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Sleep Physiology

dr Herman Mulijadi MS, SpKP

Lecturer :
Learning Objective

• Describe the physiology of normal sleep

• Describe some of abnormal sleep patterns and their

Sleep: This is the state of unconsciousness
from which a subject can be aroused by
appropriate sensory or other stimuli.

Sleep may also be defined as a normal,

periodic, inhibition of the Reticular
Activating System.

Awake: This is the state of readiness /

alertness and ability to react consciously to
various stimuli.

Coma: This is the state of unconsciousness

from which a person cannot be aroused by
any external stimuli
• Naturally recurring state
• Characterized by total or partial unconsciousness
• Inactivity of nearly all voluntary muscles
• Can vary by age and among individual
• Adequate when no daytime sleep or dysfunction

The principal value of sleep is to restore natural balances
among the neuronal centers. The specific physiologic
functions of sleep remain a mystery, and they are the
subject of much research.
• Restoration theory: Body wears out during the day and
sleep is necessary to put it back in shape. Restoration of
the brain and body.
• Preservation and protection theory: Sleep emerged in
evolution to preserve energy and protect during the time
of day when there is little value and considerable danger
• Memory consolidation
• Boost mood
Basic Theories of Sleep
1. The old theory of sleep “ The passive process”.
• Discharging of RAS neurons for many hours of wakefulness
 Fatigue of RAS neuron  sleep

2. The new theory of sleep “ The active sleep inducing inhibitory

• Different mediator actively inhibit RAS  sleep:
 Serotonin – secreting Raphe fibers inhibit the RAS  sleep
 Melatonin “ hormon secreted by pineal gland “ during
darkness  inhibit RAS  Sleep


• New born = 15 - 20 hours.
• Children = 10 -15 hours.
• Adults = 6-9 hours.
• Old age = 5-6 hours.
Sleep center
The sleep center located below the mid pontile level of the brain stem that is
required to cause sleep by inhibiting other parts of the brain.
1. 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. these raphe
neurons secrete serotonin. they can inhibit incoming sensory signals, including pain
2. Stimulation of some areas in the nucleus of the tractus solitarius can also cause
3. Stimulation of several regions in the diencephalon can also promote sleep,
a. the rostral part of the hypothalamus, mainly in the suprachiasmal area,
b. an occasional area in the diffuse nuclei of the thalamus.
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

Sherwood 169 guyton 739 vanders 247
Wakes state
• Various brain mechanisms are associated with wakefulness and arousal.
• The reticular formation is a part of the midbrain that extends from the
medulla to the forebrain and is responsible for arousal.
• A widespread network of interconnected neurons called the reticular
formation runs throughout the entire brain stem and into the

• Consists of two parts:
• Mesencephalic part: Mesencephalic part composed of area of grey
matter of mid brain and pons when this area is stimulated, nerve
impulses going to thalamus and disperse to the cerebral cortex. This
greatly effects the cortical activity. causes wakefulness
• Thalamic part: Thalamic part consists of gray matter in the thalamus.
When the thalamic part is stimulated there is activity in the specific part
of the cerebral cortex. causes arousal that is awakening from deep
sleep [sensory input, pain stimuli, Bright light].

• The RAS and cerebral cortex continue to activate each other through a
feedback system.
• The RAS also has a feedback system with the spinal cord.

•These fibers compose the Reticular Activating System (RAS), which controls
the overall degree of cortical alertness and is important in the ability to direct
•This network receives and integrates all incoming sensory synaptic input.
Ascending fibers originating in the reticular formation carry signals upward to
arouse and activate the cerebral cortex (ARAS).
•In turn, fibers descending from the cortex, especially its motor areas, can
activate the RAS. ( Positive feed back)
• The centers that govern sleep traditionally have been considered to be
housed within the brain stem, although recent evidence suggests that the
center promoting slow-wave sleep lies in the hypothalamus.

Brain Mechanisms
• The pontomesencephalon is a part of the midbrain that contributes to
cortical arousal.
– Axons extend to the thalamus and basal forebrain which release
acetylcholine and glutamate
– produce excitatory effects to widespread areas of the cortex.
• Stimulation of the pontomesencephalon awakens sleeping individuals and
increases alertness in those already awake.

