Allostasis and allostatic load

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In the biology of the human living system, 'allostasis' refers to physiological mechanisms that enable the system to adjust beneficially to diverse stressors through adaptive changes in physiology, in the process mitigating potentially seriously injurious perturbations of system viability from external and internal sources.[1]

Two defining features of allostasis are its emphasis on

(1) adaptive changes and diverse range of physiological and behavioral options that emerged with central nervous system involvement in peripheral physiological regulation, and
(2) the breakdown of regulatory systems when pushed beyond adaptation. ([1]Preface)

In implementing adaptive changes of physiology, allostasis complements homeostasis, which implements processes that tend to maintain stability of physiology in the face of perturbation.

Introduction

'Stressors' refer to "events that are threatening to an individual and that elicit physiological and behavioral responses".[2] They include events that occur routinely during the cyclic course of the day, as well as non-routine physically and/or psychologically health-threatening events. Allostasis achieves adaptative adjustment to stressors by resetting target values for physiological variables, a different way of sustaining system viability than Bernard-Cannon homeostasis, which attempts to re-achieve a steady-state with the pre-stressed values for physiological variables .[3]

The new formulation [of allostasis] moves beyond Cannon’s concept of “homeostasis,” which posits an ideal set of conditions for maintenance of the internal environment. The notion of allostasis recognizes that there is no single ideal set of steady-state conditions in life, and different stressors elicit different patterns of activation of the sympathetic nervous and adrenomedullary hormonal systems. Allostasis reflects active, adaptive processes that maintain apparent steady states, via multiple, interacting effectors regulated by homeostatic comparators—"homeostats." "Allostatic load" refers to the consequences of sustained or repeated activation of mediators of allostasis. From the analogy of a home temperature control system, the temperature can be maintained at any of a variety of levels (allostatic states) by multiple means (effectors), regulated by the thermostat (homeostat). Allostatic load and risks of system breakdown increase when, for example, the front door is left open in the winter. Applying these notions can aid in understanding how acute and chronic stress can exert adverse health consequences via allostatic load.[3]

Allostatic physiological mechanisms help maintain system viability in health-threatening circumstances through changes in the system’s properties — its bodily state, its set-points of physiological variables — viz., 'adapting' the system to the stressor, achieving a kind of stability/viability through change.[1] [3]

What are some examples of allostasis? Sterling and Eyer (1988)[4] used variations in blood pressure as an example: in the morning, blood pressure rises when we get out of bed, and, to maintain consciousness, blood flow is maintained to the brain when we stand up. This type of allostasis helps to maintain oxygen tension in the brain. There are other examples: catecholamine and glucocorticoid elevations during physical activity mobilize and replenish, respectively, energy stores needed for the brain and body to function under challenge.[2]

Those responses to stressors (i.e., to changes in posture, physical activity level) do not exemplify directly Bernard-Cannon homeostasis, as they do not constitute attempts to maintain a steady-state of set-points (blood pressure in the case of postural change, blood hormone level in the case of physical activity change). Rather they constitute attempts to adapt the organism to the stressor's potential injurious effects (loss of consciousness in the case of the postural change, lack of energy in the case of increased physical activity) through a change in the physiological state of the body, a change in blood pressure, in hormone levels.

In their [Sterling and Eyer's] paper, they state, "Allostasis emphasizes that the internal milieu varies to meet perceived and anticipated demand."[2]

On the other hand, those variations in the internal milieu serve to maintain homeostatic set-points (or set-ranges) critical for survival, such as oxygen tension (by raising blood pressure and thus blood flow to the brain when assuming the upright posture after a night of reclining) and blood acidity/basicity limits (by limiting the degree of lactic acidosis when increasing physical activity). Losing consciousness might cause one to fall and seriously injure oneself, prevented by the allostatic blood pressure response, but a drop in oxygen tension in the brain below set-range might cause more serious brain damage. Likewise running out of energy might mean losing the gazelle one is chasing, but lactic acidosis might have more serious physiological consequences.

