The Pathophysiology Of Stress - University Of Washington

The Pathophysiology of Stress(Chronic Stress is Bad)(Overwhelming Stress is Worse)Frank F. Vincenzi, Ph.D.vincenzi@uw.edu

Stressl l l EmotionalEnvironmentalPhysiologicall Stress is a condition or feeling experienced when a personperceives that "demands exceed the personal and socialresources the individual is able to mobilize.” (attributed toRichard S.Lazarus)l "Stress is not what happens to you, but how you react to whathappensl “ we define stress as environmental conditions that requirebehavioral adjustment” (Benson, H. The Relaxation Response,2000, pg. 41).l Thus, change, good or bad, can induce a stress response.(Holmes and Rahe – Life Events Rating Scale)Check your own Life Events Rating Scale at:http://www.mindtools.com/pages/article/newTCS 82.htm

Selected (of 43) Life Change Unitsl l l l l l l l l l l l l l Death of SpouseDivorceJail termDeath of close family memberMarriageFired at workRetirementGain of a new family memberLarge mortgage or loanTrouble with bossChange in residenceVacationChristmasMinor violations of law10073636350474739312320131211Holmes, TH & Rahe, RH, J Psychosomatic Research 11: 213-218, 1967http://www.mindtools.com/pages/article/newTCS 82.htm

Instinct vs. CultureThe acute stress responsewas essential to survival ina time when human beingsfaced many physical threats

Instinct vs. CultureStresses of modern life aremore likely to be chronic andoften psychological andinterpersonal.(e.g., Holmes & Rahe).Unfortunately the bodyreacts to todayʼs stresses asthough it were still facing a realphysical threat.”

Some Major Avenues ofMind-Body Reciprocityl Nervous Systeml Endocrine Systeml Immune SystemOptimally, interaction of these systems maintains homeostasis and wellness

Stress-Induced Changes in theNervous Systeml Classical View of the Autonomic NervousSysteml Parasympatheticl l Rest and restorationSympatheticl Fight or flight

The Parasympathetic Nervous Systeml Integrates the ‘rest & recreation’ (feed & breed)response*l Release of acetylcholineDecreased heart rate & blood pressureDecreased respiratory rate and bronchial constrictionDecreased glycogen to glucose in liverPupillary constrictionl Increased GI activityl l l l *Also known as ʻrest and restorationʼ or ʻrest andRELAXATIONʼ (emphasis added)

The Sympathetic Nervous Systeml Integrates the ʻfight or flightʼ responsel l l l l l Release of norepinephrine & epinephrineIncreased heart rate & blood pressureIncreased respiratory rate and bronchial dilationIncreased glycogen to glucose in liverIncreased pupil diameterDecreased GI activityImportant: Sympathetic responses to acute stress normally dissipatequickly

The Fight or Flight Responsel Integrates the ʻfight or flightʼ responsel l l l l l Release of norepinephrine & epinephrineIncreased heart rate & blood pressureIncreased respiratory rate and bronchial dilationIncreased glycogen to glucose in liverIncreased pupil diameterDecreased GI activity

The Fight or Flight ResponseDissipates Quickly

Sometimes Fight or Flight is notenough

The Autonomic Nervous System:But wait there’s more!l Parasympatheticl l Rest and relaxationSympatheticl Fight or flightFreeze or feigneddeath

The Freeze or Feigned Death Response”Tonic immobility is most useful when a slow-movingvulnerable organism is confronted with a lifethreatening situation involving mobile, large predators.Tonic immobility may enhance survival when a predatortemporarily loosens its grip on captured prey under theassumption that it is indeed dead, providing the preywith an opportunity for escape. It is also a response thatmay be adaptive in humans when there is no possibilityof escaping or winning a /11/30/the-freeze-response/

A New View of the AutonomicNervous System: Polyvagal Theoryl Parasympathetic‘Mammalian’ (myelinated) vagusOrigin in the nucleus ambiguus (ventral)Fine tuning of daily life – especially social intx‘Reptilian’ (unmyelinated) vagusOrigin in the dorsal motor nucleus of the vagusActivated in perceived life-threatening dangerPorges (2011) The Polyvagal Theory, W.W. Norton

Activation of the UnmyelinatedVagusAcute-extreme threat situationsProfound bradycardiaFreezeHypotension, faintingNear death experience ?Chronic – in perceived extreme threat‘The General Inhibition SyndromeʻHelplessness and avoidancePersistent in post-traumatic stress disorderNote: Activation of the reptilian vagus also inhibits the sympatheticnervous system and somatic muscles, inactivating fight or flight.

Polyvagal TheorybyStephen W. PorgesGraphic byRavi Dykema

Some Stress-Induced Changes inEndocrine Functionl Increased cortisol, catecholamines& fatty acidsl Increased blood sugar (see above)l Increased insulin (see above)l Inc (LDL) cholesterol, (dec HDL)Brindley et al. (1993) Metabolism 42: Supp1, 3-15

Homeostasis vs. Allostasisl Homeostasis: balance of systems essential forlife, pH, body temperature, [glucose], pO2l ʻAllostasisʼ: changes in the body that occur as aconsequence of CHRONIC activation ofhomeostatic mechanisms (McEwen et al.)l l l l CatecholaminesHPA axisCytokinesEtc.?

