Sleep Physiology / Disorders (4) Flashcards
How does decreasing ambient light cause melanin to be secreted? (Path and which portion of ANS is involved?)
Decreasing light causes retinal ganglion cells (contain melanopsin) to fire and send signal to the Suprachiasmic Nucleus, which in turn activates the Paraventricular Nucleus–> activates neurons in the intermediolateral gray zone of upper spinal cord to modulate neurons in the superior cervical ganglia–> activation of sympathetic neurons traveling to pineal gland–> increased synthesis and release of melanin
What is the normal amount of sleep for average adult?
7.5 +/- 2 hours
Normal sleep decreases with age
Which nucleus is thought of as the “master clock”? Where is it located?
Suprachiasmatic Nucleus in the anterior area of hypothalamus–> controls behavioral and physiological circadian rhythms, including the wake-sleep cycle, hormonal secretion, and thermoregulation
What time of day does melatonin secretion peak?
2:00-4:00 AM (begins rising in early evening as daylight decreases)
What two hormones other than melatonin are also involved in rhythmic cycling related to the day/night and/or sleep/wake cycles?
Growth hormone and cortisol
What four things are monitored during polysomnography?
- EEG (brain waves)
- Eye movement
- Respiration
- Oxygen tension (plethysmography sensor)
What are the different frequencies and waveforms detected in EEG useful for?
They can be used to diagnose certain neuro conditionsa nodal so used to identify the various stages of sleep
What two wave frequencies are typically seen in the normal awake human? What frequency range does each have?
- Beta (over 13 Hz)
2. Alpha (8-13 Hz)
What usually happens to the amplitude of wave forms as the frequency decreases?
Amplitude increases as frequency decreases
Which stage of sleep corresponds to REM sleep?
Stage V
What generally happens to EEG frequency as sleep moves from stage I to stage IV?
The frequency decreases (so amplitude increases)
Which stage of sleep is the lightest?
Stage I
Which stage of sleep is characterized by sleep spindles and K complexes?
Stage II
Which stage of sleep is most similar to awakefulness, according to EEG?
REM sleep
What kind of waves generally are seen in stage I sleep?
Theta waves
What characterizes Stage II sleep?
Theta waves; are also spindle complexes and K-complex patterns
What type of waves characterize Stage II and IV of sleep?
Delta waves
What two types of waves are seen during REM sleep?
Theta and Beta waves
How many ~ 90 minute cycles of alternating NREM and REm sleep are there per night of sleep?
5 to 6
Which portion of sleep is get progressively longer with each cycle sat he night progresses?
REM sleep cycle
What type of sleep is associated with vivid, bizarre dreams?
REM sleep
Why can’t people usually move during REM sleep?
Usually have a muscle paralysis, if they don’t, there USA. Problem
When do sleep walking and night terrors occur?
During slow wave (non-REM) sleep
During which type of sleep is there a decrease in overall body metabolism with slower HR, RR, body temp, and BP?
Non-REM sleep
What is a feature of REM sleep that can differentiates a physiological from a psychological problem?
BONERS!!!!!!!!!
Activity in what three areas of brain may be responsible for the highly emotional content in REM dreams?
- Amygdala
- Parahippocampal gyrus
- Anterior cingulate cortex
Inhibition of what two structures may add to the bizarre nature of dreams in REM sleep?
- Frontal cortex
2. Posterior cingulate cortex
______ neurons in the pedunculopontine (PPT) and lateral dorsal tegmental (LDT) tigger the thalamocortical signaling that produces what kind of waves on EEG?
Cholinergic; Beta waves–> consistent with arousal and alertness
- these are inhibited during NREM sleep, which helps facilitate slow wave sleep
Where in the brain are the PPT and LDT located?
Nucleus basalis–> is down just inferior to the genu of corpus callous, in the cortex
Project widely tot eh forebrain and are activated during wakefulness and REM sleep
What type of NT is the output of the locus ceruleus? Where does it travel to? Where located?
