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Physiologyof Stress

To understand the stress response, we must possess a fundamental knowledgenot only of psychology but of physiology as well.—George Everly

Hans Selye’s discovery of a direct relationship betweenchronic stress and the excessive wear and tear throughoutthe body laid the foundation for a clearer understand-ing of how physiological systems work in an extremely

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complex and integrative way. Perhaps be-cause of this discovery and the fact thatphysical deterioration is so noticeable, muchattention has been directed toward thephysiology of stress. This chapter will takeyou through some basic concepts that ex-plain the physiological dynamics involvedwith the stress response—specifically, theimmediate, intermediate, and prolonged effects on the body. These processes will beexplained in terms of “pathways,” whichset in action the systematic and integrativesteps of the stress response. Because physi-ology involves specific nomenclature out-side the realm of your everyday vocabulary,you may find the nature of this chapter tobe very specific and its contents very de-tailed. Most likely it will merit more thanone reading to fully grasp, understand,and appreciate how the body responds tostress. The importance of a strong familiarity withhuman physiology as influenced by stressful stimuli becomes evident when the necessary steps are taken toeffectively deal with the symptoms they produce, espe-cially when using relaxation techniques. For example,it is important to know how the body functions whenusing specific imagery, visualization, music therapy,and biofeedback.

In many circles, this topic of study is referred to as psy-chophysiology. This term reflects the fact that a sensorystimulus that prompts the stress response must beprocessed at the mental level before it can cascade downone or more physiological pathways. In other words, theterm psychophysiology suggests that there is a mind-body relationship and supports the theory that many dis-eases and illnesses are psychosomatic, meaning that theirorigins lie in the higher brain centers. Although themind-body dualism suggested by Descartes is no longera viable model for a complete understanding of humanphysiology, to hold an appreciation of the “whole per-son” we must first examine the parts to understand howthey connect to that whole.

Three systems are directly involved with the physiologyof stress: the nervous system, the endocrine system, andthe immune system, all of which can be triggered by per-ceived threats. Because the immune system is so closelylinked to the disease process, it will be dealt with sepa-rately in Chapter 3.

Psychophysiology: A field of study based on the principle that the mind and body are one, wherethoughts and perceptions affect potentially all as-pects of physiology.

Central nervous system (CNS): Consists of thebrain, spinal column, and peripheral nervous system(PNS), comprising all neural pathways to the extremities.

Reticular activating system (RAS): The neuralfibers that link the brain to the spinal column.

The Central Nervous SystemThe nervous system can be divided into two parts: thecentral nervous system (CNS), which consists of thebrain and spinal cord, and the peripheral nervous system(PNS), comprising all neural pathways to the extremities.The human brain is further divided into three levels: thevegetative level, the limbic system, and the neocorticallevel ( ).

The Vegetative LevelThe lowest level of the brain consists of both the reticu-lar formation and the brain stem. The reticular forma-tion, or more specifically the fibers that make up thereticular activating system (RAS), is the link connect-ing the brain to the spinal cord. Several stress physiolo-gists believe that it is the bridge joining the mind and the

FIG. 2.1�

Three levels of the human brain: vegetativelevel, limbic system, and neocortical level.

FIGURE 2.1

NeocortexCingulate gyrus

Frontal lobe

Septal area

HypothalamusPituitary gland

AmygdalaHippocampus

Thalamus

Reticular formationSpinal cord

Neo

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body as one; this organ functions as a communicationslink between the mind and the body. The brain stem,consisting of the pons, medulla oblongata, and mes-encephalon, is responsible for involuntary functions ofthe human body, such as heartbeat, respiration, and vaso-motor activity. It is considered the automatic-pilot con-trol center of the brain, which assumes responsibility forkeeping the vital organs and vegetative processes func-tioning at all times. This level is thought to be the mostprimitive section of the human brain, as this portion issimilar to those of all other mammals.

The Limbic SystemThe second or mid-level portion of the brain is called thelimbic system. The limbic system is the emotional con-trol center. Several tissue centers in this level are directlyresponsible for the biochemical chain of events that con-stitute the stress response Cannon observed. The limbicsystem consists of the thalamus, the hypothalamus, theamygdala, and the pituitary gland, also known as themaster endocrine gland. These four glands work in uni-son to maintain a level of homeostasis within the body.For example, it is the hypothalamus that controls ap-petite and body-core temperature. The hypothalamusalso appears to be the center that registers pain and plea-sure; for this reason it is often referred to as the seat ofemotions. The combination of these functions in the hy-pothalamus may explain why hunger decreases whenbody-core temperature increases in extreme ambientheat, or why appetite diminishes when you are ex-tremely worried. Research evidence is clear that fear isfirst registered in the amygdala. When a threat is en-countered, the hypothalamus carries out four specificfunctions: (1) it activates the autonomic nervous system;(2) it stimulates the secretion of adrenocorticotropic hor-mone (ACTH); (3) it produces antidiuretic hormone

(ADH) or vasopressin; and (4) it stimulates the thyroidgland to produce thyroxine. All of these will be dis-cussed in greater detail later.

