Physiology of Sleep & its Disorders

- Dr. Chintan Parmar- 2nd Year Resident- Dept. of Physiology- Govt. Medi. College, Bhavnagar. - Dt. : 05/07/11

Outline• Introduction

• Brain Waves

• Sleep stages : NREM, REM

• Basic Theories of Sleep

• Physiological Effects of Sleep

• Comparative Aspect

• Sleep Deprivation

• Sleep Disorders & Rx

SLEEP• Sleep is a naturally recurring state

characterized by reduced or absent consciousness, relatively suspended sensory activity, and inactivity of nearly all voluntary muscles.

• It is distinguished from wakefulness by a decreased ability to react to stimuli.It is to be distinguished from coma, which is unconsciousness from which the person cannot be aroused.

• Sleep is observed in all mammals, all birds and many reptiles, amphibians and fish.

SLEEP• The purposes and mechanisms of sleep are

only partially clear and are the subject of intense research. Sleep is often thought to help conserve energy, but actually decreases metabolism only about 5 – 10 %.

• Hibernating animals need to sleep despite the hypometabolism seen in hibernation, and in fact they must return from hypothermia to euthermia in order to sleep, making sleeping "energetically expensive."

SLEEP• Sleep stages and other characteristics of sleep

are commonly assessed by polysomnography in a specialized sleep laboratory.

• Measurements taken include electroencephalogram (EEG) of brain waves, electrooculography (EOG) of eye movements and electromyography (EMG) of skeletal muscle activity.

• In humans, each sleep cycle lasts from 90 to 110 minutes on average.

Brain Waves• Alpha waves are rhythmical waves that occur at

frequencies between 8 and 13 cycles per second and are found in the EEGs of almost all normal adult people when they are awake and in a quiet, resting state.

• These waves occur most intensely in the occipital region but can also be recorded from the parietal and frontal regions of the scalp. Their voltage usually is about 50 µv.

• During deep sleep, the alpha waves disappear.

Brain Waves• Beta waves occur at frequencies greater than

14 cycles per second and as high as 80 cycles per second.

• They are recorded mainly from the parietal and frontal regions during specific activation of these parts of the brain.

• When the awake person's attention is directed to some specific type of mental activity, the alpha waves are replaced by asynchronous, higher-frequency but lower-voltage beta waves.

Brain Waves• Theta waves have frequencies between 4 and 7

cycles per second.

• They occur normally in the parietal and temporal regions in children, but they also occur during emotional stress in some adults, particularly during disappointment and frustration.

• Theta waves also occur in many brain disorders, often in degenerative brain states.

Brain Waves

• Delta waves include all the waves of the EEG with frequencies less than 3.5 cycles per second, and they often have voltages two to four times greater than most other types of brain waves.

• They occur in very deep sleep, in infancy and in serious organic brain disease.

Brain Waves

Sleep stages• In mammals and birds, sleep is divided

into two broad types : Rapid Eye Movement (REM) and Non-Rapid Eye Movement (NREM or non-REM) sleep – slow wave sleep.

• Each type has a distinct set of associated physiological, neurological and psychological features.

Sleep stages• The American Academy of Sleep Medicine

(AASM) further divides NREM into three stages : N1, N2 and N3, the last of which is also called delta sleep or slow-wave sleep (SWS).

• There is a greater amount of deep sleep (stage N3) earlier in the sleep cycle, while the proportion of REM sleep increases later in the sleep cycle and just before natural awakening.

NREM sleep – N1

• According to the 2007 AASM standards, NREM consists of three stages. There is relatively little dreaming in NREM.

• Stage N1 refers to the transition of the brain from alpha waves having a frequency of 8–13 Hz (common in the awake state) to theta waves having a frequency of 4–7 Hz.

• This stage is sometimes referred to as somnolence or drowsy sleep.

NREM sleep – N1• Sudden twitches and jerks, also known as

positive myoclonus, may be associated with the onset of sleep during N1.

• Some people may also experience hypnagogic hallucinations during this stage.

• During N1, the subject loses some muscle tone and most conscious awareness of the external environment.

