Sleep progresses through distinct stages in a cycle. Non-REM sleep begins with light sleep in stages 1 and 2, characterized by theta waves and sleep spindles. Stages 3 and 4 involve deep sleep with synchronized brain activity appearing as delta waves. REM sleep involves dreaming and similar brain activity to wakefulness. The circadian rhythm and homeostatic processes regulate sleep cycles, with the circadian rhythm promoting wakefulness opposed by the increasing homeostatic drive for sleep with time spent awake.

1. High lights on
Sleep physiology
By
Dr. Ashraf El-Adawy
Consultant Chest Physcian
TB TEAM Expert - WHO

2. Physiology of Sleep
 What Is Sleep ?
Every night, nearly every person undergoes aremarkable change:
we leave waking consciousness and for hours traverse a landscape
of dreams and deep sleep.
When we wake, we typically rememberlittle ornothing aboutthe
hours that have just passed.
Except in rare instances, we nevercontemplate and appreciate that we
are sleeping whilewe are asleep. .
All organisms exhibitdaily patterns of rest and activity that resemble
the daily sleep and wakefulnesspatterns seen in humans.
From observing changes in behaviorand responsiveness, scientists
have noted the following characteristics that accompany and in many
ways define sleep:
 “Sleep is a dynamicbehavior. Notsimply the absence of waking”
 Sleep is associated with a typical posture, such as lying down
with eyes closed in humans.
 Sleep results in a decreased responsiveness to external stimuli.
 Sleep is a state that is relatively easy to reverse (this
distinguishes sleep from otherstates of reduced consciousness,
such as hibernation and coma).
 Sleep is nota passive event, butrather an active process
 Sleep is notthe time for the body in general and the brain
specifically to shutdown for rest.
 Contrary to popularbelief,sleep is notsimply a state in which
the brain is resting, buta dynamic, complicated condition
during which the brain is quite active
 During some stages of sleep the brain is just as active as when we
are fully awake.
 From observationsof behavioral changes that accompany sleep
and simultaneous physiological changes, scientists now define

3. sleep in humans based on brain wave activity patterns and other
physiological changes
 Sleep is nota static condition, buta complexseries of sleep
stages that repeats itself in a characteristic pattern overa night’s
sleep. There are five distinctstages of sleep: stages 1, 2, 3, and 4
(all of which comprise “non-REMsleep”), and the fifth stage,
REM (rapid eye movement)sleep. Each stage of sleep is defined
by specificelectrical patterns in the brain.
 Sleep is an essential forlife just like food and water.
 1/3 of life is spent sleeping!
 Sleep is essential to life
 Sleep is a behavioral state that is a natural part of every
individual’s life. We spend aboutone-third of our lives asleep.
 We spend about8 hours/day, 56 hours/week, 224hours/month
and 2,688 hours/yearsleeping.
 Why do we sleep ?
 Sleep is an adaptive behavior. By sleeping, animals conserve
energy and rest when food is not as available.
 Sleep is a period of restoration. During sleep, afterthe first
occurrence of delta activity, certain growth hormones are
secreted which are not only crucial in animals'growth in
infancy, but also they are essential in bodily tissue repairs.
Furthermore, the body is given an opportunity to repairthe
wear and tear caused by activities during waking
 Sleep allows forcognitive processes. Studies by suggests that
poor retention of informationoccurs if individuals are sleep
deprived priorto learning, In addition,during sleep information
is organized, consolidated,incorporated and stored.

