Iron Metabolism

Question 1

Deficiency of Iron

Answer 1

fewer RBCs produced + those RBCs contain fewer Hgb molecules

Causes:
- nutritional deficiency
- true deficiency = increased loss (chronic hemorrhage)
- functional deficiency = sequestration + decreased absorption (with inflammation)

Question 2

Overload of Iron

Answer 2

acute + chronic toxic effects

cause:
- excess supplementation
- certain hemolytic diseases, particularly wiuth multiple blood transfusions

Question 3

Total Body Iron

in health

Answer 3

50-70% in erythrocyte Hgb
25-40% in storage (RBCs, liver, spleen, BM) = as hemosiderin or ferritin
remainder in other iron containing molecules

Question 4

Iron Absorption + Metabolism

Answer 4

regulated + occurs in proximal duodenum
- dietary iron may be ferrous Fe2+ or ferric (Fe3+) in nature
- dietary Fe3+ -> Fe2+ by enzyme 1 (ferric reductase) at intestinal mucosa
- transporter protein (DMT-1) of enterocyte villi moves Fe2+ into enterocyte
- Fe2+ moved out of enterocyte into plasma by transporter protein (ferroportin)
- Fe2+ -> Fe3+ by enzyme (hephaestin)

majority of iron used in body comes from recycled Hgb iron

total body iron stores are regulated to avoid iron overload or deficits

Question 5

Transferrin

Answer 5

in plasma -> apotransferrin + Fe3+ = tranferrin

almost all iron in plasma is in transferrin

moves iron to/from body tissues

in healthy animals, ~1/3 of Fe-binding sites on transferrin occupied

tissues with transferrin binding sites = erythoid precursors, hepatocytes, others

Question 6

Movement of Iron into RBC Hemoglobin

Answer 6

• erythroid precurors have transferrin receptors in plasma membrane
• iron-carrying transferrin binds to transferrin receptor
• entire complex is moved into cell via endosome
• Fe3+ dissociates from transferrin d/t low pH of endosome
• Fe3+ -> Fe2+ by enzyme
• DMT-1 present in endosome membrane moves Fe2+ into cytosol for use in heme synthesis

Question 7

Recycling of iron from erythrocytes

Answer 7

body preserves iron present in erythrocytes

mononuclear phagocyte system

macrophage phagocytoses erythrocyte (often senescent)
- Hgb split into heme + globin
- heme releases Fe2+ and is degraded
- iron can be stored or exported

ferroportin also found in macrophages, allowing export of Fe3+

Question 8

Storage Iron

Answer 8

Ferritin
- water-soluble, mobile, iron-protein complex
- mainly found in developing RBCs, macrophages, hepatocytes, enterocytes
- synthesis increases in inflammation + when more Fe present

Hemosiderin
- poor soluble, less mobile, more stable
- major storage form of iron
- predominantly in macrophages of liver, spleen + bone marrow

Question 9

Hepcidin

Answer 9

important systemic iron regulator

• small peptide produced by liver
• negative regulator of iron movement
• prevebts iron absorption + iron movement out of storage

binds ferroportin, causing its internalization within cell -> decreased iron export from macrophages + hepatocytes -> IC iron increases which leads to:
- decreased iron absorption from intestinal lumen
- decreased iron uptake by erythroid precursors

suspected that this mechanism of iron sequestration developed to prevent bacterial proliferation during infection
- bacteria need iron to survive + replicat

however, this also contributes to anemia of chronic/inflammatory disease

functional iron deficiency

Question 10

Hepcidin Production

Answer 10

Result of decreased hepcidin production:
- increased absorption of intestinal iron
- normal enterocyte iron export into plasma
- normal release of stored iron from tissue macrophages + hepatocytes

Results of increased hepcidin production:
- prevention of iron absorption by enterocytes
- decreased iron export from enterocytes + macrophages