The Neocortical LevelThe neocortex is the highest and most sophisticated levelof the brain. It is at this level that sensory information isprocessed (decoded) as a threat or a nonthreat and wherecognition (thought processes) takes place. Housed withinthe neocortex are the neural mechanisms allowing one toemploy analysis, imagination, creativity, intuition, logic,memory, and organization. It is this highly developedarea of brain tissue that is thought to separate humansfrom all other species.

As Figure 2.1 illustrates, the positions of these structuresare such that a higher level can override a lower level ofthe brain. Thus, conscious thought can influence emo-tional response, just as conscious thought can intercedein the involuntary control of the vegetative functions tocontrol heart rate, ventilation, and even the flow ofblood. This fact will become important to recognizewhen learning coping skills and relaxation techniquesdesigned to override the stress response and facilitatephysiological homeostasis.

Separate from the CNS is a network of neural fibers thatfeed into the CNS and work in close collaboration withit. This neural tract, the peripheral nervous system(PNS), comprises two individual networks. The first isthe somatic network, a bidirectional circuit responsiblefor transmitting sensory messages along the neural path-ways between the five senses and the higher brain cen-ters. These are called the efferent (toward periphery)and afferent (toward brain) neural pathways. The sec-ond branch of the PNS is called the autonomic nervoussystem (ANS). The ANS regulates visceral activitiesand vital organs, including circulation, digestion, respi-ration, and temperature regulation. It received the nameautonomic because this system can function without con-scious thought or voluntary control, and does so most, ifnot all, of the time.

Research conducted by endocrinologist Bruce McEwenindicates that initially a stressful encounter is etched intothe memory bank (so as to avoid it down the road), butthat repeated episodes of stress decrease memory byweakening hippocampal brain cells. Chronic stress isthought to wither the fragile connection between neuronsin this part of the brain, resulting in “brain shrinkage.”

Until recently it was believed that, unlike the voluntarysomatic system involved in muscle movement, the ANS

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limbic system: The mid-level of the brain, includingthe hypothalamus and amygdala, which is thought tobe responsible for emotional processing.

Autonomic nervous system: Often referred to as theautomatic nervous system, the ANS consists of thesympathetic (arousal) and parasympathetic (relaxed)nervous systems. This part of the central nervous sys-tem requires no conscious thought; actions such asbreathing and heart rate are programmed to functionautomatically.


could not be intercepted by conscious thought, but nowit is recognized that both systems can be influenced byhigher mental processes. (This will be discussed morein Chapters 25 and 26.) The ANS works in close coor-dination with the CNS to maintain a favorable homeo-static condition throughout the body. There are twobranches of the ANS that act to maintain this homeo-static balance, the sympathetic and parasympatheticnervous systems, and these are activated by the hypo-thalamus. Most organs are innervated (stimulated) bynerve fibers of both the sympathetic and parasympa-thetic systems.

The Autonomic Nervous SystemThe Sympathetic and ParasympatheticNervous SystemsThe sympathetic nervous system is responsible for theresponses associated with the fight-or-flight response( ). Through the release of substancescalled catecholamines, specifically epinephrine (adren-aline) and norepinephrine (noradrenaline), at variousneural synapses, a series of events occurs in severalorgan tissues to prepare the body for rapid metabolicchange and physical movement. Sympathetic drive is

FIG. 2.3 �


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Brain physiology at work. (©Bradford Veley, Marquette, MI.)

FIGURE 2.2

Sympathetic: The branch of the central nervous sys-tem that triggers the fight-or-flight response whensome element of threat is present.

Parasympathetic: The branch of the central nervoussystem that specifically calms the body through theparasympathetic response.

Epinephrine: A special neurochemical referred to asa catacholamine, which is responsible for immediatephysical readiness for stress including increasedheart rate and blood pressure. It works in unisonwith norepinephrine.

Norepinephrine: A special neurochemical referred toas a catacholamine, which is responsible for immedi-ate physical readiness to stress including increasedheart rate and blood pressure. It works in unisonwith epinephrine.

Catabolic functioning: A metabolic process in whichmetabolites are broken down for energy in prepara-tion for, or in the process of, exercise (fight or flight).

•••••

•

••

••

••

••

Pupils constricted

Salivary secretion increased

Heart rate decreased

Bronchioles constricted

Intestinal secretions increased

Pupils dilated

Salivary secretion decreased

Heart rate increased

Bronchioles dilated

Intestinal secretions decreased

SympatheticDivision

ParasympatheticDivision

The sympathetic and parasympa-thetic systems. Internal organs

are typically innervated by neural fibers from bothsympathetic and parasympathetic divisions.

