Embed Size (px)
Text of Iron metabolism
- 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.
- 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 .
- From the gut lumen, iron needs to be moved into theenterocytebefore getting to the bloodstream.
- Therefore, it needs a transporter to do this.
- 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.
- 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.
- Macrophages engulfs old RBCs and releases heme.
- Heme containsprotoporphyrinandFe .
- Heme oxygenaseseparates them and Fe is then stored asferritin.
- 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.
- Causes forraised transferrin receptor : erythroid hyperplasia.
- Iron deficiency (absence of erythroid hyperplasia)
- Not elevatedin anemia of chronic disease.
- Reduced : when iron supply is reduced.
- Anemia of chronic disease
- Increased : when iron supply is in excess.
- Ineffective erythropoiesis.
- Liver disease with reduced transferrin synthesis.
- Cellular storage protein for iron.
- Plasma level reflectsoverall iron stores.
- Also an acute phase reactant.
- Orchestrates cellular defense against oxidative stress and inflammation.
- 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.
- Hepatic Bactericidal Protein.
- Negative regulator of iron metabolism.
- 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
- Hepcidin expression is reduced.
- Leads to increased ferroportin expression.
- Therefore, more transport of Fe from cells to blood bound by Tf.
- Hepcidinincreasedin: Inflammation
- low transferrin Sat (low iron saturation)
- increased ferritin (storage of iron)
- 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.
- Whenhepcidinlevelincrease ,
- Hepdicinbinds to ferroportin .
- Inducesinternalisation and lysosomaldegradation .
- Therefore,reduces amount of iron releasedinto circulation from duodenal cells and macrophages.