Physiology of Sleep

Overview

Sleep

Sleep is a reversible phase of diminished responsiveness, motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology activity, and metabolism. The purpose of sleep is poorly understood; however, there are multiple theories:

• Survival theory:
  • Humans are diurnal by nature (creatures of the day). 
  • Awake during the day because there is better vision Vision Ophthalmic Exam and fewer predators
• Restorative theory:
  • Sleep allows the body to heal and repair tissue, including brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification reorganization, consolidation Consolidation Pulmonary Function Tests, and storage of memories. 
  • Sleep also functions as stress relief. 
• Growth theory
  • During sleep, the pituitary Pituitary A small, unpaired gland situated in the sella turcica. It is connected to the hypothalamus by a short stalk which is called the infundibulum. Hormones: Overview and Types gland releases growth hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types.

Physiology

• Characteristics of sleep in healthy persons include:
  • Closed eyes
  • Reduced brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification responsiveness to stimuli
  • Differences in heart rate Heart rate The number of times the heart ventricles contract per unit of time, usually per minute. Cardiac Physiology, BP, and respiration Respiration The act of breathing with the lungs, consisting of inhalation, or the taking into the lungs of the ambient air, and of exhalation, or the expelling of the modified air which contains more carbon dioxide than the air taken in. Nose Anatomy (External & Internal) depending on the stage of sleep
• Circadian rhythm Circadian Rhythm The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs or environmental and physiological stimuli. Cranial Nerve Palsies: physiologic changes (including physical, mental, and behavioral) that follow a 24-hour cycle, primarily responding to light and dark
• Suprachiasmatic nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles (SCN, the body’s master clock):
  • Found in the hypothalamus Hypothalamus The hypothalamus is a collection of various nuclei within the diencephalon in the center of the brain. The hypothalamus plays a vital role in endocrine regulation as the primary regulator of the pituitary gland, and it is the major point of integration between the central nervous and endocrine systems. Hypothalamus
  • Responsible for controlling circadian rhythms and the sleep cycle
  • Regulated by the environment, receiving input from the eyes (light)
  • Decrease in light → stimulation of SCN → release of norepinephrine Norepinephrine Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus. Receptors and Neurotransmitters of the CNS → stimulation of pineal gland Pineal gland A light-sensitive neuroendocrine organ attached to the roof of the third ventricle of the brain. The pineal gland secretes melatonin, other biogenic amines and neuropeptides. Hormones: Overview and Types → release of melatonin → sleep 
  • The influence of circadian rhythm Circadian Rhythm The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs or environmental and physiological stimuli. Cranial Nerve Palsies is also seen in hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types (with predominant nocturnal secretion Secretion Coagulation Studies) such as:
    •   Prolactin Prolactin A lactogenic hormone secreted by the adenohypophysis. It is a polypeptide of approximately 23 kd. Besides its major action on lactation, in some species prolactin exerts effects on reproduction, maternal behavior, fat metabolism, immunomodulation and osmoregulation. Breasts: Anatomy
    • Testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens
    • Growth hormone

Stages of Sleep

• Typically 4–5 cycles in an 8-hour period (1 sleep cycle: 90–120 minutes)
• Divided into non–rapid eye movement (NREM) and REM sleep stages
• The amount of sleep as well as duration of each stage of sleep change as humans age.

Non–rapid eye movement (NREM) sleep

• Further divided into:
  • Stage N1 (5%–10% of total sleep cycle)
  • Stage N2 (45%–55% of total sleep cycle)
  • Stage N3 (10%–20% of total sleep cycle)
• Physiologic changes:
  • ↑ Parasympathetic tone
  • Low BP, slow heart rate Heart rate The number of times the heart ventricles contract per unit of time, usually per minute. Cardiac Physiology, ↓ respiratory rate Respiratory rate The number of times an organism breathes with the lungs (respiration) per unit time, usually per minute. Pulmonary Examination
  • Less vivid dreams
  • Muscle tone Muscle tone The state of activity or tension of a muscle beyond that related to its physical properties, that is, its active resistance to stretch. In skeletal muscle, tonus is dependent upon efferent innervation. Skeletal Muscle Contraction similar to wakefulness