LE sends out NE from the lateral tegmental area in the superior Pons to the neocortex
When is the locus ceruleus active?
During wakefulness
*but unlike cholinergic input (PPT and LDT) is nearly completely in REM sleep (some activity NREM sleep)
What three circuits send out dopaminergic input to cortex?
- Mesostriatal (from SN to the striatum)
- Mesolimbic (to cingulate cortex, amygdala, hippocampus–> limbic structures)
- Mesocortical (to prefrontal cortex)
What are dopaminergic inputs to the cortex important for?
Full wakefulness
What type of input is sent from the dorsal and medial raphe nuclei to the cortex?
Serotonin
What kind of output comes out of the tuberomammillary nucleus to the cortex?
Histaminergic
When are histaminergic neurons active?
During wakefulness
- less so in NREM sleep and lower still in REM sleep; blocking these receptors increases both NREM and REM sleep
What five nuclei are found in the hypothalamus involved in sleep/wake cycles?
- Suprachiasmatic nuclei
- Paraventricular nuclei
- Tuberomammillary nuclei
- Lateral hypothalamic area
- Ventrolateral preoptic nucleus (VLPO)
What two substances are involved in signaling from the lateral hypothalamic nuclei?
Orexin and hypocretin
What type of neurons are found in the VLPO? What dot hey generally serve to do?
Has GABAergic neurons (and galanin neurons)—> inhibit all nuclei involved in wakefulness (PPT, LDT, locus ceruleus, SN, raphe nuclei, tuberomammillary nucleus, and lateral hypothalamic area)
*reciprical innervation to these nuclei; have feedback inhibition and allow for rapid change from sleep to wake state
What do lesion so f the VLPO lead to?
Insomnia
What is a somnogen? 3 examples?
Endogenous sleep-promoting chemicals that may accumulate during wakefulness and promote sleep onset
*adenosine, cytokines, melatonin
What two cytokines are thought to promote sleep?
- IL-1B
2. TNF
When are serotoninergic circuits active?
During wakefulness
- less active during NREM sleep and almost totally silent during REM sleep; is the basis for using TCAs and SSRIs in sleep disorders
In what two nuclei are REM-ON cells located that are responsible for the awake-like EEG patterns during REM sleep?
- Pedunculopontine nucleus (PPT)
- Laterodorsal Tegmental nucleus (LDT)
*removal of GABAergic inhibition of these neurons increases as sleep goes from I-IV, resulting in increasing cholinergic (Ach) transmission until REM–> Ach activates the thalamus and other higher cortical areas, resulting in the EEG patterns resembling the awake state
What is responsible for the atonic or paralyzed state seen in REM sleep?
REM-On cells activate glycine-releasing neurons in the medullary brainstem that inhibit anterior horn cells in the spinal cord–> atonic state
*these neurons activated to release glycine by glutaminergic REM-On cells
Where are REM-Off cells located (what nucleus)? How do they work to counteract activation of REM-On neurons?
Locus ceruleus–> set of NE neurons that, when activated, cause inhibition of REM-on cells to terminate REM sleep
*thus the two REM-On nuclei (located in PPT and LDT nuclei) and the REM-Off nuclei in/near the locus ceruleus work in a switch-like fashion to initiate or terminate REM sleep
During wakefulness, two _______ nuclei and 4 ______ nuclei are active and responsible for maintaining the aroused state.
Two hypothalamic nuclei and 4 brainstem nuclei
What does a Multiple Sleep Latency test measure?
the EEG-defined sleep latency, or the time it takes to fall asleep (confirmed by EEG) measured during 4-5 daytime naps
What is scale called that is the self-reported tendency to fall asleep in 8 different situations?
Epworth sleepiness scale
What is Obstructive Sleep Apnea?
repetitive blockage of the respiratory pathway during sleep causing apneic periods
How long must apneic periods in OSA last? By what percent does oxyhemoglobin desaturate?
at least 10 seconds; O2 sats drop by at least 4%
In what sex in OSA more common in? What condition icncreases incidence?