Allostasis, then, functions more broadly than homeostasis, through adaptive responses to potential injurious stressors, but, at the same time, performs homeostatic functions for critical physiological variables.

Why allostasis?

In living systems, regulation of structure and function by physiological mechanisms, from subcellular to organismal levels, serves the biological imperatives of survival and reproduction. Although many physiologists, including those who write introductory/intermediate textbooks, consider the core and guiding principle of regulation of viability by physiological mechanisms as vested in homeostasis, the maintenance of stability that characterizes the goal of homeostasis cannot fully serve the biological imperative of viability — survival and reproduction. Stability would not fit the need for viability in the face of the numerous environmental changes that challenge a human organism on a within-day, seasonal, life-cycle, and age-appropriate basis.

The steady-state set-points of the parameters of the internal milieu monitored by homeostasis need to change or lose precedence to permit infants and children to grow; women to gestate and lactate; everyone to cycle between waking and sleeping, eating and fasting, stressing and relaxing. Those, and such conditions as the stressors of jet traveling, of enduring cold winters and torrid summers, of seasonal variations in sunlight exposure, require a viability-maintaining physiological regulatory system of adaptive capability beyond the conservative capabilities of stability-maintaining mechanisms as traditionally conceptualized for homeostatic mechanisms.[5]

Overview

Allo refers to 'other' or 'different'; stasis, to stability — so that allostasis refers to a way of achieving stability (or viability) in a way different from that achieved by Bernard-Cannon homeostasis.[6] 'Allostasis' frequently colloquializes as "stability through change", or "homeostasis through change". Homeostatic flexibility.

According to Bernard Cannon homeostasis, homeostatic mechanisms target maintenance of critical biological variables (e.g., blood glucose concentations) to within a set, ideal range, in part through action of the sympathetic nervous system and regulation of adrenal cortical secretions. Further studies of the sympathico-adrenal systems indicates that they act continuously and respond to many different effects on the body by establishing new and different ideal ranges of system variables. As Goldstein and McEwen express it:

It is by now clear that the sympathico-adrenal system is active tonically and contributes to “basal” levels of key internal variables such as blood pressure and glucose. Moreover, activities of daily life, such as meal ingestion, speaking, changing posture, and movement—i.e., not only emergencies—are associated with continual alterations in sympathetic nervous system outflows, maintaining appropriate body temperature, delivery of metabolic fuel to body organs, and so forth. Each of these activities is associated with a somewhat different set of “normal” apparent steady-states, directed by the brain and determined by coordinated actions of a variety of effector systems.[3]

Allostatic mechanisms appear prominently in the central nervous system’s response to stress, manifesting by regulation of:

  • the behavior of the system-as-a-whole (e.g., eating behavior in response to hunger stress), and
  • the physiological behavior of subsystems of the system-as-a-whole (e.g., cardiovascular function in response to predator stress).

Allostatic mechanisms contribute to system viability, not by restoring physiological or behavioral variables to within a fixed set-point range, as in Bernard-Cannon homeostasis, but in effect by changing their optimal set-point range, at least temporarily, in a way that adapts the system to the potentially harmful circumstances it currently faces.[3] [7] [4] [8] However, if the stimulus to the allostatic re-set persists for long periods, or recurs too frequently, or if the re-set turns on inadequately or turns off inefficiently, the resulting so-called allostatic load causes wear-and-tear that can lead to operational dysfunction of the system.

