Simulation of calcium homeostasis: modeling and parameter estimation

Abstract

The system that regulates plasma calcium in the bird has been formalized into a model based on a series of differential equations and solved by computer simulation. Bone, kidney, and intestine have been considered as the control subsystems, with parathyroid hormone and 1,25-dihydroxycholecalciferol as the regulating hormones. The parameters used in the simulation model have been computed either from published results or by specifically designed experiments described here. For the estimation of parameters, an iterative procedure has been developed that was designed to minimize the sum of square errors between observed and system-simulated values. Parameters of 1,25-dihydroxycholecalciferol metabolism were experimentally obtained from the kinetic behavior of the 3H-labeled hormone in rachitic birds after a single dose. Model parameters have been adjusted using the results of in vivo calcium loading and validated by an EDTA infusion experiment. The simulation model has been used to study the hierarchy of the activities of the three control subsystems and of the regulating hormones, at different calcium intakes. Positive or negative errors in plasma calcium resulted in an asymmetry in the activities of the controlling systems, bone and kidney, whereas the intestine is characterized by its relatively long response time.