Question
Answered step-by-step

Explain why Sterling and Eyer felt it was necessary to coin a new...

Explain why Sterling and Eyer felt it was necessary to coin a new term to describe physiological regulation, namely allostasis. What was homeostasis unable to explain that required a new idea to account for? What does the principle of allostasis take into account and explain that cannot be explained by a homeostatic model? What, for you, are the implications of this - for teaching, for thinking about the subject, and for medical practice?

 

Below is the reference:

 

Image transcription text

1 Sterling and Eyer 1988 - Allostasi: X *Course Hero X 5 Sterling and Eyer 1988 - Allostasi X *Course Hero X + X < -> C @ File | C:/Users/domin/Downloads/Sterling%20and%20Eyer%201988%20-%20Allostasis.pdf Q E E Sterling and Eyer 1988 - Allostasis.pdf 2 / 11| 80% + from liver cirrhosis (due to alcoholism). This cohort is now reaching the age at instances the epidemiological observations that we cite are acknowledged, but are which the important causes of death become renal, cerebral, and cardiovascular given biological explanations that are unrelated to the social and psychological disease (see Figure 10 in Sterling and Eyer, 1981), causes for which hypertension patterns. Thus. a standard explanation for elevated blood pressure in modern 34 is the largest single contributor. Cancer, too, becomes an important cause of society is that salt consumption is excessive and beyond the kidney's capacity to death, though its main impact comes somewhat later. Our historical studies excrete it. This is supposed to cause retention of excess salt water in the vascular predict for this cohort an increase in mortality from these causes (Eyer and system which causes the high blood pressure. Hypertension among blacks is Sterling, 1977) commonly attributed to a genetic predisposition. Having discovered these patterns, we could find no explanation for them in These explanations beg the questions why we eat so much salt and why the Allostasis: A New Paradigm to Explain textbooks of physiology. No text explains. for example, why in modern society kidney fails to excrete it. Similarly, one needs to explain why the blood pressures Arousal Pathology blood pressure rises with age (Eyer, 1975). Nor do they explain why this rise starts of American and Caribbean blacks rise so much higher than those of the West at the age when children enter the environment of school (Figure 34.1; Africans whose genes they share (Waldron, 1979). The only possible link between Blumenthal et al. 1977). Texts do not explain why blood pressure is highest and sociopsychological and physiological phenomena is the brain. Textbooks do not hypertension most prevalent where social disruption is greatest, e.g. among the describe this link because the dominant conceptual model in physiology for a PETER STERLING unemployed and (in the US) among blacks. The most common form of hyperten century has viewed the body as operating almost independently of the brain. sion is called in textbooks 'essential', meaning of unknown cause. In certain Neurobiological studies of the 1960s and 1970s revealed many links between brain and and soma, and appreciation of the richness of these links has accelerated in the paradigm to JOSEPH EVER 1980s. By now the evidence warrants abandoning the old conceptual model and son (Eds.), University of Pennsylvania School of Medicine, Philadelphia Blood pressure mm Hg Percentile adopting a new one in which the central nervous system is the pre-eminent 629-649). regulatory influence on somatic physiology (Sterling and Eyer, 1981). Here, we 150 review briefly the old model and present the new one, which accounts quite easily INTRODUCTION for the epidemiological findings. 140 This chapter summarizes our joint effort as epidemiologist (J.E.) and neuro- 130 biologist (P.S.) to understand the physiological basis for certain broad patterns of HOMEOSTASIS VERSUS ALLOSTASIS human morbidity and mortality. Age-specific death rates rise when intimate social 120 Boys The principle of homeostasis is that to maintain stability an organism must hold all relations are disrupted. This is observed in contemporary statistics, for example 110 the parameters of its internal milieu constant (Bernard, 1865; Cannon, 1932). the mortality associated with bereavement, divorce, migration and overwork, It is also observed historically in the increased mortality of urban versus rural popula- 100 Deviations from normal are corrected automatically by local, 'negative feedback" mechanisms. Thus, normal blood sugar is about 80 mg'ml. A rise above this level tions and in the rise of age-specific death rates that accompanies modern eco- can trigger release of insulin from the pancreas which leads to uptake of glucose by nomic development. The increases in all these examples are large (two- to liver and muscle and restores blood glucose to normal. Similarly, normal blood ten-fold) and are observed for essentially all causes, so they cannot be explained pressure is about 110/70 mmHg. A rise above this level can trigger slowing of the by any single environmental factor such as air pollution or nutrition (Berkson, heart, dilatation of the vessels, and excretion of salt and water by the kidneys. 1962; Eyer and Sterling, 1977). Those three factors-reduced cardiac output, enlarged vascular reservoir, and Disruptions to intimate social relations, including war, migration, and eco- reduced blood volume-all contribute to restoring normal pressure. nomic development, affect most strongly youth entering the labor market. The 75 The major thrust in physiological research for the last century has been to study size of a particular birth cohort is especially important because this affects the competitive experience of that cohort throughout its lifecycle. A small cohort 50 Girls isolated organs and tissues. It turns out that most organs function remarkably well when they are disconnected from the rest of the body and brain and placed in a entering the labor market during an economic expansion experiences relatively 110- 25 dish. The pancreas releases insulin when glucose is added, and a slice of kidney mild competition and has lower death rates from all causes. A large cohort entering the labor market during an economic contraction experiences greater 100 pumps salt water. Consequently there has been great success in identifying the cellular and subcellular bases for local feedback control, and this has bolstered the competition and social disruption and has correspondingly higher mortality (Eyer idea that in the body the organs function autonomously. and Sterling. 1977). On the other hand, when measurements of the internal milieu are made in an The major causes of death shift as a cohort apes, but high mortality in youth 8 10 12 14 16 18 intact, unanesthetized organism, the results fit the homeostatic model very from one set of causes presages high mortality later from another set. The large Age poorly. Consider Figure 34.2a, which is a continuous record of arterial blood cohort born after World War II ("baby boom') entered the labor market in the 1960s at the end of a long cycle of economic expansion. It experienced elevated FIG. 34.1 Percentiles of diastolic blood pressure measurement (right arm. seated). pressure made from a normal adult human over a period of 24 hours (Bevan et al. mortality at ages 15-24 from accidents, homicide, and suicide, and at ages 30-34 (Reprinted from Blumenthal er al.. 1977.) 1969). The pressure is by no means constant. Instead, there are many peaks and 629 Webroot SecureAnywhere