Allostasis reflects active, adaptive processes that maintain apparent steady states, via multiple, interacting effectors regulated by homeostatic comparators—“homeostats.” “Allostatic load” refers to the consequences of sustained or repeated activation of mediators of allostasis. From the analogy of a home temperature control system, the temperature can be maintained at any of a variety of levels (allostatic states) by multiple means (effectors), regulated by the thermostat (homeostat). Allostatic load and risks of system breakdown increase when, for example, the front door is left open in the winter. Applying these notions can aid in understanding how acute and chronic stress can exert adverse health consequences via allostatic load.[3]

Elaborated definitions and examples

Jeongok Logan and Debra Barksdale at the University of North Carolina Chapel Hill articulate a succinct definition of allostasis and allostatic load:

Allostasis is the extension of the concept of homeostasis and represents the adaptation process of the complex physiological system to physical, psychosocial and environmental challenges or stress. Allostatic load is the long-term result of failed adaptation or [failed] allostasis, resulting in pathology and chronic illness.[9]

Bruce McEwen and Teresa Seeman, in collaboration with the Allostatic Load Working Group, elaborate and give specific examples:

For each system of the body, there are both short-term adaptive actions (allostasis) that are protective and long-term effects that can be damaging (allostatic load). For the cardiovascular system, a prominent example of allostasis is the role of catecholamines in promoting adaptation by adjusting heart rate and blood pressure to sleeping, waking, physical exertion (citation). Yet, repeated surges of blood pressure in the face of job stress or the failure to shut off blood pressure surges efficiently accelerates atherosclerosis and synergizes with metabolic hormones to produce Type II diabetes, and this constitutes a type of allostatic load (see (citation)). Closely related to this is the role of adrenal steroids in metabolism. Whereas adrenal steroids promote allostasis by enhancing food intake and facilitating the replenishment of energy reserves, the overactivity of this system involving repeated HPA activity in stress or elevated evening cortisol leads to allostatic load in terms of insulin resistance, accelerating progression towards Type II diabetes, including abdominal obesity, atherosclerosis, and hypertension (citations). In the brain, actions of adrenal steroids and catecholamines that are related to allostasis include promoting retention of memories of emotionally-charged events, both positive and negative. Yet, overactivity of the HPA axis together with overactivity of the excitatory amino acid neurotransmitters promotes a form of allostatic load, consisting of cognitive dysfunction by a variety of mechanisms that involve reduced neuronal excitability, neuronal atrophy and, in extreme cases, death of brain cells, particularly in the hippocampus (citations).[10]

McEwen and Seeman divide allostatic load into several distinct types of scenarios:[10]

  • Stress overload, such as that caused by severe and repeated economic burdens, which potentially leads to physical and mental dysfunctions;
  • Stress adaptation failure, where mediators of a stress response fail to diminish in response to repeated similar stress events, such as repeated taking of exams during course work;
  • Stress response persistence following cessation of the stressor;
  • Stressors that chronically disturb normal circadian rhythms, such as sleep deprivation;
  • Stress response inadequacy that leads to overreaction of other systems.

In their book on the endocrine factors in aging, Derek Chadwick and Jamie Goode characterize allostasis as follows, and contrast it with homeostasis:

Speaking generally, allostasis is distinct from homeostasis in maintaining a compensated equilibrium rather than a physiological equilibrium: stability is maintained at a price. The allostatic set point is abnormal relative to the homeostatic set point, the system is inherently less stable, and it has a relatively narrow dynamic range. Finally, a system in allostasis leads to pathology whereas a system in homeostasis does not. [11]

Chadwick and Goode go on to compare the pathology and regulatory dysfunctions caused by chronic stress (allostatic load) and by the aging process. The consider the findings supportive of the notion that allostatic load plays a role in determining longevity. They point to evidence that similar disturbances in aging and chronic stress occur in the daily rhythm of the brain's interactions between its hypothalamus and pituitary gland, and in body temperature regulation, drawing attention to allostatic load as a factor in aging.[11]

Role of brain in the physiology and neurobiology of stress

See:[12] [13]

References

Citations and notes

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Most citations to articles listed here include links to full-text. Accessing full-text may require personal or institutional subscription. Nevertheless, usually the links will show the abstracts of the articles, free without subscription. Links to books variously may open to full-text, or to the publishers' description of the book with or without downloadable selected chapters, reviews, and table of contents. Books with links to Google Books often offer extensive previews of the books' text.


