Sleep physiology and disorders Flashcards
What is sleep?
Reversible behavioral state of perceptual disengagement from, and unresponsiveness to, the environment
Is sleep essential for health? Can sleep deprivation lead to death?
Yes and yes
What regulates sleep?
Dienchephalic and brainstem nuclei
What does ambient light impinge upon?
Ganglion cells that contain the photopigment melanopsin.
The retinal ganglion cells are inhibited and stimulated by what?
Inhibited by ambient light
Stimulated by darkness
What do the retinal ganglion cells do with decreasing ambient light?
Fire off electrical signals to the suprachiasmatic nucleus.
What does the suprachiasmatic nucleus do?
Activates the paraventricular nucleus (PVN)
What is the role of the PVN?
It is a sympathetic nucleus that activates neurons in the intermedilateral gray zone of the upper spinal cord that modulate neurons in the superior cervical ganglia
Where do the sympathetic neurons of the cervical ganglia travel and what do they activate?
the pineal gland
What does the pineal gland do?
Synthesizes and releases melatonin
Role of melatonin?
Stimulates a drowsy state by modulating brainstem neurons to facilitate the onset of sleep
When does melatonin levels begin to rise? When do they peak?
Early evening, ~2:00 - 4:00 am
How is sleepiness measured?
Polysomnography
EEGs can be segregated into what classifications?
Beta >13 Hz
Alpha 8-13 Hz
Theta 4-7 Hz
Delta <4 Hz
How many stages of sleep are there?
Five
What are stages I - IV called? Stage V?
Non REM Sleep
REM Sleep
What is the lightest stage of sleep? The deepest?
Stage I
Stage IV
What is stage II of sleep characterized by?
Bursts of activity called sleep spindles and K complexes
The EEG characteristics of REM sleep are what compared to the awake sleep?
Very similar
EEG activity in awake state?
Alpha and beta
EEG activity in Stage 1 and Stage 2 sleep?
Theta activity
EEG activity in Stage 3 and Stage 4 sleep?
Delta activity
EEG activity in REM sleep?
Theta and Beta activity
Typically how many cycles are there in a 7-8 hr sleep period? How long does each cycle last?
5-6 cycles at ~ 90 mins a piece
What happens to the duration of Stages 3 and 4 as the night goes on?
They become shorter
What happens to sleep time as one ages? What about REM sleep?
It gradually becomes less.
Less time is spent in REM sleep
Characteristics of NREM Sleep?
Few eye movements - If they occurs slow, rolling
Decreased muscle tone but movement still occurs
Decreased HR, BP, RR, Temp, metabolic rate
Dreams occur but they are less vivid with low emotional content
Sleep walking and night terrors occur during slow wave sleep
Reach maximum during Stage IV sleep
Characteristics of REM Sleep?
Rapid, ballistic eye movement
Muscle paralysis
HR, BP, RR< metabolic rate approach awake level
Dreams are vivid with strong emotional content, bizarre
What areas of the brain are activated during REM sleep? Inactivated?
A - Amygdala, parhippocampal gyrus, and anterior cingulate cortex
I - Frontal cortex, and posterior cingulate gyrus
What neurons promote wakefulness in the brainstem?
Pedunculopontine (PPT) and Lateral-Dorsal tegmental (LDT) - cholinergic neurons
Locus ceruleus - Noradrenergic neurons
Substantia nigra - Dopaminergic neurons
Raphe nuclei - serotonergic neurons
What neurons promote wakefulness in the Hypothalamic nuclei?
Tuberommaillary nucleus - histaminergic neurons
Lateral hypothalamus - orexin/hypocretin neurons
What type of signal do pedunclopontine and lateral-dorsal areas trigger? Where?
Beta waves - consistent with arousal/wakefulness
Activates thalamic-cortical signaling
When are the PPT and LDT pathways activated? Inactivated?
REM Sleep
NREM Sleep
When is noradrenergic input from the locus ceruleus activated? Less activated? Silent?
Wakefulness
NREM Sleep
REM Sleep
What is the dopaminergic circuits important for?
Full wakefulness
When is serotonergic circuits from the raphe nucleus activated? Less activated? Silent?
Wakefulness
NREM Sleep
REM Sleep
When is histaminergic output from the tuberomammilary nucleus high? Lower? Still Lower?
Wakefulness
NREM Sleep
REM Sleep
What role do levels of orexin play in narcolepsy?
Pts with narcolepsy have low or undetectable levels of orexin and a reduction in the number of orexin secreting neurons
What is the role ventrolateral preoptic nucleus (VLPO)?
Harbors both GABAnergic and Galanin neurons both of which innervate and inhibit all nuclei that deal with the sleep cycle –> will lead to sleep when activated
What are somnogens?
Endogenous sleep-promoting chemicals that may accumulate during wakefulness and promote sleep onset
What role does adenosine play in sleep/arousal?
Accumulates in the CNS during wakefulness and declines during sleep
Which cytokines play a role in sleep?
IL-1Beta
TNF
How is melatonin synthesis turned on?
Decreasing light
What is obstructive sleep apnea?
Repetitive blockage of the respiratory pathway during sleep causing apneic periods lasting longer than 10 seconds and causing oxyhemoglobin desaturations of more than 4%.
There is a strong association between OSA and what?
Heart Dz
HTN
Pathogenesis of OSA?
Complex interaction between pharyngeal muscles, tongue, and soft tissues, leading to airway obstruction
What is narcolepsy?
Excessive daytime sleepiness associated with one or more of the following tetrad:
- Sleep attacks/intrusions
- Cataplexy
- Sleep paralysis
- Hypnagogic hallucinations
Pathogenesis of narcolepsy?
Loss of hypocretin/orexin secreting neurons in the posterior lateral hypothalamus
Genetics involved in narcolepsy?
HLA genes DQ1, DQb1*0602 that may predispose to an autoimmune attack on orexin secreting neurons
What is insomnia?
Difficulty falling asleep or remaining asleep
What is REM Sleep Behavior Disorder (RSD)?
Loss of atonia/paralysis during REM sleep leading to physical acting out of dream states including verablization, punching, kicking, jumping from bed - this activity can cause physical injury to the bed partner or patient.
Pathogenesis of RSD?
May be idiopathic or associated with alpha-synucleinopathies.
In what stage of sleep do narcoleptics enter?
REM