4.  Sleep research certainly has shown is that sleeping too little can
not only inhibityourproductivityand ability to rememberand
consolidate information, butlack of sleep can also lead to serious
health consequencesand jeopardize yoursafety and the safety of
individuals around you.
 For example, sleep deprivation is linked with:
1. Increased risk of motorvehicle accidents
2. Increase in body mass index – a greater likelihood of obesity due
to an increased appetite caused by sleep deprivation
3. Increased risk of diabetes and heart problems
4. Increased risk for psychiatric conditionsincluding depression
and substance abuse
5. Decreased ability to pay attention, react to signals orremember
new information
 Make sleep a priority.
You mustschedule sleep likeany other daily activity, so put it
on your"to-do list" and cross it off every night. But don’t make
it the thing you do only after everything else is done – stop
doing otherthings so you get the sleep you need

5.  Regulation of the sleep-wake
 In humans, the usual pattern is to stay awake for about 16 hours
during the day and sleep eighthours coinciding with the
nocturnal period.
 Sleeping and waking are 2 highly regulated behavioral states.
Most humans sleep at nightand are awake during the day.
Moreover, the amountof time we spend awake and asleep is
almostthe same from day to day, unless life events imposesome
alteration on the normal pattern.
 If we miss sleep, ourbodies willlikely try to make it up. If we
stay awake too long, we become sleepy and the desire to sleep
becomes progressivelystronger.
 The sleep-wake processes are regulated by the interaction
between sleep homeostasisand circadian rhythm.
 The process affects the circadian timing of sleep and the
homeostaticmechanisms governing the need for sleep.
1. Sleep homeostasis
 Homeostasis was the main physiologicalregulatory mechanism
of the body. It is defined as the set of phenomenaof self-
regulation, leading to the maintenance of relative constancy in
the compositions and the properties of the internal environment
of an organism.
 Homeostaticmechanisms,that control the bodys internal
balance also govern sleep and waking times and the need for
sleep ,whereby a wake-depended build-up of sleep propensity
increases during the day and dissipates during sleep
 The homeostaticprocess is the drive to sleep that is influenced
by the duration of wakefulness(This process can be viewed as a
propensity to sleep that accumulates overa period of waking).
 Homeostaticmechanisms,increases as a function of how long
you have been awake and decreases as you sleep. The process is
somewhatlike the sand accumulating in one end of an hourglass
and having to be emptied into the other after a certain time.
 The homeostaticprocess, which promotes sleep,is low in the
morning and act overthe propensity of, sleep, which increases

6. throughoutthe day In other words, the longeryou stay awake,
the greater the pressure you willfeel to go to sleep and when we
have sleptenough, itacts to wake up.
 Currentstudies have shown that adenosine,an inhibitory
neurotransmitterthat results from increased metabolismof
glycogen, could be the substance involved in inducing sleep
homeostasisprocess, because itis accumulated in the brain
during prolonged wakefulnessand decreases with subsequent
sleep.
 In fact caffeine, the substance mostcommonly usedto force
states of alert, blocks the adenosine receptors.
 The homeostatic propensity to sleep is opposed by a circadian
drive for wakefulness, the homeostatic drive begins to build in
the morning with time awake and continues to rise throughout
the waking day. This drive to sleep is opposed by an increasing
output from the circadian pacemaker, the suprachiasmatic
nucleus (SCN)of the hypothalamus, which promotesarousal.
 As the homeostatic drive grows in the late day, SCN output
increases and maintains wakefulness. As the time for sleep
approaches, circadian output drops, permitting homeostatic
drive to induce the onsetof sleep.

7.  If the homeostaticsleep drive, were unopposed, as occurs in the
absence of inputfrom the principal circadian pacemaker, sleep
would occurin short bouts throughoutthe day.

