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ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Ruminant Diseases and Immunology Research » Research » Publications at this Location » Publication #142177
Title: CALCIUM HOMEOSTASIS AND PARTURIENT HYPOCALCEMIA: AN INTEGRAL FEEDBACK PERSPECTIVE

Author
item EL-SAMAD, H - IOWA STATE UNIV, AMES
item Goff, Jesse
item KHAMMASH, M - IOWA STATE UNIV, AMES

Submitted to: Journal of Theoretical Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/2/2001
Publication Date: N/A
Citation: N/A

Interpretive Summary: ¿Control theory¿ is an engineering term used to explain how systems react to change. This study applied control theory principles to explain phenomena occurring in a biological system. The biological system examined a metabolic disease of dairy cattle known as milk fever. In this disease, the animal loses its ability to regulate blood calcium concentrations. Normally, two hormones (parathyroid hormone and 1,25-dihydroxyvitamin D) act in concert to maintain blood calcium within normal limits. Several crude attempts had been made in the literature to model how these hormones worked in concert to control blood calcium. These were all static models ¿ unable to predict future reactions of the cow to perturbations of blood calcium concentration. Using data collected over many years on blood calcium and calcium regulating hormone levels, an integrated approach to modeling calcium metabolism was developed. The model is not only of interest to the dairy cow world, but the same model is applicable to human conditions where blood calcium concentration is perturbed. The integrated model clearly predicts that calcium metabolism is controlled by two hormones working in concert with one another ¿ that a defect in one hormone alone can cause the disease. While interesting as applied to calcium homeostasis, the true value of this paper will be to apply this ¿engineer¿s¿ model to other biological systems. Biologists tend to think of static models and do not think in terms of control theory with its integrated models. However, biologists studying a homeostatic mechanism of the body can now apply these techniques to predict that one, two or even three hormones (known or unknown at present) might be necessary to achieve homeostasis of a given physiological process. This is where the power of this model lays ¿ to direct further research efforts by predicting the presence or absence of other control points (hormonal regulators) within biological systems. The information obtained from this study will help direct research to prevent milk fever in dairy cows, which will have significant impact on the dairy industry worldwide.

Technical Abstract: Calcium is tightly regulated in mammals because of the critical role of calcium ion concentrations in many physiological functions. In this work, we develop a model for calcium homeostasis and identify integral feedback control as a functional module that maintains this homeostasis. We argue that maintaining calcium concentrations in a narrow range and perfect adaptation seen when the calcium homeostatic mechanism is subjected to extreme disturbances are the result of a feedback control system implementing integral control through specific interactions of the regulating hormones. Based on the constraints imposed by the suggested integral control, we arrive at a simple dynamical model for calcium homeostasis. We show that the model is biologically plausible and is consistent with known physiology. Furthermore, the utility of the integral-feedback model is revealed by examining an extreme calcium perturbation, parturient paresis in dairy cows.