NREM sleep – N2• Stage N2 is characterized by sleep

spindles ranging from 11–16 Hz and K-complexes.

• During this stage, muscular activity as measured by EMG decreases, and conscious awareness of the external environment disappears.

• This stage occupies 45–55% of total sleep in adults.

NREM sleep – N3• Stage N3 (deep or slow-wave sleep) is characterized

by the presence of a minimum of 20% delta waves ranging from 0.5–2 Hz.

• This is the stage in which parasomnias such as night terrors, nocturnal enuresis, somnabulism and somniloquy occur.

• Many illustrations and descriptions still show a stage N3 with 20–50% delta waves and a stage N4 with greater than 50% delta waves; these have been combined as stage N3.

NREM sleep• Most sleep during each night is of the NREM

variety ; this is the deep, restful sleep that the person experiences during the 1st hour of sleep after having been awake for many hours.

• This sleep is exceedingly restful and is associated with decrease in both peripheral vascular tone and many other vegetative functions of the body.

• There are 10 to 30 per cent decreases in blood pressure, respiratory rate and basal metabolic rate.

NREM sleep• Although slow-wave sleep is frequently called

"dreamless sleep“, dreams and sometimes even nightmares occur during slow-wave sleep.

• The difference between the dreams that occur in slow-wave sleep and those that occur in REM sleep is that those of REM sleep are associated with more bodily muscle activity.

• The dreams of slow-wave sleep usually are not remembered.

REM Sleep (Paradoxical Sleep, Desynchronized Sleep)

• Rapid eye movement sleep, or REM sleep, accounts for 20–25% of total sleep time in most human adults.

• The criteria for REM sleep include rapid eye movements as well as a rapid low-voltage EEG.

• Most memorable dreaming occurs in this stage.

• At least in mammals, a descending muscular atonia is seen. Such paralysis may be necessary to protect organisms from self-damage through physically acting out scenes that occur during this stage.

REM Sleep• The person is even more difficult to arouse by

sensory stimuli than during deep slow-wave sleep, and yet people usually awaken spontaneously in the morning during an episode of REM sleep.

• Muscle tone throughout the body is exceedingly depressed, indicating strong inhibition of the spinal muscle control areas.

• Heart rate and respiratory rate usually become irregular, which is characteristic of the dream state.

REM Sleep

• Despite the extreme inhibition of the peripheral muscles, irregular muscle movements do occur.

• The brain is highly active in REM sleep, and overall brain metabolism may be increased as much as 20 per cent.

• The electroencephalogram (EEG) shows a pattern of brain waves similar to those that occur during wakefulness.

REM Sleep• This type of sleep is also called paradoxical

sleep because it is a paradox that a person can still be asleep despite marked activity in the brain.

• In summary, REM sleep is a type of sleep in which the brain is quite active.

• However, the brain activity is not channeled in the proper direction for the person to be fully aware of his or her surroundings, and therefore the person is truly asleep.

Hours by age

• Children need more sleep per day in order to develop and function properly.

• Up to 18 hours for newborn babies, with a declining rate as a child ages.

• A newborn baby spends almost 9 hours a day in REM sleep.

• By the age of five or so, only slightly over two hours is spent in REM.

Hours by age

Age Average amount of sleep per day

Newborn up to 18 hours

1–12 months 14–18 hours

1–3 years 12–15 hours

3–5 years 11–13 hours

5–12 years 9–11 hours

Adolescents 9–10 hours

Adults, including elderly 7–8 hours

Pregnant women 8(+) hours

Basic Theories of Sleep• Sleep Is Believed to Be Caused by an Active

Inhibitory Process. • An earlier theory of sleep was that the excitatory

areas of the upper brain stem, the reticular activating system, simply fatigued during the waking day and became inactive as a result. This was called the passive theory of sleep.

• An important experiment changed this view to the current belief that sleep is caused by an active inhibitory process : it was discovered that transecting the brain stem at the level of the midpons creates a brain whose cortex never goes to sleep.

Basic Theories of Sleep• Neuronal Centers, Neurohumoral Substances and

Mechanisms That Can Cause Sleep - A Possible Specific Role for Serotonin.

