How does the response to stress work?

While the complete story is not fully known, scientists understand much about how the response to stress works. The two main systems involved are the hypothalamic-pituitary-adrenal (HPA) axis and the SNS. (These systems are described later.) Triggered (activated) primarily by an area in the brain stem (lowest part of brain) called the locus coeruleus, the SNS secretes epinephrine and norepinephrine. The five most important concepts to remember about these two systems are that

1. they are governed by a feedback loop to regulate their response (In a feedback loop, increased amounts of a substance -- for example, a hormone -- inhibit the release of more of that substance, while decreased amounts of the substance stimulate the release of more of that substance.); 2. they interact with each other; 3. they influence other brain systems and functions; 4. genetic (inherited) variability affects the responses of both systems. (That is, depending on their genes, different people can respond differently to similar stresses.); 5. prolonged or overwhelming responses of these systems can be harmful to an individual.

What is the role of the hypothalamus-pituitary-adrenal (HPA) axis (grouping) in stress?

The HPA axis is a grouping of responses to stress by the brain and the pituitary and adrenal glands. First, the hypothalamus (a central part of the brain) releases a compound called corticotrophin releasing factor (CRF), which was discovered in 1981. The CRF then travels to the pituitary gland, where it triggers the release of a 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. Cortisol increases the availability of the body's fuel supply (carbohydrate, fat, and glucose), which is needed to respond to stress. However, if cortisol levels remain elevated for too long, then muscle breaks down, there is a decreased inflammatory response, and suppression of the immune (defense) system occurs.

Because they suppress the immune system, corticosteroids in measured doses are used to treat many illnesses that are characterized by inflammation or an overactive immune system, such as asthma and inflammatory bowel disease. For the same reason, they are used to help reduce the chances that our body will immunologically reject a transplanted organ. Corticosteroids also can cause fluid retention and high blood pressure. Therefore, it is critical that the response to corticosteroids be carefully controlled (modulated). This control usually is accomplished by a feedback mechanism in which increased cortisol levels feeding back to the hypothalamus and pituitary turn off production of ACTH. In addition, extremely high levels of cortisol can cause mental changes, including depression and psychosis, which disappear when the levels return to normal.