  1. 1.0 1.1 1.2 Schulkin J. (editor). Allostasis, Homeostasis, and the Costs of Physiological Adaptation. Cambridge: Cambridge University Press. ISBN 0521811414.
  2. 2.0 2.1 2.2 McEwen BS. (2004) Protective and Damaging Effects of the Mediators of Stress and Adaptation: Allostasis and Allostatic Load. In: Jay Schulkin (editor), Allostasis, Homeostasis, and the Costs of Physiological Adaptation. Chapter 2. Cambridge University Press. ISBN 0-521-81181-4.
  3. 3.0 3.1 3.2 3.3 3.4 3.5 Goldsteinn DS, McEwen B. (2001) Allostasis, Homeostats, and the Nature of Stress. Stress 5:55–58
  4. 4.0 4.1 Sterling P. Eyer J. (1998) Allostasis: A New Paradigm to Explain Arousal Pathology. In: Handbook of life stress, cognition, and health. Eds., Shirley Fisher and James Reason. Chichester: Wiley. ISBN 0471912697
  5. Power ML. (2004) Commentary: Viability as Opposed to Stability: An Evolutionary Perspective on Physiological Regulation. In: Schulkin J. (editor). Allostasis, Homeostasis, and the Costs of Physiological Adaptation. Cambridge: Cambridge University Press. ISBN 0521811414.
  6. Note: Compare allotrope, one of two or more different forms of a particular chemical element, such dioxygen (O2, resulting from different configurations of atoms making up the molecular or crystalline structure.
  7. McEwen BS. (1998) Stress, adaptation, and disease. Allostasis and allostatic load. Ann.N.Y.Acad.Sci. 840:33-44. PMID 9629234.
    • Abstract:
      • Adaptation [of the organism] in the face of potentially stressful challenges involves activation of neural, neuroendocrine and neuroendocrine-immune mechanisms.
      • This has been called "allostasis" or "stability through change" by Sterling and Eyer (Fisher S., Reason J. (eds): Handbook of Life Stress, Cognition and Health. J. Wiley Ltd. 1988, p. 631), and allostasis is an essential component of maintaining homeostasis.
      • When these adaptive systems are turned on and turned off again efficiently and not too frequently, the body is able to cope effectively with challenges that it might not otherwise survive.
      • However, there are a number of circumstances in which allostatic systems may either be overstimulated or not perform normally, and this condition has been termed "allostatic load" or the price of adaptation (McEwen and Stellar, Arch. Int. Med. 1993; 153: 2093.).
      • Allostatic load can lead to disease over long periods. Types of allostatic load include:
        • (1) frequent activation of allostatic systems;
        • (2) failure to shut off allostatic activity after stress;
        • (3) inadequate response of allostatic systems leading to elevated activity of other, normally counter-regulated allostatic systems after stress.
      • Examples will be given for each type of allostatic load from research pertaining to autonomic, CNS, neuroendocrine, and immune system activity.
      • The relationship of allostatic load to genetic and developmental predispositions to disease is also considered.
  8. McEwen,B.S.; Stellar,E. (1993) Stress and the individual. Mechanisms leading to disease. Arch.Int.Med 153:2093-2101. PMID 8379800.
    • Abstract:
      • OBJECTIVE: This article presents a new formulation of the relationship between stress and the processes leading to disease. It emphasizes the hidden cost of chronic stress to the body over long time periods, which act as a predisposing factor for the effects of acute, stressful life events. It also presents a model showing how individual differences in the susceptibility to stress are tied to individual behavioral responses to environmental challenges that are coupled to physiologic and pathophysiologic responses.
      • DATA SOURCES: Published original articles from human and animal studies and selected reviews. Literature was surveyed using MEDLINE.
      • DATA EXTRACTION: Independent extraction and cross-referencing by us.
      • DATA SYNTHESIS: Stress is frequently seen as a significant contributor to disease, and clinical evidence is mounting for specific effects of stress on immune and cardiovascular systems. Yet, until recently, aspects of stress that precipitate disease have been obscure. The concept of homeostasis has failed to help us understand the hidden toll of chronic stress on the body. Rather than maintaining constancy, the physiologic systems within the body fluctuate to meet demands from external forces, a state termed allostasis. In this article, we extend the concept of allostasis over the dimension of time and we define allostatic load as the cost of chronic exposure to fluctuating or heightened neural or neuroendocrine response resulting from repeated or chronic environmental challenge that an individual reacts to as being particularly stressful. [Emphasis added]
