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Milieu intérieur or interior milieu, from the French, milieu intérieur (the environment within), is a phrase coined by Claude Bernard to refer to the extra-cellular fluid environment, more particularly the interstitial fluid, and its physiological capacity to ensure protective stability for the tissues and organs of multicellular organism.
Claude Bernard used the phrase in several works from 1854 until his death in 1878. He most likely adopted it from the histologist Charles Robin, who had employed the phrase “milieu de l’intérieur” as a synonym for the ancient hippocratic idea of humors. Bernard was initially only concerned with the role of the blood but he later included that of the whole body in ensuring this internal stability. He summed up his idea as follows:
The fixity of the milieu supposes a perfection of the organism such that the external variations are at each instant compensated for and equilibrated.... All of the vital mechanisms, however varied they may be, have always one goal, to maintain the uniformity of the conditions of life in the internal environment.... The stability of the internal environment is the condition for the free and independent life.
Bernard's work regarding the internal environment of regulation was supported by work in Germany at the same time. While Rudolf Virchow placed the focus on the cell, others, such as Carl von Rokitansky (1804–1878) continued to study humoral pathology particularly the matter of microcirculation. Von Rokitansky suggested that illness originated in damage to this vital microcirculation or internal system of communication. Hans Eppinger Jr. (1879-1946), a professor of internal medicine in Vienna, further developed von Rokitansky's point of view and showed that every cell requires a suitable environment which he called the ground substance for successful microcirculation. This work of German scientists was continued in the 20th century by Alfred Pischinger (1899-1982) who defined the connections between the ground substance or extracellular matrix and both the hormonal and autonomic nervous systems and saw therein a complex system of regulation for the body as a whole and for cellular functioning, which he termed the ground regulatory system (das System der Grundregulation).
Bernard’s idea was initially ignored in the 19th century. This happened in spite of Bernard being highly honored as the founder of modern physiology (he indeed received the first French state funeral for a scientist). Even the 1911 edition of Encyclopædia Britannica does not mention it. His ideas about milieu intérieur only became central to the understanding of physiology in the early part of the 20th century. It was only with Joseph Barcroft, Lawrence J. Henderson, and particularly Walter Cannon and his idea of homeostasis, that it received its present recognition and status. The current 15th edition notes it as being Bernard's most important idea.