A cellular compartment was added to our previous mathematical model of steady-state acid-base and fluid-electrolyte chemistry to gain further understanding and aid diagnosis of complex disorders involving cellular involvement in critically-ill patients. An important hypothesis to be validated was that the thermodynamic, standard free-energy of cellular H⁺ and Na⁺ pumps remained constant under all conditions. In addition, a hydrostatic-osmotic pressure balance was assumed to describe fluid exchange between plasma and interstitial fluid, including incorporation of compliance curves of vascular and interstitial spaces. The description of the cellular compartment was validated by close comparison of measured and model-predicted cellular pH and electrolyte changes in vitro and in vivo. The new description of plasma-interstitial fluid exchange was validated using measured changes in fluid volumes after isoosmotic and hyperosmotic fluid infusions of NaCl and NaHCO₃. The validated model was used to explain the role of cells in the mechanism of saline or dilutional acidosis and acid-base effects of acidic or basic fluid infusions and the acid-base disorder due to potassium depletion. A module was created that would allow users, who do not possess the software, to determine, for free, the results of fluid infusions and urinary losses of water and solutes to the whole body.