by E. Paul Zehr
But why so much ado about stress? What is stress anyway? Are you getting stressed by all these questions? Although stress is a fundamental property of life—I mean that quite literally, as you will see—that has existed forever, stress as a scientific concept has its roots in the work of the great French scientist Claude Bernard (1813–1878). Bernard’s contributions were so important that many consider him the father of physiology. The central issue for us to consider here with Batman is that having a functioning human body is a tricky business. Your body is composed of an enormous number of cells—on average about one billion cells per gram of tissue (about a third of an ounce) or about 100 trillion cells in an adult—and they all have their own internal environments (as we discussed in Chapter 2).
Maintaining order and concentrations of nutrients and wastes in the internal and external environments is a major function of cells. However, your cells are the ultimate nosy and envious neighbors. It really is all about keeping up with the Joneses. All your cells want to be the same. OK, that may seem fine. But it isn’t quite so easy to keep the contents of each cell the same because the “walls” (membranes) of the cells are flimsy and allow movement of lots of things across them. So what happens in the external environment, held at bay by cellular processes and that flimsy membrane, has real consequences for each cell. This brings us back to Claude Bernard. He had the insight to observe that the most important issue for life that exists as a fluid environment independent from an external environment—that is to say, the life of our cells—was to have a very tight control or regulation of the fluid itself.
American physiologist Walter B. Cannon (1871–1945) picked up this concept and expanded upon it. In so doing he coined the term “homeostasis” to refer to the process by which the internal environment of the body is maintained within a range at which cells could function properly. The concept of homeostasis has embedded in it both changes and responses to change that all serve to drive the body back to its comfortable operating range. Body temperature regulation is a good example of this. Other examples include responses to extreme cold, hemorrhaging blood loss, traumatic pain, and emotional distress. These all essentially require responses related to hormones, which we will discuss shortly. Cannon also put forward the phrase “fight or flight” relating to hormonal responses to extreme stresses that challenged homeostasis. I think it is easy to imagine the relevance of fight or flight to a career as Batman!
Walter Cannon went on to say that the nervous system was very important in regulating homeostasis and that all systems were active at all times. This means that things in the body get turned up or down, not on or off. Consider the example of a thermostat. You would normally adjust the temperature up or down a little bit and not just full-blast hot or cold and then off! The best example in your body is that of your heart rate. Your heart beats constantly, but the rate is adjusted up or down depending on what you are doing. As long as things are intact and working well, homeostasis is maintained and the body is healthy. However, when failure to regulate homeostasis occurs, disease and death may follow.
Of interest scientifically and with regard to the rigors of Batman is Cannon’s description of “shock” gleaned from his experience with soldiers on the battlefields of World War I. Cannon showed that hormones reacting to stress were very much a part of how soldiers responded to life-threatening wounds.
In addition to this extreme example, routine activities such as exercise evoke homeostatic responses. Although concepts related to stress have been around for quite some time, it wasn’t until 1935 that the more modern notion of stress was clearly articulated by Dr. Hans Selye. Drawing from experiments on mammals of the order Rodentia and the genus Rattus—the common rat—Selye came up with the concept of stress.
Selye was born and trained in Prague and made his way to the Johns Hopkins University in Baltimore, Maryland, in 1931. Soon he moved on to Montreal and began his research in endocrinology at McGill University. With a background in organic chemistry and medicine, Selye was searching for new sex hormones. While testing the effects of a variety of extracts on rats, Selye was greatly surprised to discover that regardless of the extract used, a reproducible and devastatingly widespread negative response was observed—the catastrophic failure of several organ systems including the adrenal cortex (home of the adrenal glands) in the kidney and the intestines.
Selye extended this concept to something he called the general adaptation syndrome (shortened to GAS—I promise this is really the short form and that I didn’t make it up). This syndrome was meant to embody the state of an organism in relation to adapting and responding to its environment. Within this framework the catastrophic organ failure observed in the rats was indicative of a failure to adapt to stress. There are three stages within the syndrome. The first is an “alarm reaction” that mimics the “fight or flight” response that Cannon described. In the second stage, adaptation occurs, and there is an adjustment and resistance to the stressor (see Figure 3.1). However, if this adaptation is insufficient, or if the stressor is too large, we enter the third stage, which is one of exhaustion and cell death.
We typically think of stress as something negative that needs to be “reduced” or “managed.” In fact, without “stress” in a pure physiological sense, there would be no adaptation at all, no function, and life as we know it would not exist! Clearly, within a certain range—one that does not induce catastrophic organ failure, of course—stress is needed as a stimulus for biological activity. This assumption forms the backbone for most of our understanding about how the body adapts to exercise. The converse is also true: removing stresses can yield adaptations in the opposite direction to those that occurred in the presence of the stress. The key is to understand the process of stimulus and response shown in how Batman’s (and your) cells adapt.
