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SLEEP
KIRSHA K S
ASSISTANT PROFESSOR
DEPT. OF PHARMACY PRACTICE
KMCH COLLEGE OF PHARMACY
COIMBATORE-8
SLEEP
• A physical and mental resting state in which
a person becomes relatively inactive and
unaware of the environment.
• Sleep is a partial detachment from the world,
where most external stimuli are blocked from
the senses.
• So, sleep is naturally recurring state of mind and
body, characterized by altered consciousness,
relatively inhibited sensory activity, reduced
muscle activity and inhibition of nearly
all voluntary muscles during rapid eye movement
(REM) sleep, and reduced interactions with
surrounding.
• Quality sleep – and getting enough of it at the
right times -- is as essential to survival as food
and water
• There are four stages of sleep:
Non-REM (NREM) sleep (Stages 1, 2, 3
&4)
REM sleep.
• Periods of wakefulness occur before and
intermittently throughout the various sleep
stages or as one shifts sleeping position.
NREM
Stage 1
• The lightest stage of NREM sleep.
• Defined by the presence of slow eye
movements, this drowsy sleep stage can be
easily disrupted causing awakenings or
arousals.
• Muscle tone throughout the body relaxes and
brain wave activity begins to slow from that of
wake.
• People may experience hypnic jerks or abrupt
muscle spasms and may even experience
sensation of falling while drifting in and out of
stage 1.
5%
5%
Stage 2
• The first actual stage of defined NREM sleep.
• Awakenings or arousals do not occur as easily as in Stage 1
sleep and the slow moving eye rolls discontinue.
• Brain waves continue to slow with specific bursts of rapid
activity known as sleep spindles intermixed with sleep
structures known as K complexes.
• Both sleep spindles and K complexes are thought to serve as
protection for the brain from awakening from sleep.
• Body temperature begins to decrease and heart rate begins
to slow.
50%
Stage 3 and 4 Delta Sleep
• Known as deep NREM sleep.
• These are deep sleep stages, with stage 4 being more intense
than stage 3. These stages are known as slow-wave, or delta,
sleep.
• The most restorative stage of sleep, stage 3 consists of delta
waves or slow waves. Also brain produces extremely slow
waves with occasional bursts of faster brain wave activity
• Awakenings or arousals are rare and often it is difficult to
awaken someone in Stage 3 sleep.
• Parasomnias (sleepwalking, sleep talking
or somniloquy and night terrors) occur during the deepest
stage of sleep.
10-20%
• Stage 4, our brains produce extremely slow waves almost
exclusively. These stages are known as “Deep Sleep” or
“Delta Sleep”.
• It's most difficult to wake up during this stage.
• During these stages our bodies emit growth hormones and
work on repairing physical damage done during the day
REM
• Known as rapid eye movement, is most commonly known
as the dreaming stage.
• First occurs about 90 minutes after falling asleep.
• Eye movements are rapid, moving from side to side and
brain waves are more active than in Stages 2 & 3 of sleep.
• Awakenings and arousals can occur more easily in REM;
being woken during a REM period can leave one feeling
groggy or overly sleepy.
• Each REM stage can last up to an hour. An average adult
has five to six REM cycles each night. During this final
phase of sleep, your brain becomes more active.
20%
• The period of REM sleep is marked by extensive
physiological changes. These include:
Accelerated respiration
Increased brain activity
Eye movement
Muscle relaxation
• The first period of REM typically lasts 10
minutes, with each recurring REM stage
lengthening, and the final one lasting an hour.
SLEEP CYCLE
• A sleep cycle is the progression through the
various stages of NREM sleep to REM sleep
before beginning the progression again with
NREM sleep.
• The sleep cycle is an oscillation between
the slow-wave and REM (paradoxical) phases
of sleep.
• It is sometimes called the ultradian sleep
cycle, sleep–dream cycle, or REM-NREM
cycle.
• A person would begin a sleep cycle every 90-
120 minutes resulting in four to five cycles per
sleep time, or hours spent asleep.
• A sleep cycle progress through the stages of
non-REM sleep from light to deep sleep, then
reverse back from deep sleep to light sleep,
ending with time in REM sleep before starting
over in light sleep again.
