Sleep Disorders Physiology

Sleep is an active, clinically important behavior, during which many physiologic processes of the organism change. These processes are temporally organized under cerebral influence. Sleep abnormality may represent a primary disorder of mechanisms regulating sleep, or failure within a specific organ system that manifests in a unique way during sleep. Thus it is important that sleep complaints are not ignored or treated empirically with pharmacologic agents. More often than not, disordered sleep is a symptom of underlying disease.

There are two sleep states, rapid eye movement (REM) and non-REM (NREM) sleep. REM sleep was discovered by Aserinsky and Kleitman in the early 1950s. By waking subjects during REM, they also established that vivid dreaming occurs during this sleep state. Soon thereafter Dement recognized that episodes of REM sleep alternate with NREM sleep, in cycles lasting approximately 90 minutes, throughout the night.

Recordings derived from electroencephalograms (EEG), eye movements (electrooculogram; EOG), and chin tone (electromyogram; EMG) are necessary to distinguish sleep states. Polysomnography is the technique used to record multiple physiologic variables during sleep. In clinical practice several other physiologic measures are typically recorded, including respiratory effort from chest and abdomen, oral and nasal airflow, cardiac rhythm, and electromyographic activity in the anterior tibialis muscles of the legs.

NREM sleep is divided into four sleep stages, numbered I, II, III, and IV. The waking EEG with the eyes closed reveals the characteristic “alpha rhythm,” which is a posteriorly predominant 8- to 12-Hz rhythm that attenuates with eye opening. Stage I sleep is characterized by the gradual disappearance of the alpha rhythm, which is replaced by slower, 2- to 7-Hz activity, and some fast 12- to 14-Hz low-voltage activity. Stage II is distinguished by the presence of spindles (bursts of 12- to 14-Hz activity lasting at least 0.5 seconds, with a “spindle” appearance) and K complexes (high-voltage biphasic negative-positive waves best seen at the vertex, usually associated with spindles). Stages III and IV are defined by the presence of high-voltage slow-wave activity of 2 Hz or less. An epoch of 30 seconds is measured: if 20% to 50% of the record shows high-voltage slow activity, it is termed stage III; more than 50% high-voltage slow activity is termed stage IV. Stages III and IV are often described together as slow wave sleep or delta sleep. Delta sleep can be characterized as “deep sleep,” because during this stage subjects are difficult to arouse. Detailed dreaming does not occur, but subjects awakened during this sleep stage have reported “thinking.”

The normal subject descends in an orderly progression through the four NREM sleep stages. Delta sleep appears 30 to 45 minutes after sleep onset. The first REM period follows this delta sleep, about 70 to 90 minutes after sleep onset.

The polysomnogram during REM shows dramatic changes. There is a sudden decrease in the EMG reading in the chin muscles, which reflects generalized skeletal muscle atonia. Except for the eye muscles and respiratory muscles, the subject is paralyzed. Rapid eye movements occur in phasic bursts. The EEG shows mixed frequencies similar to those of stage I and waking. Characteristic sawtooth waves sometimes occur during eye movements. Respiration and heart rate are irregular.

Risk factors for sleep-disordered breathing
Advanced age
Loud snoring
Obesity
Upper-airway abnormality (tonsillar hypertrophy, micrognathia, macroglossia, nasal obstruction)
Pulmonary disease
Muscular weakness (muscular dystrophy, myasthenia, polymyositis, Guillain-Barre syndrome)
Brain stem lesions (Shy-Drager syndrome, infarct)
Cheyne-Stokes respiratory pattern (congestive heart failure, bihemispheric cerebral disease)

The first REM period is short - approximately 10 minutes. The end of the first REM period ends the first sleep cycle. Thereafter NREM continues to alternate with REM; there are four to six cycles in the healthy young adult (

Fig. 134-1). Sleep architecture is the organization of sleep stages and cycles. The normal young adult spends approximately 5% of the night in stage I, 50% in stage II, 12% in stage III, 13% in stage IV, and 20% in REM. Delta sleep is concentrated in the first third of the night, whereas REM episodes become progressively longer later in the night. Delta sleep decreases as a function of age, but REM percentage is relatively stable after early childhood. Of the newborn’s daily 17 to 18 hours of sleep, 50% is REM. Children and early adolescents sleep 10 to 11 hours. Most adults prefer to sleep 7 to 8 hr/day, but sleep needs vary. Short sleepers are classified as those individuals who feel adequately rested with less than 6 hours of sleep; long sleepers require more than 9 hours.

