The Control of Iron Balance by the Intestinal Mucosa.

IN THE LATTER YEARS of the 19th Century when concepts of metabolic balance were beginning to crystalhize, it was discerned that the fate of iron was different from that of most elements. Little iron was lost in the urine, but following the experimental ingestion or injection of large doses of iron, granular deposits giving a Prussian blue reaction appeared in macrophages in the intestinal vilhi and in epithehial cehhs of the small intestine.13 Therefore the intestine was thought to he an excretory as well as absorptive organ for iron. In 1937 McCance and Widdowson challenged this concept.4 After an analytical survey of the literature of iron metabolism they concluded: " There are indeed indications that in man and certain animals the bowel excretes prac-ticahhy no iron. If this is the case, the amount of iron in the body must be regulated by controlled absorption. " It is diffcult to overstate the importance of this idea, for it placed the metabolic balance of iron in a unique category. If the amount of absorption is indeed a reflection of requirement, then it must follow: the intestine receives information concerning deficiency or surfeit of iron, and by means of sensory and effector mechanisms it acts in response to this information. Experimental evidence in support of the concept began to accumulate. McCance and Widdowson injected large amounts of iron and found that loss of iron in excreta was not appreciably increased.5 Patients who received large numbers of blood transfusions were found to have heavy deposits of iron in their bodies;6 it seemed the transfused iron was in excess of requirement and, lacking an excretory mechanism, it was not unloaded. By extension of the concept, hemochromatosis was a disorder of iron absorption; the intestine absorbed unneeded iron and the body could not excrete it. In 1943 Hahn published evidence of increased absorption of radioactive iron in humans with iron deficiency.7 By comparison, normal humans absorbed very little iron. This ability to prevent absorption of unneeded iron resided in a " mucosa block "-according to Hahn's hypothesis-and in iron deficiency the block disappeared permitting increased absorption. To explain the mechanism of the block, hahn postulated the existence of a " mucosal acceptor " for iron. " Physiological saturation of the acceptor prevented further entry of iron through the mucosa into the body. lie suggested that the mucosal acceptor might be apoferritin, a protein which does accept …