... Show more

Image transcription text

1 Sterling and Eyer 1988 - Allostasi X *Course Hero X 5 Sterling and Eyer 1988 - Allostasi X *Course Hero X + X < -> C @ File | C:/Users/domin/Downloads/Sterling%20and%20Eyer%201988%20-%20Allostasis.pdf Q E E Sterling and Eyer 1988 - Allostasis.pdf / 11 67% + 1960s at the end of a long cycle of economic expansion, It experienced elevated FIG. 31.1 Percentiles of diastolic blood pressure measurement (right art, seated). mortality at ages 15-24 from accidents, homicide, and suicide, and at ages 30-34 (Reprinted from Blumenthal of s. 1937.) 1969). The pressure is by no means constant. Instead, there are many peaks and 629 150 It is obvious from this record that the idea of a "normal" value toward which Table 34.1 Catabolic state (arousal) automatic mechanisms drive the blood pressure is a fiction. In one behavioral - BLOOD PRESSURE state the pressure is maintained low for a long period without restoration, and in Increase another state it is held high for long periods, also without restoration. It makes no Cardiac output Arterial pressure [minkigl more sense to average the pressures from these different periods than it does to average" the states of sleep and wakefulness or the states of sexual arousal and Retention of salt and water (to support blood pressure) Blood to muscle satiety. Clearly, to achieve stability an organism must occupy each one of these Breakdown of carbohydrate, fat, protein different states and move flexibly between them. At each behavioral transition, els of glucose, fatty acids, amino acids Blood levels of great the blood pressure must be reset to match the new state (see also Pickering er at, Circulating red cells 1986). duction of red cells cal 20 20 Tone [hours) 02 04 An aroused behavioral state in which an organism is preparing to respond with Synthesis of oxidative enzymes (liver) some form of 'coping" behavior to an environmental challenge generally requires a rise in blood pressure, The early studies by Cannon emphasized acute, intense y. skin, gul 300 arousal engendered by pain, fear, and rage (Cannon, 1929). Later studies by Selye 200 emphasized aroused behavioral states of somewhat longer duration and milder Replacement of cells with high turnover (gut, skin, etc.) 260 conditions (Selye, 1956). Whereas Cannon had studied animals prepared for Production of cells for immune system (thymus, lymph nodes, bone marrow) ACTH DO immediate "fight or flight', Selye st under conditions of chron Sexual processes (endocrine, collelar, psychological, behavioural) frustration, for example a rat with its legs tied together for 24 hours. A still milder paradigm was introduced by Mason and colleagues in wt The emabove sway [relaxation] is accompanied by a reversal of the abares pamorn. 220 an electrical shock by watching for a signal and then pressing a lever (Mason, -BRAIN 1968). An aroused state can also be engendered in animals by disrupting a socially repair, replacement of the cellular lining of the gut, etc. all slow markedly. Thus. FIG. 34.3 Maltiple, mutually reinforcing mechanisms to raise blood pressure during stable community, for example among mice by intro corresponding to the behavioral'psychological state of arousal there is a bio- king a strange male into an annual. Negative feedbacksmese! or overridden. [" Indicates that cortisol acts indirectly by Arterial pressure (manHg) established colony (Henry er al, 1967). chemical state of 'catabolism', that is, breakdown of metabolic compounds to enhancing receptor binding of norepinephrine.) 160 In all such animal models, when the acute or semi ic arousing stimulus is produce energy. Corresponding to states of relaxation is a biochemical state of removed, the blood pressure falls. However, when the arousing stimulus is made "anabolism', that is, a rebuilding of energy stores, repair, and growth (Mason. logically active peptides increases as techniques in molecular biology advance. All 1972). chronic and removed only after a rather long period, the pressure may remain physiologically active substances and processes discovered so far are regulated elevated. Thus, after many months of elevation in response to an avoidance The catabolic mobilization accompanying arousal is accomplished by shifts in and therefore fluctuate with shifts in demand corresponding to shifts in behavioral conditioning paradigm, the high pressure in monkeys becomes sustained (For- essentially all the known hormones. Ca ones (those that promote 100 syth, 1969). Similarly, the elevated pressures evok as part of a 'defense energy production), e.g. epinephrine, norepinephrine, cortisol (glucocorticoid Table 34.2 Hormonal pattern during arousal response" by chronic brain stimulation also become sustained, even when the growth hormone, glucagon, and thyroxine, increase. Anabolic hormones (chose Catabolic hormones increase Anabolic hormones decrease stimulation ceases (Folkow and Rubinstein, 1956). The elevated pressures in that promote growth and repair), e.g. insulin, est 60 mouse colony fall when the stranger is removed, but only if less then 6 months has crease, The timing of these changes is complex because certain hormones, such as Cortisol (glucocorticoids) Insulin De mobilization and rise 02 06 06 10 epinephrine, cortisol, and growth hormone, s epinephrine Calaltonin [b) 40 20 22 elapsed: thereafter the pressure remains high even when the stranger is gone (Henry er al.. 1967). almost instantaneously (seconds to minutes), while others, such as thyroxine and Norepinephrine Testosterone Time (hours] Glueinon Estrogen FIG. 34.2 (a) Arterial pressure from a normal subject plowed at 5-minute intervals, (b] The question arises as to what other physiological parameters besides blood the sex hormones, have slow rodulatory roles and rise or fall over longer Growth hormone Prolactin periods (hours to weeks). Other hormones that indirectly support energy produc- Antichurctic hormone (vassprestin) Luteinineing harm Arterial pressure from a hypertensive subject. (Redrawn from Bevan et al, 1969.) pressure covary with behavioral state. The answer is, essentially off of them (Table Follicle stin 34.1; Mason 1968, 1971, 1972). As blood pressure rises during arousal, there is a tion also change (Mason, 1968), For example, vasopressin (antidaurelic hor- Kenin Arelotensin dramatic shift in the pattern of blood flow: more to muscle, less to the put, kidney, mone), renin, anglotensin II, and aldesserone all increase (see Sterling and Eyer Oonadotrophin-releasing hormone (OnRID troughs of varying size and duration, Some peaks are identified with specific and skin, Correspondingly. there is a metabolic mob alization to increase energy 1981) and atripopeptin decreases (Eskay ex al, 1986). This pattern serves the Aldosicrone (mineralocorticoids) Prolactin-releasing hormone (PRE) Erythropoietin Amopt behavioral states and environmental events. For example, the pressure fell aroused state by increasing the rate of circulation through the cardiovascular between hours 15 and 16 when the subject was dozing in a lecture, and rose production. Glucose, amino acids, and fatty acids are released from their macro- system (Fig. 34.3). Parathermane Lymphokines sharply at hour 16 when he awakened (briefly) to a jab from a pin. The pressure rose at hour 24 (midnight ) when the subject engaged in sexual intercourse, and fell Synthesis of the storage forms is halted. Red blood cells and oxidative enzymes in A list of some hormones associated with the catabolic and anabolic states is Melatonin Cytokines Thyroid.rele profoundly (as low as 50:30 mmHe) during sleep. At hour 08, when the subject the liver increase because these facilitate the ene ay mobilization. Other pr given in Table 34.2. It is notable that quite a few of them have been discovered cesses that use energy but that do not contribute to the metabolic mobilization are only recently, e.g. the opiate hormones (enkephalin, dynorphin, and endorphin: Adrenocorticotrophic hormone (ACTH) Akil et al., 1984), the cardiac hormone (atriopeptin: Manning er al., 1985; Eskaye Enkephalin was preparing to meet his work day, the pressure rose to the preorgasmic level of suppressed: the immune response declines as circulating white blood cells de- Dynorphin crease and the thymus shrinks (Selye. 1956), Wound healing. bone growth and al., 1986, Dillingham and Anderson, 1986), and the immune system hormones Endorphin opiales the previous night and remained there for hou (interleukins and thymosins: Goetzl, 1985). The discovery rate of new, physio-

