Lecture 12: Sleep Medicine Part I Flashcards
What is the suprachiasmatic nucleus?
The master clock of the brain
Present in the hypothalamus
Controls circadian rhythms
Each SCN is an individual oscillator based on a fundamental negative feedback loop
-factors stimulate transcription of genes encoding proteins
-As the proteins accumulate, they act as transcriptional repressors of their genes
-this takes one 24 hour cycle
SCN does this even in absence of light-dark cycle
What is the significance of the circadian system?
Earth’s orbital mechanics are instantiated in (and entrain) a circadian genetic “clock” and sleep need in the human brain
-unrelenting
Circadian clocks are based on negative feedback loops of SCN
Circadian system interacts with homeostatic system that regulates sleep need
What is wrong with our society today?
Society has led to self-imposed conflict between our desire to be awake 24/7 and biological imperative of sleep
What is the significance of the fact that the SCN (circadian clock) is a wake-promoting system?
It means that at certain times of the day, it sends out more wake signals than others…
-the homeostatic drive for sleep coupled with low awake signals from SCN leads to sleep
What is the significance of the nonlinear profiles produced by the interaction between need for sleep and circadian drives?
Since performance is predicated on wakefulness, the nonlinearity of the relationship makes it difficult to make simple work-hour rules relative to performance and safety during
-working for 16 hours and going to the beach for 16 hours is the same shit in your brain…all awake process
What is the significance of melanopsin cells?
Photoreceptors in retinal ganglion cell layers that transmit information about the environmental timing of Earth’s light to SCN
Blue light = awake
-light intensity and durating/timing also plays a role
What hormones do SCN control?
Melatonin
More melatonin = go to sleep
Cortisol
More cortisol = wake up
What is the purpose of melatonin?
More melatonin = go to sleep
What is the purpose of Cortisol?
More cortisol = wake the fuck up
Where can circadian clocks be found in our body?
Circadian clocks can be found in ALL tissues throughout all major organ systems
SCN is the master clock that entrains all other peripheral physiologic oscillators
What does the ability to fall asleep and remain asleep depend on?
Whether or not you are in right circadian phase
If you are in the WRONG circadian phase while sleeping, then you have disturbed sleep
What is harder? Working 30 hours straight or doing 4 straight night shifts?
Working 30 hours than 4 to 5 days of night work
Because we don’t adjust to night work
Night shifts = carcinogenic
How prevalent is sleep in animal kingdom?
It is everywhere
What is polysomnography?
Surface electrophysiological recordings of
i. brain waves (EEG) ii. eye movements (EOG) iii. muscle activity iv. heart rate v. respiration vi. behavior
What are the three aspects of sleep “recovery”?
- Adequate sleep CONTINUITY
- Adequate sleep DEPTH or intensity as seen in slow wave activity (SWA)
- Adequate sleep DURATION
What is the characteristic of REM sleep?
EEG waves look like waking EEG
- no thermoregulation
- REM dreams = bizarre, movement based
- paralyzed
- used for procedural memory
What is stage 3 and 4 sleep?
The stages right before REM when you have Slow Wave Sleep
-you won’t remember your dream
What is the average non-REM to REM cycle?
90 minutes
As you sleep longer, the more and more proportion of your sleep is going to be REM
How do Orcas and sea lions sleep?
Uni-hemispheric sleep
-an adaptation in propoise and many other aquatic mammals so that they can sleep while they swim
What is the sleep switch?
The ventrolateral preoptic nucleus (VLPO) in hypothalamus
-this is inhibited by GABA as sent by the SCN
What happens during the awake brain?
The wake drive is regulated by SCN that inhibits the VLPO activity
Allows the sleep centers to be activated and for monoamines to be passed from center to center
What happens during the sleeping brain?
VLPO send GABA signals to midbrain arousal centers including Raphe, LC, tuberomammilary nucleus (TMN), basal forebrain (BF), perifornical neurons (PeF)
What is the ventrolateral preoptic nucleus?
The putative sleep switch
Located in the hypothalamus
As we age, what happens to our sleep?
Periods of sleep during the day become more frequent and sleep during the night is a lot less
What neurobehavioral changes occur with loss of sleep?
- mentally slow and inaccurate
- variable attention and poor focus
- unreliable memory
- weak executive decision making
- emotionally unpredictable
Can the effects of sleep loss accumulate over time?
Yes
Neurobehavioral deficits can accumulate…overall slowing of brain
What do PET scan of sleep-derived adult showing areas of decreased brain metabolism?
- prefrontal cortex
- thalamus
- inferior parietal cortex
- occipital cortex
How powerful is sleep?
Sleep can overwhelm goal directed behavior
-example is when people fall asleep at the wheel
What are the areas of the brain that are affected by lack of sleep and thereby cause the lapses shown on tests?
- reduced frontal/parietal control regions to raise activation
- reduced visual sensory cortex activation
- reduced thalamic activation
- reduced connectivity
What are the candidate neurological mechanisms for regulation of waking alertness and neurobehavioral functions?
RAS Basal forebrain Orexin-hypocretin cells VLPO Thalamo-cortical dialogue
What are orexin (hypocretin) cells?
Neurotransmitter that regulates arousal, wakefulness and narcolepsy
Are people aware of how severely lack of sleep is affecting them?
No
What is front loading your sleep?
You want to have a lot of sleep before going into call
Do NOT go into call already sleep deprived
Are there differences among us in response to sleep loss?
Yes there are
- Vulnerable
- hard to recover after sleep deprivation
- Average
- recovers well after sleep deprivation
- Resistant
- doesn’t matter how long they stay up, they show little deficits
- any little bit of sleep allows resistant phenotype to recover
What is more important? Hours slept or hours worked?
Number of hours you sleep is more important than number of hours worked
What are the effects of reduced sleep duration on residents?
Interns had OR of 2.3 for motor vehicle accident
-more frequent injuries
What is the key message of IOM?
There is no substitute for adequate sleep
What are the ways to be vigilant about your sleep habits?
- Predict
- predict when you are going to have less sleep
- Prevent
- front load sleep
- Detection of fatigue
- Intervene
What is the maximum amount of time residents should go without rest?
Residents must not work more than 16 hours in a row without rest
-must have protected period of time of at least 5 hours…5 hour protected nap on call
The longer the protected nap time, the greater the behavioral alertness
What is Dinges’ takehome point?
Sleep is the single most reliable daily performance enhancer
- use it wisely and professionally
- get your sleep when you can and learn to recognize sleep loss as a safety and health risk in your patients
