Stress
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Stress: The Importance of
Allostasis
 The term came into being in the 1980’s as a
newer more appreciative way to view the
body’s rapid and efficient methods of dealing
with stress.
 Allostasis refers to the body’s ability to
maintain stability amidst change.
M Lu, N Halfon
Allostasis:
Maintain Stability through Change
McEwen BS. Protective and damaging effects of stress mediators. N Eng J Med. 1998;338:171-9.
Allostasis: Wear and Tear
 There are, however, situations that ignite
stress response in which neither fight nor
flight is an option….the response cannot
help us toward resolution. Then, deprived
of its natural result, the system designed to
protect us begins to cause wear and tear 
illness and vulnerability.
ALLOSTASIS TO ALLOSTATIC LOAD
Four Scenarios
McEwen B. New England J. Med. 1998
Stress and Biology: Allostatic
loading
 Unremitting chronic stress, or severe trauma,
particularly at windows of vulnerability and
opportunity in human development.
 Inability to adjust.
 Not hearing the “all-clear” signal
 Feedback loops impaired.
Practical leadership action: 1. Foster conditions to prevent stress
and severe trauma. 2. Strengthen capacity to deal with stress.
3. Promote healing from stress and trauma.
What we often mean by “stress”
is being “stressed out”!
Feeling overwhelmed, out of control, exhausted, anxious, frustrated, angry
What happens to us?
Sleep deprivation
Eating too much of wrong things,
alcohol excess, smoking, etc.
Neglecting regular, moderate exercise
All of these contribute to allostatic load
Psychosocial stress is a major factor
Levels of stressful experiences:
Their causes, consequences and why we experience them!
Positive Stress
- A personal challenge that has a satisfying outcome
-Result: Sense of mastery and control
--HEALTHY BRAIN ARCHITECTURE
--good self esteem, judgment and impulse control
Tolerable Stress
-Adverse life events buffered by supportive relationships
-Result: Coping and recovery
-HEALTHY BRAIN ARCHITECTURE
--good self esteem, judgment and impulse control
Toxic Stress
-Unbuffered adverse events of greater duration and magnitude
-Result: Poor coping and compromised recovery
- Result: Increased life-long risk for physical and mental disorders
-COMPROMISED BRAIN ARCHITECTURE
-Dysregulated physiological systems
HPA Axis
Hypothalamic-pituitary-adrenal axis
 Initiated in the hypothalamus gland, it is the
cornerstone of allostasis. Impaired HPA axis
function from toxic stress leads to chronic high
levels of cortisol. Prolonged high levels of
cortisol suppress immune function, increase
inflammation, and may lead to LBW,preterm
birth, diabetes, c-v disease, etc. Toxic stress
may thus result in a hyper-reactive,
dysregulated HPA axis.
 Two possible mechanisms: Cumulative “wear
and tear” (weathering) throughout the life
cycle and fetal or childhood programming.
Social environment and health
Central Role of the Brain
MacArthur Foundation Research Network on Socioeconomic Status an
Behavioral responses (“lifestyle”) as well as stressful experiences
McEwen B. New England J. Med. 1998
Prenatal Programming of the
Hypothalamic-Pituitary-Adrenal Axis
Welberg LAM, Seckl JR. Prenatal stress, glucocorticoids and the programming of the brain.
J Neuroendocrinol 2001;13:113-28.
Stress, allostasis and allostatic load
STRESS
AVP
CRH
Many targets
for cortisol
Cortisol
ACTH
Acute - enhances immune,
Memory, energy replenishment,
Cardiovascular function
Chronic - suppresses immune,
Memory, promotes bone
Mineral loss, muscle wasting;
Metabolic syndrome
Mediators of stress and adaptation
NETWORK OF ALLOSTASIS
CNS function
Cardiovascular
function
Metabolism
Immune function
Dysregulation by Biphasic and non-linear
-unhealthy lifestyle, poor sleep, toxic chemicals
-feed into network of allostasis
Positive Stress vs. Toxic Stress
 Positive Stress
 Toxic Stress

Increased cardiac output

Hypertension &
cardiovascular diseases

Increased available
glucose

Glucose intolerance &
insulin resistance

Enhanced immune
functions

Infection & inflammation

Growth of neurons in
hippocampus &
prefrontal cortex

Atrophy & death of
neurons in hippocampus
& prefrontal cortex