8. 2. Circadian rhythm
 Our typical behavioral pattern is to awaken in the morning after
roughly 8 hours of sleep and to remain awake for approximately
16 hours. Thus, sleep and wakefulness are consolidated into
definite periods of the 24-hours.
 The regularrepetition of these behavioral states represents a
biological rhythm with a period of 24 hours -- a circadian
rhythm (“Circadian” means “abouta day.”)
 The circadian rhythm is governed by yourbiological clock,
whose rhythm is endogenousbutis reset regularly by daylight.
This clock therefore produces a cycle lasting about24 hours
during which the optimal times forfalling asleep, dreaming,
waking up, and doing work occur overthe course of each day.
 This internal clock, which gradually becomes established during
the first months of life, controls the daily ups and downs of
other biological patterns, including body temperature, blood
pressure, and the release of hormones.
 The circadian rhythm makes people’s desire forsleep strongest
between midnightand dawn, and to a lesserextentin
midafternoon.
 In the 1970s, studies in rats identifiedthe suprachiasmatic
nucleus (SCN)as the location of the internal clock. This cluster
of cells is part of the hypothalamus
 Melatonin is the natural hormone which controls our biological
clock, telling us when it is time to sleep and time to wake up..
regulates sleep and awake cycle ( sleep hormone)
 Melatonin is a hormone secreted by pineal gland. The amount
of secretion of melatonin varies, it depends on age, time, sex and
also the place where a person is living.
 The suprachiasmatic nucleus (SCN) is entrained to the external
environmentby the cycle of lightand darkness.
 The retinal ganglion cells transmit light signals via the
retinohypothalamictract to stimulate the SCN.

9.  A multisynapticpathway from the SCN projects to the pineal
gland, which produces melatonin.
 Melatonin synthesis is inhibited by lightand stimulated by
darkness.
 The nocturnal rise in melatoninbegins between 8 and 10 pm
and peaks between 2 and 4 am, then declines gradually overthe
morning,Melatoninlevels are normally very low in the day.


10. Borbély’s model of sleep-wake regulation (Borbély & Achermann, 1999).
Process S represents the homeostatic built-up of sleep pressure.
Process C represents the circadian rhythm
The bigger the distance between process S and process C, the higher the sleep
pressure. So that’s the moment when sleep will normally be initiated.

11.  Two main regulatory processes are involved in producing daily
sleep-wake cycles that permits us to stay awake and alert during
the day and to sleep throughoutthe night:
1. Circadian process(C), which adjusts the period of sleep to a
certain time relative to the environmentallight-dark cycle,
2. homeostaticprocess(S), whereby awake-depended build-up of
sleep propensity increases during the day and dissipates during
sleep
 At certain times of day, for example, justbefore habitual
bedtime when the homeostaticdrive for sleep is at its peak,
and conversely at the end of the sleep episode when itis at its
lowest, a strong circadian drive for wakefulness and
sleepiness,respectively,counteracts process S.
 This interaction, referred to as the “opponentprocess,”results
in uninterrupted 8-hournocturnal sleepand 16-hourwaking
episodes each day

12.  Stages of Sleep
 For centuries, scientists scrutinized minute aspects of human
activity, but showed little interestin the time that people spentin
sleep.
 Sleep seemed inaccessible to medical probing and was perceived as
an unvarying period of inactivity
 All that changed in the 1930s, when scientists learned to place
sensitiveelectrodes on the scalp and record the signals produced by
electrical activity in the brain.
 These brain waves can be seen on an electroencephalogram, or
EEG, which today is captured on a computerscreen
 The EEG of a waking person is clearly differentthan that of a
sleeping person.
 Since then, researchers have gradually come to appreciate that sleep
is a highly complexactivity.
 Using electrodes to monitorsleepers’eye movements, muscletone,
and brain wave patterns, they identifiedseveral discrete stages of
sleep ,each has a distinctive signatureon an EEG.

