STRESS

ALI GARATLI,MDKFMC

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Stress Response Savior to Killer232.flv

The Stress Response SystemCannon proposed that the stress response (fast) was a fight‐or‐flight response marked by the outpouring of epinephrine and 

norepinephrine from the  inner adrenal glands, increasing 

heart and respiration rates, mobilizing sugar and fat, and dulling 

pain.

Physiological Responses to Stress

Endorphins are released

Pupils dilate to admit more light for more sensitive vision

Mucous membranes of nose & throat shrink while muscles force wider opening of passages to permit easier air flow

Secretion of saliva decreases

Bronchi dilate

Perspiration increases –evaporation cools body

Liver releases sugar into blood stream –energy for muscles and brain

Bone marrow throughout body produces more while blood cells

Hearing becomes more acute

Heart rate increases

Spleen releases more red blood cells

Adrenal glands release adrenalin and noradrenalin resulting in increased blood pressure, increased heart rate, increased fatty acids in blood stream and increased blood sugar

Voluntary skeletal muscles contract throughout the body

Pancreas decreases secretion

CRF & Stress

CRF plays an important role in stress responseStress exposure is associated with ↑CRFCentral CRF administration is associatedwith fear-related behaviors

↓ exploration↑ startle↓ grooming

Main biological pathways of chronic stress:

- Dysregulation of the hypothalamus-hypophysis-adrenocortical (HPA) axis and the sympathetic-adrenal-medullary system (SAM) resulting in elevations in serum catecholamin and cortisol levels. Sympathoadrenal hyperactivity contributes to the development of CVD through effects of catecholamines upon the heart, blood vessels and platelets. Sympathoadrenal activation modifies the function of circulating platelets

Stress and IllnessLeading causes of death in the US in 1900 and 2000

Stress and DiseaseNegative emotions and health-related consequences

Unhealthy behaviors(smoking, drinking,

poor nutrition and sleep)

Persistent stressorsand negative

emotions

Release of stresshormones

Heartdisease

Immunesuppression

Autonomic nervoussystem effects

(headaches,hypertension)

stress is the result of the perceived demands outweighing the perceived capability to cope

This perception is influenced by a number of factors:

personality, situational demands, previous experiencesResources any current stress state already existing

Good things about stress

Sometimes it will save your life, or help youFightAccidentTest…

Stressful Life EventsChronic Stress by Age

Stress and Individual Differences

HardinessA characteristic of people who can tolerate stress well or even thrive on it

ResilienceAbility of a person to “bounce back” after a stressful event

Self-imposed stress

Coping With Stress

Direct copingIntentional efforts to change an uncomfortable situationConfrontation⌧Acknowledging stress directly and initiating a solution

Compromise⌧Choosing a more realistic goal when an ideal goal cannot be

met

Withdrawal⌧Avoiding a situation when other options are not practical

Compromise

Sources of Extreme Stress

UnemploymentStages of relief, optimism, doubt, malaise, cynicism, Divorce and separationAmbivalence, feelings of failure, sadness, and fear

Bereavementاسهم

Signs of stress

Physical: headache, sleep disorders, racing heart, trembling, wt loss or gainMental: constant worry, forgetfulness, mood swings, loss of sense of humorEmotional: anger, anxiety, negative thinkingBehavioral: critical attitude of others, impulsive actions, withdrawal from relations, alcohol abuse

Gender differences

There are no fundamental gender differences in physiological adaptation processesAlthough male and female hormones influence it in both respectEstrogenes decrease the stress reactivityAccording to animal studies, males appear to be more vulnerable to long-lasting stress-induced hippocampal damage than females (Uno et al, J.

Neurosci,9,1705-1711,1989), the decline of circulating testosterone levels resulting from uncontrollable stress seems to play an additional role. Perinatal processes might result in dysregulation- post-natal depression

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•Improper functioning of the subunit could impair the GABA system’s ability to adapt to hormone fluctuations during the highly vulnerable post partum period

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Started before conceptionStress in pregnant mother can have detrimental effect .Increased cortisol , fetus will shift to a protection mode , from growth modeChild will be vulnerable for later CAD, DM

Early life chronic stress:Phases of disruption of mother-infantor peer bonding:1. "protest" behaviour (acute and resistance phases of stress). 2.“despair”: locomotor inactivity and a disinterst in motivationally salient external stimuli. 3."detachment""hardwired" in the brain of many social mammals and results in high stress vulnerability

Attachment theory (Bowlby, Imre Hermann)

Physiological, psychological and developmental importance of the early childhood affective mother-child bond and the negative consequences of the disruption of this relationship. According to follow up studies, insecure attachment predicts later emotional instability and health deterioration. Maltreatment at an early age can have enduring negative effects on a child’s brain development and function, and on his or her vulnerability to stress.

