Homeostasis is a widely and somewhat loosely used term for describing all kinds of responses following the principle of negative feedback control. The main concept of homeostasis is founded in the production of stability in dynamic systems by negative feedback. This concept is the basis of cybernetics, whose founding fathers were N. R. Ashby and G. Walter in the 1950s. However, the term homeostasis was coined years before cybernetics by the founders of modern physiology—C. Bernard, W. B. Cannon, and W. R. Hess. In Cannon's germinal book, Wisdom of the Body, the basic idea of feedback as a fundamental physiological principle is stated. In this context, constancy in the internal environment of the body is the result of a system of control mechanisms that limit the variability of body states. The internal milieu takes the form of a certain number of volumes called regulated variables. Without regulation, the changes in the external milieu and the functioning of the cells would make these volumes vary, when the very survival of the organism depends on their stability. Hence, stability is obtained as a result of a regulating system comprising several subsystems, each of which is subjected to control mechanisms and responsible for controlled variables. A regulated variable thus remains fixed within strict limits because of the intervention of controlled variables that have a much wider scope for variation. It is clear that this is an extremely important principle for almost all physiological processes as well as for the guiding of skilled behavior. Indeed, such a concept serves as a theoretical basis for the physiology of regulation. However, homeostasis, in the sense of constancy, does not adequately describe normal physiology, in which blood pressure, heart rate, endocrine output, and neural activity are continually changing—from sleeping to waking—in response to external factors and in anticipation of future events. At all times in the daily cycle, these parameters are maintained within an operating range in response to environmental challenges. The operating range, and the ability ofthe body to increase or decrease vital functions to a new level within that range upon challenge, particularly in anticipation of a challenge, has been defined as allostasis (or "stability through change''). The operating range for most physiological systems is larger in health than in disease, and it is larger in younger compared to older individuals. Exceeding this range can lead to disaster, as is the case when exertion leads to a myocardial infarction.
It is worth mentioning that the cell theory is inseparable from the concept of the internal milieu. The organism is composed of a host of cells that are scattered or grouped together in tissues. Each cell, individualized by its plasmatic membrane, plays out its fate under the genetic control of the nucleus. These cells are bathed with water-like fluid that forms the extracellular space, providing a medium for diffusion and homogenization around the cells. Bernard, comparing the weight of a mummy with that of a living human being of the same size, estimated the water content of the latter to be 90%—to be more precise, two-thirds water for one-third dry matter. This extracellular space, including the blood and lymph, is indeed a unifier of the organism. Unlike the external environment, which is subjected to uncontrollable change, the internal milieu oscillates slightly around normal values. Thus, the autonomy acquired by the organism relative to its external environment gives it an independent and free life since the constancy of the internal milieu does not mean fixity but rather a possibility to evolve.
The regulated variables define the constancy of the internal milieu. The most important are the gas content of the blood, acidity or pH, temperature, sugar content, blood pressure, and osmotic pressure. For example, we know that the more salty a solution, the higher its osmotic pressure. If for any reason an animals loses water, the salt concentration in the internal milieu (i.e., the osmotic pressure) increases. Because it is a regulated variable, osmotic pressure will be kept constant by regulating mechanisms: diminishing the outflow of water and/or increasing the intake. The outflow is reduced by slowing down the elimination process through the kidneys. Vasopressin, an antidiuretic hormone secreted by the brain, performs this function. The amount of this antidiuretic hormone circulating in the blood is a controlled variable that increases in responses to any increase in osmotic pressure. This is an example of hormonal regulation. The best way to increase intake is to drink. Beyond a certain level, the increase in osmotic pressure causes thirst and an urgent need to drink. Therefore, the regulating mechanisms can be of two kind: hormonal or behavioral. Despite the dry heat of the desert, a camel does not suffer from a much higher osmotic pressure than that of a bartender; it merely possesses more powerful regulating mechanisms that are adapted to the external milieu and that give the controlled variables, diuresis and water intake, a wider scope for action.
Nevertheless, there is a hierarchy to be respected. The most important constants must be maintained at all costs, even if this means sacrificing one of the lower orders. In case of need, a regulated variable can become a controlled variable. For example, blood pressure is constant, but if the oxygen content of the blood is endangered, because it is a hierarchical superior it will rise in order to provide a higher flow of gas and will thus temporarily become a controlled variable instead of remaining a regulated variable.
The internal milieu defined by Bernard—the blood and the fluids in which the cells are bathed—is thus the unifier of the organism. The cell draws from the extracellular fluid the nutrients its need, the fuel and oxygen that provide its energy, and the chemical factors that keep it in working order. It discharges into this milieu its waste and the produce of its activity. Here, we have Bernard's second idea, internal secretion, which is inseparable from the concept of the internal milieu. He discovered internal secretion while describing the glycogenic function of the liver. The hepatic cell draws from its reserves of glycogen the sugar that the organism needs and reintroduces it into the bloodstream. Internal secretion, which differs from excretion, demands a fluid medium that can receive the cell's outpourings. The term endocrinology, introduced by N. Pende (1909) to refer to the study of internal secretions, is now used only for the secretions of the so-called vascular glands, which are now called the endocrine glands. The function of these glands, which is much narrower than that of internal secretion, refers to a cellular secretion with no strictly metabolic function but that has a communicative role.
Although virtually all of the brain is involved in homeostasis, neurons controlling the internal environment are mainly concentrated in the hypothalamus, a neuronal structure located at the interface of the brain and peripheral functions. Here, I first focus on the anatomy of the limbic system and then on the anatomy of the hypothalamus, a small area that belongs to the diencephalon and that comprises less than 1% of the total brain volume. I then consider how the hypothalamus and other closely linked structures in the limbic system receive information from the internal environment and how they act directly to keep it constant by regulating endocrine secretion and the autonomic nervous system. Finally, other parts of the brain that may indirectly affect the internal environment by acting on the external environment through emotions and drives are described.
Was this article helpful?