Homeostasis, Allostasis & Allostatic Load PDF

Homeostasis, Allostasis & Allostatic Load A P P L I E D H U M AN P H Y S I OLOGY F OR R E H A B I L ITAT I ON M E D I C IN E P R OGRAM IN P H Y S IC AL T H E RAPY Why Homeostasis? Serves as one of, if not the core theoretical principle of biology and modern physiology Conceptual framework inf...

Homeostasis, Allostasis & Allostatic Load A P P L I E D H U M AN P H Y S I OLOGY F OR R E H A B I L ITAT I ON M E D I C IN E P R OGRAM IN P H Y S IC AL T H E RAPY Why Homeostasis? Serves as one of, if not the core theoretical principle of biology and modern physiology Conceptual framework informing our understanding of how the body responds to stress Why is this important for a clinician? Disease is often considered to be a state of disrupted homeostasis Influence the organization of treatments How do you use this information? Set ranges – flexibility, strength, Vital signs etc. Defining Homeostasis Ancient Greeks believed in the idea of the Four Humours. Hippocrates coined the theory that body is made up of 4 main Humours – blood, phlegm, yellow bile and black bile Stay in balance to remain healthy These were linked to the season If someone had a fever is was due to “too much blood” Cure was therefore to bleed the patient! Claude Bernard (1878) – “complex organisms are able to maintain their internal environment [extracellular fluid] fairly constant in the face of challenges from the external world”  Defining Homeostasis Walter Cannon (1929) – credited with coining the term homeostasis “organism’s capacity to maintain a Steady-State or intrinsic uniformity despite ongoing fluctuations in its internal and external processes through both active and passive processes” All organisms demonstrate constancy in an open system through specific mechanisms Organisms exist in a steady-state and resist change Governed by a regulating system made from mechanisms cooperating simultaneously Not by chance, result of purposeful organization and self- government “the purpose of the clinician was to substitute for those mechanisms until control could be restored” Regulating what? (i.e. what “conditions” are “maintained” to be “nearly constant”? ) “Powerful control systems exist for maintaining concentrations of sodium and hydrogen ions, as well as for most of the other ions, nutrients, and substances in the body at levels that permit the cells, tissues, and organs to perform their normal functions, despite wide environmental variations and challenges from injury and diseases.” “Variations in the blood hydrogen ion concentration, for example, are normally less than 5 nanomoles/L (0.000000005 moles/L).” “Much of this text is concerned with how each organ or tissue contributes to homeostasis. Normal body functions require integrated actions of cells, tissues, organs, and multiple nervous, hormonal, and local control systems that together contribute to homeostasis and good health.” Q: Why does the internal environment need to be so tightly regulated? A*: The internal environment must be regulated to enable consistent conditions in order to maintain cellular function * This asterisk denotes that this is one potential answer homeostasis is not static; it is, rather, a dynamic self-adjusting system that maintains viability in the face of changing environmental demands Billman, G. E. (2020). Homeostasis: The Underappreciated and Far Too Often Ignored Central Organizing Principle of Physiology. Frontiers in Physiology, 11. doi:10.3389/fphys.2020.00200 Billman, G. E. (2020). Homeostasis: The Underappreciated and Far Too Often Ignored Central Organizing Principle of Physiology. Frontiers in Physiology, 11. doi:10.3389/fphys.2020.00200 Homeostasis (generic version of homeostatic regulatory system) Modell et al. (2015)  Homeostatic Regulatory System (simplified version) Five critical components of a regulatory system to maintain homeostasis: 1. It must contain a sensor that measures the value of the regulated variable. 2. It must contain a mechanism for establishing the “normal range” of values for the regulated variable. In the model shown in previous figure, this mechanism is represented by the “set point,” although this term is not meant to imply that this normal range is actually a “point” or that it has a fixed value. 3. It must contain an “error detector” that compares the signal being transmitted by the sensor (representing the actual value of the regulated variable) with the set point. The result of this comparison is an error signal that is interpreted by the controller. 4. The controller interprets the error signal and determines the value of the outputs of the effectors. 