Comprehensive Overview of Sleep Physiology: Architecture, Functions, and Health Impacts

[music] Greetings to one and all. This is Dr. Sanjay, professor of physiology, Chetnar

Hospital and Research Institute, Chennai. I will be updating you on sleep, its core principles, its

architecture and functional significance in this session. These are the objectives of my session. I will begin

the session talking to you about the core principles of sleep physiology following which I will discuss the

architecture of sleep under which I will talk to you about the sleep pathways which will help us to understand the

neural regulation of sleep better and then I will talk to you about the two types of physiological sleep namely NRM

sleep and sleep and then I will talk to you about the significance of the physiological variations during sleep

after which we will discuss the functions of sleep. I will conclude the session giving you an overview of the

diagnostic intervention of sleep namely polyomnography and then I will talk to you about the consequences of sleep

deprivation and so let us begin to have an update on the core principles of sleep physiology.

There have been many definitions of sleep in the literature but a simple definition is sleep has been defined as

a physiological state of relative unconsciousness with inaction of voluntary muscle effort the need for

which recurs periodically. Sleep has been classified based on its functional depth as light sleep and deep sleep

based on its electro encapilographic characteristics as desynchronized sleep and synchronized sleep and based on its

physiological characteristics namely non-rapid eye movement sleep or NRM sleep and rapid eye movement sleep. Now

let us discuss the historical milestones in the physiology of sleep. It was in the 17th and 18th century that the

father of medicine hypocrites along with gallon proposed that sleep involved the brain and was as important for

homeostasis. And so in the 19th century sleep researchers began to record brain activity and notice changes during

sleep. The 20th century saw quite a few advances in the physiology of sleep following the invention of the

electroenapiloggram by Hansburgger. Nathaniel Clayman made landmark discoveries on the physiology of sleep

during the early 20th century and it was in the mid- 20th century that sleep and nonrem sleep were discovered. The late

20th century saw development in the neurochemistry of sleep. In the current era that is the 21st century quite a few

advances on the physiology of sleep have been discovered with the advent of radological diagnosis such as fMRI and

the PET scan. The plasticity or how brain networks change during sleep have been discovered. Sleep's role in memory

consolidation, immune function, metabolism and brain waste clearance by the lymphatic system became evident

giving to us a better understanding of the functions of sleep and the molecular mechanisms which control sleep have also

been discovered by different genetic studies which is an area of ongoing research in the physiology of sleep.

Recognition of sleep disorders such as insomnia, narcolepsy, sleep apnea improved the understanding and

treatment. Cresendo sleep refers to normal sleep during which there are gradual movements of the sleeper during

the course of sleep. The two physiological types of sleep are NRM sleep or non-rapid eye movement sleep

and sleep or rapid eye movement sleep. This is based on the movements of the eyeball during the period of sleep.

Functional sleep is graded based on changes noted in the electroenapilogram or the EEG. Since the electro

enapilogram of RM sleep is similar to that of wakefulness, sleep is also known as paradoxical sleep. Dreams are

significantly noted to take place during sleep but also occur during NRM sleep. Now let us try to understand the normal

sleep cycle. The sleep stages appear in a predictable sequence which repeats about every 90 to 100 minutes. In a

typical night in a young adult after the lights are turned out there is a period of wakefulness before sleep appears and

the duration of the this period of wakefulness is known as sleep latency. Then one then one enters the NRM sleep

and after about 1 and a half hours or 90 minutes sleep appears. The NRM cycle goes on throughout the night and a

typical night may contain four to six such cycles. This diagram shows a normal sleep cycle. The shaded area here refers

to the NRM sleep which alternates between the unshaded area which is them sleep and this keeps repeating itself

and in a typical night there are about four to five such cycles. This slide shows that sleep patterns vary during

different stages of development. Here you can see that human fetuses sleep most of the time mostly exhibiting them

type of sleep. At birth, newborn babies sleep for about 18 hours, 50% of which is occupied by the RM pattern of sleep.

