Physiology of Stress

The term "stress" evokes little reaction. "We all got that", one may think. Much like having a "cold". It evokes little sympathy, and is seen as a nuisance and a collection of symptoms that everyone gets from time to time. In fact, with a little attention it seems that we just get over it. Same for stress. It passes, and our bodies are restored. Much of this is true in the day to day experience of stressors. What is important though, is that even in the slightest stress reaction, there are important psychophysiological mechanisms at work. Understanding this is key for all clinicians. In researching the mechanisms involved, explanation of the process is complex. It is beyond the scope of this training. Understanding basic neurological processes is helpful. For a thorough description, I would recommend "A Clinical Guide to the Treatment of the Human Stress Response", Second Edition, by George S. Everly, Jr. and Jeffrey M. Lating, published by Kluwer Academic/Plenum Publisher 2002.

When one responds to a stressor, there are three known physiological pathways which are activated. They are called:

Since this response occurs on the neural level, it occurs the quickest of the three axes. It comprises of the sympathetic nervous system, the parasympathetic nervous system and the neuromuscular nervous system.

Interpretation threatening		Interpretation not threatening
*Sympathetic activation*		*Parasympathetic activation*
Neural impulses descend to the posterior* hypothalamus*		Neural impulses descend to the anterior hypothalamus
Descend through the cranial and sacral spinal chord regions and innervate the end organs
The result is the release of Norepinephrine which creates arousal		The result is some release of Acetylcholine which creates slowing, restorative functions. (relaxation)

These activations are generally short lived as they are unable to provide ongoing release of neurotransmitters. In order to maintain a high arousal level for prolonged period, the second physiological stress axis must be activated. This is the neuroendocrine "fight or flight" axis.

fight'-or-flight' reac"tion

Pronunciation: (fIt'ôr-flIt'), [key] Physiol., Psychol.
The response of the sympathetic nervous system to a stressful event, preparing the body to fight or flee, associated with the adrenal secretion of epinephrine and characterized by increased heart rate, increased blood flow to the brain and muscles, raised sugar levels, sweaty palms and soles, dilated pupils, and erect hairs. Also called fight'-or-flight' response".

Walter B. Cannon a physiologist at Harvard was the first to describe the fight or flight response as a series of biochemical changes that prepare to deal with threats of danger. Primitive man when faced in a dangerous situation like with a wild animal, needed quick bursts of energy to fight it (fight) or run from it (flight). Following either course of action, the stress reaction would then complete its cycle and the relaxation response returned man to a homeostasis state. Walter Cannon’s research in biological psychology led him to describe the “fight or flight” response of the Sympathetic Nervous System (SNS) to threats. Here's how it works.

The nervous system is divided into two branches, the sympathetic and the parasympathetic. The sympathetic nervous system is responsible for response to emergency situations that trigger the fight-or-flight response . The parasympathetic nervous system is responsible for functions related to relaxation such as digestion, pupil dilation, constriction of breathing and heart rate. Depending on sensory input to the brain, the hypothalamus will either switch on the parasympathetic nervous system and allow for digestion and relaxation or it will shut off those functions and allow energy to be used for the emergency response of the sympathetic nervous system. The nervous system relays messages through neurons with neurotransmitters. The pivotal organ in this response is the adrenal medulla. The adrenal gland gets innervated and releases two hormones: norepinephrine (noradrenaline) and epinephrine (adrenaline). The neurotransmitters are delivered to muscle cells via nerve fibers and stimulate behavior. As mentioned previously in the neural axis these two chemicals are released as well, but the hormonal release in the neuroendocrine axis has about a 20-30 second delay of onset because of the path it travels and intensity of the stressor. When it is released it has a 10 fold increase in effect duration (Usdin, Kretnansky, & Kopin, 1976). Cannon found that SNS arousal in response to a perceived threat involves several elements which prepare the body physiologically either to take a stand and fight off an attacker or to flee from the danger. Schneiderman, 1984, reformulated this system as an "active coping" system and referred it as the sympathoadrenomedullary system (SAM). What has been observed in humans which increase coping are:

The activation of the endocrine axes is seen as the most chronic and prolonged somatic response to stress. They also are the hardest to activate and require greater intensity stimulation. During the stress response, there are four known endocrine axes associated with the stress response. They are briefly described here.

The Adrenal Cortical Axis (Also referred to as the hypothalamatic-pituatary-adrenal cortical system (HPAC). From the Hippocampus, neural impulses descend to the hypothalamus and release corticicotropin-releasing factor (CRF). CRF then descends into the anterior pituitary and release adrenocorticotropic hormone (ACTH). At the same time endorphines are released. ACTH then reaches an endocrine gland called the adrenal cortex. Once present in the adrenal cortex, ACTH stimulates the release of glucocorticoids cortisol and corticosterone and begins to produce the following effects:

ACTH also secretes corticoids aldosterone and deoxycorticosterone. This allows for an increase in absorption of sodium and chloride and decrease their excretion by the salivary glands, sweat glands, and gastrointestinal tract, resulting in fluid retention. Excessive activation of this mechanism can end up in the development of Cushings's syndrome and high blood pressure.

Lastly ACTH effects the release of catecholamines (epinephrine and norepinephrine). In effect it has a rate-limiting response in the manufacturing of catecholamines synthesis.

Activation of HPAC has been associated with what has been labeled the "passive coping" system. Behaviorally, when active coping is not possible, helplessness, hopelessness, depression, passivity, the perception of no control, immunosuppression and gastrointestinal symtomotology, all have been connected.

