Gen Path Lecture 7: Iron Metabolism

Hemoglobin (Hgb)

1. Present in RBCs and carries oxygen

2. Tetrameric metalloprotein that contains 4 iron atoms (Fe2+ = ferrous iron)

Anemia

Disease in circulating erythrocyte mass

Nutritional deficiency, true deficiency, functional deficiency

Causes of iron deficiency

True deficiency (chronic blood loss)

Most common cause of iron deficiency

Excess supplementation, certain hemolytic diseases

Causes of iron overload

50-70%

What percentage range of body iron is found in erythrocyte hemoglobin molecules?

25-40%

What percentage range of body iron is found in storage (RBCs, liver, spleen, and bone marrow)?

Hemosiderin or ferritin

What is body iron stored as?

C

Where is the majority of iron present in the body?

A) Hemosiderin in the spleen

B) Ferritin in the bone marrow

C) Hemoglobin in RBCs

D) Transferrin in plasma

Proximal duodenum

Dietary iron absorption is regulated and occurs in the ___.

Recycled Hgb iron

Majority of iron used in the body comes from where?

Macrophages

Iron recycling from Hgb in old RBCs is mediated by what?

Intestine

Total body iron stores are regulated through the ___ to avoid iron overload or deficits.

Ferrous, ferric

Dietary iron may be ___ (Fe2+) or ___ (Fe3+) in nature.

Ferric reductase

Reduces dietary Fe3+ to Fe2+ at the intestinal mucosa

Ferroportin

Transport protein that moves Fe2+ out of the enterocyte into the plasma

A

Iron absorption is tightly regulated at the ___.

A) Proximal duodenum

B) Renal pelvis

C) Transverse colon

D) Gastric fundus

Apotransferrin

Transporter protein produced mainly by the liver

Binds Fe3+ in plasma, becoming transferrin (___ + Fe3+ = transferrin)

Transferrin

1. Almost all iron in plasma is in ___

2. Moves iron to and from body tissues

One-third

In healthy animals, approximately ___ of the Fe-binding sites on transferrin are occupied

Erythroid precursors, hepatocytes

Tissues with transferrin receptors

A

Plasma iron is primarily present in:

A) Transferrin

B) Ferritin

C) Hemosiderin

D) Hepcidin

C

By what means do erythroid precursors take in iron?

A) Ferritin

B) Hepcidin

C) Transferrin receptor

D) Hephaestin

Ferritin, hemosiderin

Two main forms of iron storage

Ferritin

1. Water-soluble, mobile, iron-protein complex

2. Mainly found in developing RBCs, macrophages, hepatocytes, enterocytes

3. Synthesis increases in inflammation and when more Fe is present

Hemosiderin

1. Poorly soluble, less mobile, more stable

2. Major storage form of iron

3. Predominantly in macrophages of liver, spleen, and bone marrow

C

___ are important in the recycling of iron from hemoglobin in senescent (old) RBCs.

A) Neutrophils

B) Enterocytes

C) Macrophages

D) Reticulocytes

A

Of the two storage forms of iron, which is the more labile form?

A) Ferritin

B) Hemosiderin

Hepcidin

Important systemic iron regulator

1. Small peptide produced by the liver

2. Negative regulator of iron movement

3. Prevents iron absorption

4. Prevents iron movement out of storage

Ferroportin

Hepcidin binds to ___, causing its internalization within the cell.

C

The net effect of increased hepcidin is ___ iron availability

A) Increased

B) Stable

C) Decreased

Decreased

1. Results of ___ hepcidin production

   1. Increased absorption of intestinal iron

   2. Normal enterocyte iron export into plasma

   3. Normal release of stored iron from tissue macrophages and hepatocytes

Increased

1. Results of ___ hepcidin production

   1. Prevention of iron absorption by enterocytes

   2. Decreased iron export from enterocytes and macrophages

C

Which of the following increase hepcidin production?

A) Increased iron stores

B) Inflammation

C) All of the above

B

Which organ produces several important molecules of iron metabolism?

A) Kidney

B) Liver

C) Lung

D) Pancreas

Hypoxia, iron availability, inflammation

What is hepcidin controlled by?

Serum iron concentration, serum ferritin concentration, total iron binding capacity

Tests to assess body iron

Serum iron concentration

1. Measures the amount of iron bound to transferrin

2. Since using serum, this only assesses circulating iron

Inappropriate iron injections or potentially excess dietary iron, hemolysis

Serum iron concentrations: Increases seen in ___

True or absolute iron deficiency, increased iron locked in storage forms

Serum iron concentrations: Decreases seen in ___

Ferritin

 Secreted into blood by cells (primarily macrophages)

Serum ferritin

1. Correlates with tissue iron stores in domestic animals

   1. Can be useful in separating a true iron deficiency (low ___) from anemia of chronic disease (normal to high ___)

2. Species-specific immunoassay required to measure

Diseases that cause increased storage iron, diseases that cause increased ferritin production (inflammatory disease)

Serum ferritin: Increases seen in ___

True iron deficiency

Serum ferritin: Decreases seen in ___

Elevated

If an animal has a concurrent inflammatory disease, then serum ferritin may be normal or even ___.