ICL 10.12: Sleep, Wakefulness & Disorders Flashcards

Question

where is the ventrolateral preoptic nucleus located and what NTs does it secrete?

Answer 1

it's one of the hypothalamic nuclei it secretes GABA and galanin which are both inhibitory it's important for sleep!

Answer 2

the ventrolateral preoptic nucleus in the hypothalamus secretes GABA and galanin and inhibits all of the ARAS = TMN, RN, LC, SN, PPT, and LDT adenosine, PGD2 and warmth activate the VLPO which then secretes GABA/galanin to shut everything else down

Answer 3

adenosine coffee contains caffeine and what it does it block adenosine receptors and help you stay awake by blocking the effects of adenosine on VLPO (ventrolateral preoptic nucleus of the hypothalamus)

Answer 4

AWAKE when you're awake the orexin neurons and ARAS neurons (LDT, PPT, LC, RN, TMN) are active the preoptic nucleus is relatively inactive so the orexin and wake-active neurons are dominating and inhibiting the VLPO nucleus so the person is awake SLEEP the VLPO is more active and it's inhibiting both the orexin neurons and the wake-active neurons so the person will be asleep so it's all a tug-o-war between the VLPO vs. the orexin neurons and wake-active neurons of the ARAS

Answer 5

1. NREM = non-rapid eye movement 2. REM = rapid eye movement --> aka paradoxical sleep NREM is also called slow wave sleep and it more refreshing REM is less refreshing/more active dreaming --> metabolic activity of the brain is really high so that's why you aren't as relaxed

Answer 6

there are 3 progressively slower stages = N1, N2 and N3 N1 to N3 is a progression into the deeper stages of sleep

Answer 7

they are based on frequency 1. beta = 14-30 Hz --> awake, normal alert consciousness, thinking 2. alpha = 9-13 Hz --> awake, relaxed, calm, lucid, not thinking 3. theta = 4-8 Hz --> deep relaxation and meditation, mental imagery, maybe drowsy 4. delta = 1,3 Hz --> deep, dreamless sleep so as the frequency increases, amplitude decreases -- as the frequency decreases the amplitude increases

Answer 8

BATS Drink Blood Beta rhythm --> awake Alpha rhythm --> drowsy Theta rhythm --> stage N1 of NREM Spindles and K complexes --> stage N2 of NREM Delta rhythm --> stage N3 of NREM Back to Beta --> awake so now you're asking what about REM sleep?? well REM sleep is basically low amplitude alpha, it's very similar to an awake state which is why it's called paradoxical sleep

Answer 9

sleep spindles are faster 12-14 Hz so almost alpha rhythms with a crescendo then decrescendo pattern K complex is a biphasic high amplitude discharge that goes up then down -- looks like a heart rhythm -- normally seen in the front of the brain these are the 2 phases of stage N2 NREM sleep and they come from the reticular thalamic nucleus! slide 28 and 29 (go look seriously)

Answer 10

going from beta to delta is one sleep cycle during sleep, you go from beta to delta multiple times and keep repeating each cycle takes 90-100 minutes but usually an adult goes through 4-5 sleep cycles a night

Answer 11

also called paradoxical sleep, due to loss | of muscle tone except in extraocular muscles and diaphragm

Answer 12

1. tonic stage | 2. phasic stage

Answer 13

1. EEG low amplitude 2. suppression of muscle tone except EOM and diaphragm 3. absent thermoregulation = become cold blooded 4. penile/clitoral erections 5. pupils constrict (due to parasympathetic dominance)

Answer 14

1. contraction of middle ear muscles 2. irregular respiration and heart rate 3. rapid eye movements these happen only intermittently throughout REM, not during all of REM sleep -- most of REM sleep is the tonic phase

Answer 15

the PPT and LDT nuclei have REM-on neurons which are inhibited during wake-stage by the ARAS components in the sleep state, the ARAS nuclei are shut down so the inhibition on the PPT and LDT REM-on neurons is lifted and they are dis-inhibited during sleep --> VLPO is what switches off the ARAS components when they are disinhibited they become active and release ACh which activates the medial medullar nucleus in the medulla which inhibits the motor neurons in the spinal cord this is why when you're dreaming about running you aren't actually running in your bed!

