Iron Metabolism And Microcytic Anaemia

Question 1

What are the causes of microcytic anaemia ?

Answer 1

T thalassaemia

A anaemia of chronic disease

I iron deficiency

L lead poisoning

S sideroblastic anaemia

Question 2

Why is iron important ?

Answer 2

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

Question 3

Can thebody excrete iron?

Answer 3

No , the body has NO mechanism for excreting iron.

Question 4

What are the two states that iron can exist in?

Answer 4

Ferric (Fe3+) - oxidised form

ferrous iron state (Fe2+) - reduced form

Question 5

Whwhat iron is haem iron?

Answer 5

Fe2+.

Question 6

What is non-haem iron?

Answer 6

A mixture of Fe2+ and Fe3+.

Question 7

In order for iron to be absorbed from diet , what form must it be in?

Answer 7

Ferric iron must be reduced to ferrous iron before it can be absorbed from the diet.

Question 8

How many mg of iron do we need a day in diet ?

Answer 8

10-15 mg/ day

Question 9

Where does absorption of iron occur ?

Answer 9

Dueodenum and upper jejunum

Question 10

What are good sources of haem iron?

Answer 10

Liver , beef steak , kidney , beef burger , chicken , duck , pork chop , salmon , tuna

Question 11

What are good sources of non-haem iron?

Answer 11

Raisins

Beans

Figs
Barley

Oats

Rice

Potatoes

Question 12

Outline the process by which dietary absorption of iron occurs :

Answer 12

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.

Question 13

Why is vitamin C very important when it comes to absorption of iron ?

Answer 13

Because it helps to reduce ferric iron into ferrous iron. With the help of the enzyme reductase.

Question 14

What are a few factor’s that have a negative influence on the absorption of non-haem iron ?

Answer 14

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.

Question 15

What is the role of hepcidin?

Answer 15

A peptide that inhibits the entry of ferrous iron into the blood stream - by blocking the

Secreted by the liver

Question 16

With the total iron in our body , what are the two ways it can be classified into ?

Answer 16

FUNCTIONAL IRON (2.3g)

STORED IRON(1g)

Question 17

What is functional iron?

Answer 17

Iron used for haemoglobin , myoglobin , enzymes ( for co factors in cytochromes ) ,

Question 18

What is stored iron ?

Answer 18

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.

Question 19

Outline the process by which iron is taken up from the blood into cell cytosol

Answer 19

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.

Question 20

Why is only a small fraction of total daily iron required from the diet ?

Answer 20

Most almost over 80% of our iron requirement is met from recycling damaged or senescence rred blood cells

Question 21

Is hepcidin a positive or negative regulator of iron absorption?

Answer 21

A negative

Question 22

Why is hepcidin a negative regulator of iron absorption?

Answer 22

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.

Question 23

When is hepcidin synthesis increased by the liver ?

Answer 23

When there is increased iron overload

Question 24

When is hepcidin synthesis by the liver decreased ?

Answer 24

When erythropoietin activity is high which means that

Question 25

How does anaemia of chronic disease lead to microcytic anaemia ?

Answer 25

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.

Question 26

What is the most common nutritional disorder worldwide ?

Answer 26

Iron deficiency

IT IS A SIGN NOT A DIAGNOSIS

The diagnosis would be eg bleeding , pregnancy , poor absorption , insufficient intake

Question 27

What are causes of iron deficiency?

Answer 27

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

Question 28

Why do females need more iron in their diet per day from 19-50 years old than men ?

Answer 28

Because of their menstrual bleeding

Question 29

What groups are at risk of iron defiency?

Answer 29

Infants

Children

Women of bearing age

Geriatric age group

Question 30

What are signs and symptoms of iron deficiency?

Answer 30

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 )

Question 31

What is treatment for iron deficiency?

Answer 31

1) dietary advice
2) oral supplements
3) intramuscular iron injections
4) intravenous iron
5) blood transfusion

Question 32

Why is excess iron dangerous ?

Answer 32

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

Question 33

What is transfusion associated haemosideroisis?

Answer 33

• 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.

Question 34

What is hereditary haemochromatosis?

Answer 34

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

Question 35

How would you treat hereditary haemochromatosis?

Answer 35

Venesection - removal of blood volume.P

Question 36

How would you test for someone who could potentially be iron deficient?

Answer 36

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 ).