In adulthood, between the ages 20 to 70, most of the sleep cycle is occupied by the NRM pattern of sleep. The RM pattern

accounting for only about 25% of the sleep cycle. It is interesting to note that sleep deprivation is associated

with longer periods of NRM sleep. A knowledge of the waveforms of a normal electronilogram is mandatory to the

understanding of the physiological sleep cycle. A normal electro encophy shows four types of waves namely the beta

wave, the alpha wave, the theta wave and the delta wave. These four waves are based on their amplitude and their

frequency. The beta wave occurs when a person is awake and thinking and this is how the beta wave appears. The alpha

wave occurs in a relaxed and awake person with his eyes closed and the theta wave occurs during light sleep and

the delta wave occurs during deep sleep. We will come to more on the EEG findings during sleep later in the presentation.

Now let us try to understand the differences between desynchronized sleep and synchronized sleep. This

classification is based on the EEG characteristics noted during the sleep period. Desynchronized sleep refers to

RM sleep. Here you have the EG showing low amplitude and high frequency waves. This EG pattern is also noted to occur

during wakefulness. Synchronized sleep refers to NRM sleep during which the EG shows high amplitude and low frequency

waves. Here you have the EEG tracings showing the desynchronous sleep or the RM sleep where the frequency of the

waves are increased and the amplitude decreased. And here you have the NRM sleep where the frequency is decreased

and the amplitude is increased. That is the synchronized type of sleep. Now let us take a look at the currently accepted

theory of sleep. Sleep is caused by an active inhibitory process. This is what is believed as on date. An earlier

theory of sleep proposed that the excitatory areas of the upper brain stem and the reticular activating system to

become fatigued during the waking day and become inactive as a result. It was later discovered by an experiment that

transacting the brain stem at the level of the midpoints created a brain cortex that never goes to sleep. This

experiment facilitated the current view that sleep is caused by an active inhibitory process whereby a center

located below the midpoints of the brain stem appears to be required to cause sleep by inhibiting other parts of the

brain. Now let us take a look at the genetic modulation of sleep. This slide shows three categories of genes with a

few examples in each category. You have the core clock genes which regulate the circadian rhythm and the genes which

influence the sleep duration and quality and the genes which are associated with the disorders of sleep. This slide gives

you an overview of sleep in the animal kingdom. It is interesting to note that cows sleep only for about 4 hours in a

24-hour period. And here you can see the bats and the koala bears sleep most of their lifetime that is 18 to 20 hours

per day. As far as uh humans are concerned, the functional sleep duration in an adult human is about 9 7 to 9

hours and the sleep duration in infants as I discussed earlier is about 16 hours per day. Having gone through the core

principles of sleep physiology, let us now open our eyes on the architecture of sleep. Here we shall discuss the sleep

pathways which will help us to understand the neural regulation of sleep better and then also let us take a

look at the two physiological types of sleep namely non-rapid eye movement sleep and rapid eye movement sleep. This

slide gives you the basic architecture of the sleep pathways and here you can see that wakefulness is mediated by

neurons of the reticular formation of the brain stem and these neurons project to two regions namely the cerebral

cortex and thealamus. With regards to the pathway projecting to the talamus, there are two groups of neurons namely

the histnagic neurons and the colonic neurons. The colonic neurons are also known as wakeonm on cells because they

are active during wakefulness and sleep and they become inactive only during nm sleep. Now there's another group of

neurons known as the orexogenic neurons. These are neurons which mediate the sleepwake cycle. They're located in the

hypothalamus and they use the neuropeptide orexin. They are excitatory to the neurons related to the sleepwake

cycle. These neurons are active during the wakeful state state and during sleep. These groups of neurons play a

critical role in the overall regulation of sleep. Having gone through the sleep pathways, let us take a look at NRM type

