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Biological Approaches to Stress Historical Overview

Walter Cannon: Fight or Flight Response

Hans Selye: General Adaptation Syndrome

John Mason: Critique of Selye

Bruce McEwen: Allostasis/Allostatic Load

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Walter Cannon: Fight or Flight Response Walter Cannon: Homeostasis/Fight or Flight

cf. FFF, Emergency, Defense Responses

Sympathetic branch of
Autonomic Nervous System

Adrenal Medulla
Threatening (Endocrine Gland)
Event

Energy is
Heart rate Mobilized,
Epinephrine Blood flow prepare for
Norepinephrine Respiration vigorous
(Stress hormones) Muscle strength muscle
Walter B. Cannon (1871-1945) Blood clotting
3 activity
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Figure 3.1: The human nervous system. The central nervous system consists of the
brain and spinal cord and the peripheral nervous system consists of the nerves that
cover the rest of the body (i.e., the periphery). The peripheral nervous system has
somatic and autonomic subdivisions. The Autonomic nervous system consists of the
sympathetic and parasympathetic branches.

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Adrenal Gland Fight or Flight: Mechanisms

Adrenal Medulla Sympathetic branch of Autonomic Nervous System

secretes epinephrine Responds quickly
(adrenaline) Mobilizes energy for use
May be opposed or helped by parasympathetic branch
Also: norepinephrine If PNS is activated more storage opposes mobilization for use
(noradrenaline) If PNS is de-activated less storage allows mobilization for use
and dopamine Norepinephrine is a major neurotransmitter
Widely distributed: widespread action (structure serves function)

Adrenal medulla [endocrine gland]

Slower but stronger, longer lasting
Endocrine = ductless, hormone travels in circulatory system
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Fight or Flight: Functions Fight or Flight: Major Components

Physiological effects:
Heart rate and respiration increase, oxygenated blood
Flows to large muscles
Flows out of reproductive, digestive systems
Muscle strength increases
Blood clots more quickly
FF is an evolutionary adaptation
Helps to survive physical emergencies (e.g., attacks)
This advantage increases likelihood that genes survive
More offspring with FF, and so on and so forth
But: With shorter life expectancy, negative health effects of FF
did not influence human evolution
And: FF is not effective for
Chronic physical emergencies
Emergencies that require non-physical solutions
Provoking events: Physical emergencies
Brain: Detects/evaluates event, orchestrates responses
Physiologic systems
Sympathetic nervous system (norepinephrine = noradrenaline)
Adrenal medulla (epinephrine = adrenaline)
Evolutionary basis
Physiology: energy to support vigorous muscle activity
Behavior: Fight or flight promoted survival
Health implications
We now experience fewer physical emergencies
Fight or flight is activated by psychological threats
Not useful/the behavior can make threat worse
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Physiologic changes promote disease given greater life expectancy

Hans Selye: General Adaptation Syndrome Hans Selyes General Adaptation Syndrome

Stress is a biological response caused by all

noxious stimuli (nonspecificity):

Alarm Resistance Exhaustion

Triad of
Changes:
Adrenal Cortex Cortisol Thymus
(Endocrine Gland) stress hormone Ulcers
glucocorticoid Adrenal
Hans Selye (1907 -1982) Cortex
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Adrenal Gland
The three stages of Selyes General Adaptation
Adrenal Cortex Syndrome and their consequences
secretes cortisol
(a glucocorticoid)

Additional adrenocortical hormones:

other glucocorticoids
mineralocorticoids
androgens

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GAS: Major Components A note on Definitions

Nonspecific provocation: noxious stimuli Cannon and Selye viewed stress as a response
Heat, cold, infection, starvation, emotion
Cannon did not call Fight/Flight stress
Brain detects event, orchestrates responses? But he emphasized the response to emergencies
Not according to Selye, but recognized in modern view Selye first used stress to refer to noxious stimuli
Physiologic systems Then he decided to use stress to refer to response
Adrenal cortex For both, the response was biological
Three phases
Response-based definitions are limited
Triad of changes
Health implications So are stimulus-based definitions
Depletion of cortisol is harmful
(Turns out: not the main health issue; excess cortisol is) Need concepts for both stimuli and responses
Repeated wear-and-tear is harmful And to refer to the process that links stimuli to response
Effects on thymus (foreshadows role of immune system) 15
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Beyond Cannon and Selye:

Physiological
effects of
Integrating and Updating Biological stress
Stress Mechanisms

Central Nervous System Regulation of

Adrenal Cortical Activity

and the wider

Endocrine System 17 18

The HPA Response Cortisol

Increased (sometimes decreased) by stress
Threat signaled to paraventricular
nucleus of hypothalamus