The Somatotrophic Axis. This axis responds similar to the Adrenal Cortex axis with the exception that somatropin-releasing factor (SRF) stimulates the anterior pituitary and released a growth hormone (somatrophic hormone). While its role is still under investigation it is believed to play a part in the concentration of free fatty acids and glucose in the blood.

The Thyroid Axis. From the hypothalamus, thyrotropin-releasing factor (TRF) is released and is carried to the anterior pituitary. From here the thyroid-stimulating hormone (TSH) is released and stimulates the thyroid gland producing two hormones -triiodothyrine (T3), and thyroxine (T4). These hormones circulate the system getting bound to certain plasma protein carriers. Some of these hormones remain free and unbound. When thyroid functions are tested, it is the measurement of these free hormones that is calculated. During psychosocial stimuli, the thyroid activity is likely to increase and increases general metabolism, heart rate, heart contractibility, raise blood pressure and add sensitivity to some tissues to catecholamines.

The Posterior Pituitary Axis. The posterior pituitary receives neural impulses from the hypothalamus and result in the release of hormones vasopressin and oxytocin. Vasopressin also termed antidiretic hormone (ADH) produce water retention Oxytocin hormone is believed to be involved in psychogenic labor contractions and premature birth.

Other hormones are released and are being investigated as to their role in the stress response. For instance, luteinizing hormone, testosterone and prolactin are evident.

As a clinician, having a working understanding of the three axes is expected. It has been my experience, however, that a sound understanding of the first two axes are helpful be able to intelligently educate persons that "stress" is more than just a vague indefinable nuisance that we all encounter from time to time.

Target organ systems include the cardiovascular system, gastrointestinal system, the skin, the immune system and the brain amongst others. They are the areas/organs that are effected and may become impaired, diseased, or dysfunctional when the stress response is not deactivated and/or prolonged. Ulcers are an example of a target organ in the gastrointestinal system becoming diseased. Different organs may be affected in different people. Genetic, prenatal, neonatal, the stressor itself, previous injury or vulnerability, and positive and negative coping skills, all play a role in how prolonged stress can impact a target organ.

This concludes a rather complex view of the physiological reactions to a stressor, simplified! To add further clarification the above physiological actions and the General Adaptation Syndrome (GAS) as explained earlier are combined.

Consider yourself walking along and you are confronted by a man with a gun pointed at you (stressor). For some of us, just imagining this is enough to activate a stress response.

In response to facing this event, a cognitive/affective interpretation is made "this is potential dangerous situation" and fear is experienced. This interpretation travels neurologically and activates the neural axes and soon after, the neuroendocrine axis. Neurons from the sympathetic nervous system stimulate the adrenal medulla, causing it to release within seconds epinephrine and norepinephrine, called catecholamines. These hormones produce a state of physiological arousal, raising heart rate and blood pressure while slowing digestion and other processes that might divert energy from the skeletal muscles. This catecholamine system allows a rapid initial response to the stressor ("fight or flight").

The third axes, endocrine axes, is activated. The hypothalamus stimulates the pituitary gland, triggering the release of adrenocorticotropic hormone (ACTH). ACTH circulates through the blood; within minutes it reaches the outer portion of the adrenal gland (adrenal cortex), causing it to release the hormone cortisol, called a glucocorticoid because it affects glucose metabolism. Glucocorticoids not only help convert protein to glucose for use as energy, but also speeds the release of stored fat to be burned as fuel. This glucocorticoid system provides the energy for the body to maintain a sustained effort to battle against the stressor.

As the mugger comes closer, the heart rate and blood pressure increase instantaneously.

Breathing becomes rapid and the lungs take in more oxygen.
Blood flow may actually increase 300% to 400%, priming the muscles, lungs, and brain for added demands.
The spleen discharges red and white blood cells, allowing the blood to transport more oxygen.

The effect on the immune system from confrontation with the mugger is similar to marshaling a defensive line of soldiers to potentially critical areas.

The steroid hormones dampen parts of the immune system, so that infection fighters (including important white blood cells) or other immune molecules can be redistributed.
These immune-boosting troops are sent to the body's front lines where injury or infection is most likely, such as the skin, the bone marrow, and the lymph nodes.

As the mugger gets closer, fluids are diverted from nonessential locations, including the mouth. This causes dryness and difficulty in talking. In addition, stress can cause spasms of the throat muscles, making it difficult to swallow.

The stress effect diverts blood flow away from the skin to support the heart and muscle tissues. (This also reduces blood loss in the event that the mugger cuts you.) The physical effect is a cool, clammy, sweaty skin. The scalp also tightens so that the hair seems to stand up.

The stress response shuts down digestive activity, a nonessential body function during short-term periods of physical exertion or crisis.

Instantly, you've reacted. You're ready to fight, or run. You run at the mugger to attack and as you get closer it is revealed under a light that it was only your neighbor. You sigh in relief as you perceive you are safe. Your relaxation response kicks in restoring homeostasis. The initial stress response burns out.

What you have learned or reviewed was rather sophisticated. You will not need this level of detail for most of your onsite interventions. I say most because you may get called to a university or a hospital. These are sites where you may get challenged. My suggestion is this. It is less risky to you and the intervention if you need to scale back the depth/detail of your knowledge base, then try to sound more prepared then you are. This is good information to review before you go onsite.