STRESS*YOUR FRIEND YOUR FOE

OBJECTIVES

Overview Definitions Physiologic effect on organ systems Stress effect on immune system Coping style modify the effect of stress

DEFINITIONS

STRESS: A dynamic state within the organism in response to a demand for adaptation.

STRESSOR: Any stimulus that produces a demand for adaptation

GAS: A stereotypic response to stress

OVERVIEW

Immobilized patient example Acute response: Trying to help

Increased norepinephrine/epinephrine cortisol and 17-hydroxy cortisol We have not evolved for chronic stress

EVOLUTION

Evolved to run from lions; gather food; recover from acute injuries and infections

Not adapted to chronic illness; stress of the “modern world”

Chronic illness could not happen-would die first.

Acute response is helpful, delayed response often harmful

FIGHT OR FLIGHT

Lion is chasing you Heart: increased rate and output, shunt to

muscles Brain: increased arousal, reflexes,

aggression and anxiety Metabolic: increased circulation of glucose

and fatty acids, inhibit water excretion

MEDIATION OF FIGHT OR FLIGHT

Catecholamines: Get the Hell out of Dodge

epinephrine/norepinephrine secreted from the adrenal medulla

Cortisol: Acute repair/volume expansion; don’t have time for anything else

secreted from adrenal medulla

GENERAL ADAPTATION SYNDROME

Three phase response

Alarm phase (fight or flight)

Catabolic phase

Recovery phase

GAS-Stereotypic Response

Acute disturbance of the internal milieu “Counteracting” neutralizing forces are

adaptive What if you climb a tree and lion is still

there for a week?? Or hospitalized for weeks and immobilized??

End up with the catabolic phase

CATABOLIC PHASE

Decreased protein synthesis and cell turnover Immune system and GI tract

Get infections and need H2 blockers Increased cholesterol/free fatty acids, insulin

resistance Water retention Arteriosclerosis worsens, diabetes control and

hypertension

WALTER CANNON

Homeostasis and internal milieu Concept of feedback mechanisms Direct response of the body to acute stress Hans Selye took the concept to the “next level”- “Next level” term is a “conditional stressor”.

Stressful secondary to association

WOLF

Learning and conditioning: Not all stressors are equal

“Unconditional”: independent of setting (lion chasing you)

“Conditional stressor”: hear the term next level-biologically insignificant. Significant only through association and learning

STRESS SENSITIZATION

Repeated contact will result in increased response- “Conditioning”

Neurotransmitter and genetic changes Long-term change in sensitivity of

synapses Oncogenes c-for and c-jun: neuronal

plasticity.

KINDLING

Series of sub-seizure stimuli primes the pump (resting membrane potential)

Becomes more active until a seizure occurs

Autonomous seizures develop secondary to molecular learning medicated by the oncogene systems changing synaptic strength

STRESS DIATHESIS

Catabolic phase results in oncogene initiation regardless of the stressor

Variability in the oncogene sensitivity to stress. What stresses some is fun to others

“Bow up you knucklehead” But remember effect of conditional

(indirect or symbolic stressor)

HYPOTHALAMIC PITUITARY-ADRENAL SYSTEM

Corticotrophin releasing hormone (CRH/F)

ACTH in pituitary/cortisol from adrenal ACTH is part of the prohormone

proopiomelanocortin (POMC) (ACTH/MSH/beta-endorphin)

CRH is potent stimulator of locus ceruleus

NEUROTRANSMITTERS AND HPA AXIS

Acetylcholine and serotonin stimulate ACTH release

Tryptophan increased with increased free fatty acids and get more serotonin

Continued stress and use up your tryptophan-serotonin depletion

appetite, sleep, concentration and mood

TRANSMITTERS (CONT)

From the locus ceruleus-stimulated by ACTH

Feedback loop to inhibit further ACTH release

GABA inhibits CRF release: Give benzodiazepine acutely

beta-endorphin and enkephalin (opiate receptors) “runners high”

STRESS AND IMMUNOLOGY

Humoral and Cellular systems are affected by stress

Cut down inflammation-give steroid or produce cortisol- running from that lion, that’s what you want. For about 30 minutes to 1 hr stress is helpful.

But feedback so you don’t have auto-immune trouble.

IMMUNE RESPONSE (CONT)

Moderately prolonged/chronic stress or frequent episodes of stress are the damaging aspect

IMMUNOLOGY

Very complicated, but remember a few things: ACTH inhibits NK cells

Epinephrine releases T-suppressor Norepinephrine enhances NK cells Herpes virus example- “old”brain can’t tell the

difference

ROLE OF THE CNS

HPA axis is the most important-learn this well

Midbrain and anterior hypothalamic lesions inhibit anaphylactic response

amygdala and hippocampus lesions increase mitogenic response

Condition during stress

CONDITION THE IMMUNE SYSTEM

Ader experiment Wanted to suppress the immune system

of rats Paired saccharine with cyclophosphamide NK cell conditioning is another example Subtle differences in CNS development

can lead to atopic or allergic susceptibility

INDIVIDUAL VARIABILITY

Effect of conditioning and early experience Coping: comprised of Early experience, genetic stock,

comorbidity and temperament “Re-condition” of early experience and

treatment of co-morbid depressive and anxiety disorders

LEARNING

Parachutist analogy Fear/stress activates the amygdala:

amygdala activation facilitates ACTH secretion Where did this blood come from?

Hippocampus is inhibitory: Highest concentration of cortisol receptors I need to remember this dangerous situation

BEHAVIORAL EFFECTS

Cushing’s disease: cortisol excess Pituitary tumor/adrenal tumor, but more

commonly iatrogenic with synthetic steroids

Depression or mania can be present Addison’s disease (JFK): inactive adrenal POMC, “suntan”, affective component

What difference does it make

Learn and adapt. Get back on that horse. What seems to be important is “Control”

and “Mastery”. A surgeon will impose “Control” when

stressed. Will yell and cuss you to displace stress.

You do serve a purpose.

CHRONIC ILLNESS

Social ties/support Inescapable shock Patients and caregivers need emotional

support AIDS and CD4 count Positive attitude-Denial not always a bad

thing. Hope and Faith

BEHAVIOR MODIFICATION

Slow angiogenesis of tumors Change in diet for hypertension/diabetes Don’t hand out smiley faces!! False hope

crashes and you are worse off Face the facts and get busy. Learn what

you have control over and what you don’t.

OTHER TOPICS

Reproductive function Memory Reduced growth Premature aging Poverty as a stressor and effect on health

ADAPT OR SENSITIZE

Will amygdala and “old” endocrine system predominate Natural forces

Will “newer” frontal cortex predominate Takes effort. Basis for behavioral

modification. Social engagement brings frontal cortex “online”.

Why Zebras Don’t Get Ulcers Robert M. Sapolsky