5. The effectors are those elements that determine the value of the regulated variable. ff, W., Michael, J., McFarland, J., Wenderoth, M. P., & Wright, A. (2015). A physiologist's view of homeostasis. Adv Physiol Educ, 39(4), 259-266. doi:10.1152/advan.00107.2015 Note: Control Center = error detector + controller Homeostasis Chovatiya, R., & Medzhitov, R. (2014). Stress, Inflammation, and Defense of Homeostasis. Molecular Cell, 54(2), 281-288. doi:10.1016/j.molcel.2014.03.030 Homeostatically regulated variables: values, ranges, limits Increase of body temperature >11°F can lead to ‘vicious cycle’ of increasing cellular metabolism that destroys cells. Acid-base values varying in a range only 0.1 pH levels either direction and only ± 0.5 for viability. Variations in K can affect nerve conduction and heart function Drop in Ca2+ can affect nerve impulses leading to aberrant muscle contraction. Glucose levels below half of normal value can lead to physiological and behavioral issues (e.g. mental confusion and irritability. Guyton & Hall What might cause values to rise/fall outside the range or limit(s) given previously? Control mechanisms: Positive feedback vs. Negative feedback Negative feedback mechanisms “A control mechanism where the action of the ?opposes a change in the regulated variable and returns it back toward the ? Output counteracts the effects of the original stimulus The generic model by Modell et al. (2015) is a negative feedback model and “demonstrates the minimization of an error signal.” Most common type in living systems Positive feedback mechanisms Output amplifies the effects of the original stimulus “…positive feedback leads to instability rather than stability and, in some cases, can cause death.” “initiating stimulus causes more of the same response” Modell et al. (2015)  Negative Feedback Example Billman, G. E. (2020). Homeostasis: The Underappreciated and Far Too Often Ignored Central Organizing Principle of Physiology. Frontiers in Physiology, 11. doi:10.3389/fphys.2020.00200  Negative Feedback Example Billman, G. E. (2020). Homeostasis: The Underappreciated and Far Too Often Ignored Central Organizing Principle of Physiology. Frontiers in Physiology, 11. doi:10.3389/fphys.2020.00200 Positive Feedback Positive feedback leads to instability rather than stability the initiating stimulus causes more of the same Advantages to positive feedback … Clotting ? Figure 1-4.Recovery of heart pumping caused by negative feedback after 1 liter of blood is removed from the circulation. Death is caused by positive feedback when 2 liters or more blood is removed. Guyton & Hall Figure 2 – Modified for emphasis Modell et al. (2015) Challenges with the Understanding of Homeostasis Homeostasis is a complex phenomenon which can be applied to various different processes and levels Some aspects of homeostasis are counterintuitive – positive feedback Language and terminology to describe homeostasis has evolved over time and is not always consistent The understanding of homeostasis is incomplete Does it take the entire system into consideration What is normal??? What are some examples of homeostasis? Example of “Stead-State” in Aerobic Exercise Oxygen consumption (VO2) steady-state Poole, D. C., & Jones, A. M. Oxygen Uptake Kinetics. In Comprehensive Physiology (pp. 9 Allostasis  Stress-Response & Development of Allostatic Load the process by which the body responds to stressors in order to regain homeosta sis , B. S. (1998). Protective and Damaging Effects of Stress Mediators. New England Journal of Medicine, 338(3), 171-179. doi:10.1056/nejm199801153380307  The Stress-Response “[Hans] Selye defined stress as the non-specific response of the body to any demand imposed upon it’” *Two aspects of stress: acute and chronic Selye suggested that this stressor (“threat”) can stimulate a physiologic responses to the threat, and that this response, termed “General Adaptation Syndrome” occurred in 3 Szabo, T. (2012). The legacy of Hans Selye and the origins of stress phases: Alarm, Resistance, and Exhaustion. research: A retrospective 75 years after his landmark brief “Letter” to the Editor # of Nature. Stress (Amsterdam, Netherlands), 15(5), 472–478. https://doi.org/10.3109/10253890.2012.710919 What is stress? Can be ? – can you give examples? Can be acute or chronic Occurs when homeostasis is threatened or perceived to be threatened – physiological variability?! Stress is a major contributor to psychosocial and physical pathological conditions in humans General Adaptation Syndrome (G.A.S.) Alarm reaction – mobilization of resources ? – build-up of reserves to