The first sleep cycle takes about 90 minutes.
After that, average between 100 to 120
minutes.
Typically, an individual will go through four to
five sleep cycles a night.
NNNN
BB
NREM
1
NREM
2
NREM 3
NREM
4
NREM
3
NREM
2
REM
BRIEF
AWAKENING
SLEEP-WAKE
REGULATION
THE
TWO-
PROCESS
MODEL
PROCESS
C
PROCESS
S
Maintains
wakefulness
Promotes
sleep
Electrophysiological changes
during sleep
• Process S is the homeostatic
drive for sleep.
• The need f or sleep (process
S) accumulates across the
day, peaks just before
bedtime at night and
dissipates throughout the
night.
• Process C is wake
promoting and is regulated
by the circadian system.
• Process C builds across the
day, serving to counteract
process S and promote
wakefulness and alertness.
This wake-promoting system begins to decline at bedtime, serving to enhance
sleep consolidation as the need for sleep dissipates across the night. With an
adequate night’s rest, the homeostatic drive for sleep is reduced, the circadian
waking drive begins to increase, and the cycle starts over. Process C also
works to consolidate sleep and wake into fairly distinct episodes. Through
synchronization of the circadian system, process C assists in keeping sleep-
wakefulness cycles coordinated with environmental light-dark cycles.
Sleep-Generating Systems in
the Brainstem
• Sleep process S is regulated by
neurons that shut down the arousal
systems, thus allowing the brain to fall
asleep.
• These neurons are found in the preoptic
area of the hypothalamus. These
neurons, containing molecules that
inhibit neuronal communication,
turnoff the arousal systems during
sleep.
• Initiation and maintenance of sleep
require suppression of activity in the
ascending arousal systems. This is
accomplished by inhibitory neurons of
the ventrolateral preoptic area (VLPO)
which remain active throughout sleep
• The molecular “triggers” that activate
the VLPO and initiate sleep, points to
extracellular adenosine as a
candidate.
• Adenosine accumulates in basal
forebrain during wakefulness and
diminishes with ongoing sleep.
• Adenosine receptors are expressed in
the VLPO and adenosine activates
VLPO neurons in vivo , making it a
reasonable candidate for the “sleep
switch.”
Other molecules also play important signaling roles controlling the initiation and
maintenance of sleep. The monoaminergic arousal centers project to the VLPO and
may serve to inhibit its activity. This creates the concept of “flip-flop” control of
behavioral state, in which, at any given time, activity of either arousal producing or
sleep-producing neurons dominates and suppresses the other.
In addition, the VLPO receives important circadian modulation from the
suprachiasmatic nucleus—the central circadian clock .
Wake-Generating Systems in
the Brainstem
Wakefulness is generated by an ascending arousal
system from the brainstem that activates forebrain
structures to maintain wakefulness.
The cortical activation necessary to maintain
wakefulness is supported by an extensive network of
subcortical structures and pathways.
Major neurochemicals of this “ascending arousal
system” include:
• Excitatory norepinephrine arising from the locus
ceruleus (LC)
• Serotonin from the midline raphe nuclei
• Histamine from the tuberomammillary nucleus
• Dopamine from the ventral periacqueductal gray
matter
• Acetylcholine from the pedunculopontine
tegmentum, and the laterodorsal tegmentum of the
pons
• Orexin from the perifornical area.
The main source for the ascending arousal influence includes two
major pathways that originate in the upper brainstem.
Ultimately, all of these inputs enter the cerebral cortex, where they diffusely activate
the nerve cells and prepare them for the interpretation and analysis of incoming
sensory information.
The second pathway, which originates in cell
groups in the upper brainstem that contain the
monoamine neurotransmitters enters the
hypothalamus, rather than the thalamus, where
it picks up inputs from nerve cells that contain
peptides (orexin or hypocretin and melanin-
concentrating hormone).
The first pathway, which takes origin from cholinergic neurons in
the upper pons, activates parts of the thalamus that are responsible
for maintaining transmission of sensory information to the cerebral
cortex.
These inputs then traverse the basal
forebrain, where they pick up additional
inputs from cells containing acetylcholine
and gamma-aminobutyric acid.
