The internal environment is stabilised in the process of
homeostasis. Complex homeostatic mechanisms operate to regulate and keep the composition of the ECF stable. Individual cells can also regulate their internal composition by various mechanisms. There is a significant difference between the concentrations of
sodium and
potassium ions inside and outside the cell. The concentration of sodium ions is considerably higher in the extracellular fluid than in the intracellular fluid. The converse is true of the potassium ion concentrations inside and outside the cell. These differences cause all
cell membranes to be electrically charged, with the positive charge on the outside of the cells and the negative charge on the inside. In a resting neuron (not conducting an impulse) the
membrane potential is known as the
resting potential, and between the two sides of the membrane is about −70 mV. This potential is created by
sodium–potassium pumps in the cell membrane, which pump sodium ions out of the cell, into the ECF, in return for potassium ions which enter the cell from the ECF. The maintenance of this difference in the concentration of ions between the inside of the cell and the outside, is critical to keep normal cell volumes stable, and also to enable some cells to generate
action potentials. 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. 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 that water follows the sodium ions (and accompanying
anions) osmotically. The same principle applies to the formation of many other
body fluids. 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. 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. 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. The extracellular fluid is constantly "stirred" by the
circulatory system, which ensures that the
watery environment which bathes the body's cells is virtually identical throughout the body. This means that nutrients can be secreted into the ECF in one place (e.g. the gut, liver, or fat cells) and will, within about a minute, be evenly distributed throughout the body. Hormones are similarly rapidly and evenly spread to every cell in the body, regardless of where they are secreted into the blood. Oxygen taken up by the lungs from the alveolar air is also evenly distributed at the
correct partial pressure to all the cells of the body. Waste products are also uniformly spread to the whole of the ECF, and are removed from this general circulation at specific points (or organs), once again ensuring that there is generally no localized accumulation of unwanted compounds or excesses of otherwise essential substances (e.g. sodium ions, or any of the other constituents of the ECF). The only significant exception to this general principle is the plasma in the
veins, where the concentrations of dissolved substances in individual veins differ, to varying degrees, from those in the rest of the ECF. However, this plasma is confined within the waterproof walls of the venous tubes, and therefore does not affect the interstitial fluid in which the body's cells live. When the blood from all the veins in the body mixes in the heart and lungs, the differing compositions cancel out (e.g. acidic blood from active muscles is neutralized by the alkaline blood
homeostatically produced by the kidneys). From the
left atrium onward, to every organ in the body, the normal, homeostatically regulated values of all of the ECF's components are therefore restored. ==Interaction between the blood plasma, interstitial fluid and lymph==