Iron in health and disease Flashcards
What are the functions of iron?
oxygen transport; electron transport
Why is iron dangerous?
chemical reactivity can cause oxidative stress
What transporter is responsible for iron absorption in the duodenum int othe enterocyte?
divalent metal transporter-1
What facilities iron export from the enterocyte?
ferroportin
What is responsibel for down-regulation of ferroportin?
hepcidin
What are the intraluminal factors regulating the absorption of iron?
solubility of inorganic iron; haem iron is easier to absorb; reuction of ferric to ferrous iron
What are the mucosal factors invovled in iron absoprtion regulation?
expression of iron transporters
What is hepcidin produced in reposne to?
in liver to iron load and inflammation
What is the result of hepcidin?
iron trapped in duodenal cells and macrophages
How is functional iron assessed?
haemoglobin concentration
How is iron supply to tissues assessed?
% saturation of transferrin with iron
What tissue is especcialy rich in transferrin receptors?
erythroid marrow
How many binding sites does each transferrin protein have for iron?
2
What is holotranserrin?
iron bound to transferrin
What is apotransferrin?
unbound transferrin
How is storage iron assessed?
serum ferritin or tissue biopsy
what is ferritin?
spherical intracellular protein
How much iron can ferritin store?
upto 4000 ferric (3+) ions
What does serum ferritin reflect?
intracellular ferritin synthesis
Aside from iron storage, what is ferritin involved in ?
acute phase protein- infection; malignancy
What are hte broad categories of disorders of iron metabolism?
iron deficiency; iron malutilisation eg anaemia of chronic disease; iron overload
What are the consequences of negative iron balance?
exhaustion of iron stores; iron deficiency erythropoieis; microcytic anaemia; epithelial changes
What epithelial changes are seen with iron deficiency?
skin; koilonychia; angular stomatitis
What does a hypochromic microcytic anemai indiciate?
deficiency haemoglobin synthesis- eg either haem or globin deficinecy
What are hte causes of iron deficiency?
insufficient intake; bleeding; malabsorption
What are the main causes of chronic blood loss?
menorrhagia; GI; haematuria
How much GI blood loss can occur per day without any signs of symptoms?
8-10mls (4-5mg of iron)
What is the maximum daily dietary iron absoprtion ?
4-5mg
What happens in anaemia of chronic disease?
increased transcription of ferrritin mRNA stimulated by inflammatory cytokines; increased plasma hepcidin blocks ferroportin-mediated release of iron; imparied iron supply to marrow erythroblasts
What is a primary cause of iron overload?
hereditary haemochromatosis
What are secondary causes of iron overload?
transfusional; iron loading anaemia
What is seen with priamry iron overload?
long-term excess iron absorption with parenchymal rather than macrophage iron loading
What is the most commonest form of hereditary haemochromatosis?
mutations in HFE- decreased synthessi of hepcidin
Waht are the clinical features of hereditary haemochromatosis?
weakness/fatigue; joint pain;s impotence; arthritis; cirrhosis; diabetess; cardiomyopathy
How is the diagnosis of hereditary haemochromatosis made?
transferrin sat>50%; serum ferritin >300ug/L men or >200ug/l in women
What are the causes of iron-loading anaemias?
repeated transfusions; excessive iron absorption due to over-active eryhropoiesis
What are the disorders associatedwtih iron-loading anaemia?
massive ineffective erythropoieisis: thalassaemia syndromes; sideroblastic anemias; refractory hypoplastic anaemias: red cell aplasia; myelodysplasia
How much iron does one unit of blood contain?
250mg
What ate the iron chelating agents?
desferrioxamine; deferiprone; deferasirox
