Stress is a slow but very reliable killer. It exacerbates the effects of most diseases and chronic conditions. It delays recovery from illness and it makes us age more quickly. Like nicotine it seems to affect all the systems in the body. Stress also makes us anxious and depressed. We don’t cope with problems or perform well in daily tasks. We indulge in self-comforting behaviour and relate badly to other people. Stress can make us very sick and miserable over time.

Yet stress is still a mystery. We find it hard to estimate the degree of risk or know how to treat it. Its biological effects can’t be measured well at the individual level. We even have trouble defining it. We use the word ‘stress’ in such loose and contradictory ways that many researchers don’t regard it as a scientific concept at all. ‘Stress’ is frequently used to describe both the stimulus (overwork) and the result (insomnia). This leads to a logical fallacy, namely that the cause of stress is stress. In this essay I will try to draw a few lines in the sand.

STRESSORS. A stressor is different from a stress response. A stressor is any event that stimulates an alarm reaction within us. Stressors are typically other people, work, problems, noise, overcrowding or being too busy. Being sick or lonely or overweight can be stressors in their own right. While it is easy to identify major stressors, we fail to notice the accumulating effect of minor ones.

ACUTE AND CHRONIC STRESS. The term ‘stress response’ describes the way the body reacts to any challenge. We commonly think of it as the fight-or-flight response or the adrenaline rush. Yet we also use the word ‘stress’ to describe the quite different state of chronic, low-level pressure – the grind of a long hard year, for example.

It is worth distinguishing these two. An acute response is governed by adrenaline. A chronic response is governed by cortisol. An acute fight or flight response only lasts for minutes and causes little damage. A state of chronic over-arousal can last a lifetime and be deadly.

GOOD STRESS. The stress response is not inherently bad. We need stress. Adrenaline and cortisol wake us up and get us going in the morning. Our muscles need to be used vigorously or they will atrophy. Aerobic exercise is good precisely because it pushes our hearts and lungs to the limits of their capacity. Our immune systems need to be repeatedly exposed to pathogens to maintain a robust defence. The brain needs challenges on a daily basis or the neurons lose their richness of connections. The problems come only with excessive stress and a lack of sufficient rest and recovery time.

STRESS IS AN INDIVIDUAL PERCEPTION. There is no automatic 1-to-1 causal relationship between an external stressor and our body’s response to it. Medical science is now demonstrating that each one of us is far more unique than we used to imagine. This means we can have very individual responses to the same stressors. What is nothing to one person can produce a colossal but completely genuine stress response in someone else. Some people need to climb Everest to feel alive. Others are panicked by the sight of a dog or a email.

Only you can evaluate your degree of stress. It comes down to your personal sense of competence.  I have no trouble giving public talks but I would be very stressed if I had to babysit a child. This gives us another definition. Stress is when we feel we don’t have the physical or mental resources to cope. It is when we feel we are not in control of our situation.

STRESS IS INVARIABLY UNDERESTIMATED. We are not good at assessing our own stress. We would rather not know. Stress makes us tense up, block out and go numb. It goes hand in hand with denial, suppression and escapist behaviour. When stressed, we tend to focus on action to fix or avoid the problem. We may barely notice its effect on our bodies and moods.

We often assume that we can’t be stressed if we are managing to get everything done. While failure is bad enough, even success and coping well under pressure are no guarantees against the insidious effects of stress. Many high functioning people have been stressed for years before they finally admit it to themselves.

HOMEOSTASIS. Until in the 1920s this word ‘stress’ was only used in an engineering context. It was adapted as a biological term by Walter Cannon and Hans Selye, the first stress researchers, and it rapidly moved into popular usage. Cannon also invented the term ‘fight or flight’ but he is most respected for his theory of ‘homeostasis’. This idea is so crucial to understanding stress that I will now describe in some detail.

Cannon coined this term to describe the body’s remarkable ability to regulate itself. We now know that homeostatic systems regulate the correct levels of sugar, oxygen, hormones and nutrients in the blood. They maintain body temperature, muscle tone, heart rate, balance, arousal and relaxation. These systems all need to work harmoniously for the body to be healthy.

