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Homeostasis is a core concept necessary for understanding the many regulatory mechanisms in physiology. Claude Bernard asserted that complex organisms can maintain their internal environment (extracellular fluid) constant in the face of challenges from the external world. He went on to say that “a free and independent existence is possible only because of the stability of the internal milieu”. 

Many later physiologists contributed to the idea of homeostasis, but one of the most important was Walter Cannon, whose works appeared during the late 1920s and early 1930s. Cannon coined the term “homeostasis”, and he integrated different types into a coherent framework. Among other factors, Cannon focused on five (pH, temperature, plasma osmolality, glucose, and calcium) that are critical to the normal functioning of most organisms.


There are obviously numerous other factors under homeostatic control, but Cannon’s insight is no less true today. Those five factors are controlled within narrow bounds and lead to significant dysfunction when those bounds are breached. Their importance follows from their universal biochemical effects. Temperature and pH have unavoidable effects on the structure and function of enzymes and functional RNAs; temperature and plasma osmolality have fundamental effects on the integrity and function of membranes; glucose is a key currency for moving and storing energy; and calcium plays leading roles in muscle physiology and multiple signaling pathways. 

Adaptation in the face of potentially stressful challenges involves activation of neural, neuroendocrine and neuroendocrine‐immune mechanisms. This has been called “allostasis”.


Allostasis is an essential component of maintaining homeostasis. When these adaptive systems are turned on and off efficiently and not too frequently, the body is able to cope effectively with challenges that it might not otherwise survive. There are several circumstances, however, in which allostatic systems may either be overstimulated or not perform normally. This condition has been termed “allostatic load” or the price of adaptation. 

In other words, “allostatic load” refers to the price the body pays for being forced to adapt to adverse psychosocial or physical situations, and it represents either the presence of too much stress or the inefficient operation of the stress hormone response system, which must be turned on and then off again after the stressful situation is over. 

Using the balance between energy input and expenditure as the basis for applying the concept of allostasis, it has been proposed that there are two types of allostatic overload:

Type 1 allostatic overload occurs when energy demand exceeds supply, resulting in activation of the “emergency life stage,” also called the "fight-or-flight stage”. This serves to direct the animal (human) away from normal life activities into a survival mode that is intended to decrease allostatic load and regain positive energy balance. This stage has several sub-stages that promote survival and avoid the deleterious effects of stress that may result from chronically elevated levels of circulating glucocorticosteroids over days and weeks. The normal life cycle can be resumed when the perturbation passes. 

Type 2 allostatic overload begins when there is enough or even excess energy consumption, but it is accompanied by social conflict and other types of social dysfunction. In all cases, secretion of glucocorticosteroids and activity of other mediators of allostasis such as the autonomic nervous system (sympathetic dominance), CNS neurotransmitters, and inflammatory cytokines wax and wane with allostatic load. If allostatic load is chronically high and unresolved, then pathologies develop. The term “stress” can now be circumscribed to the environmental perturbations - social conflicts and social dysfunctions - that lead to allostatic load. These are perturbations that go beyond the norm.

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