Iron Storage and Toxicity (Chapter 18)

Iron Storage and Toxicity

• Free iron is highly toxic and must be sequestered to prevent its toxic effects.
• Storage iron is bound to either ferritin or hemosiderin to prevent its toxicity.

Ferritin

• Ferritin is a ubiquitous protein-iron complex found at highest levels in the liver, spleen, bone marrow, and skeletal muscles.
• In the liver, most ferritin is stored within parenchymal cells, while in other tissues like the spleen and bone marrow, it is found mainly in macrophages.
• Hepatocyte iron is derived from plasma transferrin, whereas storage iron in macrophages is derived from the breakdown of red cells.
• Intracellular ferritin is located in the cytosol and lysosomes.

Hemosiderin

• Hemosiderin is formed from the partial degradation of ferritin protein shells in lysosomes.
• Iron in hemosiderin is chemically reactive and turns blue-black when exposed to potassium ferrocyanide (Prussian blue stain).
• With normal iron stores, only trace amounts of hemosiderin are found in the body, mainly in macrophages in the bone marrow, spleen, and liver.
• In iron-overloaded cells, most iron is stored in hemosiderin.

Iron Regulation and Balance

• Plasma ferritin levels correlate well with body iron stores, with levels below 12 µg/L in iron deficiency and up to 5000 µg/L in iron overload.
• The storage iron pool can be readily mobilized if iron requirements increase, such as after blood loss.
• Iron is both essential for cellular metabolism and highly toxic in excess, so total body iron stores must be regulated meticulously.
• Iron balance is maintained by regulating the absorption of dietary iron in the proximal duodenum.
• There is no regulated pathway for iron excretion, which is limited to 1 to 2 mg lost each day through the shedding of mucosal and skin epithelial cells.
• As body iron stores increase, absorption falls, and vice versa.