AJP - Regulatory, Integrative and Comparative Physiology, Vol 245, Issue 5 664-R672, Copyright © 1983 by American Physiological Society
Simulation of calcium homeostasis: modeling and parameter estimation
S. Hurwitz, S. Fishman, A. Bar, M. Pines, G. Riesenfeld and H. Talpaz
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.
