Stress, health, and disease: the physiology and pathophysiology of stress and the stress response

The groundwork for the scientific understanding of the physiology of mind-body interactions was first established in the 1930s by the work of Walter Cannon, and followed in the 1940s by the extensive work of Hans Selye, who first formally elaborated the concept of stress and its effects on physiology. Selye is also credited with introducing the terms corticoids, glucocorticoids, and mineralocorticoids, and through his work demonstrated the triad of stress: adrenal enlargement, GI ulcers, and thymus gland atrophy, in response to exposure to chronic stressors.51 George Chrousos summarizes stress and the stress response as follows:

Life exists by maintaining a complex dynamic equilibrium, or homeostasis, that is constantly challenged by intrinsic or extrinsic adverse forces or stressors. Stress is, thus, defined as a state of threatened homeostasis, which is reestablished by a complex repertoire of physiologic and behavioral adaptive responses of the organism. The adaptive responses may be inadequate for the reestablishment of homeostasis or excessive and prolonged; in either case a healthy steady state is not attained, and pathology may ensue.

Stressors are threats to homeostasis and the adaptive responses are the counteracting forces intended to reestablish it.43,48,52 Selye termed the adaptive stress response general adaptation syndrome, and demonstrated that it consisted of a consistent set of physiologic responses that included initial response to the stressor followed by an exhaustion phase, and eventually a recovery phase.

More recently the stress response has been renamed allostasis, the ability of the organism to maintain stability, or homeostasis, through change. McEwen elaborates:

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The terms, allostasis and allostatic overload, allow for a more accurate definition of the overused word stress and provide a view of how the essential protective and adaptive effects of physiological mediators that maintain homeostasis—the bodys optimal set points for important factors such as blood pressure, fluid balance, pH, glucose levels, oxygen levels, temperature, etc.—are also involved in the cumulative effects of daily life when they are mismanaged or overused. When mediators of allostasis, like cortisol and adrenaline, are released in response to stressors or to lifestyle factors such as diet, sleep, and exercise, they promote adaptation and are generally beneficial. However, when these mediators are not turned off when the stress is over, or when they are not turned on adequately during stress, or when they are overused by many stressors, there are cumulative changes that lead to a wear-and-tear, called allostatic load or overload, on the body and brain. The concept of allostasis refers to the network of interacting mediators by which stability, that is, homeostasis, is achieved through change. There are primary mediators of allostasis, such as, but not confined to, hormones of the hypothalamic-pituitary-adrenal (HPA) axis, catecholamines, and cytokines. These mediators interact with each other to create a network of reciprocal effects.

Our bodies possess complex and elegant mechanisms for responding to and recovering from acute exposure to stressors. The neuroendocrine system has evolved two primary pathways responsible for responding and adapting to potentially harmful or life-threatening encounters: the sympathoadrenal system (SAS) and hypothalamic – pituitary-adrenal axis (HPA). Both mediate a two-way brain-body communication that sets in motion a series of hormonal and neuroendocrine responses that switch on and switch off what has been commonly referred to as the fight or flight response.43,52 In response to the alert system being switched on, the bodys resources are mobilized for protective action: The heart rate increases and blood is diverted from digestion (who needs to digest when being chased by the proverbial saber tooth tiger?) into the periphery, especially the legs (yup, you want to be able to run away from the tiger!), the respiratory rate increases, blood pressure increases and urinary output decreases, the pupils dilate to increase sight, and other senses such as hearing and smell become keener, the mind becomes sharp and alert and vigilance is enhanced, appetite decreases, immunity is suppressed, and large amounts of sugar are delivered to the bloodstream via lypolysis and gluconeogenesis to fuel the energy needed for a massive response. Growth, reproduction, and sexual response are inhibited—resources are instead diverted to immediate life-saving needs, rather than toward what Sapolsky refers to as optimistic activities. In the recovery phase, interestingly, the body responds to the need for repair by increasing appetite and storing fat (primarily in the abdomen).

