8. Iron metabolism Flashcards
What is microcytic anaemia caused by?
- Reduced haem synthesis
- Reduced globin chain synthesis
What anaemias are due to reduced haem synthesis(which results in microcytic anaemias)?
- iron deficiency - not enough iron for haem synthesis
- lead poisoning - lead inhibits enzymes in haem synthesis
- anaemia of chronic disease - hepcidin results in functional iron deficiency
- sideroblastic anaemia - inherited defect in haem synthesis
What anaemias are due to reduced globin chain synthesis(which results in microcytic anaemias)?
- alpha thalassaemia- deletion/ loss of function of one or more of the four alpha globin genes
- beta thalassaemia- mutation in beta globin genes leading to reduction or absence of the beta globin
What happens to RBCs in microcytic anaemias?
- smaller than normal (microcytic)
- often paler than normal (hypochromic)
How is the rate of haemoglobin synthesis in microcytic anaemia?
Reduced rate of haemoglobin synthesis
What are the five main types of microcytic anaemias?
T : thalassaemia A : anaemia of chronic disease I : iron deficiency L : lead poisoning S : sideroblastic anaemia
What is iron required for?
• Oxygen carriers: - Haemoglobin in red cells - Myoglobin in myocytes • Co-factor in many enzymes: - Cytochromes (oxidative phosphorylation) - Krebs cycle enzymes - Cytochrome P450 enzymes (detoxification) - Catalase
Why are complex regulatory systems used to ensure the safe absorption, transportation and utilisation of iron?
Free iron potentially very toxic to cells - generates free radicals —> oxidative damage
Body has no mechanism for excreting iron
Which oxidation states can iron exist in?
- ferrous iron - reduced form Fe2+
- ferric iron - oxidised form Fe3+
What does dietary iron consist of?
- haem iron - Fe 2+
- non-haem - mixture of Fe 2+ and Fe 3+
Ferric iron must be reduced to ferrous iron before it can be absorbed from the diet
Under what conditions is ferrous iron converted to ferric iron?
- Oxidation
* Alkaline
Under what conditions is ferric iron converted to ferrous iron?
- Reduction
* Acidic
How much iron do you need daily?
10-15 mg
Where is iron absorbed?
duodenum and upper jejunum
What are good sources of haem iron?
Liver, kidney, beef, chicken, duck, pork, salmon, tuna
What are good sources of non-haem iron?
Fortified cereals, raisins, beans, figs, barley, oats, rice, potatoes
How is iron absorbed?
- haem iron can pass through the membrane into the cytoplasm of the enterocyte where it is degraded by the enzyme haem oxygenate to release Fe2+
- for non-haem iron, duodenal cytochrome B reductase on apical surface of enterocytes converts ferric Fe3+—> ferrous Fe2+ - vit C donates this electron
- ferrous enters enterocytes via DMT1 - every molecule in, sends a proton out into the chyme
- Fe2+ released from both haem and non-haem iron can either be stored as ferritin (Fe3+)
- or leaves basolateral surface into the blood via ferroportin
- Hephaestin facilitates conversion back to Fe3+ needed to bind to transferrin to be transported in blood
What factors have a negative influence of absorption of non-Haem iron from food?
- tannins in tea: bind non-haem iron in intestine which reduces absorption
- phytates (e.g. chapattis, pulses): binds to non-haem
- fibre: binds to non-haem
- antacids e.g. graviscon: reduces acidity needed to reduce ferric —> ferrous
What factors have a positive influence on non-haem absorption ?
Vitamin C and citrate:
- prevents formation of insoluble iron compounds
- helps reduce ferric to ferrous iron: provides acidity and also an electron donor
What are examples of functional (available) iron?
iron associated with proteins/ enzymes and transported around the body
- Hb
- myoglobin
- enzymes e.g. cytochromes
- transported iron (in serum mainly in transferrin)