PERENNIAL GIVE-AND-TAKE has been going on between living matter and its inanimate surroundings, between one living being and another, ever since the dawn of life in the prehistoric oceans,” wrote Hans Selye in The Stress of Life.1 Interactions with other human beings—in particular, emotional interactions—a ect our biological functioning in myriad and subtle ways almost every moment of our lives. They are important determinants of health, as we will see throughout this book. Understanding the intricate balance of relationships among our psychological dynamics, our emotional environment and our physiology is crucial to well-being. “This may seem odd,” wrote Selye. “You may feel that there is no conceivable relationship between the behaviour of our cells, for instance in in ammation, and our conduct in everyday life. I do not agree.”2
Despite the intervening six decades of scienti c inquiry since Selye’s groundbreaking work, the physiological impact of the emotions is still far from fully appreciated. The medical approach to health and illness continues to suppose that body and mind are separable from each other and from the milieu in which they exist.
Compounding that mistake is a de nition of stress that is narrow and simplistic.
Medical thinking usually sees stress as highly disturbing but isolated events such as, for example, sudden unemployment, a marriage breakup or the death of a loved one. These major events are potent sources of stress for many, but there are chronic daily stresses in people’s lives that are more insidious and more harmful in their long-term biological consequences. Internally generated stresses take their toll without in any way seeming out of the ordinary.
For those habituated to high levels of internal stress since early childhood, it is the absence of stress that creates unease, evoking boredom and a sense of meaninglessness. People may become addicted to their own stress hormones, adrenaline and cortisol, Hans Selye observed. To such persons stress feels desirable, while the absence of it feels like something to be avoided.
When people describe themselves as being stressed, they usually mean the nervous agitation they experience under excessive demands—most commonly in the areas of work, family, relationships, nances or health. But sensations of nervous tension do not de ne stress—nor, strictly speaking, are they always perceived when people are stressed. Stress, as we will de ne it, is not a matter of subjective feeling. It is a measurable set of objective physiological events in the body, involving the brain, the hormonal apparatus, the immune system and many other organs.
Both animals and people can experience stress with no awareness of its presence.
“Stress is not simply nervous tension,” Selye pointed out. “Stress reactions do occur in lower animals, and even in plants, that have no nervous systems…. Indeed, stress can be produced under deep anaesthesia in patients who are unconscious, and even in cell cultures grown outside the body.”3 Similarly, stress e ects can be highly active in persons who are fully awake, but who are in the grip of unconscious emotions or cut o from their body responses.
The physiology of stress may be triggered without observable
e ects on behaviour and without subjective awareness, as has been shown in animal experiments and in human studies.
What, then, is stress? Selye—who coined the word in its present usage and who described with mock pride how der stress, le stress and lo stress entered the German, French and Italian languages respectively—conceived of stress as a biological process, a wide- ranging set of events in the body, irrespective of cause or of subjective awareness. Stress consists of the internal alterations—
visible or not—that occur when the organism perceives a threat to its existence or well-being. While nervous tension may be a component of stress, one can be stressed without feeling tension.
On the other hand, it is possible to feel tension without activating the physiological mechanisms of stress.
In searching for a word to capture the meaning of the physical changes he observed in his experiments, Selye “stumbled upon the term stress, which had long been used in common English, and particularly in engineering, to denote the e ects of a force acting against a resistance.” He gives the example of changes induced in a stretched rubber band or in a steel spring under pressure. These changes may be noted with the naked eye or may be evident only on microscopic examination.
Selye’s analogies illustrate an important point: excessive stress occurs when the demands made on an organism exceed that organism’s reasonable capacities to ful ll them. The rubber band snaps, the spring becomes deformed. The stress response can be set o by physical damage, either by infection or injury. It can also be triggered by emotional trauma or just by the threat of such trauma, even if purely imaginary. Physiological stress responses can be evoked when the threat is outside conscious awareness or even when the individual may believe himself to be stressed in a “good”
way.
