![]() In particular, in this review, the brain/kidney synergistic roles in H 2O/Na balance and brain temperature control is discussed. The clinical evidence supports such a view as discussed below and reported in recent studies ( 5, 6). Hence, it can be surmised that CNS operates as the uppermost controller of the internal medium homeostasis not exclusively but especially thanks to its synergistic interactions with the kidney. ![]() As a matter of fact, Homer Smith pointed out, on the basis of evolutionary observations, that the functional interconnections between the brain and kidneys in the internal medium homeostasis are a basic requisite for a free and independent life of higher vertebrates. Against this background, the crucial role of the kidneys for internal medium homeostasis will be revised according to the proposal that Homer Smith put forward more than fifty years ago in an extraordinary book ( 4). In particular, we propose that the brain ISF has the highest hierarchic role in human beings, providing the optimal environment for brain cell survival and complex functions, hence allowing the Central Nervous System (CNS) to carry out its complex whole-body integrative actions, i.e., to operate as the uppermost controller that allows a free and independent life of higher vertebrates. Against this background, a central aspect is discussed namely the concept of the hierarchic role of the ISF of the various organs in triggering homeostatic responses, especially of those involving overriding controls. Our proposal is based on the classical assumption of the interstitial fluid (ISF) as the internal medium for multicellular organisms. In the present review, some aspects of the concept and possible further developments that could have an impact also in the clinical practice are analysed. Homeostasis is a fundamental concept in physiology hence, it is a subject of the greatest interest for medicine ( 1– 3). A general premise and the aims of the present article Finally, it is surmised that these two interrelated parameters have deep effects on the Central Nervous System (CNS) higher integrative actions such those linked to psychic homeostasis.ġ. ![]() Furthermore, the evolutionary links between brain and kidney and their synergistic role in H 2O/Na balance and brain temperature control are discussed. Thus, according to this proposal, the brain ISF represents the real internal medium since the maintenance of its dynamic intra-set-range homeostasis is the main factor for a free and independent life of higher vertebrates. Against this background, we propose that the brain ISF has the highest hierarchic role in human beings, providing the optimal environment, not simply for brain cell survival, but also for brain complex functions and the oscillatory rhythms of some parameters, such as cerebrospinal fluid sodium and brain ISF pressure waves, which may play a crucial role in brain physio-pathological states. Additionally, it is suggested that particularly for some chemico-physical parameters, oscillatory rhythms within their proper set-ranges should be considered a fundamental component of homeostasis. However, the new concept of a hierarchic role of ISF of the various organs is introduced. A brief historical survey and comments on the concept of homeostasis and allostasis are presented to introduce our proposal that is based on the classical assumption of the interstitial fluid (ISF) as the internal medium for multicellular organisms. In this review, the aspects and further developments of the concept of homeostasis are discussed also in the perspective of their possible impact in the clinical practice, particularly as far as psychic homeostasis is concerned.
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