Allostatic load

Bruce McEwen.

From Wiki:

The term allostatic load, coined by McEwen and Stellar in 1993, is defined as the physiological consequences of chronic exposure to fluctuating or heightened neural or neuroendocrine response that results from repeated or chronic stress.

It is used to explain how frequent activation of the body's stress response, essential for managing acute threats, can in fact damage the body in the long run. Allostatic load is generally measured through a composite index of indicators of cumulative strain on several organs and tissues, but especially on the cardiovascular system.

The hormones and other physiological agents that mediate the effects of stress on the body have protective and adaptive benefits in the short run and yet can accelerate pathophysiology when they are over-produced or mismanaged; this kind of stress can cause hypertension and lead to heart disease. Constant or even irregular exposure to these hormones can eventually induce illnesses and weaken the body's immune system.

Adaptation in the face of stressful situations and stimuli involves activation of neural, neuroendocrine and neuroendocrine-immune mechanisms. This adaptation has been called "allostasis" or "maintaining stability through change", which is an essential component of maintaining homeostasis. The main hormonal mediators of the stress response, cortisol and epinephrine (adrenaline), have both protective and damaging effects on the body.

In the short run, they are essential for adaptation, maintenance of homeostasis, and survival “allostasis”. Yet, over longer time intervals, when called upon frequently, the resulting “allostatic load” exacts a cost that can accelerate disease processes. Allostatic load can be measured in physiological systems as chemical imbalances in autonomic nervous system, central nervous system, neuroendocrine, and immune system activity as well as perturbations in the diurnal rhythms, and, in some cases, plasticity changes to brain structures.

Four conditions that lead to allostatic load are:

Repeated frequency of stress responses to multiple novel stressors;
Failure to habituate to repeated stressors of the same kind;
Failure to turn off each stress response in a timely manner due to delayed shut down; and
Inadequate response that leads to compensatory hyperactivity of other mediators.
The effects of these forms of dysfunctional allostasis cause allostatic load and this, over time, leads to diseases. Allostatic load effects can be measured in the body. When tabulated in the form of allostatic load indices using sophisticated analytical methods, it gives an indication of cumulative lifetime effects of all types of stress on the body.

Brain Rules has the most succinct, clear-cut description of the harmful effects of chronic stress that I've read. I've decided that chronic stress will be the next focal point of my research. I'm particulary interesting in moderating/reducing the cortisol levels in my own system.

To start with, I found a book which I'll rush to the top of the to-read pile. It a great overview at a browse, even though the title is almost certainly pure hype -- unless by that, they simply mean that McEwen has redefined toxic chronic stress as allostatic load.

From Amazon: The End of Stress As We Know It by Bruce McEwen

"There's a whole new way to think about stress. Sure, some stress is inevitable, but being 'stressed out' isn't. In fact, we can learn to rechannel the powerful stress activators in our lives to make us even more effective. "Hamlet" spoke of 'suffering the slings and arrows of outrageous fortune.' These days we simply use the word 'stress' to describe that feeling. And if you ask ten random people if they feel stressed, chances are that at least nine will reply with a resounding, 'Yes!'

Indeed, the very way we use the word implies that we are its victims - as in, 'I'm under so much stress' or 'I'm completely stressed out.' There's now a better way to look at this picture, a way to move from victim to victor.

The first step is to look to the science behind it all because in the science lies a whole new message about stress. Science allows us to understand what the stress response is and why our bodies react the way they do. Like all living creatures, we're mapped to respond instinctually in certain ways, and generally for good reasons. We know, for example, that in times of emergency, we effortlessly shift into a different biological mode. Based on our perception of the crisis, our brains initiate the 'stress response' or the 'flight-or-fight reaction. ' Our attention becomes keenly focused. Our heart and lungs accelerate to ready us for action. Our glands mobilize extra energy resources and summon the immune system to battle stations. This whole process is Nature's way of empowering us to respond swiftly, sometimes dramatically, to sudden events, while remaining mentally alert and physically prepared to meet a challenge. 

But what if the crisis situation does not present us with a foe to be fought? Or if fleeing is not the answer? Too often in modern times, the situations that bring on the stress response require neither the fight nor flight response for which our bodies are genetically programmed. The stress response is nevertheless likely to kick in - just as it's programmed to do - even though it cannot help speed us toward a resolution. Deprived of its natural successful result, the very system that's designed to protect us begins to cause wear and tear on our bodies - actually bringing on illnesses as diverse and severe as asthma, diabetes, heart disease, ulcers, and increased susceptibility to colds and infections.