FIGURE 2.3

associated with energy expenditure, a process known ascatabolic functioning, where various metabolites arebroken down for energy in preparation for movement.It is the release of epinephrine and norepinephrine that


Stress with a Human FacePerhaps no situation more clearly triggers the fight-or-flight response than face-to-face combat. This was the sit-uation for Geof Steiner, who found himself thrown into theturmoil of the Vietnam War in the late 1960s. Think of howfast your heart beats when you sense someone followingyou in an unlit parking garage. Then multiply this inten-sity by the duration of a whole year—a typical tour ofduty overseas in wartime. This is the level and durationof stress Geof experienced. Long after his return to theStates, Geof found that his memories of the war were stillat his coattails, haunting him and ruining his life. It gotso bad that the only viable option, he surmised, was sui-cide. His attempt on his life quickly brought him to a VApsychiatric hospital. But his problems didn’t end there: Healso battled chronic alcoholism and the ruins of a failedmarriage. When all was said and done, all he had to hisname was a trailer on a dirt road.

At first glance, the woods of Minnesota don’t seem tohave anything to do with the jungles of Vietnam. But thecall of the forest lured Geof out of his trailer into thewoods, where he began to find a peace in nature that hadeluded him with his fellow man. It was this bond thatgave him a vision and a purpose to live. Inspired by na-ture’s life force, Geof bought open tracts of land near andaround his trailer. On this land he vowed to plant a treefor every soldier who died on the soil of Vietnam. Today,in Cushing, Minnesota, stands the Living Memorial Forest,the only living tribute to those who fought in a war thatGeof is still trying to understand. He believes that theforest has helped him and other veterans heal the emo-tional scars and find the inner peace symbolized by thelife of each planted tree.

causes the acceleration of heart rate, the increase in theforce of myocardial contraction, vasodilation of arteriesthroughout working muscles, vasoconstriction of arter-ies to nonworking muscles, dilation of pupils andbronchi, increased ventilation, reduction of digestiveactivity, released glucose from the liver, and severalother functions that prepare the body to fight or flee. Itis the sympathetic system that is responsible for supply-ing skeletal muscles with oxygenated, nutrient-richblood for energy metabolism. Currently it is thoughtthat norepinephrine serves primarily to assist epineph-rine, as the ratio of these two chemical substances re-leased at neural synapses is 5:1 epinephrine to norepi-

nephrine during the stress response. The effects of epi-nephrine and norepinephrine are very short, lastingonly seconds. Because of their rapid release from neuralendings, as well as their rapid influence on targetedorgan tissue, the effects of the sympathetic nervous sys-tem are categorized as immediate.

Just as the sympathetic neural drive is associated withenergy expenditure, the parasympathetic drive is re-sponsible for energy conservation and relaxation. This isreferred to as anabolic functioning, during which bodycells are allowed to regenerate. The parasympatheticnervous system is dominated by the tenth cranial, orvagus, nerve, which in turn is influenced by the brainstem. When activated, the parasympathetic nervous sys-tem releases acetylcholine (ACh), a neurological agentthat decreases metabolic activity and returns the body tohomeostasis. The influence of the parasympathetic driveis associated with a reduction in heart rate, ventilation,muscle tension, and several other functions. Both sys-tems are partially active at all times; however, the sym-pathetic and parasympathetic systems are mutually ex-clusive in that they cannot dominate visceral activitysimultaneously. These two systems allow for the preciseregulation of visceral organ activity, much like the use ofthe accelerator and brake when driving. Sympatheticarousal, like a gas pedal pushed to the car floor, becomes

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Immediate (effects of stress): A neural response tocognitive processing in which epinephrine and nor-epinephrine are released, lasting only seconds.

Anabolic functioning: A physiological process inwhich various body cells (e.g., muscle tissue) regen-erate or grow.

Acetylcholine: A chemical substance released by theparasympathetic nervous system to help the body return to homeostasis from the stress response.


the dominant force during stress, and parasympathetictone holds influence over the body at all other times topromote homeostasis. In other words, you cannot bephysically aroused and relaxed at the same time.

But there are exceptions to the dynamics of these bio-chemical reactions. For example, it is sympathetic nerves,not parasympathetic nerves, that release ACh in the sweatglands to decrease body-core temperature during arousal.And sympathetic and parasympathetic stimulation ofsalivary glands is not antagonistic; both influence the secretion of saliva. In addition, all blood vessels are influ-enced by sympathetic dominance, with the exception ofthe vasculature of the penis and clitoris, which is activatedby parasympathetic innervation.

The Endocrine SystemThe endocrine system consists of a series of glands lo-cated throughout the body that regulate metabolic func-tions requiring endurance rather than speed. The en-docrine system is a network of four components: glands,hormones, circulation, and target organs. Endocrineglands manufacture and release biochemical substancescalled hormones. Hormones are chemical messengersmade up of protein compounds that are programmed toattach to specific cell receptor sites to alter (increase ordecrease) cell metabolism. Hormones are transportedthrough the bloodstream from the glands that producedthem to the target organs they are called upon to influ-ence. The heart, skeletal muscle, and arteries are amongthe organs targeted by hormones for metabolic change.

