…grant me the serenity
to accept the things I cannot change;
courage to change the things I can;
and wisdom to know the difference….

from The Serenity Prayer, by Reinhold Niebuhr

     Picture an early human moving through the quiet forest, intent on the prey he’s tracking. His pace is steady and his mind focused. Suddenly a bear bursts through the trees.  Emotional centers in primitive parts  the hunter’s brain fire off  threat messages which race through the sympathetic nervous system to his adrenal glands—little thumb size organs buried in fat and sitting on top of the kidneys.  Almost instantly, each gland responds with a burst of adrenalin from its central core, the adrenal medulla. Danger also prompts his pituitary gland to pour out a big dose of adrenocorticotropin (ACTH), a hormone that speeds through the blood to the adrenal cortex, the outer 80% of the gland. In response, the gland releases cortisol, a powerful glucocorticoid hormone involved in energy regulation.

The hunter’s pulse and blood pressure shoot up.  His airways dilate and he breathes faster.  His vision narrows and sharpens. Anticipating action, his muscles and liver free glucose and fat from storage.  By the time he races to a nearby tree to haul himself to safety,  the cascade of neural and hormonal events has shifted his metabolism from quiet homeostasis (maintenance of normal function) to an active state designed for fleeing….or for fighting if the bear climbs too.  When the bear loses interest and wanders away, our early man’s activated physiology reverts to routine functioning. He climbs down, resumes his methodical hunt and cooks his game over an open fire. From sundown to sunup, he sleeps.

Now consider a modern man as he rushes through his urban environment. He becomes anxious and then angry when his train is late. As he hails a cab he narrowly misses being hit by an oncoming car. Horns blare.  He flops down in the back seat of the cab, fumbling for his ringing cell phone, only to hear that his boss is angry because he is late.  Inside our overweight modern man’s body,  early hunter physiology whips his adrenal glands into action – over and over and over. But he does not get to fight or flee. Worse yet, the threats in his environment do not lose interest and wander away.  He will be on edge all day, and perhaps late into the night.  After a few drinks, a few smokes, a fast food meal and some paperwork, he falls asleep in front of the TV, finally stumbling into bed in the wee hours of the morning. By 6AM he’s starting over, sleep-deprived.

The adrenal gland connection

In both early and modern humans, the brain-adrenal connection is heavily influenced by environment, genetic makeup, lifestyle and memory of previous experiences. We learn fear and make habits of emotional responses. While animal research can’t take into account human mental components of stress, it has provided useful physical insights, especially about the adrenal connection to chronic stress. Experiments in “rat micro-societies” refined the fight-or-flight concept and divided it into aggressive defense and passive defeat responses, an important distinction because each type activates different parts of the adrenal glands.

Rats responded with passive defeat when a task like pushing a lever sometimes produced food, sometimes didn’t, sometimes in one place, sometimes in another, and sometimes not at all. The consequences of the rats’ actions were uncontrollable and feedback didn’t help them learn.  In these circumstances the adrenal cortex overproduced cortisol.  If you think the passive defeat experiments resemble average life, then you’ll guess, correctly, that chronic stress in people might also trigger elevated cortisol levels.

Aggressive defense responses to the rat equivalent of being mugged, in contrast, activated primarily the adrenal medulla, which takes charge of the immediate activity necessary to survive a threat by producing an adrenalin rush – a burst of the hormones epinephrine and norepinephrine. In states of fear and/or anger, we experience this rush as rapid pulse, elevated blood pressure, increased breathing rate, flushing, pallor and dry mouth.

In our early hunter these adrenal responses are sequential. First comes the adrenalin rush which helps him survive.  Following just behind,  the adrenal cortex ramps up hormone production to help restore normality–to restock energy supplies, dampen pain and divert resources from routine activities.The system is designed for short bursts of danger, not for chronic immersion in mental stress.

The metabolic syndrome connection

Beginning in 2002, researchers began to correlate adrenal hormone abnormalities with the modern plague of the metabolic syndrome—abdominal obesity, insulin resistance, diabetes and high blood pressure, all reliable side effects of exposure to excessive cortisol, whether it comes from drugs like prednisone or from  pituitary or adrenal gland diseases. (See note on Cushing’s disease below).  No one thinks cortisol and stress are wholly responsible for our metabolic epidemic, but many hope that the stress connection will help lead to a solution.

Counteracting the stress response

Stress researchers uniformly conclude that short of retreating from the world, the only major defense that counteracts the effects of stress is regular physical activity which dissipates some of the energy mobilized for action.  The best results come from superimposing physical activity on a lifestyle that accommodates enduring human needs: sufficient sleep, diet suitable for an ancient physiology, good social network and engagement in focused activity that has personal value. Even then, coping strategies are necessary.

A Note on Cushing’s Disease

    The most dramatic demonstration of the results of too much cortisol occurs in patients with Cushing’s disease, usually caused by a pituitary gland tumor which overstimulates  the adrenal cortex.  In these patients, muscles are thin and weak, and excess weight is concentrated in the trunk and face and neck.  Patients have red, jowly faces and skin scored by purplish stretch marks and poorly healed wounds. Bones are robbed of calcium and osteoporotic upper backs round forward under the characteristic “buffalo hump” of fat.  The adrenal cortex hormones also have weak male hormone effects causing male pattern baldness and excess facial hair in women.  The immune system is weakened and health is further damaged by diabetes, high blood pressure and heart disease.