Iron in Health and Disease

Question 1

how is the porphyrin ring made?

Answer 1

precursors form porphobilinogen which forms protoporphyrin

Question 2

how does iron get back to the plasma?

Answer 2

taken up by macrophages which release it back into the plasma to be bound again to transferrin so it is recycled

Question 3

iron absorption occurs where?

Answer 3

duodenum

Question 4

what dietary substances increase iron absorption? why?

Answer 4

ascorbic acid
alcohol

reduce it to Fe2+ form which is more easily binded to

Question 5

what dietary substances decrease iron absorption? why?

Answer 5

tea
cereal/nuts/seeds
calcium and dairy

bind to it and make it less available

Question 6

what substance reduces Fe3+ to Fe2+

Answer 6

duodenal cytochrome B

Question 7

what does DMT-1 do?

Answer 7

transports non-haem Fe2+ into the duodenal enterocyte

Question 8

what does ferroportin do?

Answer 8

facilitates release of iron from the enterocyte to macrophages then gives it to transferrin

Question 9

what is the major negative regulator of iron uptake?

Answer 9

hepcidin

Question 10

how does hepcidin work? what effect does it have on iron?

Answer 10

binds to ferroportin and degrades it so that Fe2+ can’t escape from the duodenal cells/macrophages

Question 11

how do non-haem iron and haem iron get into the duodenal enterocytes?

Answer 11

haem iron - via haem transporter

non-haem iron - via DMT-1

Question 12

a tissue needs to have alot of ___ receptors for iron to be deposited there

Answer 12

transferrin

Question 13

difference between holo and apotransferrin?

Answer 13

holotransferrin = iron bound transferrin
apotransferrin = unbound transferrin

Question 14

problem with serum ferritin?

Answer 14

is an acute phase protein so goes up with infection/malignancy

Question 15

what happens to the body when iron is low? name the 4 steps of progression

Answer 15

1. exhausted iron stores
2. erythropoesis
3. microcytic anaemia
4. epithelial changes eg koilonychia/angular stomatitis

Question 16

2 things needed to confirm iron deficiency

Answer 16

low Hb iron

reduced storage iron

Question 17

what blood loss equivalates to 4.5mg iron?

Answer 17

9ml (this isnt much!!)

REMEMBER TO DOUBLE THE IRON LEVEL

Question 18

globin is broken into what during recycling?

Answer 18

amino acids

Question 19

what happens to iron in anaemia of chronic disease?

Answer 19

iron is stuck in the macrophage due to inc ferritin and hepcidin stimulated by inflammatory cytokines from the chronic disease so cant be released

Question 20

cause of primary iron overload

Answer 20

hereditary haemochromatosis

Question 21

secondary cause of iron overload

Answer 21

transfusional!

iron loading anaemia

Question 22

where does iron accumulate in primary iron overload? how does this differ from anaemia of chronic disease?

Answer 22

parenchymal tissues

in ACD iron is in macrophages

Question 23

pathophysiology of hereditary haemochromatosis?

Answer 23

mutation in HFE gene causes decreased hepcidinsynthesis = inc iron absorption

Question 24

clinical features of haemochromatosis

Answer 24

middle age ++
asymptomatic! 
weakness 
fatigue
joint pain
impotence
arthritis
cirrhosis
diabetes
cardiomyopathy
basically end organ failure

Question 25

iron overload is iron levels >_g

Answer 25

5

Question 26

Ix haemochromatosis and why

Answer 26

transferrin (>50% high)
ferritin (>300ug/l men or >200ug/l women)
liver biopsy for cirrhosis
genetic testing

Question 27

Tx haemochromatosis

Answer 27

weekly venesection to get rid of Hb (450-500ml)

Question 28

what are you doing to the ferritin by venesecting in haemochromatosis?

Answer 28

get ferritin down to <20 initially

thereafter keep ferritin <50

Question 29

screening programme for HHaemo?

Answer 29

screen 1st degree relatives for gene and look at their iron stores

Question 30

how can you stop iron overload in a patient who keeps getting transfusions?

Answer 30

give a chelating agent eg desferrioxamine or deferiprone