The glands that are most closely involved with the stressresponse are the pituitary, thyroid, and adrenal glands.The pituitary gland is called the master gland due to thefact that it manufactures several important hormones,which then trigger hormone release in other organs.The hypothalamus appears to have direct influence overit ( ). The thyroid gland increases the gen-eral metabolic rate. Perhaps the gland that has the mostdirect impact on the stress response, however, is the

FIG. 2.4 �


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The endocrine system is an amazing yet delicate systemof chemical properties aligned to ensure physiologicalhomeostasis. The stress hormone dehydroepiandro-sterone (DHEA), for example, is secreted from the adrenalgland. DHEA is known as a sex hormone that decreasesin both production and secretion throughout the agingprocess. Speculation suggests that supplementation ofDHEA might increase stamina and memory, and may de-crease the aging process in much the same way as anti-oxidants; beta-carotene, vitamin C, vitamin E, and sele-nium. Results of a host of studies revealed that nosignificant changes in these aspects occurred in eitheranimals or humans. Some scientists actually suggestedthat increased amounts of DHEA, above what the body

normally produces, might actually promote cancer. Sup-plementation is recommended only on the advice ofyour physician.

Serotonin and melatonin are not stress hormones, yetthey do seem to have an effect on mood. Decreases inboth serotonin and melatonin are thought to be relatedto bouts of depression. Many things affect serotonin lev-els in the brain—from the natural and synthetic chemi-cals in the foods you eat, to the amount of sunlight youreceive in the course of a day, to perhaps things we stilldon’t know. Research is inconclusive about how sero-tonin affects mood. Most likely, stress affects serotoninlevels as well.

BOX 2.1 Hormonal Imbalance

Serotonin: A neurotransmitter that is associatedwith mood. A decrease in serotonin levels is thoughtto be related to depression. Serotonin levels are affected by many factors including stress hormonesand the foods you consume.

Melatonin: A hormone secreted in the brain that isrelated to sleep, mood, and perhaps several other as-pects of physiology and consciousness.

Pituitary gland: An endocrine gland located belowthe hypothalamus, which, upon command from the hypothalamus, releases ACTH and then com-mands the adrenal glands to secrete their stress hormones.

Hypothalamus: Often called the “seat of the emotions,” the hypothalamus is involved with emo-tional processing. When a thought is perceived as athreat, the hypothalamus secretes a substance calledcorticotrophin-releasing factor to the pituitary glandto activate the fight-or-flight response.


adrenal gland ( ). The adrenal gland, a cone-shaped mass of tissue about the size of a small grapefruit,sits on top of each kidney. The adrenal gland has two dis-

FIG. 2.5 �

tinct parts, each of which produces hormones with verydifferent functions. The exterior of the adrenal gland iscalled the adrenal cortex, and it manufactures and re-leases hormones called corticosteroids. There are twotypes of corticosteroids: glucocorticoids and mineralo-corticoids. Glucocorticoids are a family of biochemicalagents that includes cortisol and cortisone, with cortisolbeing the primary one. Its function is to help to generateglucose, through the degradation of proteins (aminoacids) during a process called gluconeogenesis in the liver,as an energy source for both the central nervous system(the brain) and skeletal muscles during physical exercise.Cortisol is also involved in the process of lipolysis, or themobilization and breakdown of fats (fatty acids) for en-ergy. Recent clinical studies have linked increased levelsof cortisol with suppression of the immune system. It ap-pears that cortisol metabolizes (degrades) white bloodcells. A metaphor to illustrate this process is the situationin which you resort to burning the furniture to keepwarm once you exhaust your supply of firewood. As the

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Anterior hypothalamus

Corticotropin-releasing factor (CRF)

Anterior pituitary

Adrenocorticotropic hormone (ACTH)

Adrenal gland (cortex)

Corticosteroids (glucocorticoids and mineralocorticoids)

Glucocorticoids (cortisol)

Mineralocorticoid (aldosterone)

Mobilizes free fatty acidsMobilizes proteinsMetabolizes amino acidsDemineralizes amino acidsInitiates gluconeogenesisIncreases serum glucose levelsDecreases body weightPromotes muscle wastingBreaks down antibodiesImpairs immune systemDepletes vitaminsCauses beta cell depletionDecreases insulin productionIncreases arterial blood pressure

Promotes Na+ retentionEnhances K+ eliminationOsmotic retention of H2OIncreases blood pressure by increasing blood volume

The physiological response tostress.

FIGURE 2.4

Adrenal gland: The endocrine glands that are lo-cated on top of each kidney that house and releaseseveral stress hormones including the catecholaminesepinephrine and norepinephrine, cortisol.

Corticosteroids: Stress hormones released by theadrenal cortex, such as cortisol and cortisone.

Glucocorticoids: A family of biochemical agents thatincludes cortisol and cortisone, produced and re-leased from the adrenal gland.

