Iron Metabolism And Microcytic Anaemia Flashcards
What are the causes of microcytic anaemia ?
T thalassaemia
A anaemia of chronic disease
I iron deficiency
L lead poisoning
S sideroblastic anaemia
Why is iron important ?
1) required for oxygen carriers in haemoglobin in red cells and myoglobin in myocytes.
2) . Co factor for many enzymes : cytochromes in OP, Krebs cycle enzymes , cytochromes in P450 enzymes , catalase
Can thebody excrete iron?
No , the body has NO mechanism for excreting iron.
What are the two states that iron can exist in?
Ferric (Fe3+) - oxidised form
ferrous iron state (Fe2+) - reduced form
Whwhat iron is haem iron?
Fe2+.
What is non-haem iron?
A mixture of Fe2+ and Fe3+.
In order for iron to be absorbed from diet , what form must it be in?
Ferric iron must be reduced to ferrous iron before it can be absorbed from the diet.
How many mg of iron do we need a day in diet ?
10-15 mg/ day
Where does absorption of iron occur ?
Dueodenum and upper jejunum
What are good sources of haem iron?
Liver , beef steak , kidney , beef burger , chicken , duck , pork chop , salmon , tuna
What are good sources of non-haem iron?
Raisins
Beans
Figs
Barley
Oats
Rice
Potatoes
Outline the process by which dietary absorption of iron occurs :
1) ferric iron (Fe3+) is reduced to Fe2+ via the reductase enzyme.
2) Fe2+ can now enter the enterocytes via the co-transporter channel DMT1 . Exports one proton for every Fe2+
3) fe2+ can now. Either enter an iron store called ferritin or enter the blood stream via the transporter FERROPORTIN.
4) Before iron can travel around the blood , it must be converted into Fe3+ again. This is done wit the help of Hephaestin.
5) once in its oxidised state , it can bind to transferrin and be transported around the body.
Why is vitamin C very important when it comes to absorption of iron ?
Because it helps to reduce ferric iron into ferrous iron. With the help of the enzyme reductase.
What are a few factor’s that have a negative influence on the absorption of non-haem iron ?
1) tannins
2) phytates ( chappati , pulses )
3) fibre
4) antacids ( gaviscon)
- they all can bind to non-haem iron in the intestine. This reduces absorption.
What is the role of hepcidin?
A peptide that inhibits the entry of ferrous iron into the blood stream - by blocking the
Secreted by the liver
With the total iron in our body , what are the two ways it can be classified into ?
FUNCTIONAL IRON (2.3g)
STORED IRON(1g)
What is functional iron?
Iron used for haemoglobin , myoglobin , enzymes ( for co factors in cytochromes ) ,
What is stored iron ?
Iron cain either be stored in a soluble protein complex ‘ ferritin’
or an insoluble complex called ‘ haemosiderin’ - which are aggregates of ferritin particles , denatured protein and lipid. This accumulates in macrophages , liver , spleen and bone marrow.
Outline the process by which iron is taken up from the blood into cell cytosol
1) Fe3+ bound transferrin binds to transferrin receptor and enters the cytosol via receptor mediated endocytosis.
2) Fe3+ within endosomes released by acidic environment and reduced into Fe2+.
3) the Fe2+ transported to the cytosol via DMT1 from the endosomes into cytosol.
4) once the Fe2+ is in the cytosol , the fe2- can be stored in ferritin OR exported by ferroportin (FPN1) into the blood stream again OR taken by mitochondria for use in cytochrome enzymes.
Why is only a small fraction of total daily iron required from the diet ?
Most almost over 80% of our iron requirement is met from recycling damaged or senescence rred blood cells
Is hepcidin a positive or negative regulator of iron absorption?
A negative
Why is hepcidin a negative regulator of iron absorption?
1) hepcidin induces internalisation and degradation of ferroportin.
2) this prevents iron from being absorbed into the blood from enterocytes or from being released by macrophages.
When is hepcidin synthesis increased by the liver ?
When there is increased iron overload
When is hepcidin synthesis by the liver decreased ?
When erythropoietin activity is high which means that
How does anaemia of chronic disease lead to microcytic anaemia ?
1) if there is an inflammatory condition eg rheumatoid arthritis
2) more cytokines are being released by immune cells ( IL-6)
3) this results in increased production of hepcidin by the liver.
4) the release of cytokines also inhibits erythropoietin production by kidneys which results in inhibition of EP in bone marrow.
5) this results in inhibitors of ferroportin. This decreases release of iron from the RES. And decreased iron absorption in the gut. This results in plasma iron reducing.
What is the most common nutritional disorder worldwide ?
Iron deficiency
IT IS A SIGN NOT A DIAGNOSIS
The diagnosis would be eg bleeding , pregnancy , poor absorption , insufficient intake
What are causes of iron deficiency?
1) insufficient iron in diet
2) malabsorption of iron
3) bleeding heavily eg menstruation.
4) increased requirement eg pregnancy
5) anaemia of chronic disease eg inflammatory bowel disease
Why do females need more iron in their diet per day from 19-50 years old than men ?
Because of their menstrual bleeding
What groups are at risk of iron defiency?
Infants
Children
Women of bearing age
Geriatric age group
What are signs and symptoms of iron deficiency?
Tiredness
Pallor
Reduced exercise tolerance
Cardiac problems - angina , palpitations
Increasing respiratory rate
Headache , dizziness , light headedness
Pica ( unusual cravings - dirt, ice )
- KOILONYCHIA ( spoon nails)
- cold hands and feet
- glossy tongue
- Angular cheilitis ( around mouth )
What is treatment for iron deficiency?
1) dietary advice
2) oral supplements
3) intramuscular iron injections
4) intravenous iron
5) blood transfusion
Why is excess iron dangerous ?
1) excess iron can exceed binding capacity of transferrin
2) excess iron deposited in organs as haemosiderin,
3) iron promotes free radical formation and organ damage.
FE2+ + H202 = FE3+ + OH* + OH-
FE3+ + H202= FE2+ + OOH* + H+ FENTON REACTION
What is transfusion associated haemosideroisis?
- the gradual increase in iron in the liver , heart , endocje organs. because of repeated blood transfusions which give gradual accumulation of iron.
- this becomes a problem with people who are dependant on blood transfusions for example thalassaemia and sickle cell anaemia.
- this can lead to liver cirrihus , diabetes , slate grey skin , cardiomyopathy.
What is hereditary haemochromatosis?
Autosomal recessive disease caused by mutation in the HFE gene.
- HFE protein normally interacts with transferrin receptor reducing its affinity for iron bound transferrin.
- mutated HFE cannot bind fo transferrin so the negative influence on iron uptake is lost.
- HFE also has a negative influence on hepcidin production so again negative influence on iron uptake is lost.
- too much iron therefore enters the cells , acclimating in organs causing damage
How would you treat hereditary haemochromatosis?
Venesection - removal of blood volume.P
How would you test for someone who could potentially be iron deficient?
Plasma ferritin is measured
- reduced plasma ferritin definitively indicates iron deficiency.
- but normal or increased ferritin does not exclude iron deficiency.
- CHR ( recticulocyte haemoglobin content ).