Brain Mechanisms
• The basal forebrain is an area anterior and dorsal to the hypothalamus containing
cells that extend throughout the thalamus and cerebral cortex.
 Cells of the basal forebrain release the inhibitory neurotransmitter GABA. Inhibition
provided by GABA is essential for sleep.
 Other axons from the basal forebrain release acetylcholine which is excitatory and
increases arousal.

 Accumulation of adenosine in
the brain to inhibit the basal forebrain
cells responsible for arousal.
 Caffeine blocks adenosine

• Orexin / hypocretin is a peptide neurotransmitter released

in a pathway from the lateral nucleus of the hypothalamus
highly responsible for the ability to stay awake.
– Stimulates acetylcholine-releasing cells in the forebrain
and brain stem to increase wakefulness and arousal.
Brain Mechanisms
• The locus coeruleus is small structure in the pons whose axons release
norepinephrine .These neurons send fibers upward to most parts of the brain limbic
system, thalamus, and cerebral cortex to arouse various areas of the cortex and
increase wakefulness. Usually dormant while asleep.
• The hypothalamus contains neurons that release “histamine” to produce
widespread excitatory effects throughout the brain.
– Anti-histamines produce sleepiness.
• 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. They
send fibers to many areas of the limbic system and to some other areas of the
brain. These raphe neurons secrete serotonin. they can inhibit incoming
sensory signals, including pain

The Hypothalamus
Green arrows indicate
The Basal forebrain excitatory connections

The Locus coeruleus

Red arrows indicate

inhibitory connections.

The Pontomesencephalon
14 The Dorsal raphe

Table 9-1, p. 280

EEG Wave
1. Alpha waves. These rhythmic waves occur at a frequency of about 8–13 cycles
per second. (The unit commonly used to express frequency is the hertz [Hz]. One hertz
is one cycle persecond.) Alpha waves are present in the EEGs of nearly all normal
individuals when they are awake and resting with their eyes closed. These waves
disappear entirely during sleep. 1 second
Awake, non attentive

Alpha waves
Awake, but non-attentive - large, regular alpha waves

EEG Wave
2. Beta waves. The frequency of these waves is between 14 and 30 Hz. Beta waves
generally appear when the nervous system is active—that is, during periods of sensory
input and mental activity.
1 second
Awake, attentive

Beta waves
Awake and attentive - low amplitude, fast, irregular beta waves

EEG Wave

3. Theta waves. These waves have frequencies of 4–7 Hz. Theta waves
normally occur in children and adults experiencing emotional stress. They also
occur in many disorders of the brain.

EEG Wave

4. Delta waves. The frequency of these waves is 1–5 Hz. Delta waves occur during
deep sleep in adults, but they are normal inawake infants. When produced by an awake
adult, they indicate brain damage.

EEG Wave

Circadian rhythm
The term circadian - Latin word:
Circa = around & diem or dies = day
Meaning literally “ approximately one day”
Meaning : A daily rhythmic activity cycle, based on 24-hour
intervals, (timed to the rotation of the earth upon its axis)
Automatically clock in the brain

• Sleep is promoted by a complex set of neural and chemical mechanisms

• Daily Basic rhythm of sleep and arousal  suprachiasmatic nucleus of
the hypothalamus  pineal gland’s secretion of melatonin
• Slow-wave sleep: Raphe nuclei of the medulla and pons and the
secretion of serotonin
• REM sleep: Neurons of the pons

Circadian Rhythm Synchronization
• The basic rhythm of the sleep–wake cycle / Circadian rhythms are internally
generated - our biological clock function of the suprachiasmatic nucleus. - and also
regulated by environmental / Zeitgeber cues such as the cycle of daylight and dark.”
• Retinal ganglion cells send direct projections to the SCN regulates the timing of
sleep and awake periods relative to periods of light and darkness, that is, the
circadian rhythm of the states of consciousness.
• The nucleus stimulates the production of melatonin by the pineal gland . Although
melatonin has become a popular “natural” substance for treating insomnia and jet
lag, it has not yet been proven that it is effective as a sleeping pill, although it has
been shown to induce lower body temperature, a key event in falling asleep.