1. Releases corticotropic-
releasing hormone (CRH)
2. CRH stimulates anterior
pituitary to release adreno-
corticotropic hormone (ACTH)
3. ACTH travels through
bloodstream to adrenal cortex
Turns out too much cortisol, not depletion, causes
many negative outcomes
Damages brain, may affect memory, mental health
Post-traumatic Stress Disorder (PTSD)
Major depressive disorder

4. Adrenal cortex stimulated by

ACTH to release cortisol Alters immune system functioning
Classic example of a negative feedback loop
5. Circulating ACTH detected by
hypothalamus, stops response
Many metabolic functions (not just a stress hormone)
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Sugar, fat, salt, electrolytes, sex

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Some Other Important Endocrine Glands John Mason: Critique of Selye

Challenged nonspecificity:
Homeostasis predicts specificity
Different stressors: different responses

Psychological causation:
Threat perception, uncertainty, emotional response
explains why GAS is elicited nonspecifically by very
different stressors

But still

Why the same GAS response to threat/uncertainty

of different stressors (e.g., abrupt changes in heat,
cold) even if psychological responses are similar?
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Recent Developments: More Dynamic View?

Allostasis: maintaining stability through change Self-Regulation per Carver, C. S., & Scheier, M. F. (1998).
On the Self-Regulation of Behavior. New York: Cambridge
Homeostasis is too static University Press.

Maintaining a steady state requires variability Negative feedback

thermostat-controlled feedback allows temperature to vary input, reference, comparator, output
Steady is a range of values, not a single point

Stability requires a balance of many systems

Lack of variability may be unhealthy

Allostatic load: wear and tear due to the bodys

efforts to maintain balance through change 23
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Elements of Feedback
Input: sensor detects room temperature
Example: Thermostat

Reference: internal standard: temperature setting

Comparator: mechanism to compare input and

reference (Is the room too hot?)

Output: action to reduce discrepancy between

input and reference (e.g., air conditioner turns on)

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Normal/Healthy Variability in Cortisol Normal/Healthy Variability in Cortisol

Heart rate varies from one beat to the next:

Cortisol levels vary throughout the day: Increases during inhalation

High in the morning Decreases during exhalation

Low in late afternoon Reflects parasympathetic activity

Lowest during sleep Low variability predicts disease, mortality

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Variability can be increased by meditation, biofeedback

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The Nervous System

The human nervous system is divided into the
STRESS AND THE central nervous system (CNS) and the
AUTONOMIC NERVOUS peripheral nervous system
SYSTEM

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The Nervous System

CNS includes the brain and spinal cord
Peripheral NS includes neural pathways and is
divided into the somatic and autonomic branches
A third, smaller branch of the Peripheral NS is the
enteric nervous system
Enervates organs of digestion
Figure 3.1: The human nervous system. The central nervous system consists of the
Part of ANS? Part of digestive system? brain and spinal cord and the peripheral nervous system consists of the nerves that
cover the rest of the body (i.e., the periphery). The peripheral nervous system has
somatic and autonomic subdivisions. The Autonomic nervous system consists of the
sympathetic and parasympathetic branches.

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Autonomic nervous system: innervates the viscera
through pre- and post-ganglionic neurons
organs, ducts, glands; smooth muscle of glands, blood
vessels; cardiac muscle and pacemaker cells
Efferent activity of the ANS: Main focus in stress
We will return to ANS afference
Sympathetic branch of ANS: activates fight-or-flight
cardiovascular, respiratory, pupillary, etc.
increased supply of oxygenated blood to skeletal muscle
Parasympathetic branch: relaxation/restoration
dampens/counters fight-or-flight
activates gastrointestinal system
reproduction (e.g., penile erection) 35
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The Peripheral Nervous System
Somatic nervous system: innervates
skeletal/striated muscles, skin, sense organs
efferent pathways brain periphery (motor)
afferent periphery brain (sensory)
Fight-flight does involve striated muscle activation
by the somatic NS (efferent)
Stress muscle tension and pain
But with FF the focus is on the ANS (vs. Somatic NS)
However, there is a functional relationship between:
ANS effects on energy mobilization/restoration
Somatic NS-driven muscle activity/inactivity 34
Autonomic nervous system: innervates the viscera
through pre- and post-ganglionic neurons
descending/preganglionic fibers ganglia
postganglionic fibers neuroeffector junctions
Preganglionic neurons: exit spinal cord
use acetylcholine as neurotransmitter
Postganglionic neurons: stimulated by preganglionic
SNS: great majority use norepinephrine (NE)
(nor)adrenergic
note: sweat glands use acetylcholine
PNS: use acetylcholine as neurotransmitter
cholinergic
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Autonomic Space
Bipolar Model
Parasympathetic Sympathetic