Cortisol: A stress hormone released by the adrenalglands that helps the body prepare for fight or flightby promoting the release of glucose and lipids in theblood for energy metabolism.

Adrenal medulla

Adrenal cortex

The adrenal gland, made up of theadrenal cortex and medulla, sits

upon the top of each kidney, and is cone-shaped inappearance.

FIGURE 2.5


number of white blood cells decreases, the efficiency ofthe immune system decreases, setting the stage for ill-ness and disease. (This will be discussed in greater detailin Chapter 3.) It has also come to light that increased cor-tisol can direct excess amounts of cholesterol into theblood, thereby adding to associated artery plaque buildupand leading to hypertension and coronary heart disease.Mineralocorticoids, specifically aldosterone, are secretedto maintain plasma volume and electrolyte (sodium andpotassium) balance, two essential functions in the regula-tion of circulation. (The exact mechanisms will be dis-cussed later in this chapter.)

The inside of the adrenal gland is called the adrenalmedulla. This portion of the gland secretes catecholamines(epinephrine and norepinephrine), which act in a similarfashion as those secreted at the endings of sympatheticnerves. The adrenal medulla releases 80 percent epineph-rine and 20 percent norepinephrine. Under the influencesof stress, up to three hundred times the amount of epi-nephrine can be found in the blood compared to theamount in samples taken at rest.

The Neuroendocrine PathwaysEvolutionary adaptations have provided several backupsystems to ensure the survival of the human organism.Not all pathways act at the same speed, yet the ultimategoal is the same: physical survival. First, not only does thehypothalamus initiate activation of the sympathetic ner-vous system to cause an immediate effect (Table 2.1), butthe posterior hypothalamus also has a direct neural path-way, called the sympathetic preganglionic neuron, thatlinks it to the adrenal medulla. Next, upon stimulationby the posterior hypothalamus, the adrenal medulla secretes both epinephrine and norepinephrine. Once in

the bloodstream, these catecholamines reinforce the efforts of the sympathetic drive, which has already re-leased these same substances through sympathetic neuralendings throughout the body. The release of epinephrineand norepinephrine from the adrenal medulla acts as abackup system for these biochemical agents to ensure themost efficient means of physical survival. The hormonalinfluences brought about by the adrenal medulla arecalled intermediate stress effects. Because their release isvia the bloodstream rather than neural endings, traveltime is longer (approximately twenty to thirty seconds),and unlike the release of these substances from sympa-thetic neural endings, the effects of catecholamines fromthe adrenal medulla can last as long as two hours whenhigh levels of secretions are circulating in the blood-stream.

In addition, there is a third and potentially more potentsystem joining the efforts of the nervous and endocrinesystems to prepare the body for real or perceived danger.Neural impulses received by the hypothalamus as po-tential threats create a chain of biochemical messages,


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With the alarming rate of chronic fatigue syndrome, theword in some medical circles is that many Americans suf-fer from adrenal fatigue, due to prolonged stress. What isadrenal fatigue? Because of the amount of chronic stressmany people admit to experiencing, the adrenal glandsbegin to work overtime. Signs of exhaustion and the in-ability to produce and release the host of catecholaminesand hormones for fight or flight, appear to give credenceto Hans Selye’s General Adaptation Syndrome. The symp-toms of adrenal insufficiency include fatigue, dizziness,

low blood sugar (resulting in cravings and subsequentweight gain), and depression. Weak adrenals are associ-ated with the incidence of autoimmune diseases, rangingfrom chronic fatigue syndrome and lupus to rheumatoidarthritis. Due to the complexities of human physiology,poor adrenal function is also associated with aggravatedsymptoms of menopause. Addison’s disease is the namegiven to those with adrenal failure, a condition where theadrenal glands are no longer able to produce and secretethe necessary hormones for metabolic function.

BOX 2.2 Adrenal Fatigue and Adrenal Failure

Mineralocorticoids: A class of hormones that main-tain plasma volume and electrolyte balance, such asaldosterone.

Adrenal medulla: The portion of the adrenal glandresponsible for secreting epinephrine and norepi-nephrine.

Intermediate stress effects: The hormonal responsetriggered by the neural aspects of the adrenalmedulla that are released directly into the blood,lasting minutes to hours.


which like a line of falling dominos cascade through theendocrine-system glands. Because the half-life of thesehormones and the speed of their metabolic reactionsvary in length from hours to weeks in some cases, thischain of reactions is referred to as the prolonged effectof stress.

The ACTH AxisPhysiologically speaking, a biochemical pathway is re-ferred to as an axis. In this section we will discuss theACTH axis. The other two axes, the vasopressin axis

and the thyroxine axis, are covered in the following sections.

