8. Iron Metabolism

Question 1

What are the 5 microcytic anaemias?

Answer 1

Reduced globin chain synthesis:
- Thalassaemia
Reduced haem synthesis:
- Anaemia of chronic disease
- Iron deficiency
- Lead poisoning
- Sideroblastic anaemia

Question 2

What is iron required for?

Answer 2

Oxygen carriers - haemoglobin in red blood cells, myoglobin in myocytes
Co-factor in many enzymes - cytochromes, Krebs cycle enzymes, cytochrome P450 enzymes, catalase

Question 3

Can iron be excreted?

Answer 3

No, the body has no mechanism for excreting iron

Question 4

What is the difference between ferrous and ferric iron?

Answer 4

Ferrous iron (Fe2+) is the reduced form
Ferric iron (Fe3+) is the oxidised form

Question 5

What does dietary iron consist of?

Answer 5

Haem iron (Fe2+) and non-haem (mixture of Fe2+ and Fe3+)
Ferric iron must be reduced to ferrous iron before it can be absorbed from diet

Question 6

How much iron is needed in the diet?

Answer 6

10-15mg/day

Question 7

Where does absorption of iron occur?

Answer 7

Duodenum and upper jejunum

Question 8

List good sources of haem iron

Answer 8

Liver
Kidney
Beef steak
Chicken 
Duck

Question 9

List good sources of non-haem iron

Answer 9

Fortified cereals
Raisins
Beans
Figs
Barley

Question 10

How is haem absorbed into the body?

Answer 10

Haem moves across enterocyte apical surface
Then converted to Fe2+ by haem oxidase
Can either then be converted to Fe3+-ferritin and stored or move into the blood via a ferroportin
It is then converted to Fe3+ by Hephaestin
Fe3+ is the bound to transferrin and transported around the body

Question 11

How is Fe3+ absorbed into the body?

Answer 11

Fe3+ is converted to Fe2+ using reductase and vitamin C (electron donor)
Fe2+ then moves into the enterocyte through DMT1 (divalent metal transporter)
Fe2+ can then either be stored as Fe3+-ferritin or transported into the blood via ferroportin
Fe2+ is then converted to Fe3+ by hephaestin and bound to transferrin to be transported around the body

Question 12

What is the role of hepcidin?

Answer 12

Produced in liver and inhibits ferroportin

Question 13

What can have a negative influence on absorption of non-haem iron from food?

Answer 13

Tannins (in tea)
Phytates (e.g. chapattis, pulses)
Fibre
Antacids (e.g. gaviscon)

Question 14

What can have a positive influence on absorption of non-haem iron from food?

Answer 14

Vitamin C and citrate

• prevents formation of insoluble compounds
• vit C also helps reduce ferric to ferrous iron

Question 15

What are the two forms of stored iron?

Answer 15

Ferritin - globular protein complex with hollow core, pores allow iron to enter and be released
Haemosiderin - aggregates of clumped ferritin particles, denatured protein and lipid, accumulated in macrophages, particularly in liver, spleen and marrow

Question 16

How is iron taken up in cells?

Answer 16

1. Fe3+ bound transferrin binds transferrin receptor and enters the cytosol by receptor-mediated endocytosis
2. Fe3+ within endosome released by acidic micro environment and reduced to Fe2+
3. Fe2+ transited to cytosol via DMT1
4. Once in cytosol, Fe2+ can be stored in ferritin, exported by ferroportin, or take up by mitochondria or use in cytochrome enzymes

Question 17

What is iron recycling?

Answer 17

Most iron requirement met form recycling damaged or senescent red blood cells
Old RBCs engulfed by macrophages (phagocytosis)
Mainly by splenic macrophages and Kupffer cells of liver macrophages catabolise haem releases from RBC
Amino acids reused and iron exported to blood or returned to storage pool as ferritin in macrophage

Question 18

What are dietary iron levels sensed by?

Answer 18

Enterocytes

Question 19

What are the control mechanisms for regulation of iron absorption?