THE 24-HOUR CLOCK
CIRCADIAN
RHYTHMS
Regulate body
temperature,
heart rate
Modulate
physical
activity and
food
consumption
Regulate
muscle tone,
and hormone
secretion
Control the
sleep-wake
cycle
Circadian
rhythms refer,
collectively, to
the daily
rhythms in
physiology and
behavior.
The main influence of the SCN on
sleep is due to a series of relays
through the dorsomedial nucleus
of the hypothalamus, which
signals to the wake-sleep systems
to coordinate their activity with
the day-night cycles.
• The rhythms are generated by neural structures in the
hypothalamus that function as a biological clock.
• The basis for these clocks is believed to be a series of
molecular pathways involving “clock” genes that are
expressed in a nearly 24-hour rhythm.
• The suprachiasmatic nucleus (SCN) is responsible for
regulating circadian rhythms in all organs.
• It receives direct inputs from a class of nerve cells in the
retina that act as brightness detectors, which can reset the
clock genes in the SCN on a daily basis.
• The SCN then transmits to the rest of the brain and body
signals that bring all of the daily cycles in synchrony with
the external day night cycle.
SUMMARY
• Sleep itself is not a homogenous process.
• There exist two fundamentally distinct types of
sleep: rapid eye movement (REM) sleep,
which is associated with active dreaming, and
non–rapid eye movement (NREM) sleep.
• Sleep cycle
• Process C and Process S
• Circadian Rhythm
REFERENCE
1. Michael Schupp, Christopher D Hanning. Physiology of sleep.
British Journal of Anaesthesia 2003;3(3):69-74
2. Sleep Physiology - Sleep Disorders and Sleep Deprivation.
https://www.ncbi.nlm.nih.gov/books/NBK19956/
3. David WC, Sarah FS .Physiology of Sleep. American Diabetes
Association. DOI: 10.2337/diaspect.29.1.5
4. https://www.ninds.nih.gov/Disorders/Patient-Caregiver-
Education/Understanding-Sleep
5. https://www.tuck.com/stages/#stages_of_the_sleep_cycle
6. https://www.sleepfoundation.org/articles/teens-and-sleep
7. https://www.deltasleeper.com/stagesofsleep/
8. https://www.sleep.org/articles/what-happens-during-sleep/
9. https://my.clevelandclinic.org/health/articles/12148-sleep-basics
Physiology of Sleep

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Physiology of Sleep

  • 1. SLEEP KIRSHA K S ASSISTANT PROFESSOR DEPT. OF PHARMACY PRACTICE KMCH COLLEGE OF PHARMACY COIMBATORE-8
  • 2. SLEEP • A physical and mental resting state in which a person becomes relatively inactive and unaware of the environment. • Sleep is a partial detachment from the world, where most external stimuli are blocked from the senses.
  • 3. • So, sleep is naturally recurring state of mind and body, characterized by altered consciousness, relatively inhibited sensory activity, reduced muscle activity and inhibition of nearly all voluntary muscles during rapid eye movement (REM) sleep, and reduced interactions with surrounding. • Quality sleep – and getting enough of it at the right times -- is as essential to survival as food and water
  • 4. • There are four stages of sleep: Non-REM (NREM) sleep (Stages 1, 2, 3 &4) REM sleep. • Periods of wakefulness occur before and intermittently throughout the various sleep stages or as one shifts sleeping position.
  • 5.
  • 6.