Alan, a forty-seven-year-old engineer, was diagnosed with cancer of the esophagus—the swallowing tube that carries food from the throat to the stomach—a few years ago. He spoke of “good stress”
when he described the relentless, self-driven existence he had led in the year before he was diagnosed with his malignancy. That “good stress” not only helped undermine his health, but it also served to distract him from painful issues in his life that were themselves constant sources of ongoing physiological disturbance in his system.
Alan’s lower esophagus has been removed, along with the upper portion of the stomach where the tumour had invaded. Because the cancer had spread to several lymph nodes outside the gut, he received ve courses of chemotherapy. His white blood cells became so depleted that another round of chemo would have killed him.A non-smoker or drinker, he was shocked by the diagnosis, since he always considered that he lived a healthy life. But he has thought for a long time that he has a “weak stomach.” He often su ered indigestion and heartburn, a symptom of the re ux of stomach acid into the esophagus. The lining of the esophagus is not designed to withstand the corrosive bath of hydrochloric acid secreted in the stomach. A muscular valve between the two organs and complex neurological mechanisms ensure that food can move downward from throat to stomach without permitting acid to ow back upward. Chronic re ux can damage the surface of the lower esophagus, predisposing it to malignant change.
Not being one to complain, Alan had only once mentioned this problem to doctors. He thinks fast, speaks fast, does everything fast. He believed, quite plausibly, in fact, that his habit of eating on the run was responsible for the heartburn. However, excessive acid production due to stress and disordered neural input from the autonomic nervous system also play a role in re ux. The autonomic part of the nervous system is the part not under our conscious control, and—as the name implies—it is responsible for many automatic body functions such as heart rate, breathing and the muscle contractions of internal organs.
I asked Alan if there had been any stresses in his life in the period preceding the diagnosis. “Yes. I had been under stress, but
there are two kinds of stress. There is stress that is bad and stress that is good.” In Alan’s estimation the “bad stress” was the complete lack of intimacy in his ten-year marriage to Shelley. He sees that as the main reason the couple have not had children. “She just has some very serious problems. Because of her inability to be romantic, intimate and all the things that I need, my frustrations with our marriage were at their absolute peak at the point I got the cancer. I’ve always felt that that was a really major thing.” The
“good stresses,” in Alan’s view, came from his work. In the year prior to his diagnosis he worked eleven hours a day, seven days a week. I asked him if he has ever said no to anything.
“Never. In fact, I love being asked. Almost never have I said yes with deep regret. I like doing things, I like taking things on. All somebody has to do is ask me and they got me.”
“What about since the cancer?”
“I’ve learned to say no—I say it all the time. I want to live! I think saying no plays a big role in getting better. Four years ago they gave me a 15 per cent chance of survival. I made a conscious decision that I wanted to live, and I set a timeline somewhere between ve and seven years.
“How do you mean?”
“Five years is supposed to be the magical thing, but I know it’s just an arbitrary timeline. I gure I’ll cheat and get two more years. Then, after seven …”
“Are you saying that after seven years you can go back to living crazily again?”
“Yes, I might. I don’t know.”
“Big mistake!”
“Probably—we’ll talk about that. But right now I’m a good boy. I really am. I say no to everybody.”
The experience of stress has three components. The rst is the event, physical or emotional, that the organism interprets as threatening. This is the stress stimulus, also called the stressor. The second element is the processing system that experiences and
interprets the meaning of the stressor. In the case of human beings, this processing system is the nervous system, in particular the brain. The nal constituent is the stress response, which consists of the various physiological and behavioural adjustments made as a reaction to a perceived threat.
We see immediately that the de nition of a stressor depends on the processing system that assigns meaning to it. The shock of an earthquake is a direct threat to many organisms, though not to a bacterium. The loss of a job is more acutely stressful to a salaried employee whose family lives month to month than to an executive who receives a golden handshake.