The human biological clock
“CR” is refers to collection of bodily rhythm (temperature, sleep, wakefulness,
physical activity, memory performance, cortisol and others)


Desynchronization :
Refers to the state in which a person’s circadian rhythm is inconsistent
with local environment’s cues as well as shift work, jet lag
10.00AM 02.00PM 07.00PM

You should
consider the
application of
rhythm in your

Stages of Sleep And Brain Mechanisms
• Decreased arousal required for sleep is accomplished via the following ways:
1. Decreasing the temperature of the brain and the body.
2. Decreasing stimulation by finding a quiet environment.
3. Accumulation of adenosine in the brain to inhibit the basal forebrain cells
responsible for arousal. Caffeine blocks adenosine receptors.

Normal sleep is under control of the

reticular activating system in the upper
brain stem and diencephalon

There are two types of sleep:1. Non Rapid Eye Movement
• Stage 1. Somnolence, Micro sleep
• Stage 2. Light sleep
• Stages 3 , deep sleep, body restoration
• Stages 4 , deep sleep, Sleep inertia, Parasomnia(night terrors, nocturnal
enuresis, sleep walking )
2. Rapid eye movement sleep [Dreamful].
• (Paradoxal sleep) 20%-25% of total sleep
• Strengthening & organizing memory
• Re-energize and replenished ATP
Both types alternate with each other.

• Slow-wave (non rapid eye movement sleep
• This stage of sleep consists of four stages.
• Stage 1: This is an initial stage between awakening and sleep.
• It normally lasts from 1-7 minutes.
• the person feels relaxed with eye closed.
• If awakened, the person will frequently say that he has not been sleeping.
• E.E.G. findings: Alpha waves diminish and Theta waves appear on EEG.

• Stage 2:
• This is the first stage of true sleep.
• The person experiences only light sleep.
• It is a little harder to awake the person.
• Fragment of dream may be experienced.
• Eyes may slowly roll from side to side.
• E.EG-findings: Shows sleep spindles (sudden, sharply, pointed waves 12-
14-Hz (cycles/sec).

• Stage3:
• This is the period of moderately deep sleep.
• The person is very relaxed.
• Body temperature begin to fall.
• B.P decreases.
• Difficult to awaken the person.
• This stage occurs about 20-25 minutes after falling asleep.
• E.E.G.findings: Shows mixture of sleep spindles and delta waves.

• Stage4: Deep sleep starts
• Person become fully relaxed.
• Respond slowly if awakened.
• E.E.G.findings: Dominated by Delta Waves.
• Note: Most sleep during each night is of a slow wave
• Lasts for 80=90 minutes.
• Dreams / night mare even occur.
• The difference is that the dreams in slow wave sleep are not
remembered but in REM, dreams can be remembered.

• In normal sleep bouts of REM sleep lasting for 5-20 minutes usually
appear on the average after every 90 minutes.
• The first such period occurring 80-100 minutes after the person falls a
• When the person is in extreme sleep, the duration of each bout of REM
is very short.
• It may even be absent.

• Active dreaming.
• Difficult to arouse by sensory stimuli.
• Decreased muscle tone through out the body.
• Heart rate and respiration usually become irregular
• which is characteristic of a dream state.
• Brain is highly active in REM sleep and brain
• metabolism may be increased by 20%.
• E.E.G.findings: Shows pattern of brain wave to those of wakefulness
that is which it is called “Paradoxical”.
• In summary, REM sleep is a type of sleep in which the brain is quite

• What are true dreams for?
• Although research has yet to answer this question, a prevalent view
today is that dreams don’t serve any purpose at all, but are side effects
of REM
• To exercise groups of neurons during sleep some are in perceptual and
motor areas
• REM occurs in other mammals and to a much greater extent in fetuses
and infants than adults
• REM sleep may help consolidate memories
• True dream - vivid, detailed dreams
• consisting of sensory and motor sensations
• experienced during REM
• sleep thought - lacks vivid sensory and motor sensations, is more
similar to daytime thinking, and occurs
during slow-wave sleep
• Physiological changes during sleep:
• CVS: Pulse Rate, cardiac output, blood pressure, and vasomotortone are
decreased but the blood volume is increased.
• Respiration: Tidal volume and rate of respiration is decreased. BMR is
decreased 10-15%.
• Urine volume: Urine volume is decreased.
• Secretions: Salivary / lacrimal secretions are reduced, gastric/sweet secretions
are increased.
• Muscles: Relaxed.
• Superficial reflexes are unchanged except plantex reflex.
• Deep reflexes are reduced.
• Effects produced by awakening after 60-100 hours:
• Equilibrium disturbed.
• Neuromuscular junction fatigue.
• Threshold for pain is lowered.
• Some cells shrink.

