Stress is a well-known term in our modern society, used to depict an overwhelming feeling of strain or mental pressure that results from adverse or demanding circumstances. However, stress also affects our biology, and even our cells.
- Homeostasis can be defined as an ideal state of equilibrium. Within our body, biological homeostasis refers to the constant process of maintaining optimal levels of every aspect our body needs to survive.
- Stressors are any external or internal factors that represent an imminent or perceived threat to the body’s homeostasis.
- Our body has a stress system devoted to deal with stressors, which involves the Central Nervous System and multiple organs.
- The stress system works through a complex network of hormones and biochemical pathways, including the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS).
- Alterations of the function of the stress system can result in behavioural and biological disorders.
- Stress is responsible for major pathological conditions, both physical and psychological.
What is stress?
In broad terms, two basic types of stress can be defined: physical and psychological. Both forms of stress can be caused by a vast number of factors, known as stressors (Table 1), which can affect your body functions. Stressors can include anything from drastic changes in temperature to social or family problems, or changes in your diet or sleep patterns1-2. Even some chemicals commonly found in everyday products, like BPA, have been shown to function as stressors3.
Whether physical or psychological, all stressors have in common the potential of threatening the state of equilibrium found within every part of the body, known as homeostasis, potentially leading to the development of diseases.
Stressors have a direct biological effect on our body, triggering specific pathways that seek to restore the balance, a process known as the stress response. A key concept tightly linked to stressors and the stress response is homeostasis4.
Is all stress bad?
There is a little known (and not extensively studied) concept known as eustress, which refers to low levels of stress that have a positive effect on your body or mind. For example, a type of eustress is what a person experiences when working towards an achievable deadline. The stress of the commitment and the time limitations serve as encouragement to complete a task.
Homeostasis: the search for equilibrium
An optimally functioning body is found is a dynamic state of equilibrium, known as homeostasis, where cells, organs or any other part of the bodywork to maintain an optimal internal environment, for factors like temperature, pH, or any other aspect needed for their function4-5.
Stress, and more specifically, stressors are factors that threaten homeostasis and include a vast number of factors, both biological and psychological.
Table 1. Common Physical and Psychological stressors.
Stressors trigger responses at various levels within our body. For example, most immune cells have built-in receptors that interact with so-called “stress hormones”. These are hormones associated with the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS). When a stressor comes into play, one or more stress hormones become active and start a chain of reactions that ultimately affects the function of different cells. These hormones can also influence the production of cytokines, important biomolecules that regulate immunity and inflammation, among other roles6.
Some chemicals are also known to function as stressors and affect the HPA axis. BPA, for example, is a very common chemical found in plastics, cans and other common household items7. A study reported that exposure to BPA alters the function of the HPA axis in pregnant women8. Here, levels of salivary cortisol and urinary BPA were measured in 174 women during pregnancy. Researchers found that high concentrations of BPA were associated with irregular patterns of cortisol levels. Women with high BPA levels tended to have low levels of cortisol at waking time and altered levels throughout the day. Other studies, using animal models, have found that exposure to BPA during pregnancy results in a hyperactive HPA axis, which results in altered hormonal functions linked to depression and anxiety-like behaviours9.
The Human Stress system
Orchestrating the body’s response to stressors as well as the role of the HPA and SNS is a complex stress response system.
The human stress system is an interconnected network of neuroendocrine, cellular and molecular structures that regulate the body’s response to stressors. The main components of this stress system are the HPA axis and the sympathetic nervous system, especially through its interaction with the adrenal medulla, sometimes called the sympathoadrenal system1, 10. Activation of the sympathoadrenal system leads to the release of epinephrine and norepinephrine, two special types of hormones also known as catecholamines, which have important roles in the body. These hormones influence blood sugar levels, heart rate, muscle relaxation in the airways, and heart contractility, which determines how hard your heart contracts. Together, these effects are meant to give your body an extra boost of energy, the so-called “adrenaline rush” or “fight or flight” response. This is the feeling you get when you are in a fearful or stressful situation, and you feel your heart beat faster, and experience increased alertness.
Focus on the HPA Axis
A central player of the body’s stress system is the HPA axis. The HPA axis is the name given to the interplay between the hypothalamus, the pituitary and adrenal glands. Both the hypothalamus and pituitary gland can be found just above the brainstem, whereas the adrenal glands are located on top of the kidneys (Figure 1). These three glands play a pivotal role in the stress response through the hormones they produce.
