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Computer Simulation of Iron Absorption: Regulation of Mucosal and Systemic Iron Kinetics in Dogs^1,2,

Departments of Medicine and Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106

The quantity and distribution of body iron normally vary little over time. This homeostasis is maintained primarily through control of intestinal iron absorption, but the mechanism of this regulation is unclear. Modern techniques for computer simulation and numerical analysis now make it possible to study the kinetics of iron absorption in vivo. We used a physiologically based mathematical model of iron metabolism to analyze tracer iron kinetics in normal and iron-deficient beagles. The model provides characteristic information about both intestinal and systemic iron exchange, thus permitting formulation of an hypothesis that may explain the regulation of iron absorption under these conditions. The results indicate that control of iron absorption is a function of independent expression of iron requirements by each tissue, including the intestinal mucosa. This hypothesis is consistent with other in vivo and in vitro observations in iron deficiency and may have implications for understanding the mechanism of the altered iron absorption in other disorders of iron metabolism.

KEY WORDS: • iron absorption • ferrokinetics • iron deficiency • compartment modeling

¹ Supported in part by Award No. 4347 from the NE Ohio Affiliate of the American Heart Association and an award from the Gustavus and Louise Pfeiffer Research Foundation. M. H. Nathanson was recipient of an NIH Medical Scientist Traineeship (GM-07250), and G. D. McLaren was recipient of a Clinical Investigator Award (AM-00665) from the National Institute of Arthritis, Diabetes, and Digestive and Kidney Diseases.

² This work was published, in part, in abstract form. Nathanson, M. H. & McLaren, G. D. (1984) Internal iron exchange in normal and iron-deficient beagle dogs: relationship to iron absorption. Clin. Res. 32: 317 (abs.).

³ Present address: Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032.

⁴ Present address: Department of Medicine, University of North Dakota, School of Medicine, % Veterans Administration Hospital, North Elm & 21st Avenue, Fargo, ND 58102 (to whom correspondence and requests for reprints should be addressed).

Manuscript received 6 June 1986. Revision accepted 29 January 1987.