• Stimulation of several specific areas of the brain can produce sleep with characteristics near those of natural sleep.

• The most conspicuous stimulation area for causing almost natural sleep is the raphe nuclei in the lower half of the pons and in the medulla.

• Nerve fibers - brain stem reticular formation - upward into the thalamus, hypothalamus, limbic system, neocortex of the cerebrum.

• Nerve fibers – downward - spinal cord - posterior horns.

Basic Theories of Sleep• Many nerve endings of fibers from these raphe

neurons secrete serotonin. When a drug that blocks the formation of serotonin is administered to an animal, the animal often cannot sleep for the next several days.

• Stimulation of some areas in the NTS can also cause sleep.

• Stimulation of several regions in the diencephalon can also promote sleep, including (1) the rostral part of the hypothalamus, suprachiasmal area and (2) an area in the diffuse nuclei of the thalamus.

Basic Theories of Sleep• Lesions in Sleep-Promoting Centers Can Cause Intense

Wakefulness.• Discrete lesions in the raphe nuclei lead to a high state of

wakefulness. This is also true of bilateral lesions in the medial rostral suprachiasmal area in the anterior hypothalamus.

• In both instances, the excitatory reticular nuclei of the mesencephalon and upper pons seem to become released from inhibition, thus causing the intense wakefulness.

• Sometimes lesions of the anterior hypothalamus can cause such intense wakefulness that the animal actually dies of exhaustion.

Basic Theories of Sleep• Other Possible Transmitter Substances Related to

Sleep.• Experiments have shown that the CSF as well as the

blood or urine of animals that have been kept awake for several days contains a substance muramyl peptide that will cause sleep when injected only in micrograms into the brain ventricular system of another animal.

• Another substance that has similar effects in causing sleep is a nonapeptide isolated from the blood of sleeping animals.

• And still a third sleep factor, not yet identified molecularly, has been isolated from the neuronal tissues of the brain stem of animals kept awake for days.

Basic Theories of Sleep• Possible Cause of REM Sleep.

• Why slow-wave sleep is broken periodically by REM sleep is not understood.

• However, drugs that mimic the action of Ach increase the occurrence of REM sleep.

• So, it has been postulated that the large Ach-secreting neurons in the upper brain stem reticular formation might activate many portions of the brain.

• This theoretically could cause the excess activity that occurs in certain brain regions in REM sleep.

Basic Theories of Sleep• Cycle Between Sleep and Wakefulness.• When the sleep centers are not activated, the

mesencephalic and upper pontile reticular activating nuclei are released from inhibition, which allows the reticular activating nuclei to become spontaneously active.

• This in turn excites both the cerebral cortex and the peripheral nervous system, both of which send numerous positive feedback signals back to the same reticular activating nuclei to activate them still further.

• So, once wakefulness begins, it has a natural tendency to sustain itself because of all this positive feedback activity.

Basic Theories of Sleep• Then, after the brain remains activated for

many hours, even the neurons themselves in the activating system presumably become fatigued.

• Consequently, the positive feedback cycle between the mesencephalic reticular nuclei and the cerebral cortex fades.

• Then the sleep - promoting effects of the sleep centers take over, leading to rapid transition from wakefulness back to sleep.

Basic Theories of Sleep• Slow waves in the EEG and slow-wave sleep,

can be produced by stimulation of at least three subcortical regions.

• The diencephalic sleep zone is in the posterior hypothalamus and the nearby intralaminar and anterior thalamic nuclei. The stimulus frequency must be about 8 Hz ; faster stimuli produce arousal.

Basic Theories of Sleep• The second zone is the medullary synchronizing

zone in the reticular formation of the medulla oblongata at the level of the NTS. Stimulation of this zone, like stimulation of the diencephalic sleep zone, produces sleep if the frequency is low but arousal if the frequency is high.

• The third synchronizing region is the basal forebrain sleep zone. This zone includes the preoptic area and the diagonal band of Broca.

