Figure

Circadian rhythms of several physiological variables in a human subject with room lights on (open bars at top) for 16 h and off (black bars at top) for 8 h. As is usual in dealing with rhythms, we have used a 24-h clock in which both 0 and 24 designate midnight and 12 designates noon. Cortisol is a hormone secreted by the adrenal glands.

Adapted from Moore-Ede and Sulzman.

sense since we ingest potassium in our food during the day, not at night when we are asleep. Therefore, the total amount of potassium in the body fluctuates less than if the rhythm did not exist.

A crucial point concerning most body rhythms is that they are internally driven. Environmental factors do not drive the rhythm but rather provide the timing cues important for entrainment (that is, setting of the actual hours) of the rhythm. A classic experiment will clarify this distinction.

Subjects were put in experimental chambers that completely isolated them from their usual external environment. For the first few days, they were exposed to a 24 h rest-activity cycle in which the room lights were turned on and off at the same time each day. Under these conditions, their sleep-wake cycles were 24 h long. Then, all environmental time cues were eliminated, and the individuals were allowed to control the lights themselves. Immediately, their sleep-wake

PART TWO Biological Control Systems

Vander et al.: Human Physiology: The Mechanism of Body Function, Eighth Edition

PART TWO Biological Control Systems patterns began to change. On the average, bedtime began about 30 min later each day and so did wake-up time. Thus a sleep-wake cycle persisted in the complete absence of environmental cues, and such a rhythm is called a free-running rhythm. In this case it was approximately 25 h rather than 24. This indicates that cues are required to entrain a circadian rhythm to 24 h.

One more point should be mentioned: By altering the duration of the light-dark cycles, sleep-wake cycles can be entrained to any value between 23 and 27 h, but shorter or longer durations cannot be entrained; instead, the rhythm continues to free-run. Because of this, people whose work causes them to adopt sleep-wake cycles longer than 27 h are never able to make the proper adjustments and achieve stable rhythms. The result is symptoms similar to those of jet lag, to be described later.

The light-dark cycle is the most important environmental time cue in our lives but not the only one. Others include external environmental temperature, meal timing, and many social cues. Thus, if several people were undergoing the experiment just described in isolation from each other, their free-runs would be somewhat different, but if they were all in the same room, social cues would entrain all of them to the same rhythm.

Environmental time cues also function to phase-shift rhythms—in other words, to reset the internal clock. Thus if one jets west or east to a different time zone, the sleep-wake cycle and other circadian rhythms slowly shift to the new light-dark cycle. These shifts take time, however, and the disparity between external time and internal time is one of the causes of the symptoms of jet lag—disruption of sleep, gastrointestinal disturbances, decreased vigilance and attention span, and a general feeling of malaise.

Similar symptoms occur in workers on permanent or rotating night shifts. Such individuals generally do not adapt to these schedules even after several years because they are exposed to the usual outdoor light-dark cycle (normal indoor lighting is too dim to function as a good entrainer). In recent experiments, night-shift workers were exposed to extremely bright indoor lighting while they worked and 8 h of total darkness during the day when they slept. This schedule produced total adaptation to the night-shift work within 5 days.

What is the neural basis of body rhythms? In the part of the brain called the hypothalamus is a specific collection of nerve cells (the suprachiasmatic nucleus) that function as the principal pacemaker (time clock) for circadian rhythms. How it "keeps time" independent of any external environmental cues is not really understood, but it probably involves the rhythmical turning on and off of critical genes in the pacemaker cells. Indeed, just such genes—one has been named clock—and the proteins that they code have recently been discovered in the mouse pacemaker—that is, in the cells of the mouse's suprachiasmatic nucleus.

The pacemaker receives input from the eyes and many other parts of the nervous system, and these inputs mediate the entrainment effects exerted by the external environment. In turn, the pacemaker sends out neural signals to other parts of the brain, which then influence the various body systems, activating some and inhibiting others. One output of the pacemaker is to the pineal gland, an offshoot of the brain that secretes the hormone melatonin (Chapter 10); these neural signals from the pacemaker cause the pineal to secrete melatonin during darkness but not to secrete it during daylight. It has been hypothesized, therefore, that melatonin may act as an important "middleman" to influence other organs either directly or by altering the activity of the parts of the brain that control these organs. Studies to determine whether administration of melatonin at specific times can reduce the symptoms of jet lag remain inconclusive (the same can be said for virtually every other proposed treatment for jet lag).

It should not be surprising that rhythms have effects on the body's resistance to various stresses and responses to different drugs. Also, certain diseases have characteristic rhythms. For example, heart attacks are almost twice as common in the first hours after waking, and asthma frequently flares at night. Insights about these rhythms have already been incorporated into therapy; for example, once-a-day timed-release pills for asthma are taken at night and deliver a high dose of medication between midnight and 6 a.m.

Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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