of sleep. Non-rapid eye movement sleep is also known as slowwave sleep or synchronized sleep because as we saw

previously in this type of sleep, the frequency of brain waves are much slower when in comparison with RM type of

sleep. In functionally fit individuals, sleep begins with the NRM type of sleep. It is a restful type of sleep in which

the individual is relieved from the task that he or she is normally subject to. Normally NRM type of sleep shows four

stages and stage one you have the low amplitude mixed frequency waves. Stage two you have waves characterized by

sleep spindles and K complexes. Stage three you have high amplitude and the slow theta waves and stage four you have

high amplitude and the slow delta waves. This can be seen in the tracing. Here you can see stage one you have low

amplitude mixed frequency waves. Stage two you have the K complexes and the sleep spindles. Stage three you have

high amplitude in the slow theta waves. And stage four you have high amplitude in the slow delta waves.

RM sleep on the other hand is also known as fastwave sleep or desynchronized sleep or paradoxical sleep or dream

sleep or deeper sleep. During sleep the EEG is characterized by high frequency low and amplitude pattern and this type

of a pattern is also seen during wakefulness. In cats, RM sleep is characterized by a type of waves known

as the PGO waves or the ponttogenic occipital waves. PGO waves are not seen in humans by scalp EG recordings, but

they're recorded in indepth EG recordings. Now, let us take a look at the physiological changes noted in NRM

and sleep. The eye movements are slow and rolling in NRM sleep and they tend to disappear in stage four of NRM sleep.

As far as RM sleep is concerned, the eye movements are rapid and that is why you have the term rapid eye movement sleep.

The muscle tone decreases progressively in NRM sleep and in RM sleep it reduces to a state of hypotonia.

Heart rate, blood pressure and respiration decrease in NRM sleep and the heart rate and respiration are

irregular in RM sleep and the blood pressure is variable in RM sleep. Body metabolism slows down in NRM sleep and

begins to rise inm sleep. Now coming to the other physiological changes we will be seeing later on. Growth hormone and

gonadotropen secretion by the pituitary gland increases during sleep and as far as sleep there are three characteristics

which are noted namely twitching of the limb musculature penile erection in males and engorgment of the clitoris in

females teeth grinding or bxism in children. Let us take a look at a few behavioral changes of NRM and sleep. In

NRM sleep there's a gradual decline of consciousness. The sleep are showing a graded increase in resistance to being

awakened. It is almost difficult to arose a person in sleep and you can say that sleep is a state of relative

unconsciousness. There's no recall of dreams in NRM sleep. There's vivid recall of dreams in RM sleep. And most

of the dreams which we remember take place during sleep. The audiary reaction time becomes longer in NRM sleep. The

visual response time to stimula is variable. Thoughts become illogical and incoherent. And there's retrograde

amnesia which can be seen with a person not being able to recall the onset of sleep or not being able to recall

dreams. Memory for the few minutes before sleep is also lost. Now we shall go on to see the

significance of the physiological variations during sleep before going on to describe the functions of sleep. With

regards to the functions of sleep, evidence-based research has been carried out on the following domains, namely

ventilatory function, cardiovascular function, endocrine function, digestive function, sexual function,

thermmorreulation and cerebral function. One must note that disruption of vital functions during sleep can trigger

pathological states and also alter the sleep wake cycle. Now we shall go through the ventilatory

functions during sleep and you can see that the regulation of respiration varies during the sleep states of sleep

and during wakefulness. This can be graded as metabolic regulation and behavioral regulation. Metabolic

regulation is what you would have studied in your textbooks of physiology as a neural regulation and chemical

regulation of respiration whereby the O2 CO2 and the pH levels are maintained in homeostatic ranges. Behavioral

ventilator control is mediated by the diaphragm whereby a person can modulate his respiratory reserve voluntarily. A

marked prevalence of respiratory dis disorders during sleep has been evidenced till date. Ventilation control

is principally under behavioral command which ensures the state of wakefulness. The onset of sleep inhibits the

behavioral ventilation control. Thus the shift from wakefulness to sleep coincides with diminished ventilation.