More common in men; obesity causes a higher incidence
There is a strong association between obstructive sleep apnea, ________ ________, and ___________.
Heart disease and Hypertension
What causes sleep apnea?
Complex pathological interactions of pharyngeal muscles, tongue, and soft tissues——> airway obstruction
__% of men and __% of women have obstructive sleep apnea (aged 30-60)
4%; 2%
What are some symptoms of sleep apnea?
- excessive daytime fatigue
- snoring
- heartburn
- memory loss
- irritability/ depression
- Morning headache
- SOB
- Nocturia
- impotence
What are some signs of OSA?
- Nasal obstruction
- Macroglossia
- Tonsillar/ Adenoid hypertrophy
- Reflux laryngitis
- Shirt collar size over 17 inches
- HTN
- CHF
- Pitting edema of lower ext
- Enlargement of hands and feet (acromegaly)
Narcolepsy is defined as excessive daytime sleepiness with one or more of what 4 symptoms?
- Sleep attack/ intrusion–> irresistible daytime sleep onset
- Cataplexy–> abrupt loss of muscle tone during waking hours
- Sleep paralysis–> persistent REM after wakening
- Hypnogogic hallucinations–> dreams persist after awakening
When do 90% of people usually have onset of narcolepsy (ages)?
Usually by 2nd-3rd decade of lfe
Secondary Narcolepsy can be seen with what 4 conditions?
- Multiple Sclerosis
- Pituitary tumors
- Vascular malformations
- Stroke
Does narcolepsy have a familial tendency?
Yes–> 1st degree relatives have a 1-2% increased risk
What two symptoms do over 90% of narcolepsy patients have?
- Excessive daytime sleepiness
- fragmented nocturnal sleep
- ~80% have cataplexy, hypnogogic hallucinations, and/or sleep paralysis, so the excessive daytime sleepiness and other tetrad of symptoms pretty common
Narcolepsy is due to loss of neurons in what area of brain?
loss of hypocretin/ orexin secreting neurons in the lateral posterior hypothalamus
What two HLA genes may predispose to automimmune attack on neurons involved in narcolepsy?
DQ1 or DQB1*0602
What lab test ca be useful in confirming narcolepsy in addition to clinical symptoms and polysomnography?
CSF fluid will be low in hypocretin-1 in 90% (10% have normal level, so not entirely specific)
How long is sleep latency in Mean Sleep Latency Test for narcoleptics?
Less than or equal to 8 mins (remember this test is done during the day, so indicates definite excessive daytime sleepiness)
What two drug classes can be used to treat the cataplexy in narcolepsy?
tricyclic antidepressants or SSRIs
What is insomnia?
Difficulty falling asleep or remaining asleep
What is the difference between transient insomnia and chronic insomnia?
Chronic—> insomnia lasting over 6 weeks; anything less than 6 is classified as transient
- Transient affects up to 50% of adults and Chronic up to 25%, so insomnia is very common
What are some causes for the failure to maintain sleep seen in insomnia?
- OSA
- Aging
- Depression
- REM sleep disorder
- CNS degenerations
- Medication side effects
What is loss of atonia/paralysis during REM sleep, leading to physical acting out of dream states, including verbalization, punching, kicking, jumping from bed?
REM Sleep Behavior Disorder
What is the cause of Primary REM Sleep disorder?
idiopathic or associated with the alpha-synucleinopathies (Parkinson’s, Lewy Body Dementia, Multisystems Atrophy, Progressive Supranuclear Palsy)
What three conditions may cause a secondary REM Sleep Behavior disorder?
- EtOH withdrawal
- TCA use
- SSRI use
Treatment for REM Sleep Behavior disorder?
Clonazepam
In what age and sex is REM Sleep behavior most common in?
Most common in adult males over 50
