Refers to the way the body responds to any kind of demand or threat.

Stress releases neurochemicals and hormones that prepare one for action.

Prolonged, uninterrupted, unexpected, and unmanageable stresses are damaging.

Physiological stress can activate the adrenal cortex and can increase the production of cortisol: cortisol concentration can be used as a surrogate to assist stress/well – being.

Stress can be managed by, regular exercise, meditation or other relaxation techniques, structured timeouts, and learning coping strategies.

Stress can be countered by social connection, spirituality, and, for men more clearly than for women, married life, all of which are associated with longevity.

Many behaviors that increase in times of stress and maladaptive ways of coping with stress, such as drugs, pain medicines, alcohol, smoking, and eating will worsen the stress and can make it more reactive to further stress.

Risk factors for unmanageable stress include a lack of support.

Management of stress is mostly dependent on the ability and willingness to make the changes necessary for a healthy lifestyle.

Stress is associated with forces from the inside or outside world that affect the individual’s emotional or physical well-being, or both.

From a biological point of view, stress can be a neutral, negative or a positive experience.

A certain amount of stress is a normal part of daily life. 

Small doses of stress help people meet deadlines, be prepared for presentations, be productive and arrive on time for important events. 

External factors include the physical environment, workplace, relationships with others,home, and all the situations, challenges, difficulties, and expectations confronted with on a daily basis.

Internal factors which influence your ability to handle stress include your nutritional status, overall health and fitness levels, emotional well-being, and the amount of sleep and rest.

Constancy, a steady state in the internal bodily environment, is essential to survival.

External changes in the environment or external forces that change the internal balance must be reacted to and compensated for

Diseases are also stressors that threaten the constancy of the milieu.

The adrenal medulla secretes two neurotransmitters, epinephrine and norepinephrine in response to stress.

Anxiety and stress elevate the body’s level of cortisol and adrenaline, which in turn can interfere with the normal functioning of the parasympathetic nervous system resulting in overstimulation of the vagus nerve.

Toxic stress can result in dysregulation of the limbic-hypothalamus-pituitary-adrenal axis.
Stress can elevate levels of catecholamine, cortisol and pro inflammatory cytokines leading to effects on the nervous, endocrine  and immune systems.

Severe stress changes can affect attention, executive functioning, impulsive behavior, brain reward systems, decision making, and response stress throughout the lifespan.

The release of these neurotransmitters leads to the physiologic effects seen in the fight or flight response, for example, a rapid heart rate, and increased alertness.

Stress can manifest in emotional, behavioral, and even physical symptoms.

The symptoms of stress vary significantly among different individuals.

Oxytocin produced by the hypothalamus and released by the posterior pituitary, is associated with social interaction and can be an indicated to assess the current state of stress and well-being.

Sex differences are prevalent in humans with respect to psychiatric stress-related disorders such as anxiety and depression, where women experience these disorders more often than men.

Common somatic symptoms in those experiencing excess stress include sleep disturbances or changes in sleeping habits, muscle tension, muscle aches, headache, gastrointestinal problems, and fatigue.

Symptoms of preexisting medical conditions can also worsen during times of stress.

Emotional and behavioral symptoms that can accompany excess stress include nervousness, anxiety, changes in eating habits including overeating or undereating, loss of enthusiasm or energy, and mood changes, irritability and depression.

Children’s neurological development can be permanently disrupted by  chronic exposure to stressful events:  physical, emotional, or sexual abuse, physical or emotional neglect, witnessing violence in the household, or a parent being incarcerated or suffering from a mental illness.


Elevated stress hormones in children interfere with the development of brain circuitry and connections, causing long term chemical damage.

Under stress there is a greater tendency to engage in unhealthy behaviors, such as excessive use or abuse of alcohol and drugs, cigarette smoking, and making poor exercise and nutritional choices, than their less-stressed counterparts.

Stress is highly individualized, so what constitutes overwhelming stress for one person may not be perceived as stress by another.

There are no external standards that can be applied to predict stress levels in individuals.

Workplace stress, may occur in a minimally stressful job due to individual responses.

The degree of stress is highly dependent upon individual factors such as our physical health, the quality of our interpersonal relationships, the number of commitments and responsibilities we carry, the degree of others’ dependence upon us, expectations of us, the amount of support we receive, and the number of changes or traumatic events that have recently occurred.

People with social support networks report less stress and improved mental health in comparison to those without adequate social support.

Children, teens, the newly married, working parents, single parents, and seniors are groups who often face common stressors related to life transitions.

Effective stress-management strategies can diminish the ill effects of stress.

A healthy adaptational response to stress must be initiated rapidly, maintained for a proper amount of time, and then turned off to ensure an optimal result.

An over-response to stress or the failure to shut off a stress response can have negative biological and mental-health consequences.

The brain mediates the immediate response to stress, and signals the adrenal medulla

to release epinephrine and norepinephrine.

The hypothalamus and the pituitary gland initiate the slower maintenance response by signaling the adrenal cortex to release cortisol and other hormones.

Neural pathways are involved in the behavioral response, as it increases arousal, attention, inhibits feeding and reproductive behavior, reduces pain perception, and redirects behavior.

The stress response maintains homeostasis and optimize energy production and utilization.

The stress response gears up the person for a quick reaction through the sympathetic nervous system.

The sympathetic nervous system during stress increases the heart rate, blood pressure, and redirects blood flow to the heart, muscles, and brain and away from the gastrointestinal tract, and releasing fuel in the form of glucose and fatty acids to help fight or flee the danger.

The major systems involved with stress are the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system.

The hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system

are activated primarily by an area in the brainstem called the locus coeruleus.

The sympathetic nervous system activation results in the secretion of epinephrine and norepinephrine.

Emotional stress leads to increased brain hemispheric activity for which the ipsilateral tympanic membrane temperature is directly correlated and can serve as a proxy measure.
Tympanic membrane temperature fluctuations can serve  is an indicator to reflect changes in current emotional state.

The hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous systems are governed by a feedback loop to regulate their responses, interact with each other, and they both influence other brain systems and functions.

There is inherited variability of both systems affecting how one responds to stress, and

prolonged or overwhelming responses of these systems can be harmful.

The HPA axis starting with the hypotalamus responds to stress by releasing corticotrophin releasing factor (CRF).

The CRF then travels to the pituitary gland, where it triggers the release of hormone, adrenocorticotrophic hormone (ACTH).

ACTH is released into the bloodstream and causes the cortex of the adrenal gland to release the stress hormones, particularly cortisol, which is a corticosteroid hormone.

The autonomic nervous system is under the control of the limbic system.
Persistent stress leads to activation of the hypothalamus-pituitary-adrenal axis and cortisol release.
Increase glucocorticoid levels inhibit salivary lysozyme secretion and immunoglobulin A antibody production increasing the risk for acute infectious respiratory illness.
Stress suppress his pulmonary Interleukin-1alpha and may contribute to  increased viral pathogenesis.

Chronic stress attenuates the immune response to influenza vaccination and inhibits the immunoglobulin G antibody response to pneumococcal antigen following vaccination.

Chronic stress of afight-or-flight reaction to constant threats to income, housing, and food availability, weakens the immune system, increases insulin resistance, lipid and clotting disorders appear more frequently, and increases the adoption of health threatening behaviors.

Chronic stress has been found to be significantly associated with chronic low-grade inflammation, slower wound healing, increased susceptibility to infections, and poorer responses to vaccines.

Cortisol increases the availability of the body’s fuel supply needed to respond to stress.

Prolonged elevated cortisol levels lead to muscle break down, a decreased inflammatory response, and suppression of the immune system.

Elevated stress and norepinephrine levels correlate with decreased effectiveness of anti-retroviral drugs and more rapid disease progression in HIV infected individuals.

Increased production of cortisol occurs during stress which increases glucose levels and availability.



Cortisol suppresses the highly demanding metabolic processes of the immune system, resulting in further availability of glucose.

Control of cortisol levels is accomplished by a feedback mechanism in which increased levels feeding back to the hypothalamus and pituitary turn off production of ACTH.

High levels of cortisol can cause mental changes, depression and psychosis.


Adult victims of childhood abuse have exhibited increased ACTH concentrations in response to a psychosocial stress task.

The locus coeruleus connects to other parts of the brain, that bring in and process sensory information, secretes norepinephrine and stimulates other brain centers to do the same.

The locus coeruleus increases arousal and vigilance and modulates the action of the autonomic nervous system, which includes the sympathetic nervous system.


Stress-related disorders, such as post-traumatic stress disorder, acute stress reaction, and adjustment disorder, are associated with a considerably higher risk of developing neurodegenerative diseases.




The study in Sweden, compared a population-matched cohort of 61,748 adults older than 40 diagnosed with stress-related disorders and 595,335 matched controls without stress-related disorders. 



A sibling cohort included 44,839 adults with stress-related disorders and 78,482 siblings without stress-related disorders. 



Participants were followed for a median 4.7 years.



For adults with stress disorders, the hazard ratio for developing vascular neurodegenerative diseases was 1.80, and for developing primary neurodegenerative diseases was 1.31, compared with people without stress disorders.according to the study. 



The hazard ratio for Alzheimer disease was 1.36 for adults with stress disorders compared with those without stress disorders.



There was  a statistically significant association for Alzheimer’s disease but not for Parkinson disease or amyotrophic lateral sclerosis.


A person’s hippocampal connectivity during a stressful event can predict the intensity of stress experienced.

Neural connections emanating from the hippocampus to the hypothalamus, which is an area of the brain known to regulate physiological stress;Associated with high stress levels.

Neural connections from the hippocampus to the dorsal lateral frontal cortex, an area associated with emotional regulation, predicts for lower stress levels. 

With anxiety disorders there may be difficulty accessing calming feedback from the frontal cortex.

Allostasis is a term which supplements the classic terms homeostasis and stress. 

It refers to an  active process that leads to adaptation to a stressor, and mediators of allostasis, which include stress hormones as well as the autonomic nervous systems and pro-inflammatory cytokines and metabolic hormones. 

Allostatic load and allostatic overload, represent the cumulative effects of chronic physiologic stress.

Chronic physiologic stress may be generated by internal processes and external factors that dysregulate the mediators of allostasis. 

Allostatic overload includes many of the common diseases of modern life. 

Prolonged maternal stress during pregnancy is associated with mild impairment of intellectual activity, language development, behavior disorders such as attention deficits, schizophrenia, anxiety and depression.

There is an association between maternal depression during pregnancy and childhood cortisol levels.

Social stress and physical stress both activate the HPA axis, though via different pathways.

The HPA axis is activated during chronic stress.



Stressors that threaten physical well being, integrity, or involve trauma appear  to have a high, flat diurnal pattern of cortisol release: lower-than-normal levels of cortisol in the morning and higher-than-normal levels in the evening.



Such stress results  in a high overall level of daily cortisol release. 



Stress that is controllable produces higher-than-normal morning cortisol. 



Stress hormone release declines gradually after a stressor occurs. 


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