Each of the body’s countless homeostatic regulators fluctuates around an ideal set point. Resting heart rate is about 70 beats a minute. The acidity of the blood needs a pH of 7.4. These set points however are nowhere near as fixed as was once thought and big deviations are quite natural.

In other words, homeostasis is not so much a fixed point as a dynamic equilibrium within a permissible zone. Levels fluctuate adaptively according to circumstances but they can only be stretched so far or for so long. Flexible as these set points are, the body exerts enormous gravitational pull to maintain them. Our lives depends on it.

Some fluctuations are very slow while others are lightning fast. Many homeostatic systems follow the sleep/wake cycle and make one big oscillation a day. Temperature and cortisol levels rise in the morning and decline at night. Growth hormone production and immune function do exactly the reverse. At the other extreme, the enzymes that govern the regulatory processes within cells switch on and off thousands of times a second.

Many set points rise and fall in an orderly fashion in response to changing conditions. When food enters the small intestine, digestive enzymes will increase to a certain ideal level. As it passes through, they drop back again. Likewise, there is a smooth economical way for muscles to tense and relax during normal activity without causing strain. In other words, many so-called set points are more about an ideal curve or sequence of actions than an ideal number.

Homeostasis used to be conceived as the rest phase of the rest-activity cycle, the still point to which all systems ideally returned. This led to the fallacy that rest is good but that activity is intrinsically harmful. We now see homeostasis as the smooth, coordinated functioning of every part of the rest-activity cycle. It is quite possible to feel relaxed, balanced and in control while running a marathon or presenting a lecture. This dynamic stability is a sign of energy economy and good health, not stress.

THE AUTONOMIC NERVOUS SYSTEM. Most homeostatic systems operate semi-independently but Walter Cannon discovered one that has a global effect. This is the Autonomic Nervous System. It operates in close conjunction with the hypothalamus and pituitary in the brain and the adrenal glands above the kidneys. This network is called the HPA axis and it governs the rate at which we burn energy. We need a lot of glucose when we are active or stressed and the HPA axis makes sure it is readily available.

The Autonomic Nervous System conveniently divides into two so-called ‘branches’, each with its own extensive network of nerve connections. Together they manage the body’s cycles of arousal and relaxation, activity and rest. The ‘sympathetic’ branch increases arousal, muscle activity and energy consumption and the ‘parasympathetic’ branch reduces them.

These two branches lend themselves to catchy phrases and images. Sympathetic activity is called the Stress Response or the Fight-or-flight Response. Parasympathetic activity is called the Relaxation Response or the Rest, Digest and Repair Response. These two branches of the nervous system are also described as being the body’s accelerator and brake. One speeds us up and the other slows us down.

This Stress-Relaxation polarity may look like a homeostatic, on-off system but this is deceptive. The Stress Response is far stronger than the Relaxation Response. It is hot-wired for speed and power. It has four or five times as many nerve connections and its effects are longer lasting. In contrast the Relaxation Response is slower, weaker and more easily interrupted. We can get stressed in a flash. It takes much longer to relax.

Hardly any of us will go into a full fight-or-flight response on any day but we can use this mechanism to illustrate how stress affects the body. Fight-or-flight starts with the perception of danger. This prompts the HPA axis to secrete adrenaline and cortisol and to release glucose into the bloodstream.

Heart rate, blood pressure and breathing will all increase dramatically to circulate this rocket fuel to where it is needed. The appropriate blood vessels dilate and contract to maximise the flow of blood to the muscles, heart and lungs. The big skeletal muscles tense up in preparation for rapid movement.

The body hasn’t got boundless supplies of glucose so it has to prioritise. To fuel the muscles it has to starve other functions. It does this mainly by constricting local blood vessels to reduce supply. In this simple but highly effective way, it winds back the processes of digestion, immunity, repair, sexuality and conscious thought. These ongoing functions consume a lot of energy. Digestion takes 10-20% of the body’s energy each day. Thinking takes just as much. In a crisis, we need that energy elsewhere. All this is positive and adaptive while the crisis lasts.