Special gender roles, crucial effect of maternal care

Maternal neglect behaviour results in attachment disturbances Naturally occuring variations in maternal care alter the expression of genes that regulate behavioral and endocrine responses to stress, as well as hippocampal synaptic development – related to oxytocin receptor gene expression (M.J.Meaney: Ann Rev

Neurosci2001, 24,1161-1192)

Learned helplessness as result of chronic stress

A condition of loss of control created by subjecting animals or humans to an unavoidable, emotionally negative life situation (such as unavoidable shocks, relative deprivation, role conflict, etc). Being unable to avoid or escape (flight or fight) an aversive situation for a long period of time produces a feeling of helplessness that generalises to subsequent situations.

Brain consequences of learned helplessness:

The hippocampus is primarily affected by the long-lasting elevations of circulating corticosteroids resulting from uncontrollable stress. Severe stress for a prolonged period causes damage in hippocampal pyramidal neurons, especially in the CA 3 and CA4 region and reductions in the length and arborization of their dendrites.

Stress and Illness

General Adaptation Syndrome

Selye’s concept of the body’s adaptive response to stress in three stages

Stressresistance

Phase 1Alarm

reaction(mobilize

resources)

Phase 2Resistance(cope with stressor)

Phase 3Exhaustion(reservesdepleted)

The body’s resistance to stress canlast only so long before exhaustion sets in

Stressoroccurs

Stage 1: Alarm

= stress response – stressor has been detected and a response made to alarm. Adrenaline is produced leading to fight or flight activity.

Stage 2: Resistance

= Apparent coping, if stress continues it is necessary to find some means of coping and resist collapse. In this stage the body is adapting to the demands of the environment, but at the same time resources are being used up. Thus = apparent coping because in reality things are deteriorating

Stage 3: Exhaustion

= breakdown, onset of stress-related illness. Eventually the body can no longer maintain normal functioning.

Initial physiological changes may appear, e.g. sweating, increased heart rate. The adrenal gland (produces adrenaline) may be damaged due to over activity and the immune system may unable to cope due to the production of proteins being needed elsewhere = ulcers, depression, cardiovascular problems etc

More GAS

3) ExhaustionDefenses depleted at this pointVery vulnerable

Lots of this is badLeads to destruction of hippocampal cells caused by cortisol releaseSo, memory loss!

Hippocampal Volume Reduction In PTSD

NORMAL PTSD

MRI scan of the hippocampus in a normal control & patient with PTSD secondary to childhood abuse. The hippocampus, outlined in red, is visibly smaller in PTSD. Overall 12% reduction in volume in PTSD.

(Bremner 1995; Bremner1997)

↑ Cortisol↑ Cortisol

NormalNormal

Other neuronal insults:

Hypoxia-IschemiaHypoglycemiaNeurotoxinsViruses

Other neuronal insults:

Hypoxia-IschemiaHypoglycemiaNeurotoxinsViruses

Normal Survival &

Growth

Normal Survival &

Growth

StressStress AntidepressantsAntidepressants

Genetic FactorsGenetic Factors

↓BDNF↓BDNF

Survival & GrowthSurvival & Growth

Serotonin & NE↑

Serotonin & NE↑

↑ BDNF↑ BDNF↓↓

( Duman, Heninger & Nestler 1997)

Cortisol

Atrophy & death

Questions

Can stress, anxiety, depression, social support, and optimistic view alter our ability to resist infection, autoimmune diseases or cancer?

What are the biological pathways through which psychological state or characteristic will influence in disease susceptibility?

Can we alter immunity and therefore disease susceptibility through psychological intervention?

1981 David Felten: Discover a “hard-wire connection between the immune system and the CNS (trace nerves to bone marrow, lymph nodes, thymus and the spleen) Psychoneuroimmunology (PNI): study of interrelations between the CNS and the immune system (David Felten, 1981)Existence of neurologic terminations directly into lymphoid tissues in the spleen and release of neurochemicals in this location2000 Bellinger: NA innervation of BM, thymus , spleen and nodes in animal models (immune system cells have adrenergic receptorsreceptors for NE ): Herbert, 1994; Bachen, 1995

Human research: establish the association between psychological states and immunity

Psychoneuroimmunology

B lymphocytes fight bacterial infections, T lymphocytes attack cancer cells and viruses, and microphages ingest foreign substances. During 

stress, energy is mobilized away from the immune system making it vulnerable.

