Iron absorption and deficiency Flashcards

1
Q

why is iron essential in all living cells?

A
  • required for oxygen carriers : HB in red cells, myoglobin in myocytes.
  • co-factor in many enzymes : krebs, cytochromes, P450.
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2
Q

why must iron be closely regulated?

A
  • free iron potentially very toxic to cells so must be ensured safe absorption, transportation, utilisation.
  • No mechanism in body for excreting iron.
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3
Q

differentiate between ferrous and ferritin.

A
  • ferrous Fe2+ is the reduced form and ferric Fe3+ oxidised form.
  • dietary iron consists haem iron Fe2+ and non-haem mix of Fe2+ and Fe3+.
  • Ferric iron must be reduced to ferrous to be absorbed, requires acidic conditions.
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4
Q

whats the difference between haem vs non-haem iron?

A
  • Haem iron ( Fe2+ ) is the best source and found in animal base origins.
    eg : liver, kidney, chicken, steak.
  • Non-Haem (Fe3+ and Fe 2+ ) iron is found in plant based food and not absorbed as well by body.
    eg : raisin, beans, barley, rice.
    *absorption at duodenum & upper jejunum.
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5
Q

briefly describe the dietary absorption of iron.

A
  • DMT1 in enterocytes facilitates uptake of Fe2+.
  • Ferric iron reduced to ferrous in intestinal lumen by DcytB before uptake by DMT1.
  • stored as ferritin or transported around blood via ferroportin.
  • most transported to BM or taken up by macrophages as storage pool in reticuloendothelial system.
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6
Q

how is absorption of iron regulated?

A

*regulated by hepicidin by liver, binds on ferroportin causing degradation so prevents iron leaving cell and down-regulates iron uptake by inhibiting transcription of DMT1 gene.

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7
Q

what factors may affect absorption of non-haem iron from food?
- negative and *positive.

A
  • tannins in tea, phytates like pulses may bind to the non-haem iron in intestine reducing absorption.
  • fibres negatively.
  • antacids make environment alkaline affects reduction.

*vitamin C and citrate prevents formation of insoluble iron compounds and helps reduction of ferric to ferrous.

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8
Q

Iron is stored as Ferritin or Haemosiderin. what are these?

A
  • Ferritin : globular protein with hollow core allowing iron to enter and be released. SOLUBLE
  • Haemosiderin : aggregates of ferritin, denatured protein and lipid accumulated in macrophages in liver, spleen and marrow. INSOLUBLE
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9
Q

how is Iron taken up by cell?

A
  • Fe3+ bound to transferrin enters cytosol via receptor mediated endocytosis.
  • reduced by acidic environment to ferrous.
  • transported via DMT1.
  • then ferrous stored as ferritin, exported by ferroportin or taken up by mitochondria for cytochromes.
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10
Q

how is iron recycled?

A
  • recycling of damaged or senescent RBC engulfed by macrophages in spleen or liver by Kupffer cells.
  • macrophages catabolise haem released from RBC, aa reused and iron transported to blood (transferrin) or returned to storage pool as ferritin in macrophage.
    *regulated by hepcidin, cytokines or crosstalk between epithelia cells.
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11
Q

why is Hepcidin a key player in all things iron?

A
  • Hepcidin synthesis increased in iron overload and decreased when high EPO.
  • INDUCES INTERNALISATION AND DEGRADATION OF FERROPORTIN.
  • affects iron transport in blood.
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12
Q

what is iron deficiency and what are its causes?

A
  • sign not a diagnosis, so must work to determine underlying cause.
  • could be dietary, physiological (pregnancy) or pathological (bleeding).

*insufficient iron intake, malabsorption, bleeding, increased requirement in pregnancy or puberty, anaemia of chronic disease.

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13
Q

what groups are generally at risk from iron deficiency?

A
  • infants.
  • children.
  • women of child bearing age.
  • geriatric.
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14
Q

what are the signs and symptoms of iron deficiency?

A
  • tiredness, dizziness, headache.
  • pallor.
  • reduced exercise tolerance as reduced O2 capacity.
  • cardiac : angina, palpiations.
  • Tachypnea : increased RR.
  • Pica (unusual cravings ).
  • Cold hands and feet.
  • epithelial changes as rapid mitosis affected.
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15
Q

what are the features that can be seen in FBC and peripheral blood smear that can be associated with iron deficiency anaemia.

A
  • FBC : low mean corpuscular volume, low HB, thrombocytosis, normal or elevated WBC, low serum ferritin, iron, low reticulocyte.
  • Blood smear : Microcytic and hypochromic changes, anisopoikilocytosis (change in shape and size), pencil cells and target cells.
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16
Q

how would you test for iron deficiency?

A
  • plasma ferritin : small amounts found in blood where it is a functional iron carrier. REDUCED.
  • normal or increased may suggest cancer, infection, inflammation, liver disease.
  • CHr reticulocyte recommended by NICE, which will be LOW during inflammation (also low in thalassaemia).
17
Q

how would you treat iron deficiency.

A
  • dietary advice.
  • oral iron supplements : first line, GI side effects.
  • intramuscular Iron injections.
  • intravenous iron.
  • blood transfusion : at severe anaemia with cardiac compromise.
    *should see 20g/L rise in Hb in 3 weeks.
18
Q

why would excess iron be dangerous?

A
  • if exceeds binding capacity of transferrin, deposits in organs as insoluble haemosiderin.
  • iron promotes free radical formation and organ damage. (hydroxyl and hydroperoxyl causing lipid peroxidation, protein damage, DNA damage)
19
Q

what is transfusion associated haemosiderosis?

A
  • repeated blood transfusions cause gradual accumulation of iron.
  • seen in transfusion dependent anaemias like thalassaemia, sickle cell.
  • Iron chelating agents like desferrioxamine (bonds to iron, water soluble so excreted) can delay but not stop effects like liver cirrhosis, cardiomyopathy, arthropathy, diabetes mellitus.
20
Q

what is hereditary haemochromatosis?

A
  • autosomal recessive by HFE mutation which normally interacts with transferrin receptor reducing affinity for iron bound transferrin.
  • also promotes hepcidin normally.
  • mutated results in too much iron in cell, and accumulation at organs leading to cirrhosis, cardiomyopathy, increased skin pigmentation, diabetes mellitus.

*treated with venesection to remove blood.