8. Iron Metabolism Flashcards by Livy John

What are the 5 microcytic anaemias?

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

How well did you know this?

Not at all

Perfectly

What is iron required for?

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

How well did you know this?

Not at all

Perfectly

Can iron be excreted?

No, the body has no mechanism for excreting iron

How well did you know this?

Not at all

Perfectly

What is the difference between ferrous and ferric iron?

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

How well did you know this?

Not at all

Perfectly

What does dietary iron consist of?

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

How well did you know this?

Not at all

Perfectly

How much iron is needed in the diet?

10-15mg/day

How well did you know this?

Not at all

Perfectly

Where does absorption of iron occur?

Duodenum and upper jejunum

How well did you know this?

Not at all

Perfectly

List good sources of haem iron

Liver
Kidney
Beef steak
Chicken 
Duck

How well did you know this?

Not at all

Perfectly

List good sources of non-haem iron

Fortified cereals
Raisins
Beans
Figs
Barley

How well did you know this?

Not at all

Perfectly

How is haem absorbed into the body?

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

How well did you know this?

Not at all

Perfectly

How is Fe3+ absorbed into the body?

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

How well did you know this?

Not at all

Perfectly

What is the role of hepcidin?

Produced in liver and inhibits ferroportin

How well did you know this?

Not at all

Perfectly

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

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

How well did you know this?

Not at all

Perfectly

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

Vitamin C and citrate

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

How well did you know this?

Not at all

Perfectly

What are the two forms of stored iron?

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

How well did you know this?

Not at all

Perfectly

How is iron taken up in cells?

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

What is iron recycling?

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

What are dietary iron levels sensed by?

Enterocytes

What are the control mechanisms for regulation of iron absorption?

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

What is hepcidin?

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

What is anaemia of chronic disease?

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

How much iron is in erythrocytes?

2500mg

How much iron is in the plasma iron pool?

2-3mg

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

1000mg

What are the causes of iron deficiency?

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

What are the groups at risk of iron deficiency?

Infants Children Women of child bearing age Geriatric age group

What are the signs and symptoms of iron deficiency?

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)

What are the FBC results in iron deficiency anaemia?

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

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

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

How to test for iron deficiency

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

What is the treatment of iron deficiency anaemia?

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

Why is iron excess dangerous?

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

What can cause excess iron?

Transfusion associated haemosiderosis | Hereditary haemochromotosis

What is transfusion associated haemosiderosis?

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

What can transfusion associated haemosiderosis cause?

``` Liver cirrhosis Diabetes Hypogonadism Cardiomyopathy Arthropathy Slate grey colour of skin ```

What is hereditary haemochromotosis?

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

What is the treatment for hereditary haemochromotosis?

Venesection

What can hereditary haemochromotosis cause?

``` Liver cirrhosis Diabetes Hypogonadism Arthropathy Cardiomyopathy Increased skin pigmentation ```