When there is a stimulus in our bodies, the body responds in such a way so as to remove or minimize the effect of the original stimulus. This is known as a biological feedback system. Let’s look at a simple example of a biological adaptation to training stresses that Batman might experience: a callus on his foot. Suppose when he is training and working, his foot repeatedly rubs inside of his boot. If this action is not strong enough to form a blister, what will occur instead is that the superficial skin layers will harden and thicken. As these layers build up, a callus will develop. The adaptation of the increased layering of the skin serves to reduce the effect of the stimulus on the deeper layers of tissue. So, the callus winds up reducing the possible effect of the stimulus.
This basic example illustrates the underlying principle at work for adaptations to training and exercise stress for pretty much all our tissues. Basically, adaptations minimize the effect of the stress. The next thing to appreciate is the way in which physiological systems can adapt and change when exposed to a training stress. We will focus on this phenomenon as it relates to muscle, bone, and connective tissue, and the metabolic processes associated with each, in Part II, where we will specifically address each in turn. The overall message that I want you to take away from the discussion of stress is that it is a fundamental principle of life. Without stress and adaptation, we really would not have life as we know it. And we certainly wouldn’t have a Batman or Bruce and Bob Wayne to talk about.
Figure 3.1. Basic negative feedback concept. The X indicates that the response to the stimulus stops the effect of the stimulus.
Turning our attention back to hormones, hormones can be defined as chemical messengers secreted into blood by endocrine cells or by certain special types of neurons. The eight major endocrine (or hormone-producing) glands of the body are shown for men and women in Figure 3.2.
Hormones from these glands act to regulate aspects of almost every bodily function. These encompass three general types of functioning. First there are things you have already experienced but paid little attention to, like the growth and development of your body. Second, there are things happening in you right now that you are not aware of, including wa
ter and electrolyte balance. And finally, there are things happening inside your body of which you probably are aware—at least indirectly—such as metabolism and body temperature control. If you feel cold, hot, hungry, or full right now, those sensations are direct outcomes of your hormones and of your homeostatic control systems at work.
Because many of these control mechanisms operate “silently” in the background, it is only when things go wrong that we pay much attention to them. A fairly simple example of dysfunction is one that may occur in thyroid hormone levels and results in goiters. Goiters are essentially a malfunction of the thyroid gland that causes a rather large lump to appear on the front of the neck, where the gland is located. The simplest form of goiter can be treated by administering iodine, which is needed to produce several thyroid hormones. The inflammation occurs—and here is an excellent example of the interplay between different systems—because when low thyroid hormone levels are detected, the pituitary gland at the base of the brain releases a chemical to provoke the thyroid to produce more hormones. When the gland does this, a dramatic enlargement of the thyroid gland itself takes place. Physicians in ancient China, while unaware of the specifics of iodine, successfully treated goiter by prescribing the consumption of seaweed extracts, which happen to be high in iodine. The relation to thyroid hormone was what led to the present-day use of iodized salt. In addition, thyroid hormone is an important regulator of metabolism and protein building in the body.
Figure 3.2. The eight major endocrine glands of the body for both men and women. Courtesy U.S. National Institutes of Health.
When it comes to chemicals and scientific manipulation of bodily functions, a good example is one of Batman’s most misunderstood foes: Man-Bat. Man-Bat first appeared in “The Challenge of the Man-Bat” (Detective Comics #400, 1970) and is truly more bat than man. In human form the creature is the zoologist Dr. Kirk Langstrom who studies bats. Because he was becoming deaf, Langstrom decided to create a serum from extracts of the blood of bats in the hope that he would gain some of the “sonar” (actually, echolocation) abilities from them. The good news was that, despite no scientific validity behind it—echolocation and hearing are not the same thing—the serum did improve his hearing. The bad news was that he was transformed into a real gigantic bat. Stories with Man-Bat (who never did lose the hyphen) involved numerous interventions by Batman. Some led to successful outcomes, some did not.
Batman always has another plan of action, another attack, or another defense prepared in case the first one fails. This parallels the general features of the endocrine system, where hormones tend to work together with other hormones. In this way the combination of several hormones has a bigger effect than any one hormone operating alone. Some hormones only work when other hormones are present, and some act in completely opposite directions (a feature called antagonism), like Batman versus Joker.
Hormones come in three types—this theme of threes recurs throughout the book, by the way—and can be amines, steroids, or peptides. Amines come from amino acids and include thyroid hormones and the hormones that respond to stress—epinephrine, norepinephrine, and L-dopa—which are also known as catecholamines. We will look at melatonin and adrenaline, which are also amines, later in the book. Steroids, by far the most discussed and most often found in the daily sports news, come from the adrenal cortex, gonads, and placenta. All steroids are derived from cholesterol. This is a telling reminder that despite the possible negative cardiovascular complications associated with high cholesterol, cholesterol is essential for life. Peptides are hormones that affect, among other things, insulin and testosterone production and certain functions of the heart and kidneys.