CHRONIC STRESS. The problem only comes if we don’t return to balance quickly enough. If we stay aroused for too long and too frequently over too many years, we push the benchmark steadily higher. Chronic over-arousal becomes ‘normal’ for us and pathologies start to emerge.

It is easy to see how this happens. Constantly elevated heart rate and blood pressure contribute to cardiovascular disease. Tense rapid breathing leads to respiratory problems, poor oxygenation of the body and anxiety. Chronically tight muscles leads to pain and injury. High blood sugar lead to diabetes. These all destabilize homeostasis by over-stimulating certain systems.

Conversely, chronic over-arousal impairs other systems by under-stimulating them. It starves them of the resources they need to function adequately. High cortisol is the main culprit. By conserving sugar in the bloodstream, it stops the cells of the body from absorbing the proteins and fats they need to maintain their vital metabolic functions. Those systems that require a rapid turnover of cell production suffer most, namely digestion and immunity.

When we are stressed we don’t digest food at all well. Immune function goes on hold, making us susceptible to disease or infection. The processes of growth and repair, which work best in deep sleep, are inhibited. Libido fades and the rhythms of the reproductive process are disturbed. We lose the capacity for memory formation and deliberate thought.

Cannon hypothesised that stress, by exacerbating these imbalances, can speed the onset of an illness or cause one or slow the recovery. This brings us to another definition: stress is what disturbs the body’s ability to regulate itself.

The first proof that stress is damaging to health came from Hans Selye. In his era the germ theory of disease was king. This is the view that a particular disease is caused by a unique pathogen. Therefore you cure the disease by killing the pathogen.

What Selye discovered to his great surprise was the opposite of this. Rather than one stressor causing one particular illness, Selye found that any number of different stressors had a similar convergent effect. Stress, as anything that upsets homeostatic balance, could cause illness and death in itself just as Cannon had predicted it would.

Selye spend years torturing thousands of small animals to death and then dissecting them. He found that regardless of the methods he used, his animals all died with similar symptoms. Their adrenal glands were enlarged. This indicated that their stress response was working overtime. Their thymus and lymph glands had atrophied. This indicated that their immune systems were shot. And they commonly suffered from bacterial and fungal infections and ulcers, just as stressed humans do.

Selye also made the key distinction between acute, transient stress governed by adrenaline and persistent, low-level arousal mediated by cortisol. This idea is wonderfully explained by Robert Sapolsky in his book ‘Why Zebras don’t get Ulcers’.

If a zebra is attacked by a lion, the adrenaline rush will massively dilate blood vessels to its heart, lungs and leg muscles all in the service of explosive speed. It simultaneously shuts down the blood supply to digestion and other functions which matter little at that time.

A textbook fight or flight response doesn’t last very long and doesn’t need to. A zebra that hasn’t escaped the lion within five minutes is probably dead. Because the adrenaline rush spikes and fades away very quickly, zebras don’t get ulcers. They have a few minutes of high stress to which they are well adapted, but their adrenaline levels soon drop back to normal.

Stress only becomes a health risk when chronic over-arousal sets in and cortisol takes over. In this context, don’t think of zebras. Think of baboons or humans. A group of baboons in its ideal environment doesn’t need to worry much about food supply or predators. Baboons get stressed by other baboons.

Baboons are aggressive hierarchical animals. They maintain their status by routinely attacking their inferiors, particularly females and juveniles. As a result, baboons can be anxious all day long and so, unlike zebras, they do get ulcers, heart disease, opportunistic infections and other stress-related problems.

This is more like our human situation. Hardly any of us will go into a full fight-or-flight response in any day. We don’t face violence on a daily basis. Instead, we suffer from the low-level, unresolvable stress that comes from being social animals, vulnerable to the opinions and emotions of others. It is our families and colleagues rather than our enemies that cause us the most grief.