Metabolic control gradually takes command of ventilation but only becomes effective when sleep stabilizes. As a

result, you have a state of periodic breathing where there is irregularity in the rhythm of respiration and uh this

continues till the metabolic control fully takes over. The period between wakefulness and stage two of NRM sleep

is thus characterized by respiratory instability and it is only during stages 2 3 4 and four of NRM sleep that the

metabolic regulation of respiration confers stability to respiration. In RM sleep, ventilation decreases, but it's

particularly unstable during this type of sleep. Age and sex have no significant differences in ventilation

and in general regulation. Ventilatory dysfunction during sleep involves periods of awakening in order to ensure

satisfactory ventilatory or respiratory homeostasis and the survival of the individual. With regards to

cardiovascular function during sleep, bradic cardia occurs during RM sleep and deep NRM sleep and this is attributed to

veagal activation and decreased sympathetic tone. Systemic cardial blood pressure diminishes during NRM sleep

especially in deep NRM sleep. This is related to peripheral vessel vasodilation and bradicardia in in RM

sleep. Contrary to NRM sleep, there's a wide variability in artiller pressure with absures of pressure simultaneous

with rapid eye movements. The main changes in artiller pressure during NRM and RDM sleep are related to the

reduction in overall perip peripheral vascular resistance related to the reduction in sympathetic tone. No change

has been demonstrated in the ventricular cylic ejection fraction in both types of sleep and cereal blood flow increases

slightly during sleep. With regards to the endocrine functions during sleep, the following have been noted. Prolactin

secretion reaches high levels at night during the period of sleep. And as far as TSH secretion is thyroid stimulating

hormone secretion is concerned. Now a normal circuit in rhythm of TSH secretion has been described. But V weak

amplitude secretary episodes of TSH occur throughout the sleepwake cycle. Growth hormone has a secretary peak

during NRM sleep and renin increases in transition from RDM sleep or wakefulness to deep NRM sleep and diminishes as

sleep becomes lighter or with awakening. Cortisol and ACT usually have a circadian rhythm with high plasma levels

in the morning which gradually diminish as the day progresses. This rhythm is however not modified by sleep per se.

Melatonin as you may be aware of has a gradual increase in its secretion during the night starting before the onset of

sleep. The secretary profile of the repetitive hormones testosterone and luteinizing hormone are independent of

the sleepwake cycle. Now altered gastro function during sleep is attributed to varied autonomic nervous system

responses. Salivary secretion and the phenomenon of deglutration are particularly reduced during sleep. The

resting pressure of the upper esophagal sphincta and the frequency of peristaltic contractions in the body of

the esophagus and the lower sphincta seem to diminish during sleep. The duration of the migrating motor

complexes appear to be longer and the speed of propagation slower in NRM than RM sleep. Reduce motor mechanical and

electromyographic activity at the colonic level has also been reported. These changes are extremely important to

maintain continents during sleep and also facilitate the process of digestion. With regards to the sexual

function during sleep, RM sleep is associated with penal erection in males belonging to the physiological age

limit. Puberty and old age are two periods in life where nocturnal erections occur as frequently in NRM

sleep too. This is spinal erection during sleep is attributed to vascular, muscular and hormonal mechanisms. With

regards to thermal regulation during sleep, internal temperature evolves according to a circadian rhythm with

about minimum occurring at 3 to 4:00 a.m. and a maximum occurring at 6 p.m. An altradian temperature modulation has

also been reported in relation to the sleep sleepwake cycle with a reduction in temperature during nm sleep. During

sleep the body temperature changes in function to the surrounding environment and a sleeping man represents a

efficient thermmore regulator. The maintenance of internal temperature is subject subject to regulatory mechanisms

which come into place when the thermonutral zone is exceeded. The thermutral zone is characterized by a

zero balance of exchanges between the body and its surrounding. It differs in wakefulness and sleep. At wakefulness

it's 28° C and at sleep it's about 30 to 32° C. In the naked man it also different differs according to the sleep

stage. The hypothalamus and especially the preoptic region are structures which play a role in thermmorreulation. Each

sleep state has its own zone of thermutrality. The most effective vaso regulation occurs during deep nm sleep.