Physiologic Effects of Sleep • Sleep causes two major types of physiologic effects:

first, effects on the nervous system itself, and second, effects on other functional systems of the body.

• Lack of sleep certainly affect the functions of the CNS.

• Prolonged wakefulness is often associated with progressive malfunction of the thought processes and sometimes even causes abnormal behavioral activities.

Physiologic Effects of Sleep• Increased sluggishness of thought that occurs

toward the end of a prolonged wakeful period, but in addition, a person can become irritable or even psychotic after forced wakefulness.

• So, we can assume that sleep in multiple ways restores both normal levels of brain activity and normal "balance" among the different functions of the CNS.

• The specific physiologic functions of sleep remain a mystery.

Physiologic Effects of Sleep

• Wound healing

• Immune system

• Development of the brain

• Memory processing

• Preservation

Comparative Aspect• Neurological sleep states can be difficult to

detect in some animals. In these cases, sleep may be defined using behavioral characteristics such as minimal movement, postures typical for the species, and reduced responsiveness to external stimulation.

• Herbivores, who require a long waking period to gather and consume their diet, typically sleep less each day than similarly sized carnivores, who might well consume several days' supply of meat in a sitting.

Comparative Aspect

• Horses and other herbivorous ungulates can sleep while standing, but must necessarily lie down for REM sleep (which causes muscular atony) for short periods.

• Giraffes only need to lie down for REM sleep for a few minutes at a time.

Comparative Aspect• Bats sleep while hanging upside down.

• Some aquatic mammals and some birds can sleep with one half of the brain while the other half is awake, so-called unihemispheric slow-wave sleep.

• Birds' cycles are much shorter and they do not lose muscle tone to the extent that most mammals do.

• Many mammals sleep for a large proportion of each 24-hour period when they are very young. However, killer whales and some dolphins do not sleep during the first month of life.

Sleep deprivation• Aching muscles

• Confusion, memory lapses or loss

• Depression

• Hallucinations

• Hand tremors

• Headaches

• Periorbital puffiness

• Increased blood pressure

Sleep deprivation

• Increased stress hormone levels

• Increased risk of diabetes

• Irritability

• Nystagmus

• Obesity

• Temper tantrums in children

• Yawning

• Symptoms similar to ADHD & Psychosis

Sleep deprivation

• Randy Gardner holds the scientifically documented record for the longest period of time a human being has intentionally gone without sleep not using stimulants of any kind. Gardner stayed awake for 264 hours (11 days), breaking the previous record of 260 hours held by Tom Rounds of Honolulu.

• Other sources claim that the Guinness World Records record stands at 449 hours (18 days, 17 hours), held by Maureen Weston, of Peterborough, Cambridgeshire in April, 1977, in a rocking-chair marathon.

Sleep deprivation

Sleep disorders (somnipathy)

• Primary insomnia : Chronic difficulty in falling asleep and/or maintaining sleep when no other cause is found for these symptoms.

• Bruxism : Involuntarily grinding or clenching of the teeth while sleeping.

• Delayed sleep phase syndrome (DSPS) : inability to awaken and fall asleep at socially acceptable times but no problem with sleep maintenance, a disorder of circadian rhythms - jet lag and shift work sleep disorder

• Hypopnea syndrome : Abnormally shallow breathing or slow respiratory rate while sleeping.

Sleep disorders• Narcolepsy : Excessive daytime sleepiness often

culminating in falling asleep spontaneously but unwillingly at inappropriate times.

• Cataplexy : a sudden weakness in the motor muscles that can result in collapse to the floor.

• Night terror : Pavor nocturnus, sleep terror disorder : abrupt awakening from sleep with behavior consistent with terror.

• Parasomnias : Disruptive sleep-related events involving inappropriate actions during sleep ; sleep walking ( Somnabulism ) and talking (Somniloquy).

Sleep disorders• Periodic limb movement disorder : Sudden involuntary

movement of arms and/or legs during sleep, for example kicking the legs. Also known as nocturnal myoclonus.

• Restless legs syndrome : An irresistible urge to move legs.

