Why Zebras Don't Get Ulcers: The Acclaimed Guide to Stress, Stress-Related Diseases, and Coping

by Robert M. Sapolsky

A stressor is anything in the outside world that knocks you out of homeostatic balance, and the stress-response is what your body does to reestablish homeostasis.

the stress-response can be mobilized not only in response to physical or psychological insults, but also in expectation of them.

Homeostasis is about tinkering with this valve or that gizmo. Allostasis is about the brain coordinating body-wide changes, often including changes in behavior.

Thus, during stress, digestion is inhibited—there isn’t enough time to derive the energetic benefits of the slow process of digestion, so why waste energy on it? You have better things to do than digest breakfast when you are trying to avoid being someone’s lunch.

is never really the case that stress makes you sick, or even increases your risk of being sick. Stress increases your risk of getting diseases that make you sick, or if you have such a disease, stress increases the risk of your defenses being overwhelmed by the disease.

Epinephrine is secreted as a result of the actions of the sympathetic nerve endings in your adrenal glands (located just above your kidneys); norepinephrine is secreted by all the other sympathetic nerve endings throughout the body.

Thus, when the sympathetic nerve endings in your heart secrete norepinephrine, which causes heart muscle to work differently, norepinephrine is playing a neurotransmitter role. If a neuron (or any cell) secretes a messenger that, instead, percolates into the bloodstream and affects events far and wide, that messenger is a hormone.

The pituitary contains a whole array of hormones that run the show throughout the rest of the body; it is the pituitary that actually knows the game plan and regulates what all the other glands do.

It is now recognized that the base of the brain, the hypothalamus, contains a huge array of those releasing and inhibiting hormones, which instruct the pituitary, which in turn regulates the secretions of the peripheral glands.

(Steroid is used to describe the general chemical structure of five classes of hormones: androgens—the famed “anabolic” steroids like testosterone that get you thrown out of the Olympics—estrogens, progestins, mineralocorticoids, and glucocorticoids.)

Together, glucocorticoids and the secretions of the sympathetic nervous system (epinephrine and norepinephrine) account for a large percentage of what happens in your body during stress. These are the workhorses of the stress-response.

What good are glucocorticoids if some of their actions occur long after your typical dawn-on-the-savanna stressor is over with?

Moreover, epinephrine and glucocorticoids, both secreted by the adrenal, can potentiate each other’s release.

You also want to increase the force with which your heart beats. This involves a trick with the veins that return blood to your heart. Your sympathetic nervous system causes them to constrict, to get more rigid. And that causes the returning blood to blast through those veins with more force. Blood returns to your heart with more force, slamming into your heart walls, distending them more than usual…and those heart walls, like a stretched rubber band, snap back with more force.

there is a subtler but easier way of detecting a problem. Whenever you inhale, you turn on the sympathetic nervous system slightly, minutely speeding up your heart. And when you exhale, the parasympathetic half turns on, activating your vagus nerve in order to slow things down (this is why many forms of meditation are built around extended exhalations).

Instead, complex food matter is broken down into its simplest parts (molecules): amino acids (the building blocks of protein), simple sugars like glucose (the building blocks of more complex sugars and of starches [carbohydrates]), and free fatty acids and glycerol (the constituents of fat).

postprandial daze.

Eat a huge meal and insulin pours out of the pancreas into the bloodstream, stimulating the transport of fatty acids into fat cells, stimulating glycogen and protein synthesis.

Turn up the activity of the sympathetic nervous system, turn down the parasympathetic, and down goes insulin secretion: step one in meeting an emergency accomplished.

Cholesterol also plays into this. As is well understood, there is “bad” cholesterol, also known as low-density lipoprotein-associated cholesterol (LDL) and “good” cholesterol (high-density lipoprotein-associated cholesterol, HDL).

you don’t want to have tons of LDL-cholesterol floating around and not enough HDL to counteract it. And during stress, you increase LDL-cholesterol levels and decrease HDL.*

As noted earlier, during stress, glucocorticoids act on fat cells throughout the body to make them less sensitive to insulin, just in case there’s some still floating around.

So a big reason why most of us become hyperphagic during stress is our westernized human capacity to have intermittent psychological stressors throughout the day. The type of stressor is a big factor.