• 70 million people in the US suffer from sleep problems [50% have chronic
sleep disorder]
• Insomnia = 30 million
• sleep apnea= 18 million
• Narcolepsy= 250,000 Americans have Motor Car Accidents= 100,000 traffic
fatalities =1500 drowsy driving / annum
• Approximately $16 billion annually to the cost of health care in the US and
result in $50 billion annually in lost productivity
• Disorder of sleep:
 Insomnia: Inability to sleep
 Somnolence: Extreme sleepness
• Disorder of slow wave sleep:
 Sleep talking / sleep walking ‘ [common in children]
 Night tremors: Are seen in III, IV stage of slow wave sleep [common in
• Disorder of REM sleep:
 Night mare = Frightening dream.
 Sleep Paralysis= Subject is awake but unable to speak or
35 move. Sleeping Sickness.
• Somnambulism – Sleep Walking occurs mostly in children runs in families
expressed early in the night during stage 3 and 4 sleep
• Nightmares - frightening dreams that wake a sleeper from REM
• Night terrors - sudden arousal from sleep and intense fear accompanied by
physiological reactions (e.g., rapid heart rate, perspiration) that occur during slow-
wave sleep. Experience of intense anxiety from which a person awakens screaming
in terror occur during non REM sleep more common in children
• Insomnia: Habitual sleeplessness
• possible causes: excessive noise, stress, drugs, medications, pain,
uncomfortable temperature, sleep apnea, periodic limb movement disorder
three forms: onset, maintenance, termination
• Narcolepsy: Frequent, unexpected periods of sleepiness during the day
affects about 1 in 1000 people
• Narcolepsy - overpowering urge to fall asleep that may occur while talking or
standing up
• symptoms: extreme daytime sleepiness, cataplexy,
sleep paralysis, hypnagogic hallucinations.
involvement of orexin

Sleep apnea - failure to breathe when asleep

Epidemiology [Sleep Apnoea]
• Incidence of sleep disordered breathing:
• Males: 4-9% of Americans
• Females: 1-5% of Americans
• Estimate - 15 million Americans have sleep disordered breathing (many
remain undiagnosed)
• Sleep apnea incidence higher:
 African Americans/Native Americans/Hispanics
 With increasing age
 With increasing body weight

• Pathophysiology [Sleep Apnoea]
 Complete or partial pharyngeal obstruction during sleep
 Narrowing at one or more sites along the upper airway
 Between soft palate and posterior pharyngeal wall
 Between base of the tongue and posterior pharyngeal wall
 Between epiglottis and laryngeal vestibule
Symptoms of Obstructive Sleep Apnea
Day time
Witnessed Apnea
Morning headaches
Poor concentration
Decreased attention
Personality changes
Sleep deprivation: “Four to six hours of sleep each night results in a
progressive, cumulative deterioration in neurobehavioral function including
vigilance, neurocognitive performance, and mood.
• This reduction in performance is also associated with changes in
cerebral activation during cognitive tasks.
• Physiologic changes also occur: insulin resistance, increased
sympathetic activation, decreased immune system function.”


Lauralee Sherwood: Human Physiology;. Department of Physiology and

Pharmacology School of Medicine West Virginia University. rooks/Cole
10 Davis Drive Belm
Arthur C. Guyton, M.D., John E. Hall, Ph.D:Text Book of Medical Physiology;.
Department of Physiology and Biophysics University of Mississippi Medical
Center Jackson, Mississippi, 11th ed. Philadelphia, Saunders.
Vander et al's : Human Physiology: The Mechanisms of Body Function,
9th ed , the McGraw-Hill Publishing
W.F.: Ganong MD: Review of Medical Physiology, 12th ed , Lange Medical

Gerard J. Tortora.,Bryan Derrickson: Principles of Anatomy and

Physiology. 12th ed, John Wiley & Sons, Inc.

Other sources,