... Show more

Image transcription text

1 Sterling and Eyer 1988 - Allostasi: X *Course Hero X 5 Sterling and Eyer 1988 - Allostasi X *Course Hero X + X < > C @ File | C:/Users/domin/Downloads/Sterling%20and%20Eyer%201988%20-%20Allostasis.pdf Q E E Sterling and Eyer 1988 - Allostasis.pdf / 11 - 67% + It is obvious from this record that the idea of a "normal" value toward which 140 Table 34.1 Catabolic state (arousal) automatic mechanisms drive the blood pressure is a fiction. In one behavioral - BLOOD PRESSURE- state the pressure is maintained low for a long period without restoration, and in Increase another state it is held high for long periods, also without restoration. It makes no Blood pressure more sense to average the pressures from these different periods than it does to Cardisc output Arterial pressure ImmHigh "average" the states of sleep and wakefulness or the states of sexual arousal and Retention of salt and water (to support blood pressure) satiety. Clearly, to achieve stability an organis Blood to muscle must occupy each one of these Breakdown of carbohydrate, fat, protein different states and move flexibly between them. At each behavioral transition, Blood levels of glucose, fatty acids, amino acids 40 the blood pressure must be reset to match the new state (see also Pickering er al, Circulating red cells 1986). duction of red cells al 204 16 18 20 22 24 02 04 06 An aroused behavioral state in which an organism is preparing to respond with Synthesis of oxidative enzymes (liver) some form of 'coping" behavior to an environmental challenge generally requires Decrease a rise in blood pressure. The early studies by Cannon emphasized acute, intense Blood to kidney, skin, gut 300 arousal engendered by pain, fear, and rage (Cannon, 1929). Later studies by Selye on, fat. protein Repair, replacement, growth of bone 280 emphasized aroused behavioral states of somewhat longer duration and milder Replacement of cells with high turnover (gut, skin, etc.) 260 conditions (Selye, 1956). Whereas Cannon had studied animals prepared for on of cells for immune system (thymus, lymph nodes, bone marrow) Immediate "fight or flight', Selye studied an anditions of chron sexual processes (endocrine. cellular. psychological, behavioural) frustration, for example a rat with its legs tied together for 24 hours. A still milder The anabolic state (relaxation] is accompanied by a reversal of the above powern 220 paradigm was introduced by Mason and colleagues in which an animal could avoid an electrical shock by watching for a signal and then pressing a lever (Mason. BRAIN- 200 1968). An aroused state can also be engendered in animals by disrupting a socially repair, replacement of the cellular lining of the gut, etc. all slow markedly. Thus, FIG. 34.3 Multiple, mateally reinforcing mechanisms to raise blood pressure during stable community. for example among mice by corresponding to the behavioral/psychological state of arousal there is a bio- cing a strange male into an arousal. Negative feedbacks reset or overridden. (" Indicates that cortisol nets indirectly by Arterial pressure Comming established colony (Henry er al-, 1967). chemical state of 'catabolism', that is, breakdown of metabolic compounds to enhancing receptor binding of norepinephrine.) 160 In all such animal models, when the acute or semi produce energy. Corresponding to states of relaxation is a biochemical state of ic arousing stimulus is removed, the blood pressure falls. However, when the arousing stimulus is made "anabolism'. that is. a rebuilding of energy stores, repair, and growth (Mason, logically active peptides increases as techniques in molecular biology advance. All chronic and removed only after a rather long period, the pressure may remain 1972)- physiologically active substances and processes discovered so far are regulated elevated. Thus, after many months of elevation in to an avoidance The catabolic mobilization accompanying arousal is accomplished by shifts in and therefore fluctuate with shifts in demand corresponding to shifts in behavioral 100 conditioning paradigm. the high pressure in monkeys becomes sustained (For- essentially all the known hormones. Catabolic hormones (those that promote syth. 1969). Similarly, the elevated pressures evok energy production), e.g. epinephrine, norepinephrine, cortisol (glucocorticoids), Table 34.2 Hormonal pattern during arousal response" by chronic brain stimulation also become sustained, even when the growth hormone, glucagon, and thyroxine, increase, Anabolic hormones (those Catabolic hormones increase Anabolic hormones decrease stimulation ceases (Folkow and Rubinstein, 1965). The elevated pressures in a that promote growth and repair), e.g. insulin, estrogen, an mouse colony fall when the stranger is removed, but only if less then 6 months has crease. The timing of these changes is complex because certain hormones, such as Cortisol (glucocorticoids) epinephrine, cortisol, and growth hormone. so mobilization and rise (b) 40 5 elapsed; thereafter the pressure remains high even when the stranger is gone epinephrine 20 22 02 OB almost instantaneously (seconds to minutes), while others, such as thyroxine and Testosterone Time (hours) (Henry er al.. 1967). the sex hormones, have slow rise or fall over longer Glucagon Estrogen FIG. 34.2 (a) Arterial pressure from a normal subject plotted at 5-minute intervals. (b] The question arises as to what other physiological parameters besides blood periods (hours to weeks). Other hormones that indirectly support energy produc- Growth bo Prolactin Luteininzing hormone Arterial pressure from a hypertensive subject. (Redrawn from Bevan er ev, 1969.) pressure covary with behavioral state. The ansu sentially all of them (Table Antidiuretic hormone (vasopressin) 34.1; Mason 1968, 1971, 1972). As blood pressure rises during arousal, there is a tion also change (Mason, 1968). For example, vasopressin (amidiuretic hor Follicle-stimulating ho mone), renin, angiotemsin II, and aldosteronism (see Sterling and Eyer, Areintensin Gonadotropin-releasing hormone (GnRH) troughs of varying size and duration. Some peaks are idemitied with specific dramatic shift in the pattern of blood flow: more to muscle, less to the put, kidney, 1981) and atripopeptin decreases (Eskay or at., 1986). This pattern serves the Aldesicrane (mineralocorticoids) Prolactin-releasing hormone (PRE) and skin. Correspondingly, there is a metabolic mob alization to increase energy aroused state by increasing the rate of circulation through the cardiovascular Erythropoietin behavioral states and environmental events. For example, the pressure fell AlnopeTin production. Glucose, amino acids, and fatty acids are released from their macro- Thymosina between hours 15 and 16 when the subject was dozing in a lecture, and rose molecular storage forms (glycogen, pr system (Fig. 34.3). Pandharmane Lymphokines sharply at hour 16 when he awakened (briefly) to a jab from a pin. The pressure A list of some hormones associated with the catabolic and anabolic states is Melatonin Cytokines rose at hour 24 (midnight) when the subject engaged in sexual intercourse, and fell Synthesis of the storage forms is halted. Red blood cells and oxidative enzymes in given in Table 34.2. It is notable that quite a few of them have been discovered Thyroid-rele profoundly (as low as 5030 mmHg) during sleep, At hour 08, when the subject the liver increase because these facilitate the By mobilization. Other pro cesses that use energy but that do not contribute to the metabolic mobilization are only recently, e.g. the opiate hormones (enkephalin, dynorphin, and endorphin: Adrenocorticotrophic hormone (ACTH) was preparing to meet his work day, the pressure rose to the preorgasmic level of Akilet al., 1984), the cardiac hormone (atriopeptin: Manning er al., 1985; Eskay er Enkephalin the previous night and remained there for hours. suppressed: the immune response declines as circulating white blood cells de al., 1986, Dillingham and Anderson, 1986), and the immune system hormones Jynorphin opiates crease and the thymus shrinks (Selye, 1956), Wound healing. bone growth and Endorphin (interleukins and thymosins: Goetzl, 1985). The discovery rate of new, physio-

