Examples of Homeostatic Systems
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KEY POINTS • Contemporary concepts of homeostasis have a long history, reaching back
to the ancient Greeks. • Homeostasis is a state of equilibrium, of balance within the organism. • Homeostatic responses refer to systems whose purpose is specifically to
normalize selected physiologic variables. • Allostasis is the overall process of adaptive change necessary to maintain
survival and well-being. • Allostasis may involve altering multiple physiologic variables to match the
resources of the body to environmental demands. It helps the body achieve homeostasis.
STRESS AS A CONCEPT Referring to stress as an “ambiguous” term is an understatement. Its ubiquitous use in everyday parlance is matched by its frequent presence in the health and psychology literature. Stress often is interpreted as a physical, chemical, or emotional factor that produces tension in the body or the mind (“He’s experiencing a lot of stress”). But it also can mean the actual physical and mental state of tension (“I feel stressed”). Others use the term stress in relation to the response by the body to internal and external demands. Stress can be defined as a real or perceived threat to the balance of homeostasis. The neuroendocrinologist Robert Sapolsky more specifically distinguishes between the stress terminology and defines a stressor as anything that throws the body out of allostatic balance, whereas the stress response is the body’s effort to try to restore the balance. To that end, stress is a natural outgrowth of the concept of homeostasis, but is even more applicable to the dynamic concept of allostasis. Sapolsky’s definition also underscores an important point: The stress response by the body is meant to be helpful, at least in the short term; however, it becomes damaging when repeatedly activated or when it does not cease.
As early as the 1920s, Walter Cannon used the term stress in relation to humans and medicine. Hans Selye, however, often is erroneously credited with being the first person to borrow the term from the fields of engineering and physics and apply it to the human condition. In the
14 UNIT I Pathophysiologic Processes
enable the body to rapidly take action to fight or flee the stressor. This series of events is part of the sympathetic-adrenal-medullary system, originally referred to as the fight-or-flight response by Walter Cannon. Additionally, the hypothalamus secretes CRH to stimulate the anterior pituitary gland to release adrenocorticotropic hormone (ACTH). ACTH then causes the adrenal cortex (the outer portion of the adrenal gland) to release substantial amounts of the glucocorticoids, specifically cortisol, eliciting its diverse responses. This cascade of effects is termed the hypothalamic-pituitary-adrenal (HPA) axis. Once the pituitary gland is activated, the alarm stage progresses to the stage of resistance. This coordinated systemic response to stress is illustrated in Fig. 2.2.
Allostasis is essentially the activation of these stress responses to evoke changes that return the organism to homeostasis. Mediators of allostasis include the aforementioned hormones and neurotransmitters of the HPA axis and the sympathetic-adrenal-medullary system (e.g., cortisol, epinephrine, and norepinephrine), various other hormones presented later in this chapter, and also cytokines from the immune system. The alarm stage of the stress response with the release of its various substances is meant to be helpful to the organism in overcoming the stressor.
Resistance or Adaptation Stage If the alarm stage were to persist, the body would soon suffer undue wear and tear and become subject to permanent damage and even death. To survive, the body must move beyond the alarm stage to a stage of resistance (also called adaptation) supportive of the allostatic return to a state of homeostasis. As the body moves into the stage of resistance, the sympathetic nervous system and adrenal medulla and cortex are functioning at full force to mobilize resources to manage the stressor. The resources include glucose, free fatty acids, and amino acids. Concentrations of these chemicals are elevated through the effects of cortisol and the catecholamines (i.e., epinephrine and norepinephrine). These resources are used for energy and as building blocks, especially the amino acids, for the later growth and repair of the organism after
1930s Selye was experimenting with assorted ovarian and placental hormonal preparations and other tissue extracts and toxic agents. He was injecting these into rats when he serendipitously uncovered a biologi- cal basis for stress. Selye was expecting to find different physiologic responses in the rats, depending on which of the various substances was injected; however, to his surprise and disappointment, the same three changes occurred each time. In every animal tested, the cortex of the adrenal gland enlarged, lymphatic organs (thymus, spleen, and lymph nodes) shrank, and bleeding peptic ulcers developed in the stomach and duodenum. When Selye experimented with other noxious stimuli, such as exposing the rats to temperature extremes, surgery, or forced exercise, the same three changes occurred. Any kind of harmful physical stimuli he used produced the same observed physiologic changes. Selye termed the harmful stimuli or causative agents stressors and concluded that the changes observed represented a nonspecific response by the body to any noxious stimulus or demand, a general “stress” response. Because so many different agents caused the same changes, Selye called this process a general adaptation syndrome (GAS) with three components: an alarm reaction, a stage of resistance, and a stage of exhaustion. According to Selye, when confronted by stressors during daily life, individuals move through the first two stages repeatedly and eventually become adapted and “used to” the stressors.
Selye’s original conceptualization of the stress response and GAS has been criticized as being too simplistic for the complexities of humans. In particular, evidence suggests the body does not produce the same responses to all types of stressors. Depending on the type and severity of stressor, different patterns of hormone release occur, with more of some substances and less of others being produced and at different speeds and for varying lengths of time. Moreover, Selye’s early work in the 1930s concentrated on stimuli of a physical or biological nature. Beginning in the 1970s, researchers began to realize that perception of these stimuli was important to individuals’ responses to stress and that responses could be physiologic, as Selye described, as well as behavioral in nature. When stress is generated by extreme psychological or envi- ronmental demands, balance is disrupted, and allostatic reactions are initiated to restore balance. The discussion that follows presents the GAS as a reflection of the responses to these diverse stimuli and incorporates much of the knowledge acquired since Selye’s early pioneer- ing work.