thalassaemia may require transfusion every 2-3 weeks lifelong
red cell transfusion (iron overload (total >5g)) or liver >15mg/g dry weight
treatment of secondary iron overload?
iron chelating agents (desferrioxamine)
why?
venesection not usually an option in already anaemic patients