... Show more

Image transcription text

1 Sterling and Eyer 1988 - Allostasi X *Course Hero X 5 Sterling and Eyer 1988 - Allostasi X *Course Hero X + X < > C @ File | C:/Users/domin/Downloads/Sterling%20and%20Eyer%201988%20-%20Allostasis.pdf Q E Sterling and Eyer 1988 - Allostasis.pdf 6 / 11| 67% + andfor psychological state. Thus the contextual fluctuation of blood pressure illustrated in Figure 34.2 is not exceptional. Rather, is exemplifies a critical mechanisms. By controlling all the mechanisms simultaneously, the brain can environment. All of these anticipatory regulations are achieved by allostmic principle of physiology: to maintain stability an organism must vary all the enforce its command. Furthermore, it can effect the changes rapidly. The mechanisms. parameters of its internal milieu and match them appropriately to environmental existence of these multiple, mutually reinforcing mechanisms is of great thera- The insight provided by the allostatic model, that specific appetites serve demands. We refer to this principle as allostasis, meaning 'stability through pextic significance, as we shall see. anticipatory mechanisms for physiological regulation, is crucial. It makes compre- change'. The hormones and metabolites whose levels in allostasis are set by the brain hensible the relation between physiological need, diet, and pathology. An also feed back to the brain, where they reinforce the original command. These individual's tendency to eat salt and his kidney's tendency to save salt are driven in feedbacks, like the feedforward mechanisms, also have the general form of a concert by the same hormones (aldosteronismgiotemsin II; Figure 34.3) as MECHANISMS OF ALLOSTASIS cascade. For example, the hormones angiotensin II and aldosteron part of an allostatic response to arousing stimuli. Because salt consumption and peripheral roles in raising blood pressure are shown in Figure 34.3, affect multiple To create allostatic fluctuations, connections are required from brain to soma. salt excretion are matched to the level of arousal by means of neuroendocrine Such connections, elucidated in considerable detail by new methods introduced regions in the brain. Angiotensin stimulates the area postrema in the medulla to mechanisms, they cannot logically be considered 'excessive'. If anything is to be -Many others over the last few decades, are now known to be extremely rich. Electron cause further neural drive on the heart, vessels and kidney. Angiotensin also acts Pre ] cess considered 'excessive' in the sense that it leads to pathology, it must be the level of on the hypothalamus to increase release of vasopressin (Miselis, 1986). Most arousal itself. activated microscopy permits nerve terminals to be visualized in direct contact with specific ACTH TSH remarkably, angiotensin and aldosteroni cause the kidney to types of cell, and immu endorphin save salt, act on the brain to increase the appente for sam (Zhang er al., 1983). This application of antibodies to specific neurochemicals. Such methods show that cells makes perfect sems e is served by both mech- ALLOSTATIC REGULATION OF THE IMMUNE RESPONSE most of the classical endocrine glands are contacted by cells in Sammonatin" anisms: increase the available salt in order to support the elevation of blood The organism's response to an infectious agent involves an extraordinary web of HCG OH UPSH pancreas that secrete insulin, glucagon, and somatostatin are directly innervated; so are cells in thyroid that secrete calcitonin (see Sterling and Ever, 1981). Organs pressure. The newly discovered saltwater regulatory hormone, atriopeptin, is centrally organized, mutually reinforcing connections between the brain, endo- also found in the brain (Standaert er at, 1986). at formerly consi crine, and immune systems. To fight a virus optimally requires: (1) recognizing it Allostasis, because it involves the whole brain and body rather than simply local endocrine cells and these too are under neural control, for example cells in kidney as foreign, (2) selectively producing white blood cells (lew ocytes) to attack it feedbacks, is a far more complex form of regulation than homeostasis. Yet it or stimulating lation that crete renin (see Sterling and Ever, 1981) and in h specifically and not the body's own cells, (3) suppressing viral replication by offers definite advantages. One is that it permits a fine matching of resources to atriopeptin (Eskay er al.. 1986). Tissues previously thought to be free of nerves. raising body temperature, (4) redirecting metabolic needs. In homeostasis, negative feedback mechanisms, uninformed as to need, for example the metabolically active surfaces of bone (Hohmann er al., 1986) and activities, and (5) suppressing activities (and the hormones that promote them) force a parameter to a specific "setpoint". If blood pressure were actually deter- cells in tissues of the immune system such ass and lymph node that would compete with these needs. Thus, even though the immune system can mimed in this way, that is, set to an average. 'normal" value, it would almost the bode now known to be innervated (Felten er al., 1985). All blood vessels, including esponse to the virus through local ho FIG. 34.4 Multiple pathways for the brain's influence on the immune system and for brain itself, are richly inne invariably be too high or too low for whatever was going on rated. Thus, required to develop full response. The brain needs information regarding the Allostasis provides for continuous re-evaluation of need and for continuous signals from the immune system to the brain. (See Goetzl (1985) for details.) through nerves to every tissue and especially to all the internal signalling systems intensity of the infectious challenge so that it may weigh the seriousness of readjustment of all parameters toward new setpoints. This makes the most uch as the endocrines. blood vessels, and he system demands. The brain also needs me isms to suppress the immune response in effective use of the organism's resources. The brain also synthesizes its own hormones which it releases into the blood; case other demands are more pressing (Kanigel, 1986; Goetzl, 1985). the opiate hormones also act on the brain to promote euphoria (Barnes, 1986; Another advantage of allostasis is its design for anticipating altered need and It has been discovered recently that secrete a host of Shavit ed af., 1965). Interleukin ILI binds to thermoregulatory neurons in the dozens are now identified, with the certainty that more are still to come. Each achieving the necessary adjustments in advance. In hom chemical factors, called lymphokines and cytokines, that affect the brain (Figure hypothalartru e a rise in metabolic rate (e.g. by promoting TSH sues and organs, need creates an 'error' signal, negative feedback mechanisms may try to correct 34.4; Hall er al., 1985: Felten et al., 1985). These include many pep hormones secretion and thus activation of the thyroid) (Besedovsky er al, 1986). ILI also (2) peripheral endocrine secretions that in turn affect tissues, and (3) pituitary the error. but by then the required resources may and the time secretion of that are also secreted by endocrine glands such as the adrenal and pituitary promotes sleep. Interferon acts peripherally to block viral replication and on the needed for correction may be too long, Errors corrected by negative feedback can (Blalock et al., 1985). For example, leucocytes can release ACTH (Smith et al brain to cause lethargy. Thymosin B, pr ut of the cellular example, vasopressin released by the brain causes blood vessels to constrict, the get dangerously large. For example, if one is called upon to leap into action from a immune response in the thymus and also binds in the hypothalamus to promote y to decrease urine output, and the heart to increase blood output. It also 1986), endorphins (Smith et al., 1945), enkephalin (Zurawski er al., 1986), and sitting position, blood pressure to the head tends to fall as blood d release from pituit- thyroid-stimulating hormone (TSH; Geenan er al., 1986). The amount of ACTH secretion of luteinizing ho romotes elevation of sex hormones imulates aldosteronism from the adrenal, and lower body by gravity, Homeostatic mechanisms would correct this, of course, but that in turn promote anabolic chemistry, mood, and behavior (Hall ez al-, 1985). ary. All these actions of vasopressin tend to increase blood pressure. Thus, neural released is substantial-enough to evoke from the ad rise in cortisol control is multileveled, with the general form the error signal (fall in blood pressare so the head) would be associa Thus, if the response to the virus were the only coping demand, the organism e Figure 34.3)- comparable to that produced by moderate arousal (Besedovsky et al., 1986). momentary dizziness. The most advantageous time for resetting is before one All the elements in the cascade tend to be mutually reinforcing and this provides There are additional factors secreted by leuco would tend to develop fever and go to sleep, accompanied by dreams of nurtur- leaves the chair. ance and pleasure that promote the endocrine state optimal for supporting its the brain with powerful means to override local nega Similarly, if blood pressure is to be elevated. the time to save salt and water to leukins, and interferons (Figure 34.4; Goetal, 1945). All of these secreted factors. as in the case of hormones that control blood pressure, have local effects and also developing immune response. that would tend to oppose its commands. This can be appreciated in Figure 34.3, support the rise is at the moment of elevation and not after much salt and water which summarizes the multiple mechanism for raising blood pressure. Clearly, if reinforcing effects on the brain. The details are far from completely clear. but the On the other hand, if for some reason the level of arousal is very high, the brain has been lost to urine so that new supplies are required. Further, if the elevation is the brain raised pressure only be increasing cardiac output, pressure would tend to to be sustained, new supplies will be needed eventually and the time to seek them following examples may give some feeling for the broad organization. will evoke secretion of much higher levels of ACTH, cortisol, and the other be reduced automatically by local mechanisms for vascular dilatation and remall The glucocorticoid hormones, whose secretions are evoked by leucocyle catabolic hormones (Bourne er al., 1974). The immune system and the inflamma is before the body's supply is exhausted. Finally, there is no way for a homeostatic excretion of salt and water. Similarly, if the brain raised pressure by suppressing ACTH, suppress production of leucocytes except for those that specifically bind tory response will be suppressed until the arousal resolves (Laudenslager et al., regulatory system to benefit from experience. One learns to get up from the chair 1983; Keller eraf., 1983; Schleiffer es af., 1985). Then the body and brain can turn salt-water excretion, cardiac output would be reduced automatically by local slowly if dizziness is a problem and to bring supplies of water and salt to a dry the infectious agent. Thus, these hormones play a key role in the development of selectivity in the immune response (Besedovsky ex al., 1985). ACTH, cortisol, and their attention once again to internal affairs and fight the infection. This general