REM sleep

• Stage R sleep
• Usually begins 90 minutes after onset of sleep and averages 4–5 episodes/night
• Duration increases throughout the night, with increased percentage during the latter half of the night.
• Constitutes 20%–25% of the total sleep duration
• Believed to have a role in memory Memory Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. Psychiatric Assessment consolidation Consolidation Pulmonary Function Tests
• Physiologic changes:
  • Surges of sympathetic and parasympathetic activity
  • Rapid irregular eye movement occurs because of activity of paramedian pontine reticular formation Paramedian Pontine Reticular Formation Internuclear Ophthalmoplegia ( PPRF PPRF Internuclear Ophthalmoplegia), which is the conjugate gaze center.
  • Transient increase in BP and respiration Respiration The act of breathing with the lungs, consisting of inhalation, or the taking into the lungs of the ambient air, and of exhalation, or the expelling of the modified air which contains more carbon dioxide than the air taken in. Nose Anatomy (External & Internal)
  • Variability in heart rate Heart rate The number of times the heart ventricles contract per unit of time, usually per minute. Cardiac Physiology 
  • Penile/clitoral erection Erection The state of the penis when the erectile tissue becomes filled or swollen (tumid) with blood and causes the penis to become rigid and elevated. It is a complex process involving central nervous system; peripheral nervous systems; hormones; smooth muscles; and vascular functions. Penis: Anatomy (due to increased blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure)
  • Vivid dreams
  • Absent muscle tone Muscle tone The state of activity or tension of a muscle beyond that related to its physical properties, that is, its active resistance to stretch. In skeletal muscle, tonus is dependent upon efferent innervation. Skeletal Muscle Contraction

Study of Sleep

Polysomnography

• Also known as a sleep study, a multimodal test evaluating processes in sleep:
  • EEG EEG Seizures: measures brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification electrical activity
  • Electro-oculography (EOG): measures eye movements
  • Electromyography Electromyography Recording of the changes in electric potential of muscle by means of surface or needle electrodes. Becker Muscular Dystrophy (EMG): measures muscle movements 
• Important parameters:
  • Sleep latency: period of time to transition from “lights out,” or initiation of sleep, to onset of sleep 
  • REM latency: period of time from initiation of sleep to reaching 1st REM stage
  • Total sleep time: amount of sleep time during the recording time
  • Sleep efficiency: percentage of total sleep time over total time in bed 
  • Wake after sleep onset: period of wakefulness after onset of sleep
  • Wake after sleep offset: period of wakefulness after sleep offset (i.e., long wakeful time after an atypical early morning awakening may be a sign of depression)
  • Apnea index: measures apneic episodes ≥ 10 seconds per 1 hour of sleep
  • Nocturnal myoclonus Myoclonus Involuntary shock-like contractions, irregular in rhythm and amplitude, followed by relaxation, of a muscle or a group of muscles. This condition may be a feature of some central nervous system diseases; (e.g., epilepsy-myoclonic). Nocturnal myoclonus is the principal feature of the nocturnal myoclonus syndrome. Neurological Examination index: measures number of periodic leg Leg The lower leg, or just “leg” in anatomical terms, is the part of the lower limb between the knee and the ankle joint. The bony structure is composed of the tibia and fibula bones, and the muscles of the leg are grouped into the anterior, lateral, and posterior compartments by extensions of fascia. Leg: Anatomy movements per hour

Awake and sleep stages

Generally, an adult is awake for ⅔ of the day. The body relaxes before going through different stages of sleep.

Mnemonic

The following mnemonic summarizes the sleep waves in the different stages of sleep:
“At night, BATS Drink Blood”

• B: beta (awake, eyes open)
• A: alpha (awake, eyes closed)
• T: theta (stages N1 and N2)
• S: sleep spindles (stage N2)
• D: delta (stage N3)
• B: beta (REM)

Sleep and Associated Disorders

Sleep-associated disorders

NREM sleep:

• Related disorders:
  • Sleepwalking Sleepwalking A parasomnia characterized by a partial arousal that occurs during stage IV of non-rem sleep. Affected individuals exhibit semipurposeful behaviors such as ambulation and are difficult to fully awaken. Children are primarily affected, with a peak age range of 4-6 years. Parasomnias
  • Night terrors
  • Confusional arousals Confusional arousals Parasomnias
  • Sleep-related eating disorder Sleep-related eating disorder Parasomnias (sleep eating)
• Bedwetting ( enuresis Enuresis Involuntary discharge of urine after expected age of completed development of urinary control. This can happen during the daytime (diurnal enuresis) while one is awake or during sleep (nocturnal enuresis). Enuresis can be in children or in adults (as persistent primary enuresis and secondary adult-onset enuresis). Elimination Disorders) 

REM sleep:

• Related disorders:
  • Narcolepsy Narcolepsy Narcolepsy is a neurological sleep disorder marked by daytime sleepiness and associated with cataplexy, hypnagogic hallucinations, and sleep paralysis. There are 2 types of narcolepsy: type 1 is associated with cataplexy and type 2 has no association with cataplexy. Narcolepsy
  • Nightmares
  • REM sleep behavior disorder
• Bedwetting ( enuresis Enuresis Involuntary discharge of urine after expected age of completed development of urinary control. This can happen during the daytime (diurnal enuresis) while one is awake or during sleep (nocturnal enuresis). Enuresis can be in children or in adults (as persistent primary enuresis and secondary adult-onset enuresis). Elimination Disorders)

Conditions associated with sleep problems

• Depression:
  • Increased REM sleep
  • Decreased REM sleep latency
  • Decreased N3
  • Repeated nighttime awakenings
  • Early morning awakening (terminal insomnia Insomnia Insomnia is a sleep disorder characterized by difficulty in the initiation, maintenance, and consolidation of sleep, leading to impairment of function. Patients may exhibit symptoms such as difficulty falling asleep, disrupted sleep, trouble going back to sleep, early awakenings, and feeling tired upon waking. Insomnia)
• Pulmonary disease Pulmonary disease Diseases involving the respiratory system. Blastomyces/Blastomycosis and obstructive sleep apnea Sleep apnea Repeated cessation of breathing for > 10 seconds during sleep and results in sleep interruption, fatigue, and daytime sleepiness. Obstructive Sleep Apnea ( OSA OSA Obstructive sleep apnea (OSA) is a disorder characterized by recurrent obstruction of the upper airway during sleep, causing hypoxia and fragmented sleep. Obstructive sleep apnea is due to a partial or complete collapse of the upper airway and is associated with snoring, restlessness, sleep interruption, and daytime somnolence. Obstructive Sleep Apnea):
  • Reduced N3 in OSA OSA Obstructive sleep apnea (OSA) is a disorder characterized by recurrent obstruction of the upper airway during sleep, causing hypoxia and fragmented sleep. Obstructive sleep apnea is due to a partial or complete collapse of the upper airway and is associated with snoring, restlessness, sleep interruption, and daytime somnolence. Obstructive Sleep Apnea
  • REM (with atonia Atonia Flaccidity, no resistance to passive motion Neurological Examination) affects those dependent on intercostal and accessory respiratory muscles for ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing → hypoventilation and desaturation