13.  Scientists divide sleep into two majortypes:
1. Rapid eye movement(REM) sleep ordreaming sleep,
2. Non-REMor quietsleep.
Surprisingly, they are as differentfrom each other as eitheris from
waking.
 Each stage of sleep serves an importantpurpose in keeping your
brain and body healthy.
 When you are awake, billions of brain cells receive and analyze
sensory information, coordinate behavior, and maintain bodily
functions by sending electrical impulses to one another.
 If you’re fully awake, the EEG will record a messy, irregular
scribble of activity.
 The EEG pattern of our brain during wakefulness is very rapid,
irregularand low on voltage. This means that many neurons are
firing at differentintervals and at differenttimes, with different
strengths too.
 Itwould be like going to a crowded bar and hearing people taking
with each other, some here, some there; it's noisy and you can only
hear a unified hum of voices withoutcleardifferentiation between
them.
 This type of irregularelectrical activity in the brain during
wakefulness is called beta waves or beta activity.
 Once youreyes are closed and yournerve cells no longerreceive
visual input,brain waves settle into a steady and rhythmicpattern
of about 10 cycles per second
 When we are relaxed, withoutany mental arousal, the EEG records
a waveform called alpha waves or alpha activity, slowerthan beta
waves.
 Brain activity is desynchronized while in alphaand beta activity.

14.  Sleep is nota random process; instead, it is a very organized one.
Sleep has five stages: stage 1-4 (non-REMsleep)followed by REM
sleep. This process is cyclical.
 Once REM sleep is achieved, the cycle reverses itself and goes back
though stages IV, III,II and again to III, IVand REM. Throughout
the night, this cycle occurs at 90-to-100 minute intervals.

15.  Non-REM or quiet sleep
Stage One (Transition to sleep)
 In making the transition from wakefulness into lightsleep,you
spend about 5 to 10 minutes in N1 sleep.
 Stage one counts for more or less 5% our total sleep during the
night.
 Stage one is characterized on the EEG,by the presence of theta
waves, slower(fourto seven cycles per second ) and stronger
waves ( has highervoltage )than alpha and beta waves , This
suggestthat mental relaxation has started and within 5 to 10
minutes,we enterstage 2.
 Body temperature begins to drop, muscles relax, and eyes often
move slowlyfrom side to side.
 People in stage N1 sleep lose awareness of their surroundings,
but they can be easily awakened.
 if awakened people say they weren’tasleep.
Stage Two: Light Sleep
 In stage 2 sleep, we still get theta waves plus K complexes and
sleep spindles.
 Sleep spindles are sudden and intense bursts of electrical activity
that last for a second or two.
 K complexes are also sudden and sharp waves of a longer
frequency, often butnot always triggered by noises. They
naturally occur at a rate of one per minute too.
 Some researchers believethat sleep spindleshelp us disconnect
from the outside world (noises, etc) ,aid sleeping in the presence
of disruptive external sounds. The elderly have fewersleep
spindles and they are easy to wake up.

16.  The EEG tracings also show a pattern called a K-complex, which
scientists think represents a sort of built-in vigilance system that
keeps you poised to awaken if necessary. K-complexes can also
be provoked by certain sounds orother external or internal
stimuli.
 Stage 2 sleep is the first stage of true sleep lasts 10 to 25 minutes.
You spend abouthalf the night (45-555%)in stage N2 sleep.
This stage involves the following:
 Youreyes are still, and your heart rate and breathing are slower
than when awake, body temperature drops.
 The person experiences only lightsleep.
 Itis a little harder to awake the person.

17. Stage Three and Four or Slow Wave Sleep: Deep Sleep
 When we enter Stage 3, our brain activity is synchronized. This
means that big groups of cells are firing at about the same time.
 Think aboutthe example with people in the bar, but now
instead of talking to each other randomly, they are all singing at
the same. Now voices are unified; there is little noise outsidethe
singing. This unified activity in the brain is represented in the
EEG recordings by large waves called delta waves.
 Delta waves are the slowestand strongestwaves that ourbrain
produces.
 Stage 3 has about20-50% of delta waves. Stage 4 is all delta
activity. Stage 3 and 4 are also called slow wave sleep because of
the appearance of delta waves.
 During this stage, known as deep sleep or slow-wave sleep,the
brain becomes less responsive to external stimuli, making it
difficultto wake the sleeper,the highestarousal threshold also
occurs, However, if awakened the person seem confused and
acts slow.
 Deep sleep seems to be a time for your body to renew and repair
itself.
 A young adultspends about8% of sleep time in stage 3 and 11%
in stage 4. (Normally,young people spend about20% of their
sleep time in deep sleep, butdeep sleep is nearly absent in most
people overage 65).
 Stages 3 and 4 sleep are the deepeststage of sleep. Brain waves
are extremely slow.Blood flow is directed away from the brain
and towards the muscles, restoring physical energy.

