Physiology of sleep
BY
AHMAD YOUNES
PROFESSOR OF THORACIC MEDICINE
Mansoura Faculty of Medicine
Definition
• Sleep is an ACTIVE process. It is a reversible state
of unresponsiveness to stimuli of the outside world
and to responses within the brain which underlie
perception.
• Sleep is a state of reversible un-conciousness in
which the brain is relatively more responsive to
internal than external stimuli
Sleep function
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Memory consolidation
Energy conservation
Body growth
Regulation of immune function
Protective behavioral adaptation
General information
• NREM and REM occur in alternating cycles, each lasting
approximately 90-100 minutes, with a total of 4-6 cycles.
• In the healthy young adult, NREM sleep accounts for 75-90% of
sleep time (3-5% stage I, 50-60% stage II, and 10-20% stages III and
IV). REM sleep accounts for 10-25% of sleep time.
• Total sleep time in the healthy young adult approximates 7.5-8
hours.
• The newborn sleeps approximately 16-20 hours per day; these
numbers decline to a mean of 10 hours during childhood.
• In the full-term newborn, sleep cycles last approximately 60 minutes
(50% NREM, 50% REM, alternating through a 3-4 h inter-feeding
period).
General information
• Pregnancy:
st trimester (increase in total sleep time ,daytime sleepiness
and nocturnal awakening )
2nd trimester (normal sleep )
3rd trimester (increased nocturnal awakening with subsequent
daytime sleepiness and decreased total sleep time)
• In elderly, SWS decrease and N2 compensatory increase,
increase in latency to fall asleep and the number and
duration of overnight arousal periods, time in bed increase
with subsequent complaint of insomnia .
Brain Mechanisms Controlling Sleep
• Sleep is promoted by a complex set of neural and
chemical mechanisms
• Daily rhythm of sleep and arousal
– Supra-chiasmatic nucleus of the hypothalamus (body clock)
– pineal gland’s secretion of melatonin
• Light is called a Zeitgeber, a German word
meaning time-giver because it set the suprachiasmatic clock
Evidence for the SCN as biological clock
• Circadian = diurnal + nocturnal
• Zeitgebers and the SCN: Biological clock
– Altering light/dark cycles produces phase shift and
entrainment
– SCN lesions disrupt circadian rhythms
– Transplanted SCNs set rhythms of donor animal
Neural control of sleep
• Ventrolateral Preoptic Area (VPA) triggers
sleepiness and slow-wave sleep
• Stimulation of the RAS produces EEG
desynchronization by suppressing slow cortical
waves (0.3–1 Hz), delta waves (1–4 Hz), and
spindle wave oscillations (11–14 Hz)
Light and Melatonin
The pineal gland is a tiny endocrine gland situated at
the centre of the brain
• The major pineal hormone, however, is melatonin, a
derivative of the amino acid tryptophan.
• Melatonin secreted by pineal gland signals brain
that it is time to sleep
• Light suppresses melatonin secretion.
• Bright light very early in the morning can cause a
phase advance
Bright lighting can reduce fatigue
for workers forced to work at night
The reticular activating system
• The reticular activating system (RAS) is located in
the brain stem. it is believed to play a role in sleep
and waking, behavioral motivation, breathing, and
the beating of the heart.
• The ascending RAS connects to the cortex, the
thalamus, and the hypothalamus.
• The descending RAS connects to the cerebellum
and to nerves responsible for the various senses.
• It is believed to control sleep, wakefulness, and the
ability to consciously focus attention on something
Autonomic nervous system physiology
• Parasympathetic tone increase and sympathetic tone decrease during
NREM sleep
• During arousals , sympathetic tone increase in bursts .
• During tonic REM sleep ,Parasympathetic tone increase even further
whereas sympathetic tone reaches its lowest level .
• During phasic REM sleep sympathetic tone transiently increases .
• Muscle tone is maximal during wakefulness but decrease during NREM
sleep and decrease even further during REM sleep
• During REM sleep , myotonic bursts (phasic twitches ) as evidenced by
intermittent surges in EMG .
• Overall decrease in upper airway dilator muscles during NREM sleep
,the reduction is even greater during REM sleep .
Respiratory physiology
• Minute ventilation falls by 0.5-1.5 liters during
NREM sleep due to a reduction in tidal volume
rather than in respiratory rate .
• During REM sleep the fall in minute ventilation is
similar but being irregular during phasic REM.
• Functional residual capacity decrease by 10%
during sleep.
• Arterial Pao2 decrease by 3-10 mmHg and Sao2
decrease by <2%.
• Arterial Paco2 increase by 2-8 mmHg during sleep .
Respiratory physiology
• Hypoxic ventillatory response and hyper-capnic
ventillatory response decrease during NREM sleep
and decrease further during REM sleep due to
decreased chemo-sensitivities.
• Cough reflex decrease during NREM and REM
sleep .