Lennart Nilsson/ B

oehringer Ingelhein International Gm

bH

Immunity and DiseaseHow the immune system works

Stress and ColdsPeople with the highest life stress scores were also 

the most vulnerable when exposed to an experimental cold virus.

Stress and Heart Disease

Adrenal CORTEX

Cortisol(associated with long-term effect of stress) – loss of control

Adrenal MEDULLA

Adrenalin (associated with acute or short term response to stress.

Increased FFA, increased Platelet numbers, increased Serum Cholesterol, decreased Potassium, direct injury producing effect of coronary artery walls.

Increased Platelet stickiness,direct injury producing effect on

coronary artery walls, over contractibility of myocardium, increased FFA, shearing effect on plaques

resulting in clotting system.

GP IIb/IIIa Receptor Final Pathway to Platelet Aggregation

o Platelet activation and aggregation are early events in the development of coronary thrombosis

o GP IIb/IIIa receptors on activated platelets undergo a conformational change allowing recognition and binding of fibrinogen

o Fibrinogen”acts like glue”,bridging GP IIb/IIIa recptors on adjacent platelets, leading to platelet aggregation

Pathophysiology in Motion

yIncreases the Risk of a Heart Attack

1. Stress Hormones (Cortisol & Adrenaline) elevate Blood Pressure.

2. Adrenalin increases blood platelet stickiness.3. Cortisol increases blood platelet numbers.4. Adrenalin & Cortisol have a direct injury-

producing effect on artery walls (contributes to atherosclerosis).

5. Adrenaline causes over-contractibility of heart muscle (rupture fibers?).

6. Cortisol increases cholesterol levels and lowers potassium levels.

INTERHEART: Measured Factors

Stress and the HeartStress that leads to elevated blood pressure may result in coronary heart disease, a clogging of the 

vessels that nourish the heart muscle.

Plaque incoronary artery Artery

clogged

Stress and the Heart

Hopelessnessscores

3.5

3

2.5

2

1.5

1

0.5

0 Heart attack DeathLow risk Moderate risk High risk

Men who feel extreme hopelessnessare at greater risk for heart attacksand early death

Stress and type A’ person ,competitive, hostile /aggressive, time-conscious, ‘workaholic’ and easily frustrated with others.Respond to life events with impatience and hostility 70%of this sort of person died from heart attacks –Have two fold risk of CV disease and 5-fold risk of MI

1970s, Friedman and Rosenman

Stress and the Heart

Stress, Depression and Heart DiseaseManaging Stress

Learn to accept things you can’t change. You don’t have to solve all of life’s problemsCount to 10 before answering or responding when you feel angryDon’t use smoking, drinking, overeating, drugs or caffeine to cope with stress

. They make things worse

Coping with stress

Assert yourself: honest and upfrontExercise regularlyControl what you can and leave that you cantExamine your values and live by themSet realistic goalsSell yourself to yourselfGet enough rest sleep in the dark, early night Eat and drink sensiblyStop smoking

meditationKeep positive attitude

Negative Self Talkwords our inner dialogue uses when we thinkcan increase our stress levels by limiting our potentialCan color our experience in a negative lightWhen you tell yourself something is ‘difficult’ or ‘unfair’, it becomes more stressful to deal with than if you tell yourself it’s a ‘challenge’, or even a ‘test’Patterns of negative self-talk typically begin in childhoodthe negative self-talk habit may have been coloring thinking for yearsCBT

Promoting Positive Self Talk1.Notice your patterns: The first step

toward change is to become more aware of the problem. You may not realize how often you say negative things in your head, or how much it affects you

2.Journal Writing: keeping a journal can be an effective tool for examining your inner process.

3.Thought-Stopping: As you notice yourself saying something negative in your mind, try to alter your thought mid-stream my saying to yourself “Stop”.

Methods of Reducing Stress

Calm downExerciseRelaxation training

Reach outSocial support network

ReligionStudies have shown an association between religion and lower stressMay be related to social support

AltruismGiving to others because is gives you pleasureShown to be a good way to reduce stress

Coping With Stress at College

Plan aheadPrioritizeExerciseListen to music, watch TV, or go out as a study breakTalk to othersMeditate or use other relaxation techniques

The Key Word Is….Balance

Sleep-Wake Cycle:Role of Endogenous Melatonin

Circadian and Homeostatic Regulation of Sleep

Wake

Sleep

Wake Propensity

9 am 3 pm 9 pm 3 am 9 amAsleepAwake

Melatonin

Sleep Drive

Circadian Alerting

Signal