Sleep efficiency is defined as the time spent asleep divided by the time spent in bed. Sleep efficiency decreases in old age, as both the number of arousals and time spent in bed increase. This does not necessarily represent “normal” aging. Arousals usually have a cause (see Sleep Disorders).

If there are frequent external or internal disrupters of sleep, the sleep patterns change. After arousal, the patient develops stage I sleep, followed by stage II sleep, repetitively, and the percentages of delta sleep and REM sleep decrease. Drugs can also inhibit REM and delta sleep. Monoamine oxidase inhibitors and tricyclic antidepressants, for example, decrease the percentage of REM sleep dramatically. Alcohol and caffeine increase arousal. If patients are deprived of either REM or delta sleep, “rebound” is usually seen on recovery nights. REM rebound can be intrusive and frightening, with an abundance of vivid dreams. Chronic partial sleep deprivation results in inattentiveness in monotonous tasks, mood deterioration, irritability, and even mild paranoia.

REM sleep and NREM sleep differ physiologically. REM sleep is characterized by both phasic and tonic changes. The drop in baseline EMG correlates with a tonic change. Rapid eye movements correlate with phasic changes. Tonic physiologic changes also include impaired thermoregulation, hypotension, bradycardia, increased cerebral blood flow and intracranial pressure, increased respiratory rate, and penile erection. Intercostal and upper airway muscles become atonic, but the diaphragm maintains activity. Phasic changes include vasoconstriction, increased blood pressure, tachycardia, and further increases in cerebral blood flow and respiratory rate. During NREM the physiologic state is more stable, but blood pressure, heart rate, cardiac output, and respiratory rate decrease. Growth hormone is secreted during stages III and IV, in the first third of the night. Many other rhythms occur during sleep, but these need not be directly tied to sleep, as discussed later.

Experimentally created lesions of the anterior hypothalamus in animals cause insomnia. Recent evidence suggests that this area is selectively active during sleep and may be important in the initiation of sleep. REM sleep can be abolished by lesions restricted to a cholinergic cell group in the pons, but the generator of REM/NREM cycling has not been established. Multiple neurotransmitters other than acetylcholine are known to influence sleep including serotonin, catecholamines, gamma-aminobutyric acid (GABA), histamine, and adenosine. “Hypnogenic peptides” have been isolated, including delta sleep inducing peptide (DSIP), substance S (a muramyl peptide), and interleukin-1.

The science of the temporal organization of physiologic processes is called chronobiology. Sleep is the most obvious example of a circadian rhythm - body rhythms that occur approximately every 24 hours. There are multiple other circadian rhythms, including body temperature, growth hormone secretion, and cortisol secretion. In an environment free of external time cues, human beings have a “free-running” period of approximately 24.3 hours (previously thought to be 25 hours); the subject tends to go to bed later each day. This means that if a regular schedule is maintained, circadian clocks are “reset” backward each day by environmental cues. It follows that it is easier to delay, rather than to advance bedtime, because circadian rhythms move in the direction of daily delay. In the free-running environment, rhythms that usually occur together may desynchronize. The sleep/activity cycle can become longer than the body temperature rhythm, which remains at slightly longer than 24 hours. Two separate pacemakers emerge, termed X (body temperature-driven) and Y (rest/activity driven). REM sleep and cortisol secretion follow the X pacemaker, whereas slow-wave sleep and growth hormone secretion follow the Y pacemaker. The Y pacemaker is thought to reside in the suprachiasmatic nucleus of the hypothalamus. The location of the X pacemaker is unknown.

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Revision date: July 6, 2011
Last revised: by Andrew G. Epstein, M.D.