Q. I’ve never been clear on the way iron is handled and was hoping you could clarify. Basically, I don’t understand the difference between serum iron and serum ferritin. And then to confuse me even more is distinguishing the difference between serum ferritin and transferrin.I was hoping you could walk me through the journey that iron takes among these various proteins.

A. Let’s break down our discussion of iron into 5 categories: absorption, circulation, distribution, metabolism, and storage. And then we’ll talk a little bit about how you might actually use this information in the real world of pathology…

Iron is absorbed (in the ferrous state) in the duodenum and proximal jejunum. Generally, we eat about 1-2 mg of iron per day. By the way, we lose about 1-2 mg of iron a day too (through mucosal cell sloughing and menstruation, mostly). How balanced is that!

In the blood, iron moves about bound to a molecule called transferrin. Transferrin carries iron (in the ferric state) to the bone marrow (where red cell precursors await) and to other organs.

Most of the iron in the body is found in hemoglobin (in the adult male that accounts for about 2300 mg; in the female, it’s about 1750 mg). A smaller percentage is present in storage forms (1000 mg in males, 400 mg in females), even less is found in organs, such as the liver (500 mg in males, 350 in females), and a very small amount (3 mg) is present in the transport form (attached to transferrin).

Most of the circulating iron is taken up by red cell precursors and incorporated into heme (which is then combined with globin chains to make hemoglobin).

There are two storage forms of iron: ferritin and hemosiderin. Ferritin is the main storage form of iron. It is a protein released by the reticuloendothelial system, and it is a reflection of the tissue stores of iron (in other words, if you’ve got a ton of iron in your tissues, your ferritin levels will go up). It is a labile form of iron storage, meaning that iron can get in and out of this form quickly. It’s also an acute phase protein, which means that it goes up in certain conditions, like chronic inflammation. Hemosiderin, which consists of ferritin and cell debris, is a stable form of storage, but iron in this form is less readily accessible.

And this is important why?
Well, for one thing, you can measure serum iron, total iron-binding capacity of transferrin (TIBC), and ferritin to help you diagnose different types of anemia. In iron-deficiency anemia, for example, the serum iron is down (well, obviously). The TIBC is increased (because the body makes more transferrin, plus much of the transferrin is sitting around without iron bound to it – hence the iron-binding capacity is increased), and the ferritin is decreased (because there’s less iron around, so there’s less in storage form).

In another form of anemia known as anemia of chronic disease, there is a problem with iron but it is different than the problem in iron-deficiency anemia. It seems to have something to do with the over-production of something called hepcidin, a liver protein that regulates iron metabolism. Anyway – in this type of anemia, the serum iron is decreased, the ferritin is increased and the TIBC is normal to decreased (because the body is producing less transferrin, for reasons that are not well explained).

The image of the cool Iron Maiden keyring was posted on Flickr by Howard Gees (http://www.flickr.com/photos/cyberslayer/523100679/) under cc license.