The good news is that there are definite things that we can do to prevent this process from ultimately taking this wrong turn. New research in brain functioning allows us to understand the reactions our bodies have to various stressful circumstances.That knowledge is power - the power to harness the energy stored within us and to channel it in positive ways. "The End of Stress as We Know It" leads us to a new appreciation of the mind - body connection so that we learn how to reduce stress and increase our overall sense of health and well-being-and even turn aside the slings and arrows of life."

An Interview with Stafford Lightman, Endocrinologist, Bristol University, England

Q:  What are the origins of the stress response?

A:  Stress is an extremely important protective mechanism for human beings, and in fact for all animals, because if you're being chased by a lion it's important to get away. In order to get away you need to give as much oxygen and as much sugar to your muscles to make them work as fast as they can, so your blood flow needs to go faster. When you're being frightened, your brain detects the danger, it sends signals down your spinal cord to your adrenal medulla to release adrenaline. The adrenaline increases the amount of sugar in your blood and increases your heart rate, and this helps your efficiency of getting away from the lion. Your brain also sends signals down to the pituitary gland, which releases another hormone which acts on the outside of the adrenal, the adrenal cortex, and that releases cortisol. Cortisol is also very important in keeping your blood sugar up, keeping your blood pressure up, and helping allow the body to have maximal exertion to get away from danger.

Q:  What happens to the body as a result of the stress response in the brain?

A:  One of the fascinating things that happens is [that] the body is being prepared only to use its really essential functions, so the muscles work well, the liver releases more sugar, for energy, but things are actually being turned off as well. Although the heart rate is going up and more blood is going round the body, parts of the body which aren't needed urgently are being turned off. The blood supply to the gut and areas like this is actually decreased, so your digestion diminishes—you don't need digestion when you're running away from a lion—obviously your sexual function is turned off, and a lot of the non-essential activities of the body just decrease so that you preserve the really essential ones to get away from the dangerous situation.

In a modern situation we don't have these same sorts of dangerous problems, but what we have are other very stressful situations. And the interesting thing, of course, is that your blood sugar goes up, your heart rate goes up and your blood pressure goes up, but you're not utilizing all of this, you're not running away, you're not having energy, so all of these hormonal responses are happening, but they're actually not being used.

Q:  When does the stress response become dangerous?

A:  The important thing about the stress response is it's adapted for short-term responses. It becomes dangerous when you get multiple stress responses, one after the other, or experience chronic stress that goes on for weeks or years. When that happens your levels of cortisol can be raised for very prolonged periods of time, and it can have lots of nasty effects on the body. It can damp down your immune system, for instance, so that you can't respond to diseases as well as you should. It can also have effects on the brain, actually decreasing the number of brain cells in certain parts of the brain and decreasing your memory. It also can affect your blood pressure, and it can affect the fats in the blood and make it more likely for you to have heart attacks and strokes. So when you have chronic stress, that's when stress becomes dangerous.

Q:  Can caring for people with chronic illnesses actually lead to illnesses in caregivers?

A:  There's been quite a lot of interest recently about what chronic stress can do to cause disease. We did a study on caregivers of patients with Alzheimer's disease…We've looked at their hormones and we find that their cortisol is indeed raised, so they have a hormonal stress response which is prolonged for a very long period of time. We've also looked at their immune function by giving them influenza vaccination, which is routinely given to elderly people, and we've found that their antibody response to the influenza vaccination is much poorer than equivalent people of the same age who aren't caring for a loved one with Alzheimer's or some other disease.

So it's clear that chronic stress does damp down the immune system. And other people have also shown that chronic stress can decrease your ability to heal wounds, so that if you've got small wounds they just don't heal as well. The body just doesn't function quite as well when you have large, high levels of cortisol circulating through it for long periods of time.

Q:  Has stress been linked to depression and other mental illnesses?

A:  It's quite clear that chronic stress is related with depression. Depression is a very major common disease in our society, and it is undoubtedly related to the chronic stress that we have in our society.

The ability of stress to cause depression as well as other problems like heart disease and high blood pressure are connected in an interesting way. [Patients who are depressed after a] heart attack are much more likely to die within the next few years than people who've had heart attacks and who aren't depressed. So again this depression, which is related to chronic stress, actually has a major effect on life expectancy.

Q:  Might there someday be a pill to reduce the effects of stress?

A:  We are involved in an intensive program to develop an anti-stress pill, and the only way we can do this really is to try and block the beginning of the pathway in the brain that causes the response to stress. And this happens at the hypothalamus, which makes a hormone called CRH. We're making a pill that blocks the effect of CRH, and therefore blocks all of the effects of stress on the body, including the effects of stress in causing an increase in cortisol. We're not designing a drug to give to everybody who's stressed. But this can be very important and hopefully should actually be an extremely useful treatment for … depression that's associated with severe stress.