Description of guyton thirst, drinking and salt appetite module

Model Status

This CellML model has been validated. Due to the differences between procedural code (in this case C-code) and declarative languages (CellML), some aspects of the original model were not able to be encapsulated by the CellML model (such as the damping of variables). This may affect the transient behaviour of the model, however the steady-state behaviour would remain the same. The equations in this file and the steady-state output from the model conform to the results from the MODSIM program.

Model Structure

Arthur Guyton (1919-2003) was an American physiologist who became famous for his 1950s experiments in which he studied the physiology of cardiac output and its relationship with the peripheral circulation. The results of these experiments challenged the conventional wisdom that it was the heart itself that controlled cardiac output. Instead Guyton demonstrated that it was the need of the body tissues for oxygen which was the real regulator of cardiac output. The "Guyton Curves" describe the relationship between right atrial pressures and cardiac output, and they form a foundation for understanding the physiology of circulation.

The Guyton model of fluid, electrolyte, and circulatory regulation is an extensive mathematical model of human circulatory physiology, capable of simulating a variety of experimental conditions, and contains a number of linked subsystems relating to circulation and its neuroendocrine control.

This is a CellML translation of the Guyton model of the regulation of the circulatory system. The complete model consists of separate modules each of which characterise a separate physiological subsystems. The Circulation Dynamics is the primary system, to which other modules/blocks are connected. The other modules characterise the dynamics of the kidney, electrolytes and cell water, thirst and drinking, hormone regulation, autonomic regulation, cardiovascular system etc, and these feedback on the central circulation model. The CellML code in these modules is based on the C code from the programme C-MODSIM created by Dr Jean-Pierre Montani.

This particular CellML model describes the mechanisms underlying salt appetite and thirst. The salt appetite is considered in this model to be related to the adequacy of body metabolism, as measured by the PO2 level in the non-muscle tissue cells (POT). Also when the concentration of angiotensin increases (ANM), this too increases salt intake. For instance in circulatory shock, when the adequacy of metabolism falls, the person develops a salt appetite. Due to a lack of information, no control function of salt concentration per se has been assumed, merely that when the body salt falls, circulatory effectiveness falls, angiotensin increases, and a salt appetite develops. Regarding thirst, three separate factors are assumed to drive the thirst mechanism: first, the concentration of antidiuretic hormone, which in turn is driven by changes in electrolyte composition (as detailed in another model); second, the effect of angiotensin on thirst, and; thirdly, the effect of the salt appetite stimulation on thirst.

A systems analysis diagram for the full Guyton model describing circulation regulation.

A schematic diagram of the components and processes described in the current CellML model.

There are several publications referring to the Guyton model. One of these papers is cited below:

Circulation: Overall Regulation, A.C. Guyton, T.G. Coleman, and H.J. Granger, 1972, Annual Review of Physiology , 34, 13-44. PubMed ID: 4334846