1- iron

Question 1

where is iron absorbed? and what form is iron best absorbed in?

Answer 1

duodenum as ferrous (Fe2+)

Question 2

what is function of duodenal cytochrome B?

Answer 2

reduces fe3+ to Fe2+

Question 3

what is function of DMT-1?

Answer 3

transports ferrous ion into duodenal enterocyte

Question 4

what is function of ferroportin?

Answer 4

passes iron from DMT-1 to transferrin for transport around body

*transferrin = 2 binding sites for iron

Question 5

what is function of hepcidin?

Answer 5

major negative regulator of iron uptake, produced in the liver in response to increased iron load + inflammation. binds to ferroportin causing degradation so traps iron in duodenal cells (hepcidin levels decrease if iron deficient)

Question 6

what are 3 ways to measure iron levels in body? (hint: think of where iron is in body and how to measure that)

Answer 6

1. Hb concentration (as most iron in Hb)
2. % saturation transferrin (as some in transport)
3. serum ferritin (as some iron is being stored)

Question 7

what are the negatives of %saturation of transferrin and serum ferritin testing?

Answer 7

% saturation transferrin = measuring alone isn’t ideal as changes a lot throughout day

serum ferritin = also acts as acute phase protein so ferritin will go up if infection or malignancy etc

Question 8

what is holotransferrin and apotransferrin?

Answer 8

holotransferrin = iron bound to transferrin
apotransferrin = unbound transferrin

Question 9

what are causes of iron overload?

Answer 9

primary = hereditary haemochromatosis
secondary = transfusional, iron loading anaemias

Question 10

what is hereditary haemochromatosis?

Answer 10

long term excess iron absorption - instead of iron safely stored in macrophages, they build up in parenchymal tissues

• this is due to mutations in HFE gene (most common form). which causes decreases synthesis of hepcidin (means no trapped iron so increases & increases iron level until overload)

Question 11

what is clinical presentation of hereditary haemochromatosis?

Answer 11

= presents later in life (middle aged), but now picked up earlier in blood tests
- fatigue
- irritability
- joint pains
- impotence
- endocrine glands
- liver damage = cirrhosis & cancer →biggest risk

*can not present until irreversible organ damage

Question 12

what is treatment of hereditary haemochromatosis?

Answer 12

weekly venesection = take 400-500mls blood a time. removing lots of iron (every week or fortnight until ferritin stores get super low) and then just do occasional venesection to keep from coming back up

*also do family screening

Question 13

what are causes of secondary iron overload?

Answer 13

• if transfusions too often - repeated red cell transfusion. people like thalassaemia
• if have chronic anaemia - which would stimulate iron absorption (since body knows not enough iron to tissues but doesn’t understand it’s just because iron not being used well)

Question 14

what is treatment of secondary iron overload?

Answer 14

iron chelating drugs like desferrioxamine (subacute or iV)
(bind to iron & make complexes that are excreted)