Stress

Homeostasis is a concept central to the idea of stress. In biology, most biochemical processes strive to maintain equilibrium, a steady state that exists more as an ideal and less as an achievable condition. Environmental factors, internal or external stimuli, continually disrupt homeostasis; an organism’s present condition is a state in constant flux wavering about a homeostatic point that is that organism’s optimal condition for living. Factors causing an organism’s condition to waver away from homeostasis can be interpreted as stress. A life-threating situation such as a physical insult or prolonged starvation can greatly disrupt homeostasis. On the other hand, an organism’s effortful attempt at restoring conditions back to or near homeostasis, oftentimes consuming energy and natural resources, can also be interpreted as stress. In such instances, an organism’s fight-or-flight response recruits the body’s energy stores and focuses attention to overcome the challenge at hand. The ambiguity in defining this phenomenon was first recognized by Hans Selye in 1926 who loosely described stress as something that “…in addition to being itself, was also the cause of itself, and the result of itself.”[3] First to use the term in a biological context, Selye continued to define stress as “the non-specific response of the body to any demand placed upon it.” Present-day neuroscientists including Bruce McEwen and Jaap Koolhaas believe that stress, based on years of empirical research, “should be restricted to conditions where an environmental demand exceeds the natural regulatory capacity of an organism.”[4] Despite the numerous definitions given to stress, homeostasis appears to lie at its core.

Biology has progressed in this field greatly, elucidating complex biochemical mechanisms that appear to underlie diverse aspects of stress, shining a necessary light on its clinical relevance and significance. Despite this, science still runs into the problem of not being able to settle or agree on conceptual and operational definitions of stress. Because stress is ultimately perceived as a subjective experience, it follows that its definition perhaps ought to remain fluid. For a concept so ambiguous and difficult to define, stress nevertheless plays an obvious and predominant role in the every day lives of humans and nature alike.

 Immune response

Cortisol can weaken the activity of the immune system. Cortisol prevents proliferation of T-cells by rendering the interleukin-2 producer T-cells unresponsive to interleukin-1 (IL-1), and unable to produce the T-cell growth factor.[35]Cortisol also has a negative-feedback effect on interleukin-1.[36] IL-1 must be especially useful in combating some diseases; however, endotoxic bacteria have gained an advantage by forcing the hypothalamus to increase cortisol levels (forcing the secretion of CRH hormone, thus antagonizing IL-1). The suppressor cells are not affected by glucosteroid response-modifying factor (GRMF),[37] so the effective setpoint for the immune cells may be even higher than the setpoint for physiological processes (reflecting leukocyte redistribution to lymph nodes, bone marrow, and skin). Rapid administration of corticosterone (the endogenous Type I and Type II receptor agonist) orRU28362 (a specific Type II receptor agonist) to adrenalectomized animals induced changes in leukocytedistribution. Natural killer cells are not affected by cortisol.[38]

Effect of stress on the immune system

Stress is the body’s reaction to any stimuli that disturb its equilibrium. When the equilibrium of various hormones is altered the effect of these changes can be detrimental to the immune system.[7] Much research has shown a negative effect stress has on the immune system, mostly through studies where participants were subjected to a variety of viruses. In one study, individuals caring for a spouse with dementia, representing the stress group, saw a significant decrease in immune response when given an influenza-virus vaccine compared to a non-stressed control group.[7][8] A similar study was conducted using a respiratory virus. Participants were infected with the virus and given a stress index. Results showed that an increase in score on the stress index correlated with greater severity of cold symptoms.[7] Studies with HIV have also shown stress to speed up viral progression. Men with HIV were 2-3 times more likely to develop AIDS when under above average stress.[7]

Chronic stress

Chronic stress is defined as a “state of prolonged tension from internal or external stressors, which may cause various physical manifestations–eg, asthma, back pain, arrhythmias, fatigue, headaches, HTN, irritable bowel syndrome, ulcers, and suppress the immune system”. Chronic stress takes a more significant toll on your body than acute stress does. It can raise blood pressure, increase the risk of heart attack and stroke, increase vulnerability to anxiety and depression, contribute to infertility, and hasten the aging process. For example, results of one study demonstrated that individuals who reported relationship conflict lasting one month or longer have a greater risk of developing illness and show slower wound healing. Similarly, the effects that acute stressors have on the immune system may be increased when there is perceived stress and/or anxiety due to other events. For example, students who are taking exams show weaker immune responses if they also report stress due to daily hassles.[9]

