Body Fluid Metabolism in the Rat: A Computer Simulation

Evans, Robert Anthony St.John (1985). Body Fluid Metabolism in the Rat: A Computer Simulation. PhD thesis The Open University.



Toates and Oatley (1970) presented a computer simulation of rat body fluid dynamics. Whilst their two- compartment (intracellular and extracellular) model was a significant contribution, it does not adequately represent cardiovascular, renal or hormonal aspects of water metabolism.

Two models are presented. The simpler model ('small rat') was designed to meet educational criteria, whilst the more complex model ('large rat') is more research-oriented. Both supercede existing models, but the large rat is the more detailed representation. Both are three-compartment models- intracellular, interstitial and vascular. The cardiovascular system is well represented; this has permitted the realistic simulation of many renal, neuronal and endocrine systems important to water homeostasis. Many other related systems are also described, such as the gastro-intestinal tract, energy balance, insensible water loss and electrolyte metabolism in each of the body compartments.

The inclusion of such systems has permitted analyses of the 'volemic' (extracellular) drinking stimuli, and their interactions with other stimuli. The concept of redundancy in drinking stimuli is examined, and a new theory presented that permits its inclusion in current drinking models.

The functional significance of central osmoreceptor siting is discussed, in the light of simulations of fluid absorption dynamics following drinking. Simulations of drinking responses following deprivation are studied. The results indicate an explanation for 'voluntary dehydration',
in which water-deprived rats do not restore fluid balance to pre-deprivation levels when subsequently offered water.

The inclusion of 'peripheral' drinking stimuli in the 'small rat' has enabled an analysis of such phenomena as sham drinking.

The nature of the intracellular stimulus to thirst is examined, and a new energy-based theory is presented, which promises to resolve many apparent paradoxes.

Finally, potential improvements and future developments are discussed.

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