• Sleep Apnea, and mostly Obstructive sleep apnea : Obstruction of the airway during sleep, causing lack of sufficient deep sleep ; often accompanied by snoring.

• Rapid eye movement behavior disorder : Acting out violent or dramatic dreams while in REM sleep (REM sleep disorder or RSD).

Sleep disorders• Sleep paralysis : is characterized by temporary

paralysis of the body shortly before or after sleep. Sleep paralysis may be accompanied by visual, auditory or tactile hallucinations. Not a disorder unless severe. Often seen as part of narcolepsy.

• Nocturia : A frequent need to get up and go to the bathroom to urinate at night. It differs from Enuresis, or bed-wetting, in which the person does not arouse from sleep, but the bladder nevertheless empties.

SymptomsDo you . . .• feel irritable or sleepy during the day? • have difficulty staying awake when sitting still, watching

television or reading? • fall asleep or feel very tired while driving? • have difficulty concentrating? • often get told by others that you look tired? • react slowly? • have trouble controlling your emotions? • feel like you have to take a nap almost every day? • require caffeinated beverages to keep yourself going? If you answered “yes” to any of the previous questions, you

may have a sleep disorder.

Insomnia• Insomnia, the inability to get to sleep or sleep

well at night — the most common sleep complaint.

• Insomnia can be caused by a wide variety of things including stress, jet lag, a health condition, the medications , or the amount of coffee .

• Insomnia can also be caused by other sleep disorders or mental health conditions such as anxiety and depression.

Insomnia

- Common signs and symptoms of insomnia include:

• Difficulty falling asleep at night or getting back to sleep after waking during the night.

• Waking up frequently during the night.

• Sleep is light, fragmented or unrefreshing.

• There is need to take sleeping pills in order to get to sleep.

• Sleepiness and low energy during the day.

Sleep apnea• Sleep apnea is a common sleep disorder

in which breathing temporarily stops during sleep due to blockage of the upper airways. These pauses in breathing interrupt sleep, leading to many awakenings each hour.

• While most people with sleep apnea don’t remember these awakenings, they feel the effects in other ways, such as exhaustion during the day, irritability and depression, and decreased productivity.

Sleep apnea• Sleep apnea is a serious, and potentially life-

threatening, sleep disorder.

• Sleep apnea can be successfully treated with Continuous Positive Airway Pressure (CPAP), a mask-like device that delivers a stream of air while sleeping.

• Losing weight, elevating the head of the bed, and sleeping on one side can also help in cases of mild to moderate sleep apnea.

Sleep apnea

- Symptoms of sleep apnea include :

• Loud, chronic snoring

• Frequent pauses in breathing during sleep

• Gasping or choking during sleep

• Feeling unrefreshed after waking and sleepy during the day

• Waking up with shortness of breath, chest pains, headaches, nasal congestion, or a dry throat.

Restless legs syndrome• Restless legs syndrome (RLS) is a sleep disorder that causes

an almost irresistible urge to move legs (or arms). The urge to move occurs while resting or lying down and is usually due to uncomfortable, tingly, aching or creeping sensations.

- Common signs and symptoms of restless legs syndrome include :

• Uncomfortable sensations deep within the legs, accompanied by a strong urge to move them.

• The leg sensations are triggered by rest and get worse at night.

• The uncomfortable sensations temporarily get better when you move, stretch or massage your legs.

• Repetitive cramping or jerking of the legs during sleep.

Narcolepsy• Narcolepsy is a sleep disorder that

involves excessive, uncontrollable daytime sleepiness. It is caused by a dysfunction of the brain mechanism that controls sleeping and waking.

• The person may have “sleep attacks” while in the middle of talking, working, or even driving.

Narcolepsy- Common signs and symptoms of narcolepsy

include :

• Seeing or hearing things when the person is drowsy or starting to dream before he is fully asleep.

• Suddenly feeling weak or losing control of muscles while laughing, angry or experiencing other strong emotions.

• Dreaming right away after going to sleep or having intense dreams.

• Feeling paralyzed and unable to move while waking up or dozing off.

Circadian rhythm sleep disorders

• We all have an internal biological clock that regulates our 24-hour sleep-wake cycle, also known as our circadian rhythms.