Bivariate model

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Stress and the Endocrine System

Endocrine system: a system of organs and glands
that secrete hormones into the blood stream to
STRESS AND THE send messages to cells and organs (vs. exocrine)
ENDOCRINE SYSTEM Hormonal action slower than neural, but longer lasting
Endocrine system works with SNS during fight-or-flight
activation to reach a common outcome

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Sympathetic-Adrenomedullary Axis
Hypothalamus: Primary command center for
endocrine stress response:
Paraventricular nucleus brain stems nucleus of
solitary tract preganglionic SNS fibers
Adrenal glands: Primary target organs
A primary system for fight-or-flight
Located on top of the kidneys
Medulla is at their core
Cortex is the outer portion (bark)
Neuroeffector junction is cholinergic
Preganglionic SNS fibers adrenals
Norepinephrine (Noradrenaline)
Effects somewhat like epinephrine
Released in smaller amounts (1 to 5 ratio)
Effects of circulating NE last longer than its
neurotransmitter effects (10-fold)
E: more involved in mental stress/fear?
NE: more involved in physical stress/anger?
E/NE effects depend on different types of receptors in
different target organs
E: greater effect on heart, metabolic rate
E/NE effects are moderated by other physiologic
processes (e.g., effects of thyroxine)
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Epinephrine (Adrenaline)
Mimics SNS effects on target organs
Myocardial
Increased heart rate
Increased stroke volume
Vascular
Constriction (arterioles of skin, abdomen)
Dilation (arterioles of skeletal muscles)
Respiratory
Dilation of bronchi (increases oxygen intake)
Metabolic
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Stimulates gluconeogenesis 42
Hypothalamic-Pituitary-Adrenocortical Axis
Paraventricular nucleus of hypothalamus
corticotropic releasing hormone (CRH)
pituitary portal system of anterior pituitary
adrenocorticotropic hormone (ACTH) adrenal cortex
Pituitary: pea-sized gland at base of the brain
ACTH: signals adrenal cortex to release glucocorticoids
including cortisol, major stress hormone in humans
pituitary also secretes beta-endorphin:
temporary inhibition of pain (analgesia)
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Glucocorticoids
Steroid compounds that blood glucose levels
Cortisol is also known as hydrocortisone
Cortisol accounts for 95% of glucocorticoid effects
Gluconeogenesis + reduction of cellular glucose use
amino acids in blood: converted to glucose (liver)
Cortisol
SNS activates F-F/stress response; cortisol regulates it
Without cortisol, stress response might be more damaging
In normal conditions, cortisol has many functions
plays a permissive role
cf. Addisons disease, Cushing Syndrome

Lipolysis: liberates free fatty acids as fuel source

catecholamine synthesis at neuronal level Other Stress Hormones
adrenergic receptor sensitivity Stress can affect many other hormones
sensory sensitivity (thalamus) and memory One example is beta-endorphin (an endogenous opiate)
(hippocampus) produced by anterior pituitary in response to CRF
inflammation plus other immune system effects agonist for opiate receptors
water diuresis, sodium retention 45 analgesia, positive mood 46

Some Implications for Research

Stress and Stressors
What is stress? What is the stress response?
How Biologically-oriented scientists view stress:
Which biological response should be measured? Stress is a state of imbalance produces by stressors
Heart rate? Comes from structural engineering
SNS influences on the heart? Stress or load on structures such as bridges
PNS influences on the heart? Stressors are anything that can produce that imbalance
In psychophysiological usage, the term stressors means anything
Blood pressure? that can challenge homeostasis
Degree of vasoconstriction? People
Temperature extremes
Force of myocardial contraction? Starvation
Cortisol levels? Dangerous events
Pain
Catecholamine levels? And many others
Stress can be either good (eustress) or bad (distress)
What can be inferred from each of the above? Both have a profound effect on physical and psychological well-
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Cinematic Depictions of Stress Biology Cinematic Depictions of Stress Biology

Crank (2006) (click here) Falling Down (1993) (click here)

Get Him to the Greek (2010)(click here) E. T. (1982) Part 1 (click here)

Godfather (1972) Part 1 (click here) E. T. (1982) Part 2 (click here)

Godfather (1972) Part 2 (click here)

Hulk/Avengers (2012) (click here)

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