The Physiological Stress Response: What Happens and How It Can Affect Your Health?

The word stress holds generally negative connotations, but the cascade of hormones that triggers this physiological

response in humans and other animals, known to many as the flight-or-fight response, is essential for survival. The term fight or flight was originally coined by Walter B. Cannon, the physiologist who first described changes in adrenal gland secretion in response to threats to homeostasis, including “exposure to cold, traumatic pain,” and “emotionally distressing antagonistic encounters.” Today, the scientific community continues to identify stress as

any perceived threat to homeostasis, which is a relatively stable equilibrium between interdependent elements, especially as maintained by physiological processes. The intensity of the stress response varies based on several factors, including the particular challenge presented (i.e., a house fire versus being late for work), and, importantly, our perceptions of the stressor and our ability to cope with it.1

The stress response in humans has evolved to allow us to react quickly to situations that could cause injury or death. However, when this process isn’t controlled, the human
body can experience this same reaction
to daily life stressors such as deadlines,
traffic, or relationship conflicts that are not life threatening. Unmitigated stress in the context of contemporary life can lead to the degradation of physical and psychological health. The stress response, when activated over and over again in the face of non-life- threatening situations, raises our risk for high blood pressure, clogged arteries, and brain changes that might contribute to anxiety, depression, and addiction. In addition, stress can indirectly contribute to health decline through decreased sleep and exercise and/or unhealthy coping mechanisms like overeating, smoking, and alcohol consumption.2


Upon the initial encounter of a threat, perceived or actual, the hypothalamus, part of the brain’s limbic system and responsible for releasing hormones that maintain bodily homeostasis, activates the autonomic nervous system, which controls automatic bodily functions such as breathing and heart rate. When activated in this context, the autonomic nervous system releases the hormones epinephrine (adrenaline) and norepinephrine (noradrenaline) via the adrenal gland.3

The adrenal gland is the most active component of the endocrine system during the stress response. The adrenal gland consists of two parts: external and inner. The exterior part, called the adrenal cortex is responsible for releasing corticosteroid hormone. Glucocorticoids, such as cortisol
and cortisone, are corticosteroids that break down amino acids in order to generate glucose for use during physical activity. The adrenal cortex also releases mineralocorticoids, which maintain sodium and potassium balance in the blood, thus ensuring proper regulation of blood circulation. The inner part of the adrenal gland is called the adrenal medulla. This part of the adrenal gland secretes epinephrine and norepinephrine in a 5 to 1 ratio. Epinephrine and norepinephrine prepare the body for rapid physical change (e.g., running from a threat) and rapid metabolic change that will allow for the increased energy required for these rapid physical changes. Up to 300 times the normal amount of epinephrine can be present in the blood when an individual is under stress, and the effects of epinephrine and norepinephrine can persist up to two hours.3

After this, the hypothalamus signals the pituitary gland to secrete adrenocorticotropic hormone (ACTH), which is responsible for activating the adrenal cortex, which then releases the hormones cortisol, cortisone, and aldosterone. The hypothalamus then directly produces antidiuretic hormone (ADH), also referred to as vasopressin. ADH regulates fluid loss through water reabsorption and decreased perspiration. Increased levels of ADH and the stress hormones aldosterone, epinephrine, and norepinephrine all work to increase blood pressure during stressful situations to ensure that oxygen-rich blood is being delivered to the muscles in preparation for intense physical activity. This part of the stress response can lead to hypertension in cases of chronic stress. Regulatory mechanisms will degrade under uncontrolled stress, and increased secretions of ADH can raise blood pressure even when blood pressure is already high, at rest. Hypertension due to chronic stress can potentially lead to coronary heart disease over time.3

Lastly, the hypothalamus stimulates the release of thyroxine and triiodothyronine in the thyroid gland. Thyroxine is a potent hormone that is able to double basal metabolic rate and can take two days to 10 weeks to take effect. Effects of thyroxine include increased exertion of the heart, gastritis, anxiety, insomnia, and the onset of a cold or flu.3


Starting in the mid-20th century, the most likely causes of death among Americans began to shift from infectious diseases (i.e., influenza, pneumonia, and tuberculosis) to lifestyle diseases, such as coronary heart disease, which are brought on by a combination of inactivity, poor nutrition, and uncontrolled stress.4 Hans Selye was the first scientist to research the prolonged effects of stress, and now the connection between stress and disease is widely accepted.1

When the stress response, though essential for physical survival, is triggered frequently, this leads to illness and disease. Even though the stress response prepares the body to survive physical threats, the body cannot differentiate between physical, mental, and emotional stress, and can commence this cascade of hormones and bodily processes when presented with nonphysical threats. When the stress response is triggered too frequently, it prevents the body from maintaining homeostasis, encouraging illness and disease. The effects of uncontrolled stress, despite originating in the brain, will spread and degrade several bodily systems, including the cardiovascular system, the digestive system, the musculoskeletal system, and the immune system.3 Even short- lived, sudden bouts of stressful emotions, mainly anger, have been shown to trigger heart attacks, irregular heartbeat (i.e., arrhythmia), and sudden death.5

Chronic stress and cardiovascular health. Excess cortisol from uncontrolled stress can lead to unhealthy amounts of cholesterol circulating in the blood, which can lead to clogged arteries, hypertension, and coronary heart disease.3 Another link between chronic stress and heart health lies in the unhealthy ways people manage stress. Unhealthy coping mechanisms to deal with stress might be utilized, such as smoking, physical inactivity, seeking out artery-clogging comfort foods, and abusing alcohol, all of which negatively affect cardiovascular health.6

Detrimental effects of stress on the brain. Research has shown that chronic stress can weaken brain cells in the hippocampus, an area of the brain critical for learning and memory. When encountering initial stress, this process is useful for etching the stressful encounter into the memory so that the encounter can be avoided in the future. However, when these stressful episodes are repeated, this chronic stress degrades the connections between hippocampal neurons, resulting in “brain shrinkage.”8 In addition to changes in the hippocampus, chronic stress exerts functional and structural changes on the prefrontal cortex, which is responsible for emotional regulation and executive functioning, and the amygdala, which is responsible for fear and pleasure responses.9 However, further research suggests that some of the stress-related adverse neurological effects can be reversed if stress is managed or decreased.10

Endocrine conditions related to stress.

Chronic stress can bring about adrenal fatigue. If the adrenal gland is overexerted repeatedly for too long, it becomes unable to produce and release epinephrine and norepinephrine.3

Stress and immune system dysfunction. Psychological distress and immune function are so closely connected that there exists a specific discipline, known as psychoneuroimmunology, to study it. Excess cortisol as a result of chronic stress has been shown to degrade white blood cells, compromising immune function.11 Lab studies in which participants were exposed to only a few minutes of stress showed markers of impaired immune function, and in a review of nearly 300 studies on stress and immune function, long-term stress was shown to weaken every aspect of the immune system.12

Despite the long list of adverse health effects that can arise from uncontrolled stress, there are many tested methods of stress relief that have been shown to significantly reduce chronic stress and the illness it causes. Head over to page 20 to read more about these tried-and-true stress relievers.

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