Internal Environment and the Formation of Intercellular Fluid

One of the generalizations to emerge from physiological studies in the present century is that the conditions in which cells can function properly are narrow. Even quite small fluctuations in osmotic pressure, temperature or the amounts of certain chemical substances, can disrupt biochemical activities and in extreme cases may kill the cells altogether. This basic tenet of biology was first recognized by the French physiologist Claude Bernard. In 1857 he wrote La fixite du milieu interior est la condition de la vie libre (‘the constancy of the internal environment is the condition for free life’). Later we will examine the meaning of ‘free life’. For the moment let us concentrate on the internal environment and the formation of Intercellular fluid.


Claude Bernard, 1813-1878, has been aptly described as the father of modern experimental physiology. He was the first person to appreciate the importance of the “internal environment’ in the functioning of organisms. Born in Villefranche, France, Bernard studied medicine. However, he abandoned the idea of medical practice in favor of scientific research and eventually became professor of General Physiology at the Sorbonne. From all accounts he was harsh man who worked relentlessly in his laboratory and expected the same to others. At one stage in his career he supplemented his income by teaching science in a girl’s school. 


By internal environment is meant the immediate surroundings of the cells. In mammalian tissues the cells are generally surrounded by tiny channels and spaces filled with fluid. The later called intercellular fluid, interstitial fluid or tissue fluid. It provided the cells with the medium in which they have to live, and represents the organism’s internal environment. It is this that must be kept constant if the cells are to continue their vital functions. To see how this is achieved we must first understand how intercellular fluid is formed.


How is Intercellular Fluid formed? Intercellular fluid is formed from blood by a process of ultra-filtration in which small molecules and ions are separated from the larger molecules and cells. When blood reaches the arterial end of a capillary it is under high pressure because of the pumping action of the heart and the fine bore of the capillaries. This pressure forces the fluid part of the blood through the walls of the capillaries into the intercellular spaces. Analysis of intercellular fluid shows that it consists of all the constituents of blood plasma, less the proteins. The walls of the capillaries act as a filter holding back the plasma protein molecules together with the cellular components of the blood, but allowing everything else to go through.

Once formed, the intercellular fluid circulates amongst the cells and eventually returns to the blood vascular system by one of two routes. At the venous end of the capillary system the hydrostatic pressure of the blood is comparatively low, and is exceeded by the osmotic pressure of the plasma proteins which, owing to the removal of the other constituents of the plasma, are now much more concentrated than that were at the arterial end of the system. This cause intercellular fluid to be drawn back into the capillaries, and so returned to the circulation. Excess intercellular fluid, however, is drained into the lymph vessels, whence it eventually passes back into the veins.

Intercellular fluid is the medium in which the cells are bathed. Through it respiratory gases diffuse, from it the cells extract all their metabolities, and into it they shed unwanted substance. This is Claude Bernanrd’s milieu interieur, and since it is formed from the blood, it is the blood which must be kept constant. Much of an animal’s physiology is concerned with doing just this.


 The most important features of the internal environment that must be kept constant are:

  1. Its chemical constituents, for example, glucose, ions etc;
  2. Its osmotic pressure, determined by the relative amounts of water and solutes;
  3. The level of carbon(iv) oxide;
  4. Its temperature.

In addition certain chemical ingredients must be virtually eliminated from it altogether. The most important of these are nitrogenous waste products arising from protein metabolism, and toxic substance liberated by pathogenic micro-organisms.

The importance of a constant internal environment to the well-being of cells can be shown by removing tissues from the body. If they are subjected to conditions markedly different from those prevailing in the body they will die; but if maintained under the correct conditions they will survive. This was appreciated by the nineteenth century physiologist Sidney Ringer who perfected the art of keeping tissues and organs alive outside the body. He found, for example, that an excised heart of a frog or mammal would continue beating for a long time in a mixture of sodium, potassium and calcium ions. It is now known that virtually all tissues can be kept alive in a suitable ‘cocktail’ of ions similar to the tissue fluids. Such solutions, which vary according to the species, are known as physiological salines or ringer’s solutions.

Maintenance of a constant internal environment is known as homeostasis’, a Greek word meaning ‘staying the same’. Many physiological processes are homeostatic in that they are responsible, directly or indirectly, for regulating the internal environment. It is possible to exaggerate their importance. Without them life would be impossible. As an example let us take the control of sugar.