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 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 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 hours. The newborn sleeps approximately 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 ) 2 nd trimester (normal sleep ) 3 rd 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 supra- chiasmatic 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)delta waves spindle wave oscillations

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. thalamushypothalamus The descending RAS connects to the cerebellum and to nerves responsible for the various senses.cerebellum 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 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 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 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 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 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

33 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

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 Stage 3 sleep (~15-20 minutes) –Beginning of slow-wave sleep –Combination of theta and delta activity 20-50% Delta waves Stage 4 sleep (~45 minutes) –> 50% delta waves Stages 1-4 are non-REM sleep

Sleep Architecture W REM 75% SWS75% REM (SWS)

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 well- being

Interventions - caffeine ‘ World’s most popular drug’ Mild CNS stimulant 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 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