• Light influences circadian rhythms. When the sun comes up in the morning, the brain tells the body that it’s time to wake up. At night, when there is less light, brain triggers the release of melatonin, a hormone that triggers sleep.

Circadian rhythm sleep disorders

• When circadian rhythms are disrupted , there is disorientation & sleep at inconvenient times.

• Circadian rhythms have been linked to a variety of sleeping problems and sleep disorders, including insomnia, jet lag and shift work sleep difficulties.

• Abnormal circadian rhythms have also been implicated in depression, bipolar disorder and seasonal affective disorder.

Jet lag

• Jet lag is a temporary disruption in circadian rhythms that occurs when traveling across time zones.

• Symptoms include daytime sleepiness, fatigue, headache, stomach problems and insomnia.

• The symptoms typically appear within a day or two after flying across two or more time zones.

Jet lag

• The longer the flight, the more pronounced the symptoms.

- Jet lag can be worse if the person :

• lost sleep during travel

• are under a lot of stress • drink too much alcohol or caffeine

Shift work• Shift work sleep disorder is a circadian rhythm

sleep disorder that occurs when work schedule and biological clock are out of sync.

• In our 24-hour society, many workers have to work night shifts, early morning shifts, or rotating shifts.

• These schedules force them to work when their body is telling them to go to sleep, and sleep when their body is signaling them to wake.

Shift work• While some people adjust better than others to

the demands of shift work, most shift workers get less quality sleep than their daytime counterparts.

• As a result of sleep deprivation, many shift workers struggle with sleepiness and mental lethargy on the job. This cuts into their productivity and puts them at risk of injury.

Shift work

There are a numbers of things that reduce the impact of shift work on sleep :

• Minimize the frequency of shift changes

• Use bright lights at work and take regular breaks

• Create a dark bedroom environment

Delayed sleep phase disorder

• Delayed sleep phase disorder is a sleep disorder in which 24-hour cycle of sleep and wakefulness is significantly delayed. As a result, the person goes to sleep and wakes up much later than other people.

• Delayed sleep phase disorder makes it difficult to keep normal hours — to make it to morning classes, get the kids to school on time, or keep a 9-to-5 job.

Delayed sleep phase disorder

• People with delayed sleep phase disorder are unable to get to sleep earlier than 2 to 6 a.m. no matter how hard they try. They struggle to go to sleep and get up at socially acceptable times.

• But when allowed to keep their own hours (such as during a school break or holiday), they fall into a regular sleep schedule.

• Delayed sleep phase disorder is most common in teenagers, and many teens will eventually grow out of it.

Treatment of Sleep Disorders

1. Keep a sleep diary

2. Improve sleep hygiene and daytime habits

- Keep a regular sleep schedule

- Set aside enough time for sleep

- Make sure that the bedroom is dark, cool and quiet

- Turn off TV, smartphone and computer

Treatment of Sleep Disorders

3. Eat right and get regular exercise - Stay away from big meals at night. - Avoid alcohol before bed - Cut down on caffeine - Avoid drinking too many liquids in the evening - Quit smoking4. Get anxiety and stress in check • A relaxing bedtime routine• Abdominal breathing • Progressive muscle relaxation

Treatment of Sleep Disorders

5. Sleeping Pills

• Only take a sleeping pill when there is enough time to get a full 7 to 8 hours of sleep.

• Pay careful attention to the potential side effects, dosage instructions.

• Never mix alcohol and sleeping pills. 

• Never drive a car or operate machinery after taking a sleeping pill

Sleeping Pills

1. OTC – Antihistaminics : Diphenhydramine

2. Benzodiazepine : Estazolam, Flurazepam, Quazepam, Temazepam, Triazolam

3. Non-benzodiazepine : Eszopiclone, Zalepon, Zolpidem

4. Melatonin receptor agonist : Ramelteon

5. Antidepressants : Imipramine, Amitryptiline, Fluoxetine , Fluvoxamine, Sertraline, Citalopram, Bupropion, Venlafaxine, Duloxetine

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