Equally important is the personality and current psychological state of the individual on whom the stressor is acting. The executive whose nancial security is assured when he is terminated may still experience severe stress if his self-esteem and sense of purpose were completely bound up with his position in the company, compared with a colleague who nds greater value in family, social interests or spiritual pursuits. The loss of employment will be perceived as a major threat by the one, while the other may see it as an opportunity. There is no uniform and universal relationship between a stressor and the stress response.
Each stress event is singular and is experienced in the present, but it also has its resonance from the past. The intensity of the stress experience and its long-term consequences depend on many factors unique to each individual. What de nes stress for each of us is a matter of personal disposition and, even more, of personal history.
Selye discovered that the biology of stress predominantly a ected three types of tissues or organs in the body: in the hormonal system, visible changes occurred in the adrenal glands;
in the immune system, stress a ected the spleen, the thymus and the lymph glands; and the intestinal lining of the digestive system.
Rats autopsied after stress had enlarged adrenals, shrunken lymph organs and ulcerated intestines.
All these e ects are generated by central nervous system pathways and by hormones. There are many hormones in the
body, soluble chemicals that a ect the functioning of organs, tissues and cells. When a chemical is secreted into the circulation by one organ to in uence the functioning of another, it is called an endocrine hormone. On the perception of a threat, the hypothalamus in the brain stem releases corticotropin-releasing hormone (CRH), which travels a short distance to the pituitary, a small endocrine gland embedded in the bones at the base of the skull. Stimulated by CRH, the pituitary releases adrenocorticotrophic hormone (ACTH).
ACTH is in turn carried by the blood to the adrenals, small organs hidden in the fatty tissue on top of the kidneys. Here ACTH acts on the adrenal cortex, a thin rind of tissue that itself functions as an endocrine gland. Stimulated by ACTH, this gland now secretes the corticoid hormones (corticoid, from “cortex”), the chief among them being cortisol. Cortisol acts on almost every tissue in the body one way or another—from the brain to the immune system, from the bones to the intestines. It is an important part of the in nitely intricate system of physiological checks and balances by which the body mounts a response to threat. The immediate e ects of cortisol are to dampen the stress reaction, decreasing immune activity to keep it within safe bounds.
The functional nexus formed by hypothalamus, pituitary and adrenal glands is referred to as the HPA axis. The HPA axis is the hub of the body’s stress mechanism. It is implicated in many of the chronic conditions we will explore in later chapters. Because the hypothalamus is in two-way communication with the brain centres that process emotions, it is through the HPA axis that emotions exert their most direct e ects on the immune system and on other organs.
Selye’s triad of adrenal enlargement, lymphoid tissue shrinkage and intestinal ulcerations are due, then, to the enhancing e ect of ACTH on the adrenal, the inhibiting e ect of cortisol on the immune system and the ulcerating e ect of cortisol on the intestines. Many people who are prescribed cortisol-type drugs in treatment for, say, asthma, colitis, arthritis or cancer are at risk for intestinal bleeding and may need to take other medications to
protect the gut lining. This cortisol e ect also helps to explain why chronic stress leaves us more susceptible to developing intestinal ulcers. Cortisol also has powerful bone-thinning actions. Depressed people secrete high levels of cortisol, which is why stressed and depressed postmenopausal women are more likely to develop osteoporosis and hip fractures.
This cursory description of the stress reaction is necessarily incomplete, for stress a ects and involves virtually every tissue in the body. As Selye noted, “A general outline of the stress response will not only have to include brain and nerves, pituitary, adrenal, kidney, blood vessels, connective tissue, thyroid, liver, and white blood cells, but will also have to indicate the manifold interrelations between them.”4 Stress acts on many cells and tissues in the immune system that were largely unknown when Selye was conducting his pioneering research. Also involved in the immediate alarm response to threat are the heart, lungs, skeletal muscles and the emotional centres in the brain.