18.  Delta sleep is generally considered the mostrestorative stage of
sleep
 During stage 3 and 4, growth hormone is secreted by the pineal
gland. This hormone encouragesbone and muscle growth in
children, whilein adults it is involved in tissue repair.
 Other hormonal activities, likethe secretion of prolactin and
gonadotropin occurin these stages, making slow wave sleep a
phase of rest and healing.
 Blood levels of substances that activate yourimmune system
increase, raising the possibilitythat slow-wave sleephelps the
body defend itself againstinfection.
 Typically during this stage: heartbeat and respiration are slow
and regular. Blood pressure drops Muscles are relaxed
 Dreams / nightmare even occur. ,The difference is that the
dreams in slow wave sleep are not remembered but in
REM, dreams can be remembered.
o Non-REMsleep, which is divided into fourdistinctstages,
seems to be designed specifically forresting. You muscles
are more relaxed, and you move them only infrequently,
to adjust yourbody’s position in bed.
o As the parasympatheticnervous system becomes
predominant during this phase of sleep, yourgeneral
metabolismslows down:yourtemperature,energy
consumption,heart rate, respiration rate, and kidney
function are all reduced.
o The slow brain waves recorded on EEGs during non-REM
sleep indicate that the brain too seems to be resting. The
extensive synchronizationof neural activity observed in
the brain during non-REMsleep providesfurther
evidence that mostof the sensory information from the
outside world doesn’teven reach the cortex during this
kind of sleep.

19. o Itis no surprise that in experiments where peopleare
awakened from non-REMsleep, they can recall only
vague thoughts and, on rare occasions, detailed dream
scenes. ,William Dement, an importantsleep researcher,
has summarized non-REMsleep as an idling brain in a
moving body.

20.  REM Sleep (Rapid Eye Movement)
 Normally, REMsleep makes up about20-25% of total sleep in
young adults.
 REM sleep occurs every ninety minute intervals afterwe fall
asleep. This means that in an 8 hoursleep we will experience
fouror five REM sleep stages and every time we enter REM, we
stay a bit longerin it.
 As sleeperenters REM sleep. , The first episode usuallylasts only
for a few minutes,butREM time increases progressively over
the course of the night. The final period of REM sleep may last a
half-hour.
 At around ninety minutes afterthe onsetof sleep and following
stage 4, the synchrony of brain waves is suddenly interrupted by
desynchronized activity, similarto when we are awake (Alpha
and Beta activity). At this pointourmuscles are very relaxed; in
fact, we are paralyzed.
 During REM sleep brain waves are very desynchronized
(desynchronized means unregulated, e.g. trying to listen to
several conversations simultaneously). Thisstage is also referred
to as paradoxical sleep since brain activities during REM are
comparable to those during wakefulness
 Although the entire nervous system becomes very active during
REM, movements such as walking and talking are not present,
because the muscles become atonicor paralyzed
 Dementdescribes REM sleepas the state of an active,
hallucinating brain in a paralyzed body. “active brain in a
paralyzed body.” (“brain on, body off”)
 REM sleep sets the stage for dreams
 In REM stage, the electrooculogramorEOG (a device that uses
electrodes to pick up muscularactivity of the eyes)senses that
the eyes of the sleeperare moving rapidly.

