physiology and neuroanatomy of sleep by ahmad younes professor of thoracic medicine mansoura faculty...

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  • Physiology and Neuroanatomy of sleep BY AHMAD YOUNES PROFESSOR OF THORACIC MEDICINEMansoura Faculty of Medicine

  • Behavioral Definition:Wakefulness: is a state in which the person is aware of and responds to sensory input from the environment.Sleep: is a state of behavioral quiescence accompanied by an elevated arousal threshold and a species-specific sleep posture (recumbent sleep posture, closed eyes, diminished responsiveness to external stimuli and decrease in or absence of movements) 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 functionMemory consolidation Energy conservation Body growth Regulation of immune function Protective behavioral adaptation

  • Sleep architectureSleep architecture is a term used to describe the division of sleep among the different sleep stages using specific EEG, EOG, and chin EMG criteria. It also involves the relationship of the individual sleep stages to each other .Sleep can be differentiated into NREM sleep and REM sleep. NREM sleep can be further subdivided into stages 1, 2, 3, and 4 sleep. NREM stages 3 and 4 sleep are often collectively referred to as slow wave or delta wave sleep.

  • Sleep Architecture 1 2 3 4 5 6 7 8 W123+4REM 75% SWS75% REM(SWS)

  • General informationNREM and REM occur in alternating cycles, each lasting approximately 90-100 minutes, with a total of 4-5 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 6-8 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 informationPregnancy: 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 .

  • Regulation of Sleep and Wakefulness:Two basic intrinsic components 1-Circadian rhythm (process C) 2-Sleep homeostasis (process S), Sleep homeostasis is characterized by an increase in sleep pressure following sleep deprivation that is related to the duration of prior wakefulness followed by a decline in sleep need as sleep accumulates. Circadian process There are two circadian peaks in wakefulness : one occurring (early evening) and a second peak (late morning). Sleep propensity is least during these peaks of circadian rhythms of arousal Greatest sleep propensity during periods of (overnight between 3:00 and 5:00 am; early-mid afternoon between 3:00 and 5:00 pm). 3-Sleep inertia (process W), refers to the short-lived reduction of alertness that occurs immediately following awakening from sleep and disappears within 2 to 4 hours.

  • Brain Mechanisms Controlling SleepSleep is promoted by a complex set of neural and chemical mechanismsDaily rhythm of sleep and arousalSupra-chiasmatic nucleus of the hypothalamus (body clock)pineal glands secretion of melatoninLight is called a Zeitgeber, a German word meaning time-giver because it set the supra-chiasmatic clockAltering light/dark cycles produces phase shift and entrainment

  • Evidence for the SCN as biological clockCircadian = diurnal + nocturnalZeitgebers and the SCN: Biological clockAltering light/dark cycles produces phase shift and entrainmentSCN lesions disrupt circadian rhythmsTransplanted SCNs set rhythms of donor animal

  • 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 sleepLight suppresses melatonin secretion.Bright light very early in the morning can cause a phase advanceBright lighting can reduce fatigue for workers forced to work at night

  • Neuroanatomy of WakefulnessThe 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.RF has two major ascending projections into the forebrain:1. Dorsal pathway thalamus cerebral cortex (thalamocortical system)2. Ventral pathway subthalamus and posterior hypothalamus basal forebrain and septum cerebral cortex The ascending reticular activating system also receives input from visceral,somatic, and special sensory systems.The descending RAS connects to the cerebellum and to nerves responsible for the various senses.Neurotransmitters Acetylcholine , Dopamine ,Glutamate ,Histamine ,Hypocretin (orexin) ,Norepinephrine, Serotonin

  • Most wake circuits originate in the Brain stem arousal nuclei (BAN), which stimulate the thalamus, hypothalamus (Hyp) and basal forebrain. These projections also inhibit sleep centers

  • Neuroanatomy of NREM sleep NREM sleep Forebrain (anterior hypothalamus-preoptic region, including ventrolateral preoptic area [VLPO] and basal forebrain)Neurotransmitters serotonin and gammaaminobutyric acid (GABA). Other neurotransmitters include adenosine, norepinephrine,

  • The ventrolateral preoptic nucleus (VLPO) in the hypothalamus inhibits the BAN and the parts of the hypothalamus involved in wakefulness. This leads to inhibition of other wake-centers including the thalamus, basal forebrain, and the cortex, and thus the initiation and maintenance of sleep.

  • Neuroanatomy of REM sleepREM sleep Pons (pedunculopontine tegmental nuclei and the laterodorsal tegmental nuclei) Brainstem reticular formation, especially oral pontine reticular formation ,Other brainstem (lower medullary) and spinal cord neuronsNeurotransmitters: The main REM sleep neurotransmitter is acetylcholine. Other neurotransmitters include GABA and glycine.

  • The SCN is the circadian pacemaker and is influenced by light, activity, and melatonin to promote either wake or sleep. Signals from the SCN are amplified by the SPZ and the DMN, which project to the VLPO (promotes sleep), the lateral hypothalamus (promotes wakefulness), and the PVN (controls pineal melatonin release).

  • The PVN is stimulated by the SCN, in a circadian fashion, to produce corticotrophin-releasing factor (CRF). This acts on the pituitary gland (Pit), which in turn produces adrenocorticotrophic hormone (ACTH). ACTH is then released into the bloodstream where it initiates the release of cortisol from the adrenal glands. Cortisol is one of the factors involved in the sleep/wake cycle through a feedback system whereby it can then influence activity in the hypothalamus. Thus the HPA axis is important to regulation of sleep and arousal.

  • Summary Circadian arousal is largely influenced by ocular exposure to light; thus it rises in the morning, declines with a gradual slope throughout the day, and then declines further beginning in the late evening. Body temperature is also at its lowest in the early morning, rising throughout the morning and then staying fairly steady until it begins to decline again in the late evening. Combined with this, a morning pulse of cortisol, which binds to circadian hypothalamic receptors, stimulates arousal from sleep with levels declining throughout the day.In addition, certain brain chemicals (e.g., adenosine, a byproduct of energy metabolism), accumulate during waking time and decline during sleep. The varying levels of these chemicals affect ones wake propensity, with wake propensity declining as they accumulate and then increasing as the sleep debt is paid.

  • Hyperarousal is considered an underlying cause of insomnia and may be related to dysfunction of the HPA axis. With hypoarousal, there is thought to be reduced basal ACTH secretion and a reduction of central CRF. Extreme hypoarousal underlies excessive sleepiness present in numerous sleep/wake disorders.

  • 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 physiologyMinute 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
  • Respiratory physiologyHypoxic ventillatory response and hyper-capnic ventillatory re


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