Implementation of a Model of Bodily Fluids Regulation
Julie Fontecave-Jallon 0 1
S. Randall Thomas 0 1
0 IR4M UMR8081 CNRS, University Paris-Sud , Orsay , France
1 CNRS, TIMC-IMAG Laboratory CNRS UMR 5525, PRETA Team, University Joseph Fourier- Grenoble 1 , 38041 Grenoble , France
The classic model of blood pressure regulation by Guyton et al. (Annu Rev Physiol 34:13-46, 1972a; Ann Biomed Eng 1:254-281, 1972b) set a new standard for quantitative exploration of physiological function and led to important new insights, some of which still remain the focus of debate, such as whether the kidney plays the primary role in the genesis of hypertension (Montani et al. in Exp Physiol 24:41-54, 2009a; Exp Physiol 94:382-388, 2009b; Osborn et al. in Exp Physiol 94:389-396, 2009a; Exp Physiol 94:388-389, 2009b). Key to the success of this model was the fact that the authors made the computer code (in FORTRAN) freely available and eventually provided a convivial user interface for exploration of model behavior on early microcomputers (Montani et al. in Int J Bio-med Comput 24:41-54, 1989). Ikeda et al. (Ann Biomed Eng 7:135-166, 1979) developed an offshoot of the Guyton model targeting especially the regulation of body fluids and acid-base balance; their model provides extended renal and respiratory functions and would be a good basis for further extensions. In the interest of providing a simple, useable version of Ikeda et al.'s model and to facilitate further such extensions, we present a practical implementation of the model of Ikeda et al. (Ann Biomed Eng 7:135-166, 1979), using the ODE solver Berkeley Madonna.
-
Computational physiology Acidbase balance
Virtual physiological human (VPH)
1 Introduction
Computational modelling in physiology has contributed to many significant
breakthroughs, but the models themselves have usually not become working tools
for experimentalists nor even for other modellers outside the developers own
group. We provide here a practical implementation of one of the classic and most
complete models of body fluid and acidbase regulation, and we give several
examples of the use of the model. We give the complete model description in the
language of Berkeley Madonna, which is very easy to read and can readily be
converted for other numerical solvers. Physiologists and clinicians will find this
model easy to use, and this complete example will facilitate extensions in order to
simulate related clinical situations or new experimental findings.
Inspired by the classic model of blood pressure regulation by Guyton et al. (1972a),
Ikeda et al. (1979) adopted the same symbolic representation to illustrate model
structure, but since their focus was on body fluids and acidbase balance, which have a
slower time course than, say, autonomic regulation of cardiovascular variables, they
simplified the representation of the cardiovascular system but greatly extended the
renal and respiratory systems. Their model consists of a set of nonlinear differential
and algebraic equations with more than 200 variables and has subsystems for
circulation, respiration, renal function, and intra- and extra-cellular fluid spaces.
2 Materials and Methods
2.1 Model Description
The original article of Ikeda et al. (1979) describes the details of the model, so we
will not give a complete description here (the program code, Online Resource 01,
given in the Electronic Supplementary Material and described in the Appendix, has
all the explicit equations); our implementation closely follows the description in
their article, especially in their diagrams of the seven blocks that constitute the
model, namely, the circulation and body fluids (blocks 1, 3, and 4), respiration
(block 2), and renal function (blocks 5, 6, and 7). Initial values and many other
details are given not only in the text but also on the diagrams and in the tables of the
original article. Here, we give just a brief explanation of the basic content of the
model and Ikeda et al.s general strategy.
As in Ikeda et al. (1979), the model assumes a healthy male of approximately
55 kg body weight, and parameter values used here are those given in the original
article. Calibration of the model for other body weights or for females would be a
valuable extension of the model but is beyond the goals of the present work. Such
extension would involve re-calibration not only of extracellular and intracellular
fluid volumes (and thus with impact on solute contents of those compartments), but
also of less straightforward parameters such as metabolic rate, respiratory volume,
cardiac output, and the like.
The cardiovascular/circulatory (CV) system, quite complex in Guytons model,
was considerably simplified by Ikeda et al. (1979) to a simple steady state that
represents the systems state after settling from transient local autoregulation or
stress relaxation.
By contrast with the simplified CV system, and in keeping with their focus on
acidbase and fluid physiology, Ikeda et al. (1979) included much more elaborate
represe (...truncated)