Answer 16

N3 sleep becomes less prevalent as you go through the night so you don't sleep as deep towards the end of the night as the N3 decreases, your REM increases which is why we dream a lot towards the end of the night and early morning and remember those dreams when we get up

Answer 17

it's super unusual for a healthy person to go straight into REM without going through N1 --> N3 first if someone does go straight into REM it usually indicates depression or narcolepsy however, awake directly into REM in babies is totally normal

Answer 18

the depiction of sleep stages vs. time slide 31

Answer 19

N2 50-60% of your sleep is in N2

Answer 20

REM SLEEP rapid eye movement muscle twitches fluctuating vital signs decreased muscle tone penile erections are common dreams are common EEG is low voltage, high frequency alpha waves NON-REM SLEEP slow eye movements muscle relaxation but not totally atonic stable vital signs some tone in postural muscles penile erections rare dreams are rare EEG has spindles, V-waves, K-complexes and slow waves

Answer 21

25-75 REM:non-REM in adults 50-50 in babies

Answer 22

it's what explains circadian rhythmicity! there are 2 determinants called process S and Process C --> process S makes us tired which process C makes us alert as we go through the day, process S increases and peaks at 9 PM -- but to keep us awake throughout the day, process C is also increasing so it counteracts the effect of the sleep load so you don't just fall asleep in the middle of the day --> process S and C both peak at 9 PM the process C signal being generated by the superchiasmatic nucleus in the brain and counteracts sleep load which is adenosine! so the SCN sends out alerting signals throughout the day to counteract rising adenosine signals throughout the day around 9 PM, your SCN stops sending out alerting signals via process C and you fall asleep because the adenosine sleep load is unopposed (process S) when you fall asleep, your adenosine decreases over time until you wake up and the sleep load is the lowest in the morning when you get up which is why you're awake the most in the morning! slide 34*

Answer 23

1. rhythm has an endogenous free-running (approximately) 24 h period 2. should be entrainable (ie, be capable of phase reset by environmental cues and synchronisation to the 24h day like moving from the east coast to the west coast) 3. should exhibit temperature compensation = temperature doesn't effect phase of circadian rhythm If all these criteria are not fulfilled, the term diurnal rhythm is often used

Answer 24

light activates the suprachiasmatic nucleus of the hypothalamus to activate process C which inhibits melatonin secretion from the pineal gland so in the day time because of abundant light and SCN activation, melatonin levels are low and that's why you don't fall asleep during the day! once it's night time and there's no light, the activation of the SCN decreases so it is no longer inhibiting melatonin release and that's why you get sleepy in the dark so light activates the SCN which then inhibits the paraventricular nucleus of the hypothalamus -- the PVH is the seat of autonomic function including melatonin secretion so that's why SCN inhibition of the PVH decreases melatonin levels and keeps you awake --> so process C is actually just a lack of melatonin!!

Answer 25

1. NE, TSH and cortisol are under circadian control and TSH peaks at 2 AM while cortisol peaks at 7 am whether you are sleeping or not 2. however, GH and PRL are also under circadian control but they ARE sleep controlled so they will be secreted when the person is in slow wave sleep 3. leptin from the fat which promotes satiety increases during sleep 4. ghrelin from the stomach which promotes eating decreases during sleep if someone has sleep loss then your leptin levels will be decreased and ghrelin will be increased and both of them together will lead to excessive eating and weight gain! sleep loss can also effect growth because GH is released during sleep!

Answer 26

sleep difficulty aka difficulty initiating or maintaining sleep, early morning awakening, or both it is associated daytime consequences because of night time sleep difficulty, with the supposition that the nighttime or daytime problems are not explained by an inadequate opportunity to sleep the most common type is Psychophysiological Insomnia, due to anxiety about sleep and heightened arousal when in bed

Answer 27

1. Cognitive Behavioral Theory (CBT-I) 2. hypnotic medications --> most act directly or indirectly via GABA the VLPO turns of all ARAS centers so hypnotic medications act through GABA which is the major NT of the VLPO!

Answer 28

GABA A is mostly in the brain GABA B is mostly in the brainstem and spinal cord

Answer 29

5 subunits which surround a Cl- pore and activation of the receptor leads to influx of Cl- into the neuron --> once Cl- gets into the cell it's hyperpolarized and inactivated it has binding sites for various different ligands = GABA and benzodiazepines GABA binds between the alpha and beta subunits of the receptor benzodiazepines bind between the alpha and gamma subunits and they do not open the Cl- channel but instead increase the affinity for channel gating by GABA

Answer 30

1. benzodiazepines 2. non-benzodiazepines 3. orexin receptor antagonists 4. melatonin receptor agonists 5. antidepressants 6. antihistaminics

Answer 31

1. triazolam 2. estazolam 3. temazepam adverse effects = dependence, increased tolerance, and slowed responses they bind between the alpha and gamma subunits of the GABA(A) receptors and increase the affinity for channel gating by GABA

Answer 32

they are GABA agonists which bind to the GABA(A) receptor between the alpha and beta subunits on the OTHER side of the receptor, so *not* at the same binding site as actual GABA

Answer 33

1. zaleplon 2. zolpidem 3. eszopiclone "the 3 Z's of sleep!" adverse effects = less dependence producing than BZD but patients can develop nocturnal eating

Answer 34

orexin is released from lateral hypothalamus and makes you awake so if you block it you'll fall asleep ex. suvorexant (Belsomra)

Answer 35

melatonin binds to superchiasmatic nucleus and turns it off ex. ramelteon = melatonin 1 and 2 receptor agonist which is 17x more potent than melatonin in binding to the melatonin receptor

Answer 36

have some anti-histaminic actions which puts you to sleep because histamine keeps you alert

Answer 37

there's either intrusion of sleep into the awake state or intrusion of the awake state into the sleep state if the switch-model of sleep and wake is unsteady, then the patient might flip from sleep to awake unexpectedly or vice versa --> like with narcolepsy!