... Show more

Image transcription text

1 Sterling and Eyer 1988 - Allostasi: X *Course Hero X 5 Sterling and Eyer 1988 - Allostasi X *Course Hero X + X < > C @ File | C:/Users/domin/Downloads/Sterling%20and%20Eyer%201988%20-%20Allostasis.pdf Q E E Sterling and Eyer 1988 - Allostasis.pdf 8 / 11 - 67% + scheme may help explain why one often falls ill immediately after a period of cultural adaptation to ensure regular periods of physiological, interpersonal, and intense arousal. The internal challenge has already been present for some time but spiritual anabolism, lis progressive corruption in modern society reflects the continued unrestricted expansion of arousing activities and the loss of a potential- part, why blood pressure in humans that is first labile in response to arousal can the symptoms have been suppressed. When the level of catabolism called forth by become permanently regulated at much higher than normal levels long after the the brain falls to a certain level, the ngaged by the system y important source of anabolic time. chronically arousing stimuli are gone. Figure 34.2b, a 24-hour recording from a lymphokines and cytokines are then asserted. Thus, as for the cardiovascular When demand and thus arousal become chronic, the brain-body system adapts hypertensive individual, gives some feeling for this point. It can be seen that the system, the critical reason for having feedforward connections from the immune at essentially all levels of organization. The muscle in blood ves and so becomes more effective in raising blood pressure. On the other hand, when pressure is not fixed at a specific level, but is modulated over a considerable range, system to the brain is to permit allostasis, enabling the brain to weigh the internal the muscle is maximally relaxed, it no lowers the pressure quite as much falling in sleep and rising by day, just as the normal individual whose record was versus external demands and to allocate resources accordingly. Furthermore, since the vessels are now always more constricted, they require shown in Figure 34.2a. There continues to be allostatic regulation, but the average higher blood pressure than formerly to maintain the same resting blood flow setpoint is much higher than normal. REGULATION OF AROUSAL (Folkow and Neill, 1971; Lund-Johanson, 1984). The vascular system becomes in a sense "addicted" to higher pressure. PATHOLOGY FROM CHRONIC AROUSAL Weiss (1972) documented four factors that regulate arousal. He measured the extent of gastric ulceration in pairs of rats 24 hours following their exposure to the Similarly, the body becomes addicted to its own catabolic hormones. Many One may expect. because arousal alters the level of virtually every regulatory hormones act by binding to specific protein 'receptors' on the surfaces of and intervals, ulceration in both rats was severe. However, when one rat was provided inside cells. It is now appreciated that a hormone's potency depends on the chemical in the body and affects the metabolism and function of every system, that chronic arousal would lead to a variety of pathologies. Figure 34 5 indicates some with a warning signal before each shock, its ulcers were greatly reduced comp number of its receptor molecules available for bis of the main pathologies of the renal cerebral-cardiovascular system and how they to the control rat which received the identical shocks. the hormone. Chronic elevation of a hormone generally leads to downward regulation of its receptors (see Fried and Miller. 1963). T ore, to obtain arise in a cooperative n In by arouse prevent some shocks by pressing a lever, its ulcers were fewer than in the control The main problems are that chronic hypertension damages blood vessels in every rat which received the identical number of shock given effect eventually requires a larger dose of the hormone, To the extent the organ and that elevated cholesterol and other blood lipids cause atherosclerosis in inescapable. When, following a lever press, a signal was provided to indicate a subjective states such as appetite and mood are regulated by hormones binding to damaged vessels. Add to that increased viscosity and clotting tendency of the correct response, ulcers declined still further. Thus, predictability, a sense of receptors in the brain, there will tend to be addict blood, and the potential for rupture or occlusion of vessels in kidney, brain, and control, and feedback all permit the organism to reduce its level of arousal. s. the higher the chronic levels of one's own opiates, cortisol, ACTH. heart becomes significant. Chronic stim However, when demand, that is, the rate of required response, is made very high, angiotensin, and so on, the more depend compromised heart by continuing signals of arousal, as well as by drugs whose consumption tends to these factors are overridden and the ulcers increase. them high. When the level of arousal has been high for a long period due to high FIG. 34.5 Multiple mechanisms for renal, cer These experiments have been repeated in rats using several measures of demand, entry into a relaxed condition may create an unpleasant state of accompany arousal (e.g. nicotine and caffeine), increase the chances of sudden arenal, cerebral and cardiovascular pathology from coronary death (see Sterling and Byer, 1981). chronic arousal. (Reprinted from Sterling and Eyer, 1981.) immune response se with the same result, The random, inescapable shocks cause withdrawal from one's own catabolic hormones. This could provide a physio logical basis for an individual's continuing to seek conditions of high demand Diabetes, the fifth leading cause of death in the US, is a condition in which immune suppression. When there is predictability, control, and feedback with "workaholicm', Type A behavior). regulation of carbohydrate, fat, and protein metabol s abnormal. Its sequelae regard to the shocks, the immune suppression declines, but when the demand for are accelerated atherosclerosis and other forms of cardiovascular deterioration, ly contribute to colon cancer. The allostatic model suggests connections between bar pressing to prevent shocks is elevated, the hume system is once more Another neurophysiological mechanism for adaptation to chronic arousal is that the brain tends to create fixed automatisms out of previously flexible increased protein breakdown, reduced imm appetite and physiological state; therefore, the modern craving for nicotine, suppressed (Schleiffer er af., 1965; Keller er af., 1983; Laudenslager et al, 1983), alcohol, fat, and fiberless food may all be related to appetites driven by chronic The Weiss experiment usal in anticipatory responses. Just as a bell that has come to presage food cause hormonal pattern in childhood onset diabetes, lowered insulin and elevated glucagon, resembles the hormonal pattern of arousal. This is not to say that arousal. The progressive contamination of our environment by asbestos, radia- humans-for example, they omit the role of psychological defense mechanisms salivation and a rise in insulin, so do hosts of signals. previously neutral, come to arousal causes the disease, but it certainly exacerb symptom see Wolff er al., 1964)-but they make presage arousing events and automatically reinfo ms, This has tion, and organic chemicals is widely recognized to contribute to cancer. This is been shown clearly for diabetic children in families in which interparental conflict not linked to chronic arousal in any single individual; nevertheless, like the lapsing purpose of the aroused state is to allow a pe" physiologically. subjective states. One potential consequence of all the mechanisms men be switched is discharged through the child (Minuchin er bates of the Sabbath already noted, it reflects a change of values that arises from and behaviorally, and emotionally with specific environmental demands. When the that specific genes whose activities are ass helps to reinforce chronic arousal as a societal pattern, irreversibly into the active state (Reisine ev al,, 1956; Yamamoto 1985). IF the timing of insulin secretion is abnormal so that the hormone is relatively environmental demands are iden ineffective and ultimately causes down regulation of its ov Cancers are also regulated by the body's in ne and endocrine systems. when coping has been successful, arousal must be followed by a period of were so for the penes controlling f the catabolic hormones or Cuatrecasas, 1977), Chronic arousal would send to exacerbate this conditon since Immunosuppressed humans and animals develop cancer at up to one hundred relaxation. This allows anabolic hormone their receptors, the chronically aroused state could persis objectively arousing situations. Thus there are pathways at all levels from that of the arousal hormones tend to antagonize insulin. Chronic arousal, because it times the mormal rate (Harris and Sinkovics, 1970). Female mice chronically energy stores, the immune system, gut lining, and so on. It also allows restoration tends to suppress insulin secretion, may also be one of the initi the genes, receptors, tissues, neural systems, subje ve states, and the social dull-onset aroused by handling and exposure to strangers st zetion of cortisol. of a relaxed subjective state so that intimate social relations and spiritual ties can suppressed immune organs such as the thymus, and die at higher rates and earlier system that send through natural adaptive mechanisms to become addicted to diabetes. This disorder is especially prevalent among the obese. The prevalence of be restored that tend to be disrupted by the agonistic moods and behavior obesity is greatest in the most disrupted segments of the population, leading one ages of virally evoked mammary tumors (Riley, 1975). In this case it appears that accompanying arousal. (In this context, it must be appreciated that essentially all chronic arousal and thereby make it permanent; the catabolic hormones. including epinephrine, cortisol, A The tendency for the physiological consequences of chronic arousal to become to wonder whether the appetite for food, like salt, may be strongly driven by the replication of the oncogenic virus is also directly stimulated by cortisol () self-maintaining is evident in the studies already cited. This includes the failure of catabolic hormones of chronic arousal. 10, 1985). Rats subjected in the Weiss paradigm to inescapable and unpredictable TRH, and the opiates. in addition to their metabolic effects, tend to elevate Cancer. another leading cause of death at older ages, is connected in several shock develop tumors at higher rates than animals who can prevent or predict the mood. suppress fatigue and pain, and promote agonistic behavior (see Nemeroff blood pressure in monkeys. cats, and mice to return to normal when the chronically arousing stimuli are removed, It probably also explains, at least in ways to arousal level. There are external factors such as drug consumption and shocks (Schleiffer er af., 1955). Recently, specific genes have been discovered and Dunn, 1984).) From this point of view one might consider the Sabbath as a diet. Thus smoking contributes to lung cancer and alcohol consumption to cancers whose activities are related to the development of cancer. It has been learned that of the liver and pancreas, while excess animal fat and deficiency of fiber apparent the proteins coded by at least two of these so-called oncogenes are identical in structure to the receptor molecules for thyroid hormone and cortisol (Sap et al., tion of responsiveness is not limited (for reasons already noted) to the therapeuti 1986; Weinberger er af.. 1986). Thus, some of the molecules that help determine cally targeted parameter. The drug treatments that reduce the tolerance of a Yet, the experience of several decades with mass drug treatment for hypertension hypertensive person for exercise may also render him lethargic and impotent (see has raised doubts regarding its true practicality. Long-term drug treatment for REFERENCES whether cells become cancerous are direct targets for certain catabolic hormones. Sterling and Ever 1981). mild and moderate hypertension reduces mortality from stroke but increases Abrams, 1. er al. (1972). Suicidal behavior in chronic dialysis patients. American Journal

