<P> In several cell types voltage - gated ion channels in the cell membrane can be temporarily opened under specific circumstances for a few microseconds at a time . This allows a brief inflow of sodium ions into the cell (driven in by the sodium ion concentration gradient that exists between the outside and inside of the cell). This causes the cell membrane to temporarily depolarize (lose its electrical charge) forming the basis of action potentials . </P> <P> The sodium ions in the ECF also play an important role in the movement of water from one body compartment to the other . When tears are secreted, or saliva is formed, sodium ions are pumped from the ECF into the ducts in which these fluids are formed and collected . The water content of these solutions results from the fact water follows the sodium ions (and accompanying anions) osmotically . The same principle applies to the formation of many other body fluids . </P> <P> Calcium ions have a great propensity to bind to proteins . This changes the distribution of electrical charges on the protein, with the consequence that the 3D (or tertiary) structure of the protein is altered . The normal shape, and therefore function of very many of the extracellular proteins, as well as the extracellular portions of the cell membrane proteins is dependent on a very precise ionized calcium concentration in the ECF . The proteins that are particularly sensitive to changes in the ECF ionized calcium concentration are several of the clotting factors in the blood plasma, which are functionless in the absence of calcium ions, but become fully functional on the addition of the correct concentration of calcium salts . The voltage gated sodium ion channels in the cell membranes of nerves and muscle have an even greater sensitivity to changes in the ECF ionized calcium concentration . Relatively small decreases in the plasma ionized calcium levels (hypocalcemia) cause these channels to leak sodium into the nerve cells or axons, making them hyper - excitable, thus causing spontaneous muscle spasms (tetany) and paraesthesia (the sensation of "pins and needles") of the extremities and round the mouth . When the plasma ionized calcium rises above normal (hypercalcemia) more calcium is bound to these sodium channels having the opposite effect, causing lethargy, muscle weakness, anorexia, constipation and labile emotions . </P> <P> The tertiary structure of proteins is also affected by the pH of the bathing solution . In addition, the pH of the ECF affects the proportion of the total amount of calcium in the plasma which occurs in the free, or ionized form, as opposed to the fraction that is bound to protein and phosphate ions . A change in the pH of the ECF therefore alters the ionized calcium concentration of the ECF . Since the pH of the ECF is directly dependent on the partial pressure of carbon dioxide in the ECF, hyperventilation, which lowers the partial pressure of carbon dioxide in the ECF, produces symptoms that are almost indistinguishable from low plasma ionized calcium concentrations . </P>

Where is most of the body fluid found