Iron Metabolism & Iron-Deficiency Anemia

Question 1

How much Iron is found in use, in circulation and in storage in the body?

Answer 1

• 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)

Question 2

What are the four forms by which dietary iron exists?

Answer 2

• Heme iron

- Non-heme iron: Ferrous (Fe3+), Ferric (Fe2+) and Elemental iron (Fe0)

Question 3

Which of the four forms of iron is most bioavailable? Rank the other three from most bioavailable to least

Answer 3

Heme iron is THE most bioavailable followed by Fe2+, then Fe3+ then F0

Question 4

What are the primary foods by which we obtain dietary iron?

Answer 4

• Heme iron: meat

- Non-heme iron: vegetables, fruit and eggs

Question 5

Which of the two forms of iron are insoluble at physiological pH and what pH level do they require?

Answer 5

Ferrous (Fe3+) and Elemental iron (Fe0) are both insoluble at physiological pH (require a more acidic pH like in the stomach)

Question 6

What are the two clinical applications for decreased Ferrous (Fe3+) absorption (explain the mechanism)?

Answer 6

• Achlorhydria decreases iron bioavailability (low gastric pH so iron remains insoluble)
• Antacids diminish iron availability (also lower gastric pH)

Question 7

What are the three enhancers of dietary iron? Provide a food example for each

Answer 7

• Reducing molecules: Vitamin C
• Amino acids (AAs): Meat, fish
• Acidic foods: chocolate

Question 8

What are the five inhibitors of dietary iron? Provide a food example for each

Answer 8

• Phytates: cereal grains, legumes
• Polyphenols: tannins in tea, coffee
• Phosphates & Phosphoproteins: egg yolk
• Oxalate: spinach
• Zn2+ & Ca2+: Zn2+ & Ca2+ supplements

Question 9

What are the four steps of iron metabolism? (hint: last step has 3 options)

Answer 9

1. Dietary iron
2. Absorption
3. Transport
4. Iron loss, for usage or for storage

Question 10

Where does iron absorption happen and how does this occur?

Answer 10

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)

Question 11

How would the surgical removal of the duodenum or upper jejunum affect iron absorption?

Answer 11

Iron absorption would be decreased

Question 12

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?

Answer 12

Iron is associated with proteins (transferrin) during transport
SAFE:
- Fe3+
- Fe3+/protein
- Fe2+/protein

TOXIC:
- Fe2+ (can undergo Fenton reaction)

Question 13

What is the Fenton reaction?

Answer 13

In the Fenton reaction, Fe2+ reacts with H2O2 to catalyze the formation of free radicals which damage cell membrane, cell proteins and nucleic acids

Question 14

What is Transferrin and for what step of the iron metabolism pathway is it utilized?

Answer 14

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

Question 15

What is Apotransferrin?

Answer 15

Apotransferrin is the unbound form of Transferrin (no iron bound to it)

Question 16

What is a Transferrin Receptor (TfR) and how is it utilized?

Answer 16

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

Question 17

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?

Answer 17

• Heme group is most abundant (found in Hb, Mb and cytochromes)
• Iron-sulfur compounds
• Directly bound to proteins

Question 18

What is the protein used to store iron? Where is it found in the body?

Answer 18

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

Question 19

What is Apoferritin?

Answer 19

Apoferritin is the unbound form of Ferritin (no iron bound to it)

Question 20

What is Hemosiderin? Under what conditions is it found in humans?

Answer 20

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

Question 21

What are the only two ways by which iron is lost? Is either voluntary?

Answer 21

• Sloughing of skin and mucosal cells
• Bleeding

Not really - cannot eliminate excess iron from the body voluntarily except via intentional blood loss

Question 22

How much iron is found per 1 mL of blood?

Answer 22

1 mL of blood contains 0.5 mg of iron

Question 23

What are the two laboratory tests used to evaluate iron deficiency? What is the best test to assess iron stores?

Answer 23

• Serum Transferrin

- Serum Ferritin (best test for iron stores)

Question 24

When iron is low, what will lab results show for Serum Transferrin and Serum Ferritin? What about when iron is high?

Answer 24

Low iron:

• Serum Transferrin: high
• Serum Ferritin: low

High iron:

• Serum Transferrin: low
• Serum Ferritin: high

Question 25

What are the three common causes of iron-deficiency anemia in the U.S.?

Answer 25

• Decreased iron intake
• Increased requirements
• Increased loss

Question 26

What are the two reasons (and population type) for decreased iron intake?

Answer 26

• Nutritional insufficiency in infants/children

- Malabsorption

Question 27

What are the two population types that require increased iron intake?

Answer 27

• Children

- Pregnant women

Question 28

What are the three reasons for increased iron loss?

Answer 28

• Parasites in developing countries
• Menstruation
• Chronic blood loss (not due to menstruation