      • CONCLUSIONS: This new formulation emphasizes the cascading relationships, beginning early in life, between environmental factors and genetic predispositions that lead to large individual differences in susceptibility to stress and, in some cases, to disease. There are now empirical studies based on this formulation, as well as new insights into mechanisms involving specific changes in neural, neuroendocrine, and immune systems. The practical implications of this formulation for clinical practice and further research are discussed.
  9. Logan JG, Barksdale DJ. (2008) Allostasis and allostatic load: expanding the discourse on stress and cardiovascular disease. J.Clin.Nurs. 17:201-208. PMID 18578796.
    Abstract:
    • AIM: The aim of this discursive paper is to introduce allostasis and allostatic load, which are relatively new concepts proposed to explain physiological responses to stress, and to suggest ways in which allostasis theory can be applied to the development of clinical interventions to increase resilience for producing better health outcome.
    • BACKGROUND: Common explanations of stress have failed adequately to explicate its association with health and chronic illness. Allostasis is the extension of the concept of homeostasis and represents the adaptation process of the complex physiological system to physical, psychosocial and environmental challenges or stress. Allostatic load is the long-term result of failed adaptation or allostasis, resulting in pathology and chronic illness.
    • DISCUSSION: The concepts of allostasis and allostatic load introduced the idea that external challenges initiate allostasis and chronic stress causes allostatic load that can be measured with multiple biomarkers. Finding from several studies suggests that higher allostatic load is associated with worse health outcomes. Resilience represents successful allostasis and strategies can be implemented to enhance resilience and thereby improve health outcomes.
    • CONCLUSIONS: This theoretical model provides a comprehensive explanation of the human body's adaptation processes in response to stress and the results of failed adaptation over time. In addition, combining the concepts of allostasis and resilience may help us to understand and implement clinical strategies better to reduce or prevent the debilitating physiological and psychological effects of chronic stress and chronic illness.
    • RELEVANCE TO CLINICAL PRACTICE: Clinical practice should be based on a solid theoretical foundation to improve health outcomes. Strategies to manage stress and increase resilience along with clinical interventions to manage the physiological responses to chronic stress are necessary to assist in preventing and controlling the detrimental effects of chronic disease on human life.
  10. 10.0 10.1 Bruce McEwen and Teresa Seeman in collaboration with the Allostatic Load Working Group. (1999) Allostatic Load and Allostasis.
  11. 11.0 11.1 Chadwick D., Goode J. (2002) Endocrine Facets of Ageing. John Wiley and Sons. ISBN 0471486361, ISBN 9780471486367.
    • ”Social and medical developments have recently led to a dramatic increase in life expectancy. This has inspired the study of organismic changes associated with healthy ageing, in particular the erosion of homeostatic capabilities in multiple endocrine systems. This book reviews advances in the understanding of endocrine facets of ageing. It considers the relative magnitudes and time courses of different endocrine adaptations in the ageing human and experimental animal, addressing the influence of external factors on the rates of progression of endocrine sequelae in ageing, the mechanisms that underlie the disarray of endocrine axes in ageing, and the implications of therapeutic reconstitution of hormones in ageing. This book: Considers the mechanisms of ageing and hormonal changes that occur with age. Discusses healthy ageing and the relationships between hormonal changes and pathophysiological conditions such as atherosclerosis and age-related bone loss. Draws together contributions from basic and clinical research, to identify and stimulate promising new research directions.”