21.  At the same time, the electromyogram orEMG (picks up muscle
activity) senses no activity in the rest of muscles: skeletal
muscles are paralyzed, atonic during REM ,. The reason we
mightloose muscle tone is so that we do not act out ourdreams,
to keeps us away from trouble
Other characteristics of REM
1. Heart rate & respiratory rate become irregular;
2. Body temperature rises
3. Blood flow to the brain is increased
4. Penile erection and clitoral engorgement,these notnecessarily
indicate that the sleeperis experiencing adream of sexual
content.
5. The sympatheticnervous system, becomes predominant during
this phase of sleep, is twice as active as when you’re awake.
 Reaching REM sleep,we are mostly disconnected from the
outside world, butwe mightwake up to something meaningful
like ournames being called out, or loud sounds
 When sleepers in REM stage are awaken, usually they seem alert
and can react normally.
 However,If the sleeperwas awaken during slow wave sleep, it
takes a few instants to wake up and react.
 This mightbe due to the presence of alpha and beta waves in
REM sleep and deltaactivity in slow wave sleep.
 Rememberthat alpha and beta are brain waves are also present
when we are awake, not only in REM. This is why some
researchers believe that REM sleep is an evolutionary adaptation
to wake up and be fully alertto a potential emergency in the
middle of sleep.

22.  REM sleep restores the mind , Itis importantfor both learning
and memory.
 Just as slow-wave sleep restores yourbody, scientists believe
that REM or dreaming sleep restores yourmind, perhaps in part
by helping clearout irrelevantinformation.
 During REM sleep, yourbrain consolidates and processes the
information you have learned during the day, forms neural
connections that strengthen memory, and replenishits supply of
neurotransmitters
 The relative proportion of REM and non-REMsleep per cycle
changes across the night, such that slow wave sleep
predominates in the first third of the nightand REM sleep in the
last third.
 A single REM cycle lasts about 20 to 30 minutes in a healthy
person in his/hertwenties. But, this period is very prolonged in
newborn and children and is drastically shortened in the elder.

23.  Sleep architecture
 During the night, a normal sleepermoves betweendifferent
sleep stages in a fairly predictable pattern, alternating between
quietsleep (non-REM)and dreaming sleep (REM).
 When these stages are charted on a diagram, called a
hypnogram, the differentlevels resemble adrawing of a city
skyline. Sleep experts call this pattern sleep architecture.
 In a young adult, normal sleep architecture usually consists of
fouror five alternating non-REMand REM periods.
1. Sleep in different age groups
1. Sleep in adults
 In adults, sleep of 8-8.4 hours is considered fully restorative.
 In some cultures, total sleep often is divided into an overnight
sleep period of 6-7 hours and a midafternoon nap of 1-2 hours.
 Stage I is considered a transition between wake and sleep. It
occurs upon falling asleep and during brief arousal periods
within sleep and usually accounts for5-10% of total sleep time.
 Stage II occurs throughoutthe sleep period and represents 40-
50% of total sleep time.
 Stages III and IV of sleep occurmostly in the first third of the
night. They are distinguished from each other only by the
percentage of deltaactivity and representup to 20% of total
sleep time.
 REM represents 20-25%of total sleep time.

24. 2. Sleep in infants
 Infantshave an overallgreater total sleep time than any other
age group; their sleep time can be divided into multiple
periods.
 In newborns, the total sleep duration in a day can be 14-16
hours.
 REM sleep in infantsrepresents a larger percentage of the total
sleep at the expense of stages III and IV.
 More REM sleep – 50%, which may provide essential
stimulation to the developing nervoussystem
3. Sleep in the elderly
 Less deep sleep and more lightersleep
 In the elderly, the time spentin stages III and IV sleep decreases
by 15% and the time in stage II increases by 5% compared to
young adults, representing an overall decrease in total sleep
duration.
 Latency to fall asleep and the numberand duration of overnight
arousal periods increase.
 Increased napping through outthe day
 Decreased REM sleep percentage and duration.
 REM sleep appears to be equally distributed through sleep
cycles. I.e. there is no increase in REM at the end of the sleep
period.
 Reduced sleep efficiency
 Decreased melatonin levels

25. Human Sleep PatternsChange with Age
Average Daily Hours of Sleep for Different Mammals