Cereal metabolism during sleep was studied using the PET scan, the spect and the MRA. During NRM sleep, PET

studies showed a net direction in cereal activity in the talamic nuclei, the brain stem, the basal ganglia, the

hypothalamus, the basal forbrain, the orbital frontal and the anterior single cortical regions, the precunius as well

as the right medial temporal regions. In RM sleep, high activation in the brain stem particularly in the tegmentum

pawns, the talamic and the lyic systems namely the amydala, the hippocampus and the single cortex. Intense activity in

the lyic system was also found during NRM sleep. So in summary, NRM sleep has a decrease in cerebal metabolism while

RM sleep there's a increase in cerebral metabolism. Now let us take a look at the functions of sleep. In the previous

eras the functions of sleep was not very well understood. It is in the 21st century that with the advent of lot of

radio diagnosis a lot of new functions of sleep are being discovered. So this tableau column gives you a summary of

the functions of sleep. The table column on the upper part of the screen differentiates the functions between RM

sleep and NRM sleep. And the tableau column below talks about the functions which are common to both types of sleep.

So here you can see in RM sleep there is strengthening of emotional and procedural memory which takes place and

in NRM sleep you can see there is restoration and energy conversation with the lowering of the BMR, body

temperature and energy conversation, consolidation of declarative memory and cardiovascular health is also maintained

in NRM sleep with the lowering of heart rate and blood pressure. In both types of sleep as far as the homeostasis

within the nervous system and toxin clearance is concerned there is something called the glymphatic system

which is mediated by the neurogly cells of the brain and they get rid of metabolic waste products and prevent

neuro degeneration during sleep. There's also pro promotion of new connections between neurons a phenomenon known as

synaptic plasticity. Sleep is associated with hormone regulation also contributing to endocrine homeostasis.

As we saw previously, immune surveillance and cytoine production is also stepped up during sleep

contributing to immunity within the body. And as we conclude this session, I'd like to give you an overview of

polyomnography, which is the conclusive diagnostic intervention of sleep either physiologically or pathologically. And

an assessment of sleep is carried out using this technique. And during this technique, the electroenphilogram, the

electromyogram and the electrogram are recorded. So here you can see a diagrammatic representation of a

polyomography going on and uh here you can see the electrogram and the electromyiogram and the

electroenapiloggram are recorded. In addition you have the recording of the respiratory reserve which is going on on

this side. Now I'll talk to you about the consequences of sleep deprivation which has been evidenced by research.

This has begun from the year 1988 till date and they have found out these functional indices have been impaired

during sleep. So there's an increase in reaction time preservation and reduced flexibility, impaired sense of humor,

increased risk takingaking, impaired moral judgment, reduced emotional intelligence, redu increased negativity

with enhanced memory of adverse events and increased distractability. I'm sure we would have gone through some of these

uh indices when we were deprived of sleep. And as I've given you an overview on the basic principles of sleep

physiology, I'm sure my colleagues will empower you to a higher level in the subsequent sessions. And I would like to

thank the flag bearsers of Niptel for continuing to give us opportunity to share our knowledge one and all on this

forum. The flag bearsers of our institute Chetnner Hospital and Research Institute for always motivating us to

excel in our endeavors of teaching and research. to all my teachers and students around the world for empowering

me with the wisdom of physiology and medicine. And last but not the least, I'd like to thank one and all on this

forum, the participants of this forum for participating in this learning exercise. Thanks to one and all.