Stress and Development of Allostatic LoadPerception of stress is influenced by one's experiences, genetics, andbehavior. When the brain perceives stress, physiologic and behavioralresponses are initiated leading to allostasis and adaptation. Over time,allostatic load can accumulate, and the overexposure to neural, endocrine,and immune stress mediators can have adverse effects on various organsystems, leading to disease.McEwen (1998) N Engl J Med 338:171-179

Allostatic Overload: Wear and Tear on the BodyCaused by Chronic Stressl l l l l l l l Decreased immune functionsHypertensionAtherosclerosisIncrease platelet reactivityAbdominal obesityBone demineralizationAtrophy of neurons in hippocampus andprefrontal cortexIncreased activity of amygdalaMcEwen (2004) Ann.NY Acad.Sci. 1032: 1-7

Stressassociatedhormonal andneurohormonalchangesHenry and Wang (1998)Psychoneuroendocrinology23: 863-875

Items in the AL indexA clinical allostatic load(AL) is associated withburnout andhypocortisolemic profilesin ‘healthy’ workerscortisolc-reactive proteincreatininefibrinogenglycosylated haemoglobininsulinpancreatic amylasesystolic and diastolic BPtotal cholesteroltriglycerideswaist-hip ratioalbumindehydroepiandrosteroneHDL cholesterolJuster et al. (2011) Psychoneuroendocrinology 36: 797-805

Chronic stressversus ALBurnout symptomsversus ALJuster et al. (2011) Psychoneuroendocrinology 36: 797-805

Hypocortisolemicprofiles in subjectwith high allostaticload index.Juster et al. (2011) Psychoneuroendocrinology 36: 797-805

Stress-Induced Changes in ImmuneFunctionl ʻEustressʼ (acute, physiologically adaptive)l l Increased delayed type hypersensitivity, associated with acutespikes in corticosterone and decreased leukocytes in blood (bymovement to skin)ʻDistressʼ (chronic, physiologically maladaptive)l Decreased delayed type hypersensitivity, associated withchronically increased basal corticosterone and lessdecrease in blood leukocytes (i.e., less movement ofleukocytes to skin)Dhabhar & McEwen (1997) Brain Behav Immun 11: 286-306

Stress and Illness in Practicel l l l Review of audiotapes of primary care practice of patientswith ʻchronic-diseaseʼ (better, chronic illness)439 interactions with 49 physiciansStress was by far the most time consuming topic.Nearly 60% of the discussions were not perfunctory butattempts to counsel or encourage behavior change in thepatient(It has been estimated that 70-80% of primary care visits involve anillness that is caused or augmented by stress)Russell & Roter (1993) Am J Public Health 1993; 83: 979-982

Nortin Hader on NPR Oct 4, 2007Medical care can change what you die of,but does not change much when you die“We can capture about 80% of the mortal risk[of WHEN you die] by the answer to twoquestions:”Are you comfortable in your socio-economic status?Are you happy in your job?Hadler (2004) The Last Well Person: How to Stay Well Despite theHealth-Care System, McGill-Queen’s University Press

Work-Related Stress and Illnessl 10,308 civil servants in the UKl Work stress poor work social support, high jobdemands, and low job controll Associated with increased risk of BMI obesity (oddsratio, 1.73), and waist obesity (odds ratio,1.61)l Men were more likely than women to suffer thenegative effects of job strain in terms of obesity;women did not experience a significant increase inwaist obesity with stress.Brunner et al. (2007) Am J Epidemiol 165:828-837

A Gender Difference in StressManagement?l l l l Female responses are more marked by a pattern of"tend-and-befriend.”!Nurturant activities designed to protect the selfand offspring promote safety and reduce distress!The tend-and-befriend pattern appears to draw onthe attachment-caregiving system!Neuroendocrine evidence suggests that oxytocin, inconjunction with female reproductive hormones andendogenous opioid peptide mechanisms, may be atits core!Taylor et al. (2000) Biobehavioral responses to stress in females:tend-and-befriend, not fight-or-flight, Psychol. Rev. 107: 411-429

The Tending InstinctFight or Flight may assure survival in the short term,but an individual is not likely to survive for long if he orshe tries to go it alone. “Tend and befriend” is criticalto our social nature and is vital to our survival as aspecies.Taylor (2002) The Tending Instinct: How Nurturing is Essential toWho we Are and How we Live, Henry Holt & Co.

In both males and females l Release of oxytocin is stimulated by non-noxiousstimuli:l l l l l l l l Touch, especially massage & consensual sexual activityWarm temperatureVibrationElectroacupunctureOlfactory cluesSocial interactionWith repeated exposures release of oxytocin ishighly conditionableMental images of positive experiences may alter thephysiological state; at least in part via oxytocin

Relaxation andpositive socialinteraction; thelinchpins of“Healing”Uvnas-Moberg (1998) Psychoneuroendocrinology 23: 819-835

Is a deficiency of oxytocin functionassociated with autism spectrumdisorder?

Magnitude of Stressand Cognitive EfficiencyGoleman (2006) Social Intelligence, the new science of human relationships, Random House

Management of Stressl Many techniques – most bring on the ʻRelaxationResponseʼ - typically, at least one technique ʻclicksʼl Exercisel Meditationl silent, focused, prayer, guided (imagery,progressive relaxation), active (yoga, shaking )l Autogenicsl Hypnosisl Mindfulness-based stress reduction (MBSR)

Summary:The BrainMindBody and Stressl Interprets life situations as stressful, or notl Modifies behavior that increases or decreases theallostatic load imposed by perceived stressl Multiple mind/body techniques exist to manage andreduce stress – find what works for you!

demands, and low job control! Associated with increased risk of BMI obesity (odds ratio, 1.73), and waist obesity (odds ratio,1.61)! Men were more likely than women to su"er the negative e"ects of job strain in terms of obesity; women did not experience a significant increase in waist obesity with stress. Work-Related Stress and Illness