  12. McEwen BS. (2000) Allostasis and allostatic load: implications for neuropsychopharmacology. Neuropsychopharmacology 22:108-124.
    • Abstract (bulleted for ease of reading): The primary hormonal mediators of the stress response, glucocorticoids and catecholamines, have both protective and damaging effects on the body. In the short run, they are essential for adaptation, maintenance of homeostasis, and survival (allostasis). Yet, over longer time intervals, they exact a cost (allostatic load) that can accelerate disease processes.
    • The concepts of allostasis and allostatic load center around the brain as interpreter and responder to environmental challenges and as a target of those challenges.
    • In anxiety disorders, depressive illness, hostile and aggressive states, substance abuse, and post-traumatic stress disorder (PTSD), allostatic load takes the form of chemical imbalances as well as perturbations in the diurnal rhythm, and, in some cases, atrophy of brain structures.
    • In addition, growing evidence indicates that depressive illness and hostility are both associated with cardiovascular disease (CVD) and other systemic disorders. A major risk factor for these conditions is early childhood experiences of abuse and neglect that increase allostatic load later in life and lead individuals into social isolation, hostility, depression, and conditions like extreme obesity and CVD. Animal models support the notion of lifelong influences of early experience on stress hormone reactivity.
    • Whereas, depression and childhood abuse and neglect tend to be more prevalent in individuals at the lower end of the socioeconomic ladder, cardiovascular and other diseases follow a gradient across the full range of socioeconomic status (SES).
    • An SES gradient is also evident for measures of allostatic load. Wide-ranging SES gradients have also been described for substance abuse and affective and anxiety disorders as a function of education. These aspects are discussed as important, emerging public health issues where the brain plays a key role.
    • Section Contents:
    • Abstract
    • Protective And Damaging Effects Of Stress Mediators
    • Allostasis And Allostatic Load
    • Measurement Of Allostatic Load
    • The Role Of Behavior In Allostatic Load
    • The Relationships Of Genetics To Stress And Allostatic Load
    • The Brain As A Target Of Allostatic Load
    • Early Life Experiences
    • Cardiovascular Disease, Hostility, And Depression
    • Sociological Aspects Of Stress And Health
    • Conclusions
    • References
  13. McEwen BS. (2007) Physiology and neurobiology of stress and adaptation: central role of the brain. Physiol Rev 87:873-904.
    • Abstract (bulleted for ease of reading):
    • The brain is the key organ of the response to stress because it determines what is threatening and, therefore, potentially stressful, as well as the physiological and behavioral responses which can be either adaptive or damaging.
    • Stress involves two-way communication between the brain and the cardiovascular, immune, and other systems via neural and endocrine mechanisms.
    • Beyond the "flight-or-fight" response to acute stress, there are events in daily life that produce a type of chronic stress and lead over time to wear and tear on the body ("allostatic load").
    • Yet, hormones associated with stress protect the body in the short-run and promote adaptation ("allostasis").
    • The brain is a target of stress, and the hippocampus was the first brain region, besides the hypothalamus, to be recognized as a target of glucocorticoids.
    • Stress and stress hormones produce both adaptive and maladaptive effects on this brain region throughout the life course.
    • Early life events influence life-long patterns of emotionality and stress responsiveness and alter the rate of brain and body aging.
    • The hippocampus, amygdala, and prefrontal cortex undergo stress-induced structural remodeling, which alters behavioral and physiological responses.
    • As an adjunct to pharmaceutical therapy, social and behavioral interventions such as regular physical activity and social support reduce the chronic stress burden and benefit brain and body health and resilience