Over time, our bodies adapt by recalibrating upwards our set-point levels of both stress and relaxation. Instead of relaxing completely whenever possible, we maintain a persistent low level of arousal ‘just in case.’ Gradually it feels natural and ordinary to be edgy and restless all day long, whether the immediate circumstances warrant it or not.

None of this is life-threatening but it wears us down. A full-on fight-or-flight response shuts down digestion and immune function completely. In times of low-level stress however, the factories remain open but operate with reduced capacity.

When stressed we still digest food but with long interruptions. We still fight off infections but badly. We still think but inefficiently. We go to sleep but we’re restless and easily disturbed. The body repairs itself but the workmanship is shoddy. We get tense quickly, stay tense when we don’t need to be, burn through our energy fast and push on feeling exhausted. It is that 20% of extra tension impairing crucial functions year after year that does the damage.

CORTISOL. I’ve now mentioned cortisol several times but what exactly is it? Cortisol is a hormone produced in the adrenal glands. Its function is to increase the levels of glucose in the bloodstream. Because we need energy primarily for physical action, cortisol levels rise in the morning, peak about midday and fade away at night.

As well as this one big daily oscillation, cortisol levels can rise quickly in a stressful situation. Adrenalin triggers off the immediate response by burning the available energy in the muscles and bloodstream but cortisol backs it up. Cortisol is far-sighted. It calls up new supplies for the troubles that may lie ahead. This is how we can get stressed by what never happens. The body is producing high levels of cortisol in anticipation of danger, ‘just in case.’ Many doctors regard high resting levels of cortisol as the basic medical evidence for stress.

Cortisol is crucial for our wellbeing. We need to have energy on tap to do anything at all. So what is the problem with having too much glucose in the bloodstream? The simple answer is that it upsets homeostasis. Too much of one thing means too little of something else, and the delicate rhythms of the body will not work as well they should.

Too much glucose is bad for the cardiovascular system. It make the blood viscous thereby increasing blood pressure. Sticky blood is also more likely to form the platelets that leads to atherosclerosis and vascular damage.

Cortisol keeps glucose in the bloodstream by preventing its uptake by the cells of the body. This stops the cells from absorbing the proteins and fats they need to maintain their vital metabolic functions. High blood sugar also counteracts the effect of insulin, leading down the path to diabetes.

Cortisol is very one-eyed. It is a sugar junky. It even breaks down proteins and fats into sugar. It converts everything it can find into sugar. It is like taking out extra credit cards and mortgaging the house to maximise the cash in your pocket.

In the first stages of stress this seems to work fine. The adrenaline rush and the cortisol backup really do give you more energy for a while. Robbing Peter to pay Paul seems to work. People may feel they are still coping well in difficult times but this kind of overspending can’t last forever. It eventually throws the body into that energy bankruptcy that Selye called the stage of exhaustion.

This happens because cortisol damages the production of cells and enzymes. The white blood cells of the immune system and the epithelial cells of the digestive tract are very short-lived and need to be regenerated in colossal numbers daily. They need to access the amino acids and fatty acids in the bloodstream as building blocks, but cortisol won’t let them do so.

In a similar fashion, cortisol inhibits enzyme production. Within the cells themselves, the body maintains homeostasis largely through the action of enzymes. These are proteins made up of amino acids and they are extremely potent. A single catalytic enzyme can trigger off half a million chemical reactions inside a cell within a minute. Without enzymes, all chemical interactions in the body would happen far too slowly for life. Cortisol however holds back the proteins necessary for their production.

Enzymes are also necessary for digestion and immune function. Under stress, the pancreas and liver can’t produce adequate amounts of the digestive enzymes that break down food. The white blood cells can’t produce sufficient antibodies to combat infections. This means that two of the most obvious and well-tested effects of stress are poor digestion and a person’s susceptibility to common infections like the flu.

Of course, cortisol is still a good hormone. We need it to cope with the demands of the most ordinary day. The problems only come with excess, with habitual over-arousal and the failure to balance it out with sufficient rest and recovery time.