  • 7. NREM Stage 1 • The lightest stage of NREM sleep. • Defined by the presence of slow eye movements, this drowsy sleep stage can be easily disrupted causing awakenings or arousals. • Muscle tone throughout the body relaxes and brain wave activity begins to slow from that of wake. • People may experience hypnic jerks or abrupt muscle spasms and may even experience sensation of falling while drifting in and out of stage 1. 5% 5%
  • 8. Stage 2 • The first actual stage of defined NREM sleep. • Awakenings or arousals do not occur as easily as in Stage 1 sleep and the slow moving eye rolls discontinue. • Brain waves continue to slow with specific bursts of rapid activity known as sleep spindles intermixed with sleep structures known as K complexes. • Both sleep spindles and K complexes are thought to serve as protection for the brain from awakening from sleep. • Body temperature begins to decrease and heart rate begins to slow. 50%
  • 9. Stage 3 and 4 Delta Sleep • Known as deep NREM sleep. • These are deep sleep stages, with stage 4 being more intense than stage 3. These stages are known as slow-wave, or delta, sleep. • The most restorative stage of sleep, stage 3 consists of delta waves or slow waves. Also brain produces extremely slow waves with occasional bursts of faster brain wave activity • Awakenings or arousals are rare and often it is difficult to awaken someone in Stage 3 sleep. • Parasomnias (sleepwalking, sleep talking or somniloquy and night terrors) occur during the deepest stage of sleep. 10-20%
  • 10. • Stage 4, our brains produce extremely slow waves almost exclusively. These stages are known as “Deep Sleep” or “Delta Sleep”. • It's most difficult to wake up during this stage. • During these stages our bodies emit growth hormones and work on repairing physical damage done during the day
  • 11. REM • Known as rapid eye movement, is most commonly known as the dreaming stage. • First occurs about 90 minutes after falling asleep. • Eye movements are rapid, moving from side to side and brain waves are more active than in Stages 2 & 3 of sleep. • Awakenings and arousals can occur more easily in REM; being woken during a REM period can leave one feeling groggy or overly sleepy. • Each REM stage can last up to an hour. An average adult has five to six REM cycles each night. During this final phase of sleep, your brain becomes more active. 20%
  • 12. • The period of REM sleep is marked by extensive physiological changes. These include: Accelerated respiration Increased brain activity Eye movement Muscle relaxation • The first period of REM typically lasts 10 minutes, with each recurring REM stage lengthening, and the final one lasting an hour.
  • 13.
  • 15. • A sleep cycle is the progression through the various stages of NREM sleep to REM sleep before beginning the progression again with NREM sleep. • The sleep cycle is an oscillation between the slow-wave and REM (paradoxical) phases of sleep. • It is sometimes called the ultradian sleep cycle, sleep–dream cycle, or REM-NREM cycle.
  • 16. • A person would begin a sleep cycle every 90- 120 minutes resulting in four to five cycles per sleep time, or hours spent asleep. • A sleep cycle progress through the stages of non-REM sleep from light to deep sleep, then reverse back from deep sleep to light sleep, ending with time in REM sleep before starting over in light sleep again.
  • 17.
  • 18. The first sleep cycle takes about 90 minutes. After that, average between 100 to 120 minutes. Typically, an individual will go through four to five sleep cycles a night.
  • 19.
  • 20.
  • 24. • Process S is the homeostatic drive for sleep. • The need f or sleep (process S) accumulates across the day, peaks just before bedtime at night and dissipates throughout the night. • Process C is wake promoting and is regulated by the circadian system. • Process C builds across the day, serving to counteract process S and promote wakefulness and alertness. This wake-promoting system begins to decline at bedtime, serving to enhance sleep consolidation as the need for sleep dissipates across the night. With an adequate night’s rest, the homeostatic drive for sleep is reduced, the circadian waking drive begins to increase, and the cycle starts over. Process C also works to consolidate sleep and wake into fairly distinct episodes. Through synchronization of the circadian system, process C assists in keeping sleep- wakefulness cycles coordinated with environmental light-dark cycles.
  • 25. Sleep-Generating Systems in the Brainstem • Sleep process S is regulated by neurons that shut down the arousal systems, thus allowing the brain to fall asleep. • These neurons are found in the preoptic area of the hypothalamus. These neurons, containing molecules that inhibit neuronal communication, turnoff the arousal systems during sleep. • Initiation and maintenance of sleep require suppression of activity in the ascending arousal systems. This is accomplished by inhibitory neurons of the ventrolateral preoptic area (VLPO) which remain active throughout sleep
  • 26. • The molecular “triggers” that activate the VLPO and initiate sleep, points to extracellular adenosine as a candidate. • Adenosine accumulates in basal forebrain during wakefulness and diminishes with ongoing sleep. • Adenosine receptors are expressed in the VLPO and adenosine activates VLPO neurons in vivo , making it a reasonable candidate for the “sleep switch.” Other molecules also play important signaling roles controlling the initiation and maintenance of sleep. The monoaminergic arousal centers project to the VLPO and may serve to inhibit its activity. This creates the concept of “flip-flop” control of behavioral state, in which, at any given time, activity of either arousal producing or sleep-producing neurons dominates and suppresses the other. In addition, the VLPO receives important circadian modulation from the suprachiasmatic nucleus—the central circadian clock .