Mechanisms of Chronic Stress

Studies revealing the relationship between the immune system and the central nervous system indicate that stress can alter the function of white blood cells involved in immune function, known as lymphocytes and macrophages. People undergoing stressful life events, such as martial turmoil or bereavement, have a weaker lymphoproliferative response. After antigens initiate an immune response, these white blood cells send signals, composed of cytokines and other hormonal proteins, to the brain and neuroendocrine system.[10] Cytokines are molecules involved with cell signaling. Cortisol, a hormone released during stressful situations, affects the immune system greatly by preventing the production of cytokines. During chronic stress, cortisol is over produced, causing fewer receptors to be produced on immune cells so that inflammation cannot be ended. A study involving cancer patient’s parents confirmed this finding. Blood samples were taken from the participants. Researchers treated the samples of the parents of cancer patients with a cortisol-like substance and stimulated cytokine production. Cancer patient parents’ blood was significantly less effective at stopping cytokine from being produced.[11]

Stress and Wound Healing

The immune system also plays a role in stress and the early stages of wound healing. It is responsible for preparing tissue for repair and promoting recruitment of certain cells to the wound area.[9] Consistent with the fact that stress alters the production of cytokines, Graham et al. found that chronic stress associated with care giving for a person with Alzheimer’s Disease leads to delayed wound healing. Results indicated that biopsy wounds healed 25% more slowly in the chronically stressed group, or those caring for a person with Alzheimer’s disease.[7]
Chronic stress has also been shown to impair developmental growth in children by lowering the pituitary gland’s production of growth hormone, as in children associated with a home environment involving serious marital discord, alcoholism, or child abuse.[12]

Chronic stress is seen to affect parts of the brain where memories are processed through and stored. When people feel stressed, stress hormones get over-secreted, which affects the brain. This secretion is made up of glucocorticoids, including cortisol, which are steroid hormones that the adrenal gland releases.[13]
Studies of female monkeys at Wake Forest University (2009) discovered that individuals suffering from higher stress have higher levels of visceral fat in their bodies. This suggests a possible cause-and-effect link between the two, wherein stress promotes the accumulation of visceral fat, which in turn causes hormonal and metabolic changes that contribute to heart disease and other health problems.[14]
[edit]Psychological concepts

Eustress

Selye published in 1975 a model dividing stress into eustress and distress.[15] Where stress enhances function (physical or mental, such as through strength training or challenging work), it may be considered eustress. Persistent stress that is not resolved through coping or adaptation, deemed distress, may lead to anxiety or withdrawal (depression) behavior.
The difference between experiences that result in eustress and those that result in distress is determined by the disparity between an experience (real or imagined) and personal expectations, and resources to cope with the stress. Alarming experiences, either real or imagined, can trigger a stress response.[16]

Coping

Main article: Stress management
Responses to stress include adaptation, psychological coping such as stress management, anxiety, and depression. Over the long term, distress can lead to diminished health and/or increased propensity to illness; to avoid this, stress must be managed.

Stress management encompasses techniques intended to equip a person with effective coping mechanisms for dealing with psychological stress, with stress defined as a person’s physiological response to an internal or external stimulus that triggers the fight-or-flight response. Stress management is effective when a person uses strategies to cope with or alter stressful situations.

There are several ways of coping with stress,[citation needed] such as controlling the source of stress or learning to set limits and to say “No” to some demands that bosses or family members may make.
A person’s capacity to tolerate the source of stress may be increased by thinking about another topic such as a hobby, listening to music, or spending time in a wilderness.
[edit]Cognitive appraisal

Lazarus[17] argued that, in order for a psychosocial situation to be stressful, it must be appraised as such. He argued that cognitive processes of appraisal are central in determining whether a situation is potentially threatening, constitutes a harm/loss or a challenge, or is benign.

Both personal and environmental factors influence this primary appraisal, which then triggers the selection of coping processes. Problem-focused coping is directed at managing the problem, whereas emotion-focused coping processes are directed at managing the negative emotions. Secondary appraisal refers to the evaluation of the resources available to cope with the problem, and may alter the primary appraisal.

In other words, primary appraisal includes the perception of how stressful the problem is and the seconday appraisal of estimating whether one has more than or less than adequate resources to deal with the problem that affects the overall appraisal of stressfulness. Further, coping is flexible in that, in general, the individual examines the effectiveness of the coping on the situation; if it is not having the desired effect, s/he will, in general, try different strategies.[18]
[edit]Clinical symptoms and disorders

Symptoms Signs of stress may be cognitive, emotional, physical, or behavioral.

• Cognitive symptoms
• Memory problems
• Inability to concentrate
• Poor judgment
• Pessimistic approach or thoughts
• Anxious or racing thoughts
• Constant worrying
• Emotional symptoms
• Moodiness
• Irritability or short temper
• Agitation, inability to relax
• Feeling overwhelmed
• Sense of loneliness and isolation
• Depression or general unhappiness
• Physical symptoms
• Aches and pains
• Diarrhea or constipation
• Nausea, dizziness
• Chest pain, rapid heartbeat
• Loss of sex drive
• Frequent colds
• Behavioral symptoms
• Eating more or less
• Sleeping too much or too little
• Isolating oneself from others
• Procrastinating or neglecting responsibilities
• Using alcohol, cigarettes, or drugs to relax
• Nervous habits (e.g. nail biting, pacing)