The main example I use here to illustrate the fantastic function of the endocrine system, and which is crucial for helping keep Batman working properly, is that of the regulation of the level of blood sugar—or glucose. We are going to talk about Batman’s diet and energy needs a bit later, but before getting to that we will first chat a bit about the crucial regulation of blood glucose. First of all, why is it crucial? As I said, more will be revealed later, but for now the key point is that glucose is the only energy that your nervous system will accept and metabolize for its function. Your nervous system is the ultimate picky eater. It insists on a steady diet of a simple carbohydrate made from six carbon, six oxygen, and twelve hydrogen atoms. The tight regulation of this C6H1206 molecule in the blood is probably the best example of hormonal regulation that is of direct importance for maintaining energy in the body.
A further complication for the proper function of Batman’s body is that the nervous system, in addition to being picky, doesn’t plan ahead and store glucose for use later. A steady level of bloodborne glucose is therefore essential. To be fair, there really is nowhere to store glucose molecules in the brain and spinal cord anyway. The two main players in regulating the blood glucose levels are the hormones insulin and glucagon. You are probably familiar with insulin, especially if you are or know someone who is diabetic. Insulin is a hormone that has anabolic (to build something up) functions, while glucagon is catabolic (to break something down). By the way, we will return over and over again to the idea of anabolic and catabolic. Maybe a good way to remember the difference between the two is that when Catwoman (catabolic) is on the prowl, she is constantly breaking (break down) into banks to get money and jewels. If this doesn’t work for you, think of your own way to tell the two concepts apart.
The anabolic hormone insulin builds up glucose in cells where it can be metabolized. Glucagon has completely the opposite effect, acting to release glucose into the bloodstream. You may hear concerns about proper levels of insulin, but it is in fact the ratio of insulin to glucagon in the blood that is the key issue for regulating blood sugar. They are both produced in the pancreas in a part known as the islets of Langerhans. Although this may sound like something straight out of Pirates of the Ca rib bean, the islets are in your own pancreas, which sits quietly in your abdomen tucked just under your stomach. You would also find a hormone called somatostatin in there too. Your pancreas is a busy place!
The full name for diabetes is “diabetes mellitus.” We got the word “diabetes,” meaning siphoning or moving through, from the Greek physician Aretaeus about two thousand years ago. The mellitus part (from the Latin word for honey) arises because it was known that when people have diabetes, their urine has a sweet taste from all the excess glucose in it. This name of sugar or honey urine disease has been consistent regardless of whether it was being described by ancient Egyptians, Chinese, Indians, Japanese, or Koreans. Ancient Indian physicians would observe whether insects were drawn to the urine of a patient and use that as a positive identification for diabetes. If left untreated, diabetes mellitus leads to wasting away of the body tissue, insatiable hunger, chronic thirst, and excessive urination. Damage to the nervous system can occur, causing reduced sensation in the hands and feet and visual difficulties.
Although the metabolic disorder of diabetes has been known as long as medical observations have been made, it was only fairly recently that the role of the pancreas and pancreatic hormones wa discovered. We can thank the German scientists Oskar Minkowski and Joseph von Mering for pointing out in 1889 the importance of the pancreas (which was later shown to be where insulin is produced). They established the link between the pancreas and excessive urination in diabetes. In 1922 Sir Frederick Grant Banting and Charles Herbert Best, along with colleagues James Collip and J. J. R. Macleod, at the University of Toronto created a pancreatic extract containing cells from the islets of Langerhans. This extract was shown to counteract diabetes in laboratory animals and led eventually to the creation of insulin injections that humans could use. For this work, the Nobel Prize in Physiology or Medicine was presented to Banting and McLeod in 1923. It is notable that these scientists did not patent their work for commercial gain and instead made the process and all its details freely available to the world. We thus have Banting and Best to thank for increasing our unde
rstanding of how the bodies of Bruce and Batman actually work!
What other hormones roaming around that batbody should we consider? We are particularly interested in ones that might be important for helping Batman adapt to exercise and training. Because of their significance in stress, exercise, and injury, we should also talk about testosterone, cortisol, growth hormone, insulin-like growth factors, and the catecholamines. The pituitary and the pineal gland come to mind here. These are very tiny formations at the base of the brain. The pineal gland was originally thought to have no physiological function. This is partly because it is very small in adults. It is large in adolescents but then shrinks, and it may often be calcified in adults. It secretes a hormone called melatonin, which is important for regulating our body clocks for many systems (we will talk much more about this in Chapter 12).
Let’s look at how these other hormones affect Batman’s training. We’ll look first at cortisol. It has often been called the “stress hormone” because of its importance to both rapid and long-term responses to stress. Produced by the adrenal glands found on the kidneys, cortisol is important in regulating blood glucose levels, blood pressure, and the immune system. If you had a mosquito bite or a burn recently, the steroid cream you might have put on it to help reduce the itching would probably have been hydrocortisone based and would have had a similar chemical structure to the cortisol produced by your body. During exercise, cortisol levels can increase, suggesting the triggering of catabolic processes, which in extreme cases can lead to muscle wasting. It is a very interesting byproduct of steroids that, when taken orally or injected, they interfere with cortisol and reduce its release. Because cortisol is such an important overall homeostatic hormone (say that five times fast!) it is tightly controlled in the body. However, levels of cortisol in trained people like Batman aren’t much different from those of the untrained—unless the person is overtrained and not functioning well.