Cardio-vascular physiology
• Heart rate decrease during NREM sleep but fluctuate
greatly during REM sleep .
• Brady-tachycardia seen during phasic REM sleep is due to
variations of both parasympathetic and sympathetic activities
• Cardiac output decrease during both NREM and REM sleep.
• Pulmonary blood pressure increase slightly during sleep
• Arterial blood pressure decrease by 10% during NREM
sleep ,during phasic REM sleep fluctuate due to sympathetic
activities .
• Cerebral blood flow decrease 5-20% during NREM sleep
,during REM sleep an increase in blood flow by up to 40%
Endocrine physiology
• Melatonin release peaks during sleep
• Growth hormone peak 90 minutes after sleep onset
(closely associated with slow wave sleep)
• Cortisol secretion is independent of sleep. Its peak
is in the early morning .
• Thyroid stimulating hormone decrease during sleep.
• Testosterone increase during sleep .
• No relation between GTH ,LH, FSH and sleep .
• Prolactin level increase during sleep .
Gastro-intestinal physiology
• Lower esophageal sphincter tone show no circadian variation .
• Transient lower esophageal sphincter relaxation lead to GERD during
awakening from sleep rather than during sleep .
• Most events of GERD occur during stage 2 may be due to increased
vagal tone which decreases lower esophageal sphincter tone.
• Circadian gastric acid secretion with peak in the late evening and lowest
in the morning .
• Swallowing 25/h during the day but 5/h during sleep ,most nocturnal
swallowing occurs during movement arousals in NREM .
• Gastric emptying decrease during sleep but esophageal motility shows
little circadian variation .
Studying sleep
• Electroencephalogram (EEG)
• Electromyogram (EMG)
• Electro-oculogram (EOG)
Brain wave activity
Wakefulness
– Alpha waves – regular, medium frequency waves
– Beta waves – irregular, low amplitude waves
Beta Activity
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A waveform of 14 to 30 Hz
Originates in the frontal and central regions
Present during wakefulness and drowsiness
May become persistent during drowsiness,
diminish during SWS, and reemerge during REM
sleep
• Enhanced or persistent activity suggests use of
sedative-hypnotic medications
Alpha Activity
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A waveform of 8 to 14 Hz
Originates in the parieto-occipital regions bilaterally
Seen during quite alertness with eyes closed
Eye opening causes the alpha waves to decrease
in amplitude
• Has a crescendo decrescendo appearance
• Has diminished frequency with aging
Theta Activity
• A waveform of 3 to 7 Hz
• Originates in the central vertex region
• The most common sleep frequency
Delta Activity
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A waveform of 0.5 to 2 Hz
Seen predominantly in the frontal region
Delta activity has an amplitude criterion of 75 µV
Stage-3 sleep defined when 20% to 50% of the
epoch is scored as delta activity
• Stage-4 sleep defined when >50% of the epoch is
scored as delta activity
Sleep Spindles
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A waveform of 12 to 14 Hz
Originates in the central vertex region
Has a duration criterion of 0.5 to 2-3 seconds
Typically occurs in stage-2 sleep but can be seen in
other stages
K Complexes
• Defined as slow waves, with a biphasic morphology
(first negative and then positive deflection)
• Predominantly central vertex in origin
• Duration must be at least 0.5 seconds
• Indicative of stage-2 sleep
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Brain wave activity during sleep
• Stage 1 sleep (~10 minutes)
– Theta waves – lower frequency
• Stage 2 sleep (~15 minutes)
– Theta waves continue, marked by bursts of:
• Sleep spindles
• K-complexes
Brain wave activity during sleep
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Stage 3 sleep (~15-20 minutes)
– Beginning of slow-wave sleep
– Combination of theta and delta activity
• 20-50% Delta waves
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Stage 4 sleep (~45 minutes)
– > 50% delta waves
Stages 1-4 are non-REM sleep
Sleep Architecture
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1
REM
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3+4
(SWS)
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2
3
75% SWS
4
5
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7
8
75% REM
Slow Wave Sleep deprivation is
associated with reduction in cognitive
performance
REM Deprivation
• Moodiness
• Inability to consolidate complex learning
REM appears to be important for psychological wellbeing
Interventions - caffeine
‘World’s most popular drug’
• Mild CNS stimulant
• 3.5 - 6 hr half-life
• 250 mg improves psychomotor function if sleep
deprived, 500 mg side effects w/o improvement
• Tachy-phylaxis
• Withdrawal headaches
• Affects sleep latency and sleep quality
Sedative-Hypnotics
• Alcohol causes sleep fragmentation and
decreased REM
• Most sedative-hypnotics disrupt the
architecture of sleep
Modafinil
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Narcolepsy
Obstructive Sleep Apnea
Military “short-term fatigue countermeasure”
Shift Work Sleep Disorder
The only way to completely reverse the
physiologic need for sleep is to sleep