Facilitating an understanding of integrative physiology: emphasis on the composition of body fluid compartments

As a teaching exercise, we used deductive reasoning and a quantitative analysis to convert a number of facts into a series of concepts to facilitate an understanding of integrative physiology and shed light on the composition of the different body fluid compartments. The starting point was the central need to regenerate ATP to perform biologic work. Because a large quantity of O2 must be delivered to cells at a sufficiently high concentration to aid its diffusion into mitochondria, approximately one third of the O2 in inspired air was extracted; this led to a P(CO2) in arterial blood of 40 mmHg (1 mmHg = 133.322 Pa). Blood flow to individual organs must be adjusted precisely to avoid having too low or too high a P(O2) in mitochondria--the latter augments the formation of reactive O2 species. The extracellular fluid (ECF) bicarbonate concentration (E(HCO3)) must be high to minimize H+ buffering by proteins. This high E(HCO3) sets the ECF concentrations of ionized calcium (Ca2+) and inorganic phosphate (HPO4(2-)) because of solubility issues. Three features defined the intracellular fluid (ICF) volume and composition. First, expelling monovalent anions minimized its mass (volume). Second, controlling the tissue P(CO2) ensured a relatively constant net valence on intracellular proteins. Third, the range of ICF Ca2+ concentrations must both induce regulatory signals and avoid Ca3(PO4)2 formation. All the above were incorporated into the integrated response that optimized the capacity for vigorous exercise.