... Show more

Image transcription text

1 Sterling and Eyer 1988 - Allostasi X *Course Hero X 5 Sterling and Eyer 1988 - Allostasi X *Course Hero X + X < > C @ File | C:/Users/domin/Downloads/Sterling%20and%20Eyer%201988%20-%20Allostasis.pdf Q E E Sterling and Eyer 1988 - Allostasis.pdf 10 / 11 - 67% + of the liver and pancreas, while excess animal fat and deficiency of fiber apparent- structure to the receptor molecules for thyroid hormone and cortisol (Sap er af., tion of responsiveness is not limited (for reasons already noted) to the therapeuti cally targeted parameter. The drug treatments that reduce the tolerance of a Yet, the experience of several decades with mass drug treatment for hypertension 1986; Weinberger er af., 1986). Thus, some of the molecules that help determine has raised doubts regarding its true practicality. Long-term drug treatment for REFERENCES whether cells become cancerous are direct targets for certain catabolic hormones. hypertensive person for exercise may also render him lethargic and impotent ( see Sterling and Eyer 1981). mild and moderate hypertension reduces mortality from stroke but increases Abrams, H. et al. (1972). Suicidal behavior in chronic dialysis patients. American Journal The allostatic model defines health is a state of responsiveness. A parameter mortality from heart disease (Grimm, 1986, Leven, 1986; Freis, 1986a). Further of Parchistry, 127, 1199. DEFINITIONS OF HEALTH AND APPROACHES TO THERAPEUTICS outside the normal range is not considered 'inappropriate' because more. the various unpleasant and iatrogenic effects of drug treatment cause 1. H., Watson, S.J., Young, E., Lewis, ME., Kalchaturian, H., & Walker. M.J. enough patient non-compliance that pressure in the population remains uncon- J. Endogenous opioids: biology and function. Asquel Review of Neurascience, 7. The homeostatic model defines health as a state in which all physiological every parameter is controlled by a multitude of mutally reinforcing signals. If a trolled. In fact, blood pressures in the large (baby boom) cohort that has 2:23 235. mechanisms forcing it there, and most likely the ultimate source of these signals is experienced increased competition and chronic arous Barnes. D. (198). Steroids may influence changes in mood. Science, 232, 1344. parameters have 'normal' values. A value outside the normal range is said parameter has a value above or below normal, most likely there are multiple Berkson, J. (1962). Mortality and marital status. American Journal of Public Health, $2. "inappropriate', and thus a candidate for 'treatment'. The main treatment is to than they were in the preceding small cohort at the corresponding age despite the 1318. administer drugs that stimulate or suppress the somatic mechanisms that most the brain. In this model, the elevated blood pressure of the hypertensive is considered to be entirely appropriate, and the question for exploration becomes wide availability of antihypertensive drugs (Eyer, 1980). Physicians enthusiastic ernard, C. (1865). An introduction to the study of experimental medicine. New York: directly control that parameter (Taylor and appropriate to what?'. about drug treatment for 20 years have sh red their claims and are Dover Publications. (Published ] pressure is above 14090 mmHe, drugs are directed at the three basic mechanisms now recommending for mild hypertension simple follow-up visits and possibly iesedovsky. H. at al. (1985). Immune-neuro endocrine interactions. Journal of immuno- that raise the pressare: diuretics to re The elevation of blood pressure may be appropriate to the arousing conditions relaxation training. diet and exercise (Chesney ex al-, 198 senssky, H, er al. (1986). Immuneregulatory feedback between interleukin-1 and vasodilators to increase the size of reservoir; antagonists of the beta-receptor to of modern life. The chain of evidence linking the o anditions of life to this disorder is now fairly complete. First. there is the epidemiological and behavioral evi- The highly technological treatments for the end-stages of disease related to lucacorticoid hormones. Science, 233, 652-654. reduce the heart's output. To block one of these echanisms is sometime dence: (1) hypertension is greatest among human populations subjected to chronic arousal are also proving to be of dubious practicality. Coronary artery Sevan, AT. eraf. (1969). Direct arterial pressure recording in unrestricted man. Clinical adequate, but frequently, as would be Scimet, 369, 329. the brain uses the other mechanisms to compensate. Thus, a diuretic-induced disruption of intimate social relations, (2) the bypass grafts (CABG) successfully reduce pain from angina but contribute hardly Malock, J. eval. (1985). Peptide hormones shared by the neuroendocrine and immunologic reduction of blood volume begins essentially at the moment children leave the family bosom and enter the at all to longevity (see Sterling and Eyer, 1981; Chairman er al., 1986; Cameron er al., 1986). Kidney dialysis and transplantation prolong Systems. Journal of Immunology, 135(1), Supply, 858-861. uncertain and deman life but at great psycho- Jumenthal, S. eral. (1977). Report on the task force on blood pressure control in children. and by vasoconstriction; drug-induced vasodilatation is compensated by in- ment of school, (3) hypertension can be pro 1972). Treatments for the major cancer creased cardiac output, and so on (see Sterling and Eyer, 1981), When such duced experimentally in populations of animals by social disruption and in logical cost to the patient (Abrams er Pediatrics, 59. Supple, 197- individual animals by arousing behavioral paradigms. Next, there is broad have been largely unsuccessful (Kolata, 1986). The technological approach is also ourne, H.R. er al. (1974). Modulation of inflammation and immunity by cyclic AMP compensations occur. additional drugs can be administered until all three Science. 184. 