  • 27. Wake-Generating Systems in the Brainstem Wakefulness is generated by an ascending arousal system from the brainstem that activates forebrain structures to maintain wakefulness. The cortical activation necessary to maintain wakefulness is supported by an extensive network of subcortical structures and pathways. Major neurochemicals of this “ascending arousal system” include: • Excitatory norepinephrine arising from the locus ceruleus (LC) • Serotonin from the midline raphe nuclei • Histamine from the tuberomammillary nucleus • Dopamine from the ventral periacqueductal gray matter • Acetylcholine from the pedunculopontine tegmentum, and the laterodorsal tegmentum of the pons • Orexin from the perifornical area.
  • 28. The main source for the ascending arousal influence includes two major pathways that originate in the upper brainstem. Ultimately, all of these inputs enter the cerebral cortex, where they diffusely activate the nerve cells and prepare them for the interpretation and analysis of incoming sensory information. The second pathway, which originates in cell groups in the upper brainstem that contain the monoamine neurotransmitters enters the hypothalamus, rather than the thalamus, where it picks up inputs from nerve cells that contain peptides (orexin or hypocretin and melanin- concentrating hormone). The first pathway, which takes origin from cholinergic neurons in the upper pons, activates parts of the thalamus that are responsible for maintaining transmission of sensory information to the cerebral cortex. These inputs then traverse the basal forebrain, where they pick up additional inputs from cells containing acetylcholine and gamma-aminobutyric acid.
  • 29. THE 24-HOUR CLOCK CIRCADIAN RHYTHMS Regulate body temperature, heart rate Modulate physical activity and food consumption Regulate muscle tone, and hormone secretion Control the sleep-wake cycle Circadian rhythms refer, collectively, to the daily rhythms in physiology and behavior.
  • 30. The main influence of the SCN on sleep is due to a series of relays through the dorsomedial nucleus of the hypothalamus, which signals to the wake-sleep systems to coordinate their activity with the day-night cycles.
  • 31. • The rhythms are generated by neural structures in the hypothalamus that function as a biological clock. • The basis for these clocks is believed to be a series of molecular pathways involving “clock” genes that are expressed in a nearly 24-hour rhythm. • The suprachiasmatic nucleus (SCN) is responsible for regulating circadian rhythms in all organs. • It receives direct inputs from a class of nerve cells in the retina that act as brightness detectors, which can reset the clock genes in the SCN on a daily basis. • The SCN then transmits to the rest of the brain and body signals that bring all of the daily cycles in synchrony with the external day night cycle.
  • 32.
  • 33. SUMMARY • Sleep itself is not a homogenous process. • There exist two fundamentally distinct types of sleep: rapid eye movement (REM) sleep, which is associated with active dreaming, and non–rapid eye movement (NREM) sleep. • Sleep cycle • Process C and Process S • Circadian Rhythm
  • 34. REFERENCE 1. Michael Schupp, Christopher D Hanning. Physiology of sleep. British Journal of Anaesthesia 2003;3(3):69-74 2. Sleep Physiology - Sleep Disorders and Sleep Deprivation. https://www.ncbi.nlm.nih.gov/books/NBK19956/ 3. David WC, Sarah FS .Physiology of Sleep. American Diabetes Association. DOI: 10.2337/diaspect.29.1.5 4. https://www.ninds.nih.gov/Disorders/Patient-Caregiver- Education/Understanding-Sleep 5. https://www.tuck.com/stages/#stages_of_the_sleep_cycle 6. https://www.sleepfoundation.org/articles/teens-and-sleep 7. https://www.deltasleeper.com/stagesofsleep/ 8. https://www.sleep.org/articles/what-happens-during-sleep/ 9. https://my.clevelandclinic.org/health/articles/12148-sleep-basics