When a stressor, physical or psychological, targets the body, our nervous system releases epinephrine and norepinephrine10. Among other functions, these hormones stimulate the HPA axis, and hence a chain of events is activated. The hypothalamus releases corticotropin-releasing hormone or CRH, into the bloodstream. This hormone plays two key roles: it stimulates the SNS to maintain its response to stressors and it induces the pituitary gland to produce adrenocorticotropic hormone or ACTH. ACTH then binds to cellular receptors located in the adrenal glands, which lead a series of steps that culminated with the release of special biomolecules, like cortisol.
Cortisol: the stress hormone
Cortisol has multiple effects on the body. For example, it increases blood pressure and cardiac function, which results in increased blood supply for muscles. Blood glucose levels are also elevated through the effect of cortisol, providing more energy for cells in the body. These effects may help the body deal with the effects of the stressor.
However, excessive amounts of cortisol can be detrimental to health. For example, people with chronic stress can end up high and sustained levels of cortisol in their body. Studies have shown that excess cortisol can inhibit the function of the immune system6, can increase your chances of developing a metabolic disease like obesity, heart disease or type 2 diabetes11-13. Cortisol has also been shown to affect memory and cognition14 and has been associated with the development of major depressive disorder11, 15-16.
For more information about the role of hormones in stress see Article 2.
- Guilliams TG. The role of stress and the HPA axis in chronic disease management. Stevens Point: Point Institute. 2015.
- Bellavance MA, Rivest S. The HPA–immune axis and the immunomodulatory actions of glucocorticoids in the brain. Frontiers in immunology. 2014 Mar 31;5:136.
Chrousos GP. Stress and disorders of the stress system. Nature reviews endocrinology. 2009 Jul;5(7):374.
- Cowell WJ, Wright RJ. Sex-specific effects of combined exposure to chemical and non-chemical stressors on neuroendocrine development: a review of recent findings and putative mechanisms. Current environmental health reports. 2017 Dec 1;4(4):415-25.
- Modell H, Cliff W, Michael J, McFarland J, Wenderoth MP, Wright A. A physiologist’s view of homeostasis. Advances in physiology education. 2015 Dec;39(4):259-66.
- Palaparthi S. Role of Homeostasis in Human Physiology: A Review. J Med Physiol Ther. 2017;1(101):2.
- Glaser R, Kiecolt-Glaser JK. Stress-induced immune dysfunction: implications for health. Nature Reviews Immunology. 2005 Mar;5(3):243-51.
- Giesbrecht GF, Liu J, Ejaredar M, Dewey D, Letourneau N, Campbell T, Martin JW, APrON Study Team. Urinary bisphenol a is associated with dysregulation of hpa-axis function in pregnant women: findings from the apron cohort study. Environmental research. 2016 Nov 1;151:689-97.
- Panagiotidou E, Zerva S, Mitsiou DJ, Alexis MN, Kitraki E. Perinatal exposure to low-dose bisphenol A affects the neuroendocrine stress response in rats. J Endocrinol. 2014;220(3):207–18.
- Chen F, Zhou L, Bai Y, Zhou R, Chen L. Hypothalamic-pituitary-adrenal axis hyperactivity accounts for anxiety- and depression-like behaviors in rats perinatally exposed to bisphenol A. J Biomed Res. 2015;29(3):250–8.
- Chrousos GP. Stress and disorders of the stress system. Nature reviews endocrinology. 2009 Jul;5(7):374.
- Joseph JJ, Golden SH. Cortisol dysregulation: the bidirectional link between stress, depression, and type 2 diabetes mellitus. Annals of the New York Academy of Sciences. 2017 Mar;1391(1):20.
- Kivimäki M, Steptoe A. Effects of stress on the development and progression of cardiovascular disease. Nature Reviews Cardiology. 2018 Apr;15(4):215.
- van Rossum EF. Obesity and cortisol: new perspectives on an old theme. Obesity. 2017 Mar 1;25(3):500.
- Newcomer JW, Selke G, Melson AK, Hershey T, Craft S, Richards K, Alderson AL. Decreased memory performance in healthy humans induced by stress-level cortisol treatment. Archives of general psychiatry. 1999 Jun 1;56(6):527-33.
- Moylan S, Maes M, Wray NR, Berk M. The neuroprogressive nature of major depressive disorder: pathways to disease evolution and resistance, and therapeutic implications. Molecular psychiatry. 2013 May;18(5):595-606.
- Keller J, Gomez R, Williams G, Lembke A, Lazzeroni L, Murphy GM, Schatzberg AF. HPA axis in major depression: cortisol, clinical symptomatology and genetic variation predict cognition. Molecular psychiatry. 2017 Apr;22(4):527-36