The ACTH axis, also known as the hyphothalmic-pitu-itary-adrenal (HPA) axis ( ), begins withthe release of corticotropin-releasing factor (CRF) fromthe anterior hypothalamus. This substance activates thepituitary gland to release ACTH, which travels via thebloodstream to in turn activate the adrenal cortex. Uponstimulation by ACTH, the adrenal cortex releases a setof corticosteroids (cortisol and aldosterone), which act toincrease metabolism and alter body fluids, and thusblood pressure, respectively. The effects of hormones re-leased by the adrenal cortex are considered to be pro-longed because they activate their functions for minutesto hours. Note that increased secretions of cortisol in theblood act primarily to ensure adequate supplies of bloodsugar for energy metabolism. However, when increas-ingly high levels of cortisol are observed due to chronicstress, this hormone compromises the integrity of severalphysiological systems.

The Vasopressin AxisVasopressin or antidiuretic hormone (ADH) is synthe-sized in the hypothalamus but is released by the pituitarythrough a special portal system. The primary purpose ofvasopressin is to regulate fluid loss through the urinarytract. It does this in a number of ways, including waterreabsorption and decreased perspiration. By alteringblood volume, however, it also has a pronounced effecton stroke volume, or the amount of blood that is pumpedthrough the left ventricle of the heart with each con-traction. Consequently ADH has a pronounced effecton blood pressure. Under normal circumstances, ADH

FIG. 2.6 �

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Effects Reaction TimeThe body has several backup dynamics to help ensure physical survival. Here, these dynamics are broken down into categories based on the duration of their metabolic reactions.

Immediate effects Epinephrine and norepinephrine from the 2–3 secondssympathetic nervous system

Intermediate effects Epinephrine and norepinephrine from 20–30 secondsadrenal medulla

Prolonged effects ACTH, vasopressin, and thyroxine Minutes, hours, days, or weeksneuroendocrine pathways

SOURCE: R. Allen, Human Stress: Its Nature and Control (Minneapolis, MN: Burgess, 1983).

TABLE 2.1 Pathways of Stress Response

Prolonged effect of stress: Hormonal effects thatmay take days or perhaps more than a week to befully realized from the initial stress response.

Vasopressin axis: A chain of physiological eventsstemming from the release of vasopressin or antidi-uretic hormone (ADH).

Thyroxine axis: A chain of physiological eventsstemming from the release of thyroxine.

ACTH axis: A physiological pathway whereby a mes-sage is sent from the hypothalamus to the pituitary,then on to the adrenal gland to secrete a flood ofstress hormones for fight or flight.

(HPA) axis: The hypothalamic-pituitary-adrenal axis,a term synonymous with the ACTH axis.

Adrenal cortex: The portion of the adrenal glandthat produces and secretes a host of corticosteroids(e.g., cortisol and aldosterone).


regulates blood pressure by either increasing blood vol-ume (changing the concentration of water in the blood)should it be too low, or decreasing blood volume whenit becomes too high. Under the influence of chronicstress, however, many regulatory mechanisms in thebody lose their ability to maintain physiological home-ostasis. Consequently, the increased secretions of vaso-pressin produced under duress will increase blood pres-sure even when someone already has elevated restingvalues; this is known as hypertension. The purpose ofvasopressin as well as aldosterone, epinephrine, and

norepinephrine is to increase blood pressure to ensurethat active muscles receive oxygenated blood, but underchronic stress in a resting state this hormonal response—the abundance of stress hormones—is literally overkill,leading to hypertension and death due to CHD.

The Thyroxine AxisStimulation in the hypothalamus triggers the release ofthyrotropic hormone–releasing factor (TRF). TRF istransported through a special portal system to the ante-rior portion of the pituitary, where it stimulates the secre-tion of thyrotropic hormone (TTH). Once in the blood-stream, TTH follows a path to the thyroid gland, whichstimulates the release of two more hormones: thyroxineand triiodothyronine. The purpose of these two hor-mones is to increase overall metabolism, or basal meta-bolic rate (BMR). Thyroxine is powerful enough to dou-ble one’s rate of metabolism. Note that the effects of thispathway are very prolonged. Because the production ofthyroxine takes several days, it may be ten days to twoweeks before visible signs manifest as significant symp-toms through this pathway. This explains why you maycome down with a cold or flu a week after a very stress-ful encounter rather than the day after. The metaboliceffects of thyroxine released through this pathway areincreased workload on the heart muscle, increased gastro-intestinal activity (e.g., gastritis), and, in some cases, acondition called cerebration or cerebral excitivity, whichis associated with anxiety attacks and/or insomnia.