Hormonal and neuroendocrine mediators and messengers from the sympathetic nervous system and HPA axis orchestrate all of these responses. Read more »

Get Ulcers

Stress is a fact of life. However, for most of our biological history, stress was a short-term crisis, after which, according to Robert Sapolsky, author of Why Zebras Dont Get Ulcers, its either over with or youre over with.43 Modern society, with its 24/7 work requirements and global Internet access, high level of stimulation and demand, and chronic (daily) repeated stresses, has opened us to a whole new realm of chronic, debilitating diseases. Western medicine is beginning to understand what has long been recognized by traditional medicine systems: that stress, or more traditionally viewed, ones relationship with and response to the world, has an impact on health.

What we now know scientifically is that the challenge of a small amount of stress, whether from positive or negative stressors (eustress/distress), can actually increase the overall health and performance of the individual organism, but that prolonged or repeated stress leads to wear and tear on the body—allostatic load—part of a deleterious picture leading to numerous health consequences. These may include reproductive disorders, endocrine dys – regulation, insulin resistance (Syndrome X), obesity, chronic fatigue syndrome (CFS), cardiovascular disease, osteoporosis, impaired immunity and autoimmune disorders, cognitive impairment, thyroid disorders, chronic anxiety, postpartum depression, and major depression, to name a few of the big players.43-48 It might not surprise readers that women are experiencing these conditions in increasing and significant numbers. Although stress is not the sole cause of these illnesses—as most illnesses have multifactorial etiologies—stress appears to be an underlying factor in many conditions. Unlike exposure to environmental toxins and radiation, or traffic patterns, and other factors over which we have little control, it may be one factor whose effects we have the ability to minimize.

Stress, adaptation, the hypothalamic – pituitary-adrenal-axis (hpa) and womens health

Jillian E. Stansbury, Aviva Romm

Viewed from the perspective of the evolution of the animal kingdom, sustained psychological stress is a recent invention, mostly limited to humans and other social primates.

—Robert Sapolsky, author, Why Zebras Dont

Case history: hyperthyroidism

A 32-year-old woman presented with a 3-month history of chronic vaginal and nipple candidal infection. She is 8 months postpartum and breastfeeding her daughter, who has also had recurrent thrush for the past 3 months. She reports nearly constant anxiety, heart palpations several times a day, excessive thirst and hunger, irritability, fatigue, and hot flashes. She reports that it is difficult for her to relax and she is bothered by insomnia. She reports a normal first pregnancy and birth and no menstrual cycle since the pregnancy. She experiences frequent colds and sinus infections and is chronically congested in her nasal passages, with postnasal drip, and fullness in her left ear. She complains of frequent gas and bloating and reports two or three bowel movements daily, often unformed.

She used Nystatin oral suspension several times for the yeast, as prescribed by her primary care physician, and was taking a prenatal vitamin and EPA/DHA 500 mg two times a day. Her blood pressure was 124/78;pulse 92, respirations 20 per minute. Her physician observed that the woman had extreme nervousness about the well-being of the baby, how she is caring for the baby, and breastfeeding issues.

Dietary recommendations were to increase dietary goi – trogens, including broccoli, cauliflower, Brussels sprouts, cabbage, kohlrabi, sweet potatoes, almonds, pine nuts, millet, peaches, soy, and peanuts.

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Treatment Summary

•    Achieve symptomatic relief of heart palpitations and anxiety with herbs.

•    Use herbs and antioxidant supplements to protect the liver against the oxidative stress effects of increased metabolism caused by this condition.

•    Ensure adequate nutritional intake, metabolism is significantly increased in patients with hyperthyroidism.

•    Increase intake of dietary goitrogens to help reduce excessive thyroid function.

Severe hyperthyroidism requires medical management

Additional Therapies

Stress reduction methods include biofeedback, meditation, tai chi, yoga and prayer therapy, and should be

included in a plan for hyperthyroid treatment.