Substances and associated sleep changes

Clinical Relevance

• Circadian rhythm Circadian Rhythm The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs or environmental and physiological stimuli. Cranial Nerve Palsies sleep–wake disorder: recurrent patterns of sleep disruption due to abnormalities of the circadian system or when the sleep–wake cycle is misaligned with the environment. Subtypes include delayed sleep-phase disorder, advanced sleep-phase disorder, shift-work disorder Shift-work disorder Circadian Rhythm Sleep–Wake Disorder, and jet-lag disorder Jet-lag disorder A chronobiologic disorder resulting from rapid travel across a number of time zones, characterized by insomnia or hypersomnolence, fatigue, behavioral symptoms, headaches, and gastrointestinal disturbances. Circadian Rhythm Sleep–Wake Disorder.
• Parasomnias Parasomnias Parasomnias are a pattern of sleep disorders marked by unusual actions, activities, or physiological events that occur during sleep or sleep-wake transitions. Parasomnias are divided into which sleep phase the symptoms occur, either rapid eye movement (REM) or non-REM (NREM). Parasomnias: pattern of sleep disorder marked by unusual behavior, movements, or experiences that occur during sleep or sleep–wake transitions. Symptoms may include abnormal movements, emotions, dreams, and autonomic activity.
• Restless legs Restless legs A disorder characterized by aching or burning sensations in the lower and rarely the upper extremities that occur prior to sleep or may awaken the patient from sleep. Polyneuropathy syndrome (Willis-Ekbom disease): sleep-related movement disorder that is marked by an overwhelming urge to move the legs accompanied by an unpleasant sensation that is relieved with movement. Symptoms occur during the evening and are associated with sleep disturbance. 
• Narcolepsy Narcolepsy Narcolepsy is a neurological sleep disorder marked by daytime sleepiness and associated with cataplexy, hypnagogic hallucinations, and sleep paralysis. There are 2 types of narcolepsy: type 1 is associated with cataplexy and type 2 has no association with cataplexy. Narcolepsy: sleep disorder characterized by excessive daytime sleepiness Daytime sleepiness Narcolepsy and falling asleep at inappropriate times. Narcolepsy Narcolepsy Narcolepsy is a neurological sleep disorder marked by daytime sleepiness and associated with cataplexy, hypnagogic hallucinations, and sleep paralysis. There are 2 types of narcolepsy: type 1 is associated with cataplexy and type 2 has no association with cataplexy. Narcolepsy is associated with hypnagogic hallucinations Hypnagogic hallucinations Narcolepsy (vivid tactile/auditory or visual hallucinations Hallucinations Subjectively experienced sensations in the absence of an appropriate stimulus, but which are regarded by the individual as real. They may be of organic origin or associated with mental disorders. Schizophrenia), cataplexy Cataplexy A condition characterized by transient weakness or paralysis of somatic musculature triggered by an emotional stimulus or physical exertion. Cataplexy is frequently associated with narcolepsy. During a cataplectic attack, there is a marked reduction in muscle tone similar to the normal physiologic hypotonia that accompanies rapid eye movement sleep (sleep, rem). Narcolepsy (emotionally triggered loss of muscle tone Muscle tone The state of activity or tension of a muscle beyond that related to its physical properties, that is, its active resistance to stretch. In skeletal muscle, tonus is dependent upon efferent innervation. Skeletal Muscle Contraction, during laughing, for example), and sleep paralysis Sleep paralysis A common condition characterized by transient partial or total paralysis of skeletal muscles and areflexia that occurs upon awakening from sleep or less often while falling asleep. Stimuli such as touch or sound may terminate the episode, which usually has a duration of seconds to minutes. This condition may occur in normal subjects or be associated with narcolepsy; cataplexy; and hypnagogic hallucinations. The pathophysiology of this condition is closely related to the normal hypotonia that occur during rem sleep. Narcolepsy (inability to move after awakening).
• Insomnia Insomnia Insomnia is a sleep disorder characterized by difficulty in the initiation, maintenance, and consolidation of sleep, leading to impairment of function. Patients may exhibit symptoms such as difficulty falling asleep, disrupted sleep, trouble going back to sleep, early awakenings, and feeling tired upon waking. Insomnia: disorder of sleep difficulty (problems with initiation and/or maintenance of sleep) marked by symptoms that interfere with duration and/or quality Quality Activities and programs intended to assure or improve the quality of care in either a defined medical setting or a program. The concept includes the assessment or evaluation of the quality of care; identification of problems or shortcomings in the delivery of care; designing activities to overcome these deficiencies; and follow-up monitoring to ensure effectiveness of corrective steps. Quality Measurement and Improvement of sleep despite adequate opportunity for sleep.
• Obstructive sleep apnea Sleep apnea Repeated cessation of breathing for > 10 seconds during sleep and results in sleep interruption, fatigue, and daytime sleepiness. Obstructive Sleep Apnea: episodic apnea, or cessation of breathing during sleep, in which the period of apnea lasts for ≥ 10 seconds. Obstructive sleep apnea Sleep apnea Repeated cessation of breathing for > 10 seconds during sleep and results in sleep interruption, fatigue, and daytime sleepiness. Obstructive Sleep Apnea is usually due to a partial or complete collapse of the upper airway Airway ABCDE Assessment and is associated with snoring, restlessness, daytime headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess, and somnolence.