A Parable of PsychophysiologyA metaphor can be used to illustrate the three pathwaysdiscussed earlier ( ). Let us say that your lifeis in danger because of a classified CIA document youinadvertently stumbled across, and you now pose athreat to national security. You want to deliver a mes-sage and a copy of this document to your family, wholive a few hundred miles away, to let them know yourlife is in danger. This message is, of course, very impor-tant and you want to make sure your family gets it, soyou use a couple of methods to ensure its delivery. Firstyou immediately place a phone call to your parents’

FIG. 2.7 �


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Stressor

Hypothalamus

Pituitary

ACTH

Stimulation ofsensory nerves

Adrenal Glands

Stress HormonesCortisol

AldosteroneEpinephrine

The Stress ResponseIncreased neural excitabilityIncreased cardiovascular activity Heart rate, stroke volume, cardiac output, blood pressureIncreased metabolic activity Gluconeogenesis: turning glycogen into sugar for energy Protein mobilization Decreased antibody producer Muscle wasting Fat mobilization: for breakdown into sugarIncreased sodium retention (salt)Increase in neurological sweatingChange in salivationChange in GI system tonus and motility

The ACTH axis.FIGURE 2.6

Cerebration: A term used to describe the neurologi-cal excitability of the brain, associated with anxietyattacks and insomnia.


house because it is the quickest way to deliver the mes-sage, and the message is received instantaneously ontheir answering machine. This is like the action of thesympathetic nervous system. As a backup, you send awire via Western Union in case no one listens to the an-swering machine. This form of communication is fairlyquick, taking perhaps minutes to hours, and is equiva-lent to the preganglionic nerve to the adrenal medulla.And because you also need to send a copy of the docu-ment to further explain the contents of your message,you ship a package via overnight mail delivery. Thismeans of communication allows more comprehensiveinformation to be sent, but it takes much longer. It is likethe neuroendocrine pathways. Similarly, our bodies arecomposed of several communication systems, each with

its own time element and function, the overall purposebeing to prepare the body for physical survival. As illus-trated by this story, there are many backup systems, fastand slow, to get the message through.

In the short term, the combination of these variousneural and hormonal pathways serves a very importantpurpose: physical survival. However, when these samepathways are employed continuously due to the influ-ence of chronic stressors, the effects can be devastatingto the body. In light of the fact that the body preparesphysically for threats, whether they are of a physical,mental, emotional, or spiritual nature, repeated physicalarousal suggests that the activation of the stress responseis an obsolete mechanism for dealing with stressors thatdo not pertain to physical survival. The inability of thebody to return to homeostasis can have significant effectson the cardiovascular system, the digestive system, themusculoskeletal system, and, research now indicates, the immune system. Organs locked into a pattern ofoveractive metabolic activity will eventually show signsof dysfunction. For instance, constant pressure and re-peated wear and tear on the arteries and blood vesselscan cause tissue damage to the inner lining of these or-gans. Numerous changes can also occur throughout thedigestive system, including constipation, gastritis, diar-rhea, and hemorrhoids. As was observed by Selye, theinability of the body to return to homeostasis can set thestage for signs and symptoms of disease and illness.

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Like communication networks thatsend and receive messages, the

human body has several complex messenger systems,which not only see that the information gets throughbut also ensure that the body will survive the perceived threat after the message is received.

FIGURE 2.7

Brain chemistry is a complicated subject and our under-standing of it is embryonic at best, but some facts areclear with regard to how brain physiology works. Notonly does an “active” mind release epinephrine and nor-epinephrine in the brain, compromising the ability to fallsleep, but other neurotransmitters—specifically, mela-tonin and serotonin—are affected by a host of daily rit-uals and behaviors, ranging from nutritional habits, caf-feine intake, and sunlight exposure to cell phone use.Melatonin is a hormone secreted in the pituitary of thebrain. This neurotransmitter is not only affected by realand artificial light, but is also thought to be associatedwith both sleep patterns and skin pigmentation. As day-light decreases, the melatonin level increases, giving riseto the belief that increases in melatonin help promotesleep.

The brain neurotransmitter serotonin is partially affectedby light. Decreases in light decrease serotonin levels, afactor associated with seasonal affective disorder (SAD)and depression.

While the use of artificial evening light can alter serotoninlevels, it can decrease melatonin levels, thus affectingnatural sleep patterns (sleep patterns have changed dra-matically since the turn of the twentieth century with theuse of electricity). Cell phone use is thought to decreasemelatonin with similar results. Increased consumption ofcarbohydrates (late-night snacks) can increase serotoninlevels, which may, in turn, affect melatonin levels. Med-ications for depression include selective serotonin re-uptake inhibitors (SSRIs), which act to increase serotoninlevels. This activity may, in fact, act to decrease melatoninlevels, thus affecting a full night’s sleep.

BOX 2.3 Insomnia and Brain Physiology


A Decade of Brain Imaging ResearchPrior to the start of each decade, the medical professionselects one area of human physiology to study in-depth. In1990, the brain was chosen as the target of this research.With the advancement of electromagnetic technologyand magnetic resonance imaging (neuroimaging), scoresof studies have been conducted to determine which as-pects of the brain are active in a variety of mental statesand thought processes (Zimmer, 2003). Only recentlyhave the dots been connected to provide a more accurateunderstanding of this most complex human organ. BruceMcEwen is one researcher working in this area. In hisbook The End of Stress as We Know It, McEwen synthe-sizes much of this information, including the work of hisprotégé Robert Sapolsky, author of the acclaimed bookWhy Zebras Don’t Get Ulcers. Here are some highlightsfrom McEwen’s research:

� The hippocampus and the amygdala togetherform conscious memories of emotional events.

