N323 - Week 2 (Stress and Disease)

3 Stages of General Adaptation Syndrome (GAS) - Han Selye

1. Alarm stage

2. Stage of resistance (adaptation)

3. Stage of Exhaustion

Alarm Stage

Arousal of body defenses-fight or flight

Stage of resistance (adaptation)

mobilization that contributes to fight or flight

Stage of exhaustion

progressive breakdown of compensatory mechanisms

-may lead to the onset of disease (body becomes more vulnerable due to prolonged cortisol & stress hormones)

What happens in alarm stage?

stressor triggers the hypothalamic-pituitary-adrenal (HPA) axis

-activates the sympathetic nervous system (SNS)

What happens in resistance (adaptation) stage?

begins w/ the axns of adrenal hormones:

-cortisol, epinephrine & norepinephrine

-(body tries to adapt to stress)

What happens in Exhaustion stage?

occurs only if stress continues & adaptation is not successful

What increases in the alarm & adaptation phases?

cortisol by adrenal glands (on kidneys)

-epinephrine & norepinephrine (from adrenal glands)

Hypothalamic-pituitary-adrenal axis (HPA)

See Stressor (see bee w/ our eyes) ->

hypothalamus will release cortisol release hormone (CRH) to anterior pituitary (initial alarm stage) ->

CRH causes release of ACTH from anterior pituitary ->

ACTH acts on adrenal glands of the kidneys to release cortisol

-(cortisol determines adaptation & spreads throughout the body)

HPA axis as a Negative Feedback Loop

Too much cortisol -> stop acting on HPA axis as much if stressor has been removed

Glucocorticoid: Cortisol

is released from adrenal glands due to ACTH

-is lipophilic (-> allows it to easily cross through membranes)

What does cortisol stimulate? (5)

lipogenesis & gluconeogenesis (-> elevates blood glucose levels)

-protein anabolic effect in liver & catabolic effect in out tissues

-poor wound healing

-increased illness susceptibility

-effects on body habitus (sleep deprivation, lipid abnormalities, diabetes, loss of bone density... overtime cortisol can be harmful)

Gluconeogenesis

process by which glucose is made from non-carbohydrate molecules

-allows more glucose to be available for energy & prepare body for stress

-leads to raised glucose levels

Cortisol Effect on the Immune system

T helper (Th) 1 activity is suppressed (s.a NK cells, CD8 cells, etc.)

Th-2 activity is stimulated (increases inflammation throughout the body due to cytokines)

-trying to help body adapt BUT actually leads to prolonged inflammation

Systemic responses to stress may cause..

a decrease in innate immunity and enhance adaptive immunity

Allostasis

how the body maintains homeostasis (despite stressors)

-to avoid crossing into exhaustion stage

Allostatic load

cumulative wear & tear of the body due to stressors

Allostatic overload

constant wear & tear, becomes too much & become out of balance

3 Types of Stress Responses

reactive response

anticipatory response

conditional response

reactive response

involves psychologic stressors

-considered classic stress (see a bee, flight or flight activated)

-leads to physical response

anticipatory response

anticipates a disruption in homeostasis

-worrying abt something that hasnt happened yet (lots of stress!)

-EX: abt to take a test

conditional response

associates a stimulus w/ danger

-may cause posttraumatic stress disorder (PTSD) or phobias

-EX: veterans w/ PTSD

Catecholamines (2)

norepinephrine and epinephrine

Norepinephrine

raises blood pressure by constricting the peripheral vessels

-dilates the pupils of the eye

-causes piloerection

-increases sweat gland axn in the armpits & palms

Epinephrine

has greater influence on cardiac axn (inotropic & chronotropic)

-vasodilation occurs

-metabolic regulation occurs, increasing the glucose levels

epinephrine: Inotropic & chronotropic

inotropic: increases squeeze of heart

chronotropic: increases heart rate, beats faster

Neuropeptide Y (NPY)

is a stress mediator (tries to decrease stress & maintain allostasis)

-is a growth factor for many cells

What can NPY cause?

-chronic release of NPY is implicated in atherosclerosis (thickening of vessel walls) & tissue remodeling

-can alter our fat storage & food intake (-> obesity & diabetes)

-Prolonged exposure can cause harm

Impact of Stress on Reproduction

stress can lead to problems w/ mensuration & fertility

What does cortisol & stress suppress?

cortisol suppresses release of luteinizing hormone, estradiol & progesterone

-stress suppresses hypothalamic gonadotropin releasing hormone (GnrH.. causes release of reproductive hormones)

-(estrogen stimulates HPA axis; leptin inhibits HPA axis)

Stress is directly related to..

proinflammatory cytokines (T cells)

-link btwn stress & immune fxn -> leading to various diseases & cancers

-(EX.. dementia)

Neuroendocrine Factors (stress)

affects immune system

-stress response decreases T cell cytotoxicity & B cell fxn

Potential effects of stress on healthy individuals

w/ ineffective coping, it can lead to stress response or illness

-w/ effective coping, it can have a transient effect (returning to steady state)

Potential effects of stress on symptomatic individuals/patients

w/ ineffective coping.. exacerbation of illness

w/ effective coping.. little or no effect on symptoms

Aging & the Stress Response

those who are dependent (on caregivers, family, etc...) -> minor illnesses affect them greater -> may never return to baseline

-independent individuals are affected less