So we differ as to whether stress stimulates or inhibits our appetite, and this has something to do with the type and pattern of stressors, how reactive our glucocorticoid system is to stress, and whether eating is normally something that we keep a tight, superegoish lid on. It turns out that we also differ as to how readily we store food away after a stressor. And where in the body we store it.

It turns out that when glucocorticoids stimulate fat deposition, they do it preferentially in the abdomen, promoting apple-shaped obesity.

The pattern arises because abdominal fat cells are more sensitive to glucocorticoids than are gluteal fat cells; the former have more receptors that respond to glucocorticoids by activating those fat-storing enzymes.

Growth hormone is secreted by the pituitary gland, which in turn is regulated by the hypothalamus in the brain

Once the growth period of youth is finished and the edifice is complete, the hormones of growth mostly work at rebuilding and remodeling—shoring up the sagging foundation, plastering the cracks that appear here and there.

And loss of body fat leading to androgen buildup is one of the mechanisms by which reproduction is impaired in females who are extremely active physically.

Breast feeding causes prolactin secretion. There is a reflex loop that goes straight from the nipples to the hypothalamus. If there is nipple stimulation for any reason (in males as well as females), the hypothalamus signals the pituitary to secrete prolactin. And as we now know, prolactin in sufficient quantities causes reproduction to cease.

when your immune system does encounter a novel invader, it can even form an immunologic memory of what the infectious agent looks like, to better prepare for the next invasion—a process that is exploited when you are vaccinated with a mild version of an infectious agent in order to prime your immune system for a real attack.

T cells bring about cell-mediated immunity (illustration). When

It is this, the T-cell component of the immune system, that is knocked out by the AIDS virus. By contrast, B cells cause antibody-mediated immunity

In one version of this, some perfectly innocuous compound in the world around you triggers an alarm reaction. Maybe it is something that you normally ingest, like peanuts or shellfish, or something airborne and innocuous, like pollen. But your immune system has mistakenly decided that this is not only foreign but dangerous, and kicks into gear. And this is an allergy.

Most of these glucocorticoid effects are against T cells, rather than B cells, meaning that cell-mediated immunity is more disrupted than antibody-mediated immunity.

Why would you want to bring immune function back down to the prestress level (phase B in the diagram)?

“on steroids”—to give them massive amounts of glucocorticoids.

if you falsely believe you had the power to prevent or cure cancer through positive thinking, you may then come to believe that it is your own fault if you are dying of the disease.

allodynia, which is feeling pain in response to a normal stimulus.

(Opiate refers to analgesics not normally made by the body, such as heroin or morphine. Opioid refers to those made by the body itself. Because the field began with the study of the opiates—since no one had discovered the opioids as yet—the receptors found then were called opiate receptors. But clearly, their real job is to bind the opioids.)

Not surprisingly, it turns out that they work by releasing endogenous opioids. As but one example of the evidence for that, block opiate receptors with naloxone, and placebos no longer work.

Fibromyalgia. This is the mysterious syndrome of people having markedly reduced pain tolerance and multiple tender spots throughout the body, often paralyzing extents of pain, and no one can find anything wrong—no pinched nerve, no arthritis, no inflammation.

Both of these are regions vital to memory—for example, it is the hippocampus and cortex that are preferentially damaged in Alzheimer’s disease.

think of the cortex as your hard drive, where memories are stored, and your hippocampus as the keyboard, the means by which you place and access memories in the cortex.

In a disorder called Cushing’s syndrome, people develop one of a number of types of tumors that result in secretion of tons of glucocorticoids.

First, the hippocampus is one of only two sites in the brain where these new neurons originate.

the gp120 protein is found in the AIDS virus and appears to play a central role in damaging neurons and causing the dementia.)

How did such maladaptive responses evolve? The most likely explanation is that the body simply has not evolved the tendency not to secrete glucocorticoids during a neurological crisis.

During REM sleep, metabolism in the frontal cortex goes way down, disinhibiting the limbic system to come up with the most outlandish ideas. That’s why dreams are dreamlike—illogical, nonsequential, hyperemotional.

dreaming gives some aerobic exercise to otherwise underutilized brain pathways (that is, the oft-neglected Busby Berkeley musical brain circuit).