� The hippocampus is highly sensitive to the stresshormone cortisol, which aids in memory forma-tion of stress.

� The hippocampus region is rich in receptor sitesfor glucocorticoids.

� The amygdala is responsible for the emotionalcontent of memory, particularly fear.

� Repeated excessive exposure to cortisol acceleratesthe aging process of the hippocampus and may,in fact, damage or shrink brain cells. Moreover,chronic stress may affect memory and learningprocesses [in Vietnam vets with post-traumaticstress disorder (PTSD), this region of the brainwas 26 percent smaller than in their peers withoutPTSD].

� Research by Sapolsky reveals that damage to braincells (in animals) due to chronic stress appears to beirreversible.

McEwen concludes that the human brain is, indeed,wired for stress, or “allostatic load” as he calls it. Whilesome neurophysiologists have been investigating thestress response in the brain, however, others have beenlooking at states of consciousness. This vein of researchwill be discussed in Chapter 18.


45

Allostatic load: A term coined by stress researcherBruce McEwen to replace the expression “stressedout”; the damage to the body when the allostatic(stress) response functions improperly or for prolonged states, causing physical damage to the body.


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� Psychophysiology is a term to describe the body’sphysiological reaction to perceived stressors, sug-gesting that the stress response is a mind-body phenomenon.

� There are three physiological systems that are directlyinvolved in the stress response: the nervous system,the endocrine system, and the immune system.

� The nervous system comprises two parts: the centralnervous system (CNS) and the peripheral nervoussystem (PNS). The CNS includes three levels: thevegetative, the limbic, and the neocortical.

� The limbic system houses the hypothalamus, whichcontrols many functions, including appetite and emo-tions. The neocortical level processes and decodes allstimuli.

� The most important part of the PNS regarding thestress response is the autonomic nervous system,which activates sympathetic and parasympatheticneural drives. Sympathetic drive causes physicalarousal (e.g., increased heart rate) through the se-cretion of epinephrine and norepinephrine, whereasparasympathetic drive maintains homeostasis throughthe release of ACh. The two neural drives are mutu-ally exclusive, meaning that you cannot be arousedand relaxed at the same time.

� The endocrine system consists of a series of glandsthat secrete hormones that travel through the circu-latory system and act on target organs. The majorstress gland is the adrenal gland.

� The adrenal gland has two parts, each performingdifferent functions. The cortex (outside) secretescortisol and aldosterone, while the medulla (inside)secretes epinephrine and norepinephrine.

� The nervous system and endocrine system join to-gether to form metabolic pathways or axes. Thereare three pathways: the ACTH axis, the vasopressinaxis, and the thyroxine axis.

� The body has several backup mechanisms to ensurephysical survival. These systems are classified as im-mediate, lasting seconds (sympathetic drive); inter-mediate, lasting minutes (adrenal medulla); and pro-longed, lasting hours if not weeks (neuroendocrinepathways). Each system is involved in several meta-bolic pathways.

� Stress is considered one of the primary factors asso-ciated with insomnia. Good sleep hygiene consists ofbehaviors that help promote a good night’s sleeprather than detract from it, including decreased caf-feine consumption, consistent bed times, and a hostof effective relaxation techniques that enhance sleepquality.

� A decade of brain research reveals that humans arehard-wired for stress through an intricate patternof neural pathways designed for the fight-or-flightresponse. Research also suggests that chronic stressappears to atrophy brain tissue, specifically thehippocampus.

1. What role does the nervous system play in thestress response?

2. What role does the endocrine system play in thestress response?

3. Name and explain the three pathways (axes) ofstress physiology.

4. What does new brain imaging tell us about stressphysiology?

SUMMARY

STUDY GUIDE QUESTIONS


47

As noted in this chapter, the stress response has immediate, intermediate, and prolonged effects. To reinforce yourunderstanding of each type, reflect on how your body reacts to stress through these three processes.

1. What do you feel when immediately threatened?

Yes No

a. Tingling sensations

b. Sweating

c. Muscle tension

d. Rapid heart rate

e. Rapid breathing (or holding your breath)

f. Rush of blood to the head and face (feelings of being flushed)

g. Other

2. How would you best classify your body’s intermediate (within hours) response to stress?

a. Tension headache

b. Stomachache

c. Sore neck and shoulders

d. Sore throat

e. Other

f. Other

g. Other

h. Other

3. What do you notice as long-term effects of prolonged (5–10 days) stress?

a. Cold or flu

b. Broken-out face

c. Herpes breakout (around lips)

d. Menstrual period

e. Other

f. Other

g. Other

h. Other

SELF-ASSESSMENT

Physiology of Stress© Jones and Bartlett Publishers. NOT FOR SALE OR DISTRIBUTION

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