5. Iron Flashcards
distribution of iron in the body
70% incorporated into haemoglobin as haem
4.9% in myoglobin, cytochromes and other enzymes as haem
0.1% bound to transferrin (transport protein) in plasma
25% stored in reticuloendothelial system bound into protein complexes, ferritin and haemosiderin (both storage proteins)
storage of iron
so not reliant on just diet
ferritin - physiological storage of iron
haemosiderin is pathological, if we have too much iron stored in the body we see increased levels of haemosiderin
if stores are depleted, person is iron deficient
two main forms of iron
Ferric (fe3+) : insoluble
Ferrous (Fe2+) : soluble
form depends on where we are getting the iron from and where we are transporting iron to
so form may change depending on where in body it is
sources of iron from diet
Haem Iron is more accessible to us as Fe2+ : red meat, poultry, fish
Non haem iron is insoluble, need t convert Fe3+ to Fe2+ in body, this is limiting factor. spinach, leafy greens
total body iron content of healthy adult
2-5g
daily iron cycle: uptake and excretion
Gut absorbs 1mg of iron a day
we lose 1mg of iron a day in hair, skin, urine, faeces
4mg of iron in body in transferrin can be transported to bone marrow to produce Hb that’s incorporated in rbc which then circulate for 120 days and are broken down in spleen in reticular endothelial cells eg in lungs liver as have macrophages
iron withinhealthy rbc is recycled
transferrin in iron cycle
delivers iron to tissues that have transferrin receptors eg liver hepatocytes, erythroblasts in bone marrow, tissues
ineffective erythropoiesis in iron cycle
occurs if we lack a factor needed to produce rbc or if something is wrong w the bone marrow
if rbc identified as abnormal will be broken down prematurely by macrophages and the iron recycled
iron intake and absorption
average western diet is 10-15mg iron daily
5-10%(0.5-2mg) is absorbed through the duodenum (upper small intestine)
absorption is adjusted to body needs
vitamin C increases absorption of iron
iron is converting from Fe3+ to Fe2+ by what enzyme
duodenal cytochrome B
iron inhibited by
phytates (spinach)
tannins (wine)
tetracycline (antibiotics)
iron loss
we lose small but steady amount of iron eg sweating, shedding skin cells of the mucosal lining of the gi tract, faeces
iron loss is only a problem if the body has an increased iron demand
iron absorption
mainly in the duodenum, gut lumen to enterocyte (apical cell) to storage in cell as ferritin or blood in transferrin if needed
molecular mechanism of iron absorption
ferrous iron (fe2+) is transported into the enterocyte from the gut lumen by the divalent metal transporter (DMT1) low gastric pH aids in reduction of ferric iron once incorporated into enterocyte cann then be stored as ferritin but if we need iron it is transported across the basal membrane into the plasma ie circulation by ferroportin however to be transported in transferrin must be converted back into Fe3+ by hephaestin
importance of protein levels in iron absorption
important for the rate at which iron can be absorbed
- from the lumen into the cell
- from the enterocyte into the portal blood
transport of iron
bound to transferrin in plasma
transferrin- can transport iron to any cell that expresses a transferrin receptor on its surface
transferrin is recycled each time it transports iron to a cell
after binding to its receptor the resulting transferrin receptor complex is internalised
iron is released and the receptor transferrin complex is recycled to the cell surface
transferrin is released back in the plasma ready to go again
transferrin receptor
- single membrane spanning receptor
- 2 subunits, each capable of binding a transferrin molecule
- 4 atoms of iron in total can be transferred into the cell each time transferrin binds its receptor and each internalised
iron storage - ferritin
makes up 65% of iron storage water soluble protein shell enclosing an iron core serum ferritin level is the most valuable diagnostic indicator of iron status easily measured by ELISA
iron storage - haemosiderin
makes up 35% of iron storage
- water insoluble
- derived from lysosomal digestion of ferritin aggregates
- found in macrophages
- increased in iron overload
- pappenheimer bodies (removed by spleen)
increase in haemosiderin is pathological
increased iron intake when unable to store as ferritin becomes haemosiderin
iron loss
no specific excretory mechanism for iron
daily loss
- continuous exfoliation of gut/skin epithelial cells (iron containing enzymes)
-total amount of loss for healthy people in developed world is 1mg a day for men and 1.5-2mg a day for women(menstruation)
steady loss means people must continue to absorb iron
(women have greater need )
how do we assess iron status
don’t need to remember numbers
normal iron stores
Serum ferritin (µg/L) : 200-300
Transferrin (g/L) : 1.7 - 3.4
Serum iron (µmol/L) : 10-30
Transferrin saturation (%) : >16
Iron deficiency anaemia
Serum ferritin (µg/L) : <20 decreased storage
Transferrin (g/L) : >3.4 increased transport
Serum iron (µmol/L) : <10 decreased conc
Transferrin saturation (%) : <16 decreased, not enough iron to saturate transferrin
iron requirements
varies through life additional iron requirement: - growth during childhood (0.5-1mg) - menstrual periods (0.5-1mg) - pregnancy (3-4mg) these are when youre more likely to suffer from iron deficiency as increased demand for iron
anaemia
low level of haemoglobin in the blood
WHO criteria id less than 13g/dL in men and less than 12g/dL in women
Affects 1/3 of worlds population
causes of anaemia
- decreased red blood cell production eg due to inadequate iron in diet
- increased destruction of red blood cells
- blood loss (500ml blood contains 200-250mg iron)
- in developing countries dietary deficiency and blood loss due to parasitic infections