Answer 19

Regulation of transporters (ferroportin)
Regulation of receptors (transferrin receptors and HFE protein)
Hepcidin and cytokines
Crosstalk between epithelial cells and outer cells like macrophages

Question 20

What is hepcidin?

Answer 20

Key negative regulator of iron absorption
Induces internalisation and degradation of ferroportin
Hepcidin synthesis is increased in iron overload
Decreased by high erythropoietic activity

Question 21

What is anaemia of chronic disease?

Answer 21

Functional iron deficiency
An inflammatory condition leads to cytokines released by immune cells
Therefore increased prodcution of hepcidin by liver, inhibiting ferroportin, decreasing iron release from reticuloendothelial system and decreased iron absorption in gut - reduce plasma iron
Also inhibits erythropoietin production by kidneys
All leads to inhibition of erythropoiesis in bone marrow

Question 22

How much iron is in erythrocytes?

Answer 22

2500mg

Question 23

How much iron is in the plasma iron pool?

Answer 23

2-3mg

Question 24

How much iron is in the iron stores (mainly liver)?

Answer 24

1000mg

Question 25

What are the causes of iron deficiency?

Answer 25

Insufficient iron in diet
Malabsorption of iron
Bleeding
Increased requirement
Anaemia of chronic disease

Question 26

What are the groups at risk of iron deficiency?

Answer 26

Infants
Children
Women of child bearing age
Geriatric age group

Question 27

What are the signs and symptoms of iron deficiency?

Answer 27

Physiological effects of anaemia
- tiredness
- pallo
- reduced exercise tolerance
Pica (unusual cravings for no-nutritive substances)
Cold hands and feet
Epithelial changes (angular cheilitis, glossy tongue, koilonychia)

Question 28

What are the FBC results in iron deficiency anaemia?

Answer 28

Low mean corpuscular volume (MCV)
Low mean corpuscular haemoglobin concentration (MCHC)
Elevated platelet count
Normal or elevated WBC count
Low serum ferritin, serum iron, raised TIBC
Low reticulocyte haemoglobin content

Question 29

What are the peripheral blood smear results in iron deficiency anaemia?

Answer 29

RBCs are microcytic ad hypochromic
Anisopoikilocytosis - change in size and shape
Sometime pencil cells and target cells

Question 30

How to test for iron deficiency

Answer 30

Plasma ferritin

Reduced plasma ferritin, however normal or increased ferritin does not exclude iron deficiency

Question 31

What is the treatment of iron deficiency anaemia?

Answer 31

Dietary advice
Oral iron supplements
Intramuscular iron injections
Intravenous iron
Blood transfusion

Question 32

Why is iron excess dangerous?

Answer 32

Excess iron can exceed binding capacity of transferrin
Excess iron deposited in organs as haemosiderin
Iron promotes free radical formation and organ damage

Question 33

What can cause excess iron?

Answer 33

Transfusion associated haemosiderosis

Hereditary haemochromotosis

Question 34

What is transfusion associated haemosiderosis?

Answer 34

Repeated blood transfusions give gradual accumulation of iron
Problem with transfusion dependent anaemias such as thalassaemia and sickle cell anaemia
Iron chelating agents such as desferrioxamine can delay but not stop inevitable effects of iron overload

Question 35

What can transfusion associated haemosiderosis cause?

Answer 35

Liver cirrhosis
Diabetes
Hypogonadism
Cardiomyopathy
Arthropathy
Slate grey colour of skin

Question 36

What is hereditary haemochromotosis?

Answer 36

Autosomal recessive disease caused by mutation in HFE gene
HFE protein normally interacts with transferrin receptor reducing its affinity for iron-bound transferrin
Mutated HFE can’t bind to transferrin so negative influence on iron uptake lost
HFE ha negative influence on hepcidin production
Too much iron enters cells

Question 37

What is the treatment for hereditary haemochromotosis?

Answer 37

Venesection

Question 38

What can hereditary haemochromotosis cause?

Answer 38

Liver cirrhosis
Diabetes
Hypogonadism
Arthropathy
Cardiomyopathy
Increased skin pigmentation