overcome the stressor(s) Exhaustion – resolution of the stressor(s)  Stress-Response and Resistance Exercise Responses to acute bouts of resistance exercise an, B., & Zierath, J. R. (2013). Exercise metabolism and the molecular regulation of skeletal muscle adaptation. Cell Metab, 17(2), 162-184. doi:10.1016/j.cmet.2012.12.012 Example of “Stress-Response” in Aerobic Exercise Time taken to reach oxygen consumption (VO2) steady-state (VO2 on-kinetics) Poole, D. C., & Jones, A. M. Oxygen Uptake Kinetics. In Comprehensive Physiology (pp. 933-996) Stress-Response Applied to Exercise Performance/ Function What is Allostasis & Allostatic Load? Allostasis - “achieving stability through change” or “the means by which the body re-establishes homeostasis in the face of a challenge” Feedforward and feedback mechanisms Anticipatory alterations Represents a more sophisticated system of internal regulation, minimizing the reliance upon error signaling required for homeostatic correction Allostasis now refers to the regulation of internal milieu through ? toward new set points Allostatic Load – strain placed on the body produced by repeated ups and downs of the physiologic response. Such responses can lead to ? on numerous organs and tissues and can predispose the organism to disease. Takayanagi, Y., & Onaka, T. (2022). Roles of Oxytocin in Stress Responses, Allostasis and Resilience. International Journal of Molecular Sciences, 23(1), 150. Retrieved from https://www.mdpi.com/1422-0067/23/1/150 Achieving stability through change …  Allostasis vs Homeostasis mann, R., Midgley, J. E., Hering, S., Urban, A., Dietrich, B.,... Dietrich, J. W. (2017). Thyroid Allostasis–Adaptive Responses of Thyrotropic Feedback Control to Conditions of Strain, Stress, and Developmental Programming. Frontiers in Endocrinology, 8. doi:10.3389/fendo.2017.0 Examples of prior knowledge and its use in prediction Problems with Homeostasis as a Primary Model for Regulation 1. Constancy is not a fundamental condition for life The true objective of all the vital mechanisms is not “constancy” but survival to reproduce 2. Mean value need not imply a setpoint but rather the most frequent demand 3. Physiological variability 4. How does body maintain survival outside of those homeostatic set points?? Principles of Allostasis (predictive regulation) 1. Organisms are designed for efficiency No system can be “overdesigned” or “underdesigned” 2. Efficiency requires reciprocal trade-offs Think of some examples Trade-off of resources. Reciprocity requires central control (i.e., the brain) 3. Efficiency requires ? what will be needed Type I diabetes 4. Prediction requires each sensor to adapt its sensitivity to expected range of input Lifting a known versus unknown weighted object/motor control 5. Prediction requires each effector to adapt its output to the expected range of demand Effector will adapt to the demands its subjected to 6. Predictive regulation depends on behavior whose neural mechanisms also adapt Prior experiences are stored in the nervous system to be used in future behaviors Allostatic Load Abnormal Stress-Response What are some examples of conditions which may result from excessive allostatic load (i.e., allostatic overload)? How might the understanding of allostasis and allostatic load influence the Physical Therapist? Enable recognition of the physiological status of that person, and determine : The type of stress most appropriate for our patients/clients to achieve intended goals What dosing is appropriate to affect the target, including, specifically: type, mode, frequency, duration, intensity How to adjust during the intervention/POC, short and long-term, to reach goals too much disruption = over-training, injury, illness too little disruption = regression (e.g. deconditioning), stasis (e.g. no progress), slow progress  Summary Homeostasis serves as one of the core theoretical principle of biology and modern physiology Conceptual framework informing our understanding of how the body responds to stress “organism’s capacity to maintain a steady-state or intrinsic uniformity despite ongoing fluctuations in its internal and external processes through both active and passive processes” Regulatory systems serve to maintain homeostasis Stress-Response describes the non-specific response of the body to imposed demand Three phases of the General Adaptation Syndrome The stress-response applied to exercise Allostasis – achieving stability through change Allostatic load (overload) – wear and tear Fundamental differences between allostasis and homeostasis Six principles of allostasis (efficiency and adaptation) Thank you!!