19. mechanisms have been blocked. Another pharmacotherapy in the same spirit is to physiological evidence: (1) many neural a very expensive. There are now about 250 000 CABGs per year in the US, at a cost of nearly $8 billion (Rimm ex al., 1986). When the large cohort comes of age for Cameron, A. er al. (1986). Bypass surgery with the internal mammary artery graft: available to elevate blood pressure and thus potentially to cause hypertension (see binding of this hormone to its receptors. These are potent treatments because Figure 34.3), (2) chronic hypertension can this surgery, these figures might easily double. The e of medical care now anson, W_B. (1929). Bodily changes in pain, hunger, fed changes in pain, hunger. fear and rage: An account of receiv stimulating the brain regions that activate these near and neuroand absorbs about 12% of the US GNP, and still grows. To continue on this path of researchers ino me function of emotional excitement, 2nd edn. New York; Appleton. angiotensin has many actions that affect all three of the somatic mechanisms for increasing pressure and many sites in the brain as well (see Figure 34.3). Further. anisans, (3) these mechanisms are demonstrated to be active in the natural highly technological treatment will progressively limit the possibilities for other Cannon, W.D. (1932). The wisdom of the body. New York W.W. Norton. uses of the social product. What proves practical in the long run may not be Rered. [1956). The role of coronary bypass surgery for 'left main equivalent" J. Circulation, 74. (Supp. [Il). Ill-30. in animals, blocking the central action of angiotensin is shown to reduce salt state under the arousing behavioral condi ciated with the development of technology but rather investment in social structures and activities that rebuild coronary diseases; the hypertension, (4) pharmacological suppression of one mechanism for raising 6). Behavioral treatment of beed hesney, M.A. er al. (1956). Behavioral treatment of borderlite hypertension, Cardio- appetite (Weiss et al., 1986; Moe er al., 1984). Varcaver Journal of Pharmacology. 8. (Supply 5). 557 563. The pharmacological approach, despite its impressive ingenuity, contains an pressure is compensated by the other mechanisms, and this suggests that the and enrich communal life, that reduce demand and enhance predictability, iinshan, M A-, & Anderson, R.J. target pressure is set by the brain. control and feedback. demon, R.J. (1946). Inhibition of vasopressin action by atrial inherent tendency toward iatrogenesis. Because each hormone has multiple naturetic factor. Science, 231, 1572-1573." effects and each receptor type (alpha, beta, angiosensin, etc.) is widely distri- Chronically elevated blood pressure is 'appropriate' in the allostatic model but askay. R.. Zakowska-Grojoc, Z., Haass, M., Dave, J.R.. & Zamir. N. (1986). Circulating it is certainly not healthy. When pressure is at high levels, there is no margin for SUMMARY AND CONCLUSIONS e peptides in comcious rats: regulation of release by multiple factors. buted, every drug directed at restoring one parameter to normal necessarily atrial natiur Science, 2121. 636-638. uses other parameters to become nappropriately' responding to additional challenges or to opportunities for relaxation, Further- 'Homeostasis'. the central model in physiology and therapeutics for 100 years, is the diuretic treatment causes potassium to become inappropriately low an more. high pressure leads inevitably to serious organic pathology (see Figure Ever. J. (1975). Hyperica Hypertension so a disease of modern society. International Journal of superseded by a new model. "allostasis', that emerges from recent studies in Health Services, $, glucose. cholesterol and uric acid to become gh (Gifford, 1974). 34-5). Thus the allostatic model provides a scientific framework for recognizing Ever, J. (1930). Social causes of coronary heart disease. Prychotherapy and Paychampma- Consequently. the pharmacological reduction of blood pressure reduces the the obvious, that health requires a decent balance between catabolism and neurobiology. Homeostasis emphasized that the body's internal environment is WCS, 34. 15 67. chances of a stroke, but the other effects increase the chances of a heart attack anabolism. held constant by the self-correcting (negative feedback) actions of its const ver. J., & Sterling, P. (1977), Stress-related mortality and social organization, Review of Radical Porncal Economics, 9. 1-16. (Grimm, 1986; Leren and Helgeland, 196) The therapy suggested by the allostatic model is to reduce arousal. A prime organs, Allostasis emphasizes that the lieu varies to meet perceived rugs are commonly objective. following the Weiss paradigm, would be to reduce demand by em and anticipated demand. This variation is achieved by multiple, mutually rein- elten, D. er af. (1985). Noradrenergic and peptidergic innervation of lymphoid tissue. administered to restore these other parameters to normal (see Sterling and Eyer, forcing neural and neuroendocrine mechanisms that override ide the homeostatic Journal of Immunology, 43 . 755-365. 1981). Thus the therape ed with the homeostatic model is couraging people to rest and play in proportion to their work and striving and to increase predictability, control, and feedback lives. Such steps would mechanisms. The allostatic model. in emphasizing the subordination of local Follow, B., & Neil, E. (1971). Cireadstion. London an. Londone Oxford University Press. inevitably associated with polypharmacy and iatrogenesis. Follow. B., & Rubinstein, E.H. (1960). Cardiovascular effects of acute and chronic feedbacks to control by the brain, provides a strong conceptual framework to The other serious drawback is that the resp simulation of the hypothalamusc defense area in the rat. Acre Physiologics Scandingrics, siveness of the organism is reduce all the neural and neuroendocrine drives on the multiple mechanisms for raising blood pressure. In contrast to pharmacotherapy, where blocking one explain social and psychological modulation of physiology and pathology. reduced. Pharmacological treatment that tries to clamp some parameter at its "normal' value naturally prevents it from responding to increased demand a mechanism evokes compensatory increases in others, reducing arousal would forsyth, R.P. (1969). Blood pressure responses to long-term avoidance schedules in the Acknowledgements unrestraised thesus monkey. Psychosomatic Medicine, 37, 300. moments when that would be desirable. With blood pressure clamped low, the reduce pressure by the concerted action of multiple mechanisms, itis. E.D. ine mild systemic hypertension: should it be tremed? Atser. tolerance of a drug-treated hypertensive person for exercise is diminished, even Prevention and treatment of hypertension directed at the social and psycho- We thank Professor Charles Kahn for suppesting the term 'allostasis', Dr Noga fiology, 38.(7), 642-645. 86b). Symposium on borderline hypertension. Journal of Car- though exercise might be therapeutic (L Vardi for reading the manuscript, and Ms Judy Jackson for typing. D. (ed) (1986b). Symp 984). Further. the reduc- logical levels are widely considered impractical compared to pharmocotherapy Govascular Pharmacology 5, Seppl. 5.

