4A. Sleep Medicine Flashcards
• They also realized that there were certain plants called heliotropes
◦These plants would open their leaves during the day and close at night
◦They thought it was due to light exposure
• But they experimented by putting them in a box w/o any exposure to light and they continued to keep the same cycle ALMOST on a ____ basis
◦Almost b/c it is a little over 24hrs
◦The little difference is called circadian rhythm
‣ Circa= close to Dia= day
‣ This is how sleep and physiology works.
‣ The circadian rhythm is embedded in the ____ system= clock which is
expressed in every cell including hormonal cells which secrete hormones in their own circadian way
daily
transcription
- this is showing when you’re awake during the day, when your ____ is is the highest, when you’ll have bowel movement and when the bowel movements will be suppressed
- We can see there is a pattern that repeats itself day to day which is called circadian rhythm
BP
The circadian rhythm is driven by ____
• the light enters the eye and goes to ____ -> neurotransmitters are
produced -> the go to the ____ gland where melatonin is produced
• All these mechanisms regulate how the circadian cycle works
light
suprachiasmatic nuclei
pineal
• Melatonin is maximally secreted around ____
• Melatonin starts to rise around 9pm, which is when you start getting sleepy
◦By taking melatonin, you are either advancing or delaying the melatonin concentration -> ____ the circadian rhythm
◦That’s why people who travel take melatonin to shift their hours
midnight
modifying
• melatonin is ____, but it is not a good sleep aid
• The circadian rhythm drives wakefulness, it keeps you wake in different magnitudes
throughout the day
• Ex: We are sleepy at 2pm b/c our circadian rhythm has less ____ at that time
◦During the day, there is an accumulation of ____ within the brain and CNS that actually increases your drive to sleep
◦There is a point that it doesn’t matter how strong your circadian input is, these vectors are so strong that you will fall ____
◦Ex: if you haven’t slept for 24hrs, you’re going to start having micro sleep episodes and start to fall asleep
‣ It doesnt matter how much wakefulness you have in your system, the substance drive is too much
non-toxic
input
substances
asleep
• sleep goes during through different cycles
• ____ sleep is stage 1
• very deep sleep is stage 5 (____ sleep- rapid eye movement)
• The definition of sleep stages is based on ____ patterns
◦In REM sleep, it is the deepest sleep you don’t move anything except for your ____
◦There are no other muscles moving, otherwise it is abnormal
light
deep
EDG
eyes and diaphgram
This is a hypnogram
• REM sleep occurs no earlier than ____ min before you fall asleep
• REM sleep is when you move your eyes and diaphragm and you ____
• This pattern repeats itself ____ times a night and it is ____ through life
• REM sleep tends to be quite constant through life
90
dream
3-4
continuous
- SWS (slow way sleep) is maximal in ____ children and decreases markedly with age
- REM sleep as a percentage of total sleep is maintained well into healthy ____ age
- Absolute amount of REM sleep at night correlates with ____ functioning
- Arousals during sleep ____ with age
- Most notable finding in elderly : ____
He doesnt know if this is true or not
• SSRi drugs are antidepressants and dramatically ____ REM sleep
• There is no indication that antidepressants especially SSRi correlate with poor intellectual function
young old intellectual increase interindividual variability
When we breathe, we look for oxygenation and ventilation
• when you oxygenate, you bring and deliver O2 to your lungs that is transported to
your blood
• When you ventilate, you move air that when you exhale, you wash out CO2
◦Ventilation refers to CO2 and oxygenation refers to O2
• When you breathe faster, the oxygenation will be the same, but if you breathe faster and deeper, the ____ will be larger b/c more air is being exhaled
• In different sleep stages, there is a response to hypercapnia or hypoxia
• When you don’t breathe, your ____ increases
• If he gives us an opioid and we OD -> we would stop breathing and die from
hypercapnia (too much CO2) and decrease the respiratory drive
• When you sleep, you breathe more shallow and ____ accumulates -> there are sensors in the brain and you will breathe faster or deeper, BUT they are a bit deactivated when you’re sleeping causing CO2 to ____ slightly and O2 to ____ slightly
ventilation CO2 CO2 increase decrease
REM sleep is a chaotic state
• Your cardiac output is anywhere? And your systemic BP goes down? (Not sure what he’s saying)
• There is a lot of ____ release so it is very complex even though it is deep
sleep
• Blood flow also ____ during that state
catecholamine
increases
- During sleep, regardless of the stages, you can see there is a ____ release of hormones
- They follow a ____ pattern that is not circadian except for growth hormones that has different peaks (circadian has 2 peaks like growth hormone)
- Most hormones follow a ____ pattern
- Growth hormone and aldosterone follow the ____ pattern
cyclic
pulsatile
pulsatile
circadian
Reticular Activating System
• Electrical stimulation of RAS produces generalized cortical EEG activation
• ____ is a major excitatory neurotransmitter of core reticular formation ascending neurons to the thalamus; is also the excitatory transmitter in the thalamic relay projections to the neocortex.
• Glutamatergic excitatory synaptic transmission, contributes to global ____ activation during ____ sleep.
