iron metabolism Flashcards
what are microcytic anaemias caused by
mainly caused by iron deficiency and TAILS (thalassaemia(reduced global chain synthesis), anaemia of chronic disease, iron diefeicney, lead poisoning = acquired defect which inhibits enzymes involved in harm synthesis and sidrobalstic)
how to recognise microcytic anaemias
reduced hb synthesis, smaller RBC and paler nucleus (hypo chromic)
why is iron important
carter of o2 in myoglobin and haemoglobin. its also an important cofactor in enzymes including cytochromes, Krebs cycle enzymes, cytochrome p450 and catalase
problem with iron
its very toxic in its free form and the body has no mechanism of removing it
difference between ferrous and ferric and what needs to be converted
ferrous = fe2+ and ferric = fe3+. iron can only be absorbed in the body in the for, of fe2+ and therefore ferric iron must be reduced before it can be absorbed
alkaline and acid cause oxidation or reduction?
alkaline causes oxidation and acid causes reduction
difference between haem and non-haem iron
they are both absorbed in the duodenum and jejunum. haem iron is the best source because it is readily absorbed. haem= from animal products e.g burger and non-haem is found in oats and barley ect.
explain the process of how iron is absorbed
- Haem (fe2+) is readily absorbed into the enterocyte. non-haem fe2+ is absorbed via a DMT1 cotransporter which pumps H+ out and Fe2+ in. Fe3+ non haem must be first converted using enzyme reductase and then can also be absorbed via DMT1.
- once Fe2+ has been absorbed it can be stored as ferritin (in fe3+ form) or enter the blood
function of vitamin C
it is a cofactor for the enzyme reductase
describe how Fe2+ enters the blood from an enterocyte
- enters blood via ferroportin transporter.
- once enters blood fe2+ is converted to FE3+ by hephaestin so it is able to bind to transferin transporter to take it around the body
what is hepcidin
it is a molecule which inhibits the actions of ferroportin to prevent iron entering the blood
its synthesis is increased when there is high iron and decreased when high erythropoietic activity
positive and negative factors which affect absorption of non-haem iron from the the blood
negative;(prevent the absorption of iron)
tannins (found in tea)
phytates (in chapattis)
fibre
antacids
positive (help the absorption of iron);
citrate and vitamin C- these help reductase and prevent iron turning insoluble
difference between functional and stored iron
functional is found in haem and myoglobin swell as enzymes and as its being transported. stored iron is found in the form of ferritin(soluble) held in globular protein. the other source of stored protein is haemosiderin (insoluble) which accumulates in macrophages.
how cells take up iron
- fe bound to feraportin enters cytosol by receptor mediated endocytosis
- Fe3+ is converted to Fe2+ by the acidic microenvironment
- fe2+ enters the cytosol via DMT1
- can be exported, stored in ferritin or used in mitochondria for cytochrome enzymes
how is iron recycled
most iron is recycled so don’t need that much from the diet. it is recycled by the breaking down old RBC in that they are engulfed by macrophages (especially splencic and kupfer cells) and within the macrophages the haem is catabolised and Fe is then transferred via trasnferin and stored as ferritin
how is iron absorption
this is something thats not really understood yet
mechanisms include;
regulation of ferraportin and other transporters
hepcidin and cytokine used to regulate how much iron enters the blood
cross talk by epithelial cells and macrophages to see how much iron there is
how chronic disease leads to anaemia
increased release of cytokines because of the disease increases porucditon of hepcidin by the liver. more hepcidin leads to ferroportin inhibition decreased iron absorption in the gut and decreased iron release from RES because ferritin stores full. overall reduces plasma iron.
cytokines also inhibit eryhtropoetin production by kidneys
swell as that cytokines themselves also inhibit erythropoiesis in bone marrow
talk about how iron is recycled
iron enters iron pool via macrophages and dietary absorption and leaves via bone marrow and loss due to sweat or pregnancy
causes of iron deficiency
- insufficient intake
- malabsorption
- bleeding e.g menstrual cycle
- increased requirement e.g during pregnancy
- anaemia of chronic disease e.g rheumatoid arthritis
which groups are at risk of developing anaemia
infants and children, women of child bearing age (because need more) and elderly people
symptoms of anaemia
physiological;
tieredness
pallow
reduced exercise tolerance due to reduced oxygen carrying capacity
cardiac - angina, palpitations and heart failure because the heart is compensating for lack of oxygen
increased respiratory rate because of less o2
headache, dizziness and light-headedness
pica (cravings for weird things e.g dirt)
cold hands and feet
epitelial chances
what epithelial changes are seen anaemic patients
glossy tongue, koilonychia (spoon nails and angular cheilitis which are cold sores on the edge of mouth
blood film features of iron deficient anaemia
microcytic, low hb, high platelets and WBC, low keratin, iron and transferin, low reticulocyte.
definitely iron deficient if low ferritin BUT normal value doesn’t disclude it (because levels increase in cancer and other diseases). instead CHr (reticulocyte count) used because stays low in other diseases EXCEPT thalassaemia
treatment of iron deficiency
dietary changes oral supplements intramuscular injection intravenous blood transfusion (rare and only used if have cardiac compromise) =should see improvement with oral and dietary changes within 3 weeks because RBC have life span of 120 days
what does excess iron cause
if there is excess iron it is store in organs as haemosiderin. iron promotes free radical formation which can cause damage to cells
what is hereditary haemochromostosis
autosomal resecive disease where there is a mutation in the HFE gene. HFE usually interacts with transferin and reduces its affinity for iron BUT mutated HFE can’t bind transferin so more iron enters cells, accumulate and damages. treated with venesetion
side effects of hereditary haemochromostosis and transfusion associated hamesiderosis
liver cirrhosis diabetes hypogandism athropathy cardiomyopathy increased skin pigmentation
what is transfusion associated hamesiderosis
repeated blood transfusions lead to the accumulation of iron. desferrioxamine can delay but to stop iron overload effects. its inevitable