... Show more

 

 

Answer & Explanation
Verified Solved by verified expert
Rated Helpful
<p>s ante, dapibus a molestie consequat, ultrices ac magna. Fusce dui lectus, congue vel laoreet ac, dictum vitae odio. Donec aliquet. Lorem ipsum dolor sit amet, consectetur adipiscing elit. Nam lacinia pulvinar tortor nec facilisis. Pellentesque dapibus eff</p> Fusce dui lectus, congue vel laoreet ac, dictum vitae odio. Donec aliquet

Unlock full access to Course Hero

Explore over 16 million step-by-step answers from our library

Subscribe to view answer

    ur laoreet. Nam risus ante, dapibus a molestie consequat, ultrices ac magna. Fusce

    • ipsum dolor sit amet, consectetur adipiscing elit. Nam lacinia p

    rem ipsum dolor sit amet, consectetur adipiscing elit. Nam lacinia pulvinar tortor nec facilisis. Pellentesque dapibus

    • Fusce dui lectus, congue vel laoreet ac, dictum vitae odio. Donec aliquet. Lorem ipsum dolor sit amet, consectetur adipiscing elit. Nam lacinia pulvinar tortor nec facilisi

    ultrices ac magna. Fusce dui lectus, congue vel laoreet ac, dictum vitae odio. Donec aliquet. Lorem ipsum dolor sit a

    • ec facilisis. Pellentesque dapibus efficitur laoreet. Nam risus ante, dapibus
    Step-by-step explanation

    or nec facilisis. Pellentesque dapibus efficitur laoreet. Nam risus ante, dapibus a molestie consequat, ultrices ac magna. Fusce du

    • congue vel laoreet ac, dictum vitae odio. Donec aliquet. Lorem ipsum dolor sit amet, consectetur adipiscing elit. Nam lacinia pulvinar tortor nec facilisis. Pellentesque dapibus efficitur laoreet. Nam risus ante, dapibus a molestie consequat, ultrices ac magna. Fusce dui lectus, congue vel laoree

    ur laoreet. Nam risus ante, dapibus a molestie consequat, ultrices ac magna. Fusce

    • sque dapibus efficitur laoreet. Nam risus ante, dapibus a molestie consequat, ultrices ac magna. Fusce dui lectus, congue vel laoreet ac, dictum vitae odio. Donec aliquet. Lorem ipsum dolor sit amet, consectetur adipiscing elit. Nam lacinia pulvinar tortor nec facilisis. Pellentesque dapibus efficitur laoreet. Nam risus ante, dapibus a molestie conse

    rem ipsum dolor sit amet, consectetur adipiscing elit. Nam lacinia pulvinar tortor nec facilisis. Pellentesque dapibus

    • or nec facilisis. Pellentesque dapibus efficitur laoreet. Nam risus ante, dapibus a molestie consequat, ultrices ac magna. Fusce dui lectus, congue vel laoreet ac, dictum vitae odio. Donec aliquet. Lorem ipsum dolor sit amet, consectetur adipiscing elit. Nam lacinia pulvinar tortor nec facilisis. Pellentesque dapibus efficitur laoreet. Nam risus ante, dapibus a molestie consequat, ultrices ac magna. Fusce dui lectus, congue vel laoreet ac, dictum vitae odio. Donec aliquet. Lorem ipsum dolor sit amet, consectetur adipiscing elit. Nam lacinia pulvinar tortor nec facilisis. Pellentesque dapibus efficitur laoreet. Nam risus ante, dapibus a molestie consequat, ultrices ac magna. Fusce dui lectus, congue vel laoreet ac, dictum vitae odio. Donec aliquet. Lorem ipsum dolor sit amet, consectetur adipiscing elit. Nam lacinia pulvinar tortor nec facilisis. Pellentesque dapibus efficitur laoreet. Nam risus ante, dapibus

    ultrices ac magna. Fusce dui lectus, congue vel laoreet ac, dictum vitae odio. Donec aliquet. Lorem ipsum dolor sit a

    • ultrices ac magna. Fusce dui lectus, congue vel laoreet ac, dictum vitae odio. Donec aliquet. Lorem ipsum dolor sit amet, consectetur adipiscing elit. Nam lacinia pulvinar tortor nec facilisis. Pellentesque dapibus efficitur laoreet. Nam risus ante, dapibus a molestie consequat, ultrices ac magna. Fusce dui lectus, congue vel laoreet ac, dictum vitae odio. Donec aliquet. Lorem ipsum dolor sit amet, consectetur adipiscing elit. Nam lacinia pulvinar tortor nec facilisis. Pellentesque dapibus efficitur laoreet. Nam ris

    Student review
    100% (1 rating)