The main neurotransmitter in the RAS that makes us awake is GLUTAMATE
• Glutamate is a major activator
glutamate
forebrain
waking and REM
Dopamine
• largest concentration of dopamine (DA) neurons in the brain is located in the ____ and ____
• DA neurons innervate the ____ cortex, striatum, thalamus, and limbic system
• Release of DA in the frontal cortex is higher during ____ than during sleep
• Several drugs that promote wakefulness target the DA systems.
dopamine is the 2nd neurotransmitter for keeping you awake
• it is released in the frontal cortex and there are several drugs that promote wakefulness by targeting dopamine receptors
substantia nigra
ventral tegmental area
frontal
sleep
Provigil (Modafinil)
This is a typical drug given in ____ or when they want to stay awake
• it inhibits the reuptake the ____ into the system
• This drug interacts with ____
◦If you are taking Modafinil and oral contraceptives, there is a good chance you will be ____ and have insomnia
The larger the dose, the lesser the uptake of ____
narcolepsy dopamine oral contraceptives awake dopamine
Hypocretin/Orexin
• Neurons containing the HCT peptides ____ (orexin-A and orexin-B) localized in
lateral ____
• Targets of HCT neurons are several nuclei implicated in control of ____
• Deficiency of HCT signaling is a key feature of the pathophysiology of narcolepsy.
When Orexin-A and Orexin-B are absent, people develop narcolepsy
• narcolepsy is when you fall asleep all the time and it is common to have sleep
paralysis
• There is also something called ____ where you see or hear things when you are falling asleep or waking up
◦You’re hallucinating continuously during these stages of sleep
• There is also another symptom called ____ when you are confronted by a very emotional situation and you get scared. instead of running away, your muscles get five up and you suddenly feel very sleepy.
• Narcolepsy and cataplexy sometime go together, sometimes they don’t coexist but they are both related to the absence of these peptides
HCT-1 and HCT-2
hypothalamus
arousal
hypnohallucination
cataplexy
What puts the brain to sleep: mechanisms of sleep onset and sleep maintenance
Sleep-Generating Neurons in the ____
The ____ system will keep us awake
• the ____ will keep us sleepy
preoptic hypothalamus
reticular activating
preoptic hypothalamus
These are the firing of neurons in the preoptic area during sleep
• We see in the EMG (electromyogram) that there is no ____ activity during REM sleep
• but we see the neurons firing like crazy
muscle
Endogenous Sleep Regulatory Substances
• ____ is THE sleep regulatory substance
• Acting through A1 receptors, adenosine has ____ effects on neurons in several brain regions, including wake-promoting brain nuclei
• Administration of A1 receptor ____ promotes sleep and enhances EEG slow wave activity.
• ____ is a mixed A1 and A2A adenosine receptor antagonist.
Adenosine is the sleep regulatory substance and wil make you sleepy • caffeine is an adenosine receptor antagonist
◦That’s why when you drink coffee, it antagonizes the system making you feel more awake
◦There are different responses to caffeine between individuals based on receptor sensitivity
◦Caffeine is a nonspecific adenosine ____. Their binding will depend on the each person’s phenotype
adenosine inhibitory agonists caffeine antagonist
Obstructive sleep apnea
• Complete or nearly complete cessation of airflow: ____
• Partial reduction in airflow with preservation of respiratory effort: ____
• Preservation of respiratory drive manifested as persistent respiratory muscle activity
• apnea-hypopnea index (AHI)
• The magnitude of AHI generally reflects the severity of excessive ____ sleepiness (EDS), cardiovascular risk, and the general ____ consequences of SDB
• imagine your throat is a funnel and is collapsible made out of soft tissue and muscle fat ◦The funnel is behind your tongue and in front of your throat of your oropharynx that
directs into the trachea
◦When you are awake, the structures are fully opened and you breathe ◦When you fall asleep, the structures relax and things get floppy
‣ When you blow air against something floppy, it vibrates -> creating air turbulence -> making a noise = snoring
‣ Snoring is a symptom of sleep apnea but it doesnt mean everyone who snores has sleep apnea
‣ It is a ____v flag for sleep apnea
◦If the funnel relaxes even more, your tongue is going to fold gravitationally towards
the back of your throat completely blocking the funnel -> this is where sleep apnea starts
◦It is sleep apnea b/c you’re sleeping and there’s no breathing. However, there is no cessation of ____. You are still trying to breathe, but it is blocked which is obstructive sleep apnea
◦You are trying to breathe but there is no airflow b/c it is blocked. It is different from
central sleep apnea
Somewhere between the snoring and OSA, there is something called hypopnea
• hypopnea is where it is almost closed and we are getting some air through, but the flow has decreased
• Central apnea is when there is no ____ drive so there is no airflow b/c your re
not breathing
obstructive apnea (OA) obstructive hypopnea (OH) daytime metabolic red breathing respiratory
This is an example of portable sleep study
• you put a small device on the chest and you strap it around
◦There is a sensor on your finger that measures O2 and another sensor that measures flow in your nose
• If you are breathing, the sensor on the chest will feel that your re stretching = ____ movement
◦If it translates to airflow, the sensor will feel airflow and the O2 level will remain at a ____ level
- However if I am trying to breathe and this thing closes up, there is no airflow, the O2 is going to drop, but your chest is going to continue to move = ____
- If your chest doesnt move at all, there is going to be no air movement, and the O2 is going to drop = ____
- In OA, you will see the thorax moving, but you will see no airflow and a decrease in O2
- in CA, you will see no movement in the chest, and no airflow and the O2 will drop
Top graph shows OA, bottom graphs shows hypopnea
• in OA, there is no airflow
• In hypopnea, the amplitude for airflow ____ significantly and there’s a drop of O2
downstream which means the airflow decreased enough to drop the O2 conc on the O2 saturation
◦When that happens, the airflow and ____ decreases, that’s what defines hypopnea
thoracic
normal
obstructive apnea
central apnea
decreases
SpO2
