Iron metabolism

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iron metabolism

Text of Iron metabolism

  • 1.Iron metabolism

2.

  • Iron in the body exists in the following forms:
  • Incorporated into Hb (80%)
  • Myoglobin, Enzymes,Cytochromes (15%)
  • Stored iron in the form of ferritin/hemosiderin.
  • Plasma transferrin-bound iron.

3. ( divalent metal transporter 1) 4. 5.

  • Iron exists in 2 forms:
  • Inorganic/non-heme iron (90%) Fe 3+(less soluble)
  • Organic/heme iron (10%) Fe 2+(more soluble)
  • To be soluble, Ferric (Fe 3+ ) needs to be reduced to Ferrous (Fe 2+ ).
  • The enzyme that does this is calledDuodenal cytochrome b(Dcytb)
  • This enzyme isVitamin C dependent .

6.

  • From the gut lumen, iron needs to be moved into theenterocytebefore getting to the bloodstream.
  • Therefore, it needs a transporter to do this.
  • Inorganic iron usesDMT1
  • Organic iron usesHCP1

7.

  • Once in the enterocyte, iron is moved to the bloodstream.
  • Fe 2+is transported out byferroportin1 (FPN)
  • Once it leaves the enterocyte, the Fe 2+changes back to Fe 3+byHephaestin.

8.

  • Once in the bloodstream, Fe 3+couples with Transferrin (Tf) forming aTf-Fe complex.
  • Tf-Fe complex meets up with transferrin receptor 1 ( TfR1 ) in most cells.
  • Proton ATPasedrops the pH in the endosome to release Fe 3+from Tf.
  • This reduction is achieved bySteap3.

9.

  • Macrophages engulfs old RBCs and releases heme.
  • Heme containsprotoporphyrinandFe .
  • Heme oxygenaseseparates them and Fe is then stored asferritin.

10. Transferrin

  • Major transporterfor iron trafficking through theplasma .
  • Increasedin iron deficiency.
  • Rare disease:Hypotransferrinemia .
  • Characterized by low transferrin level, severe iron deficiency anemia and iron overloading.

11. Serum soluble transferrin receptor

  • High transferrin receptor= high Erythroid mass.
  • Causes forlow transferrin receptor : erythroidhypo plasia.
  • Aplastic anemia
  • CRF
  • Causes forraised transferrin receptor : erythroid hyperplasia.
  • Chronic hemolysis
  • Thalassemia
  • Iron deficiency (absence of erythroid hyperplasia)
  • Not elevatedin anemia of chronic disease.

12. Transferrinsaturation

  • Reduced : when iron supply is reduced.
  • Iron deficiency anemia
  • Anemia of chronic disease
  • Ferroportin mutation
  • Increased : when iron supply is in excess.
  • Hemochromatosis
  • Aplastic anemia
  • Sideroblastic anemia
  • Ineffective erythropoiesis.
  • Liver disease with reduced transferrin synthesis.

13. Ferritin

  • Cellular storage protein for iron.
  • Plasma level reflectsoverall iron stores.
  • Also an acute phase reactant.
  • Orchestrates cellular defense against oxidative stress and inflammation.

14.

  • When body gets inflammation, the normal response is to save the iron (keep it in storage) so that it will be less available to the microbes.
  • Raised ferritin= Inflammation.
  • Low ferritin =iron deficiency anemia (99%)
  • Raised ferritin but no infection/inflammation =Iron overload.
  • Extremely high ferritin = hemophagocytic lymphohistiocytosis.

15. Hepcidin

  • Hepatic Bactericidal Protein.
  • Negative regulator of iron metabolism.
  • Actions:
  • It inhibits intestinal transport.
  • Blocks Fe transport across placenta.
  • Induces Fe sequestration in macrophages.
  • Iflow iron stores= hepcidin expressionreduced .
  • Ifhigh iron stores= hepcidin expressionincreased.
  • Molecular targetof Hepcidin isFerroportin.

16. Heres how it works

  • When iron is low,
  • Hepcidin expression is reduced.
  • Leads to increased ferroportin expression.
  • Therefore, more transport of Fe from cells to blood bound by Tf.

17.

  • Hepcidindecreasedin:
  • Hypoxia
  • Anemia
  • Iron deficiency.
  • Hepcidinincreasedin: Inflammation
  • leading to:
  • low transferrin Sat (low iron saturation)
  • increased ferritin (storage of iron)
  • anemia.
  • Inappropriately decreasedin chronic hemolytic anemia and thalassemias.

18. Ferro port in

  • Major ex port er of iron.
  • Transports iron from mother to fetus
  • Transferring absorbed iron from enterocytes into the circulation.
  • Allow macrophages to recycle iron from damaged red cells back into the circulation.

19.

  • Whenhepcidinlevelincrease ,
  • Hepdicinbinds to ferroportin .
  • Inducesinternalisation and lysosomaldegradation .
  • Therefore,reduces amount of iron releasedinto circulation from duodenal cells and macrophages.

20. 21.