Iron Metabolism & Iron-Deficiency Anemia Flashcards
How much Iron is found in use, in circulation and in storage in the body?
- In use: 75% (about 3 g)
- In circulation: about 4 mg (1-2 mg/day absorbed and 1-2 mg/day lost so balanced)
- In storage: 25% (about 1 g)
What are the four forms by which dietary iron exists?
- Heme iron
- Non-heme iron: Ferrous (Fe3+), Ferric (Fe2+) and Elemental iron (Fe0)
Which of the four forms of iron is most bioavailable? Rank the other three from most bioavailable to least
Heme iron is THE most bioavailable followed by Fe2+, then Fe3+ then F0
What are the primary foods by which we obtain dietary iron?
- Heme iron: meat
- Non-heme iron: vegetables, fruit and eggs
Which of the two forms of iron are insoluble at physiological pH and what pH level do they require?
Ferrous (Fe3+) and Elemental iron (Fe0) are both insoluble at physiological pH (require a more acidic pH like in the stomach)
What are the two clinical applications for decreased Ferrous (Fe3+) absorption (explain the mechanism)?
- Achlorhydria decreases iron bioavailability (low gastric pH so iron remains insoluble)
- Antacids diminish iron availability (also lower gastric pH)
What are the three enhancers of dietary iron? Provide a food example for each
- Reducing molecules: Vitamin C
- Amino acids (AAs): Meat, fish
- Acidic foods: chocolate
What are the five inhibitors of dietary iron? Provide a food example for each
- Phytates: cereal grains, legumes
- Polyphenols: tannins in tea, coffee
- Phosphates & Phosphoproteins: egg yolk
- Oxalate: spinach
- Zn2+ & Ca2+: Zn2+ & Ca2+ supplements
What are the four steps of iron metabolism? (hint: last step has 3 options)
- Dietary iron
- Absorption
- Transport
- Iron loss, for usage or for storage
Where does iron absorption happen and how does this occur?
Iron is absorbed at enterocytes of duodenum and upper jejunum
- Absorption is mediated by membrane carriers (different for heme versus non-heme but all iron ends up in same cytoplasmic pool when heme is released)
How would the surgical removal of the duodenum or upper jejunum affect iron absorption?
Iron absorption would be decreased
How is iron transported in circulation? What are the three safe forms of non-heme iron and what is the one toxic form? Why is this one form of iron toxic?
Iron is associated with proteins (transferrin) during transport SAFE: - Fe3+ - Fe3+/protein - Fe2+/protein
TOXIC:
- Fe2+ (can undergo Fenton reaction)
What is the Fenton reaction?
In the Fenton reaction, Fe2+ reacts with H2O2 to catalyze the formation of free radicals which damage cell membrane, cell proteins and nucleic acids
What is Transferrin and for what step of the iron metabolism pathway is it utilized?
Transferrin is a protein that can bind two Ferric iron atoms (Fe3+) to transport them to all “growing cells” in the body
- Transferrin is used in the transport step of the pathway
What is Apotransferrin?
Apotransferrin is the unbound form of Transferrin (no iron bound to it)
What is a Transferrin Receptor (TfR) and how is it utilized?
TfR is found on all growing cells - the Fe3+-Transferrin complex binds to the TfR where it is endocytosed > Endocytosis of the Fe3+-Transferrin complex results in the creation of an endosome > The complex releases its iron for storage or cellular use > Apotransferrin and TfR return to the extracellular area and are reused repeatedly
What are the three ways by which iron is found in the body for usage? Which is more abundant and in what three ways is this found in the body?
- Heme group is most abundant (found in Hb, Mb and cytochromes)
- Iron-sulfur compounds
- Directly bound to proteins
What is the protein used to store iron? Where is it found in the body?
Ferritin is the intracellular protein used to store iron
- It is found in all cells, but especially the macrophages in the spleen, liver and bone marrow
What is Apoferritin?
Apoferritin is the unbound form of Ferritin (no iron bound to it)
What is Hemosiderin? Under what conditions is it found in humans?
Hemosiderin is a form of Ferritin that has been partially modified in lysosomes and stores 30% more iron than Ferritin
- It is found in humans under conditions of iron overload
What are the only two ways by which iron is lost? Is either voluntary?
- Sloughing of skin and mucosal cells
- Bleeding
Not really - cannot eliminate excess iron from the body voluntarily except via intentional blood loss
How much iron is found per 1 mL of blood?
1 mL of blood contains 0.5 mg of iron
What are the two laboratory tests used to evaluate iron deficiency? What is the best test to assess iron stores?
- Serum Transferrin
- Serum Ferritin (best test for iron stores)
When iron is low, what will lab results show for Serum Transferrin and Serum Ferritin? What about when iron is high?
Low iron:
- Serum Transferrin: high
- Serum Ferritin: low
High iron:
- Serum Transferrin: low
- Serum Ferritin: high