We need to mount a stress response in order to preserve internal stability. The stress response is non-speci c. It may be triggered in reaction to any attack—physical, biological, chemical or psychological—or in response to any perception of attack or threat, conscious or unconscious. The essence of threat is a destabilization of the body’s homeostasis, the relatively narrow range of physiological conditions within which the organism can survive and function. To facilitate ght or escape, blood needs to be diverted from the internal organs to the muscles, and the heart needs to pump faster. The brain needs to focus on the threat, forgetting about hunger or sexual drive. Stored energy supplies need to be mobilized, in the form of sugar molecules. The immune cells must be activated. Adrenaline, cortisol and the other stress substances ful ll those tasks.
All these functions must be kept within safe limits: too much sugar in the blood will cause coma; an overactive immune system will soon produce chemicals that are toxic. Thus, the stress response may be understood not only as the body’s reaction to threat but also as its attempt to maintain homeostasis in the face
of threat. At a conference on stress at the National Institutes of Health (U.S.), researchers used the concept of the stable internal milieu to de ne stress itself “as a state of disharmony or threatened homeostasis.”5 According to such a de nition, a stressor “is a threat, real or perceived, that tends to disturb homeostasis.”6
What do all stressors have in common? Ultimately they all represent the absence of something that the organism perceives as necessary for survival—or its threatened loss. The threatened loss of food supply is a major stressor. So is—for human beings—the threatened loss of love. “It may be said without hesitation,” Hans Selye wrote, “that for man the most important stressors are emotional.”7
The research literature has identi ed three factors that universally lead to stress: uncertainty, the lack of information and the loss of control.8 All three are present in the lives of individuals with chronic illness. Many people may have the illusion that they are in control, only to nd later that forces unknown to them were driving their decisions and behaviours for many, many years. I have found that in my life. For some people, it is disease that
nally shatters the illusion of control.
Gabrielle is fty-eight, active in a local scleroderma society. Her naturally large eyes are magni ed by the e ect of her skin being stretched tightly on her face, her smile a barely perceptible movement of her lips over perfect white teeth. Her narrow ngers shine with the waxy translucency characteristic of scleroderma, but they also display some of the deformity of rheumatoid arthritis.
Several digits have “drifted” o centre and are swollen at the joints. Gabrielle was diagnosed with scleroderma in 1985. Usually the disease’s onset is slow and insidious, but the rst symptoms she experienced came on with u-like suddenness—probably because in her case the scleroderma is associated with a more generalized rheumatic arthritis. “I was very, very ill for close to a year,” she recalls.
“The rst ve or six months I was hardly able to get out of bed.
It was an e ort to get up and do anything because of pain everywhere there is a joint. I would respond to an anti- in ammatory or Tylenol 3 for maybe three or four weeks. Then it wouldn’t be e ective any more, so we would change and try something else. I was unable to eat. In ve weeks I lost thirty pounds. I was down to ninety-one pounds…. I had read in di erent articles that people who come down with scleroderma are those who’ve always had to feel in control. All my life I’d been the one in charge, taking care of everything. Suddenly now with the disease you are totally out of control.”
It may seem paradoxical to claim that stress, a physiological mechanism vital to life, is a cause of illness. To resolve this apparent contradiction, we must di erentiate between acute stress and chronic stress. Acute stress is the immediate, short-term body response to threat. Chronic stress is activation of the stress mechanisms over long periods of time when a person is exposed to stressors that cannot be escaped either because she does not recognize them or because she has no control over them.
Discharges of nervous system, hormonal output and immune changes constitute the ight-or- ght reactions that help us survive immediate danger. These biological responses are adaptive in the emergencies for which nature designed them. But the same stress responses, triggered chronically and without resolution, produce harm and even permanent damage. Chronically high cortisol levels destroy tissue. Chronically elevated adrenalin levels raise the blood pressure and damage the heart.
There is extensive documentation of the inhibiting e ect of chronic stress on the immune system. In one study, the activity of immune cells called natural killer (NK) cells were compared in two groups: spousal caregivers of people with Alzheimer’s disease, and age- and health-matched controls. NK cells are front-line troops in the ght against infections and against cancer, having the capacity to attack invading micro-organisms and to destroy cells with malignant mutations. The NK cell functioning of the caregivers was signi cantly suppressed, even in those whose spouses had died