Iron metabolism + microcytic anaemias Flashcards
what is microcytic anaemia
reduced rate of haemoglobin synthesis so erythrocytes smaller and paler (hypochromic) than normal
causes of microcytic anaemia (TAILS)
- thalassaemia reduced globin chain synthesis
- anaemia of chronic disease hepcidin results in functional iron deficiency so reduced haem synthesis
- iron deficiency reduced haem synthesis
- lead poisoning acquired defect that inhibits enzymes of haem synthesis
- sideroblastic anaemia inherited defect in haem synthesis
function of iron
oxygen carriers
- haemoglobin
- myoglobin
co-factor in many enzymes
- cytochromes in ETC
- catalase protecting against oxidative stress
- Krebs cycle enzymes
why is free iron toxic to cells
- catalyst in formation of free radicals from ROS
- complex regulatory systems to ensure safe absorption, transportation and utilisation of iron
- body has no mechanism for excreting iron
ferrous vs ferric iron
- ferrous iron Fe2+ is reduced form of iron
- ferric iron Fe3+ is oxidised form of iron
- haem iron (Fe2+) is more readily absorbed than non-haem iron (mixture of Fe2+ and Fe3+)
- ferric iron must be reduced to ferrous iron before being absorbed from diet
how much iron is needed in diet
10-15 mg/day
1-2mg lost from body each day from skin and GI mucosa
dietary sources of haem iron (Fe2+)
- liver
- kidney
- beef
- chicken
- duck
- pork chop
- salmon/tuna
dietary sources of non-haem iron (Fe2+ and Fe3+)
- fortified cereals
- raisins
- beans
- figs
- barley
- oats
- rice
- potatoes
where does iron absorption occur
- duodenum
- upper jejunum
factors affecting absorption of non-Haem iron from food
negative influence
- tannins(tea) and phytates(chapattis, pulses) bind non-haem iron, inhibiting absorption
- antacids(Gaviscon) inhibit reduction of ferric to ferrous iron
- fibre
positive influence
- vitamin C prevents formation of insoluble iron compounds and helps reduce ferric to ferrous iron
- citrate prevents formation of insoluble iron compounds
iron absorption and transport
- DMT1 on apical surface of enterocytes facilitates uptake of non-haem ferrous iron (Fe2+) from intestinal lumen
- ferric iron (Fe3+) in intestinal lumen is reduced to ferrous iron by reductase (DcytB) before uptake by DMT1
- haem iron readily absorbed by enterocytes via folate transporter
- inside enterocyte haem degraded by haem oxygenase to release ferrous iron to join cytoplasmic pool of Fe2+
- iron in the enterocytes can be stored as ferritin or transferred into bloodstream via ferroportin
- in blood hephaestin converts Fe2+ to Fe3+
- transferrin binds to ferric iron in blood to transport around body
- mostly transported to bone marrow for erythropoesis or taken up by macrophages in RES as storage pool
regulation of iron absorption
- depends on dietary factors, body iron stores and erythropoiesis
- dietary iron levels sensed by enterocytes
control mechanisms
- regulation of transporters e.g ferroportin
- regulation of receptors e.g transferrin receptor
- hepcidin and cytokines
- crosstalk between epithelial cells and other cells
how does hepcidin regulate iron absorption
- hepcidin directly binds to ferroportin resulting in its internalisation and degradation, preventing iron from leaving cell (enterocytes and macrophages)
- down regulates iron uptake by inhibiting transcription of DMT1 gene
hepcidin synthesis increased in iron overload and decreased by high erythropoietic activity
iron recycling
- only small fraction of total daily iron requirement gained from diet
- most from recycling old or damaged red blood cells engulfed by macrophages in RES
- mainly by splenic macrophages and liver Kupffer cells
- macrophages catabolise haem from RBC
- amino acids reused and iron exported to blood (transferrin) or returned to storage pool as ferritin
where is functional iron
- haemoglobin ~2000mg
- myoglobin ~300mg
- enzymes ~50mg
- transported iron (transferrin) ~3mg