Answer 38

1. sleep attacks = patients will sleep from sleep to awake rapidly 2. sleep paralysis (usually due to sleep deprivation) 3. sleep related hallucinations = hypnogogic and and hypnopompic which is hallucinating when you're going to sleep or waking up, respectively 4. cataplexy = loss of muscle tone related to positive or negative emotions

Answer 39

narcolepsy with cataplexy 98% have HLA-DQB1*06:02!!!! flu or vaccination can also trigger narcolepsy

Answer 40

narcolepsy without cataplexy about 50% have the HLA-DQB1*06:02

Answer 41

any emotional trigger which is either positive or negative can trigger a partial cataplexy in the face eventually they'll just be down on the ground totally unable to move even though they'll be totally conscious

Answer 42

1. to treat the excessive daytime sleepiness you can use: dopamine enhancers like methylphenidate or amphetamine (adderall) but they are dependence producing and can stunt growth in kids wake promoters like modafinil and armodafinil which are also dopamine enhancers but they can cause headaches 2. to treat the cataplexy you can use antidepressants or sodium oxybate which is a GABA(B) receptor agonist but it can cause mood changes, bedwetting and sleepwalking 3. timed daytime naps

Answer 43

undesirable physical events or experiences that occur during entry to sleep, within sleep, or during arousals from sleep so it's when someone goes from sleep to awake unexpectedly they can occur during REM or non-REM sleep

Answer 44

it's a type of parasomnia so it's when someone goes from sleep to awake unexpectedly there's absence of the normal loss of muscle tone during REM sleep + Dream-enactment behavior (oneirism) --> so when they're dreaming they're acting out their dreams! limb and body movements often are violent (e.g., hitting a wall, kicking) and may be associated with emotionally charged utterances patient may or may not remember the dream pathophysiology includes dysfunction of areas of the brain responsible for atonia during REM sleep and also other areas of the brain (limbic system and others) involved with the generation of the violent dreams so it's lack of atonia! the REM-on neurons will inhibit the medulla which inhibits the spinal neurons but without this, that's why the patient can act out their dream

Answer 45

it's a prelude to neurodegenetive disorders like Parkinson's 81% of patients who get diagnosed with RBD later develop Parkinson's like 10 years later

Answer 46

1. patient safety 2. clonzepam (BZD) 3. melatonin besides this there really aren't many other things....

Answer 47

1. confusional arousals = awakening with confusion 2. sleepwalking 3. sleep terrors in children, NREM parasomnias occur out of stage N3 in the first part of the night while in adults they can occur out of any N1-N3 stage during any part of the night

Answer 48

1. reassurance 2. BZD if needed these are benign and don't cause long term problems and resolve on their own with age

Answer 49

B. Nocturnal polysomnography he has obstructive sleep apnea! chest goes in and abdomen goes out when he sleeps because of obstruction of the upper airway

Answer 50

breathing disruption for at least 10 seconds repeatedly during sleep that is either complete cessation (apnea) or partial (hypopnea) --> sleep disruption --> arousals and less deep sleep --> daytime fatigue/ memory problems (# of apneas + hypopneas)/hours of sleep = apnea-hypopnea index (AHI) normal is <5/hour, anything higher is sleep apnea

Answer 51

1. central sleep apnea | 2. obstructive sleep apnea

Answer 52

no respiratory effort due to decreased CNS drive

Answer 53

physical airway obstruction due to: 1. decreased pharyngeal muscle tone 2. thick neck pressing on the upper airways 3. enlarged tonsils (usually in kids) more common in men

Answer 54

1. polysomnography 2. blood-polycythemia due to EPO release from chronic hypoxia 3. EKG for cardiac arrhythmias

Answer 55

1. chronic fatigue 2. morning headache 3. loud snoring (usually for obstructive) 4. hypertension

Answer 56

central sleep apnea is treated with a BPAP to provide mechanical ventilation obstructive sleep apnea is treated with a CPAP, weight loss or surgical tonsillectomy

Answer 57

1. arrhythmias 2. pulmonary hypertension due to chronic hypoxia stimulating pulmonary vasculature constriction = pulmonary hypertension

Answer 58

``` URGE U = urge to move R = rest induced G = gets better with activity E = evening/night is worse ```

Answer 59

1. so it's a circadian problem and most patients have an underlying iron deficiency so people will have low serum ferritin iron deficiency can lead to underactive tyrosine hydroxylase and hence low dopamine because TH is the enzyme that makes dopamine -- low dopamine means more restless leg syndrome (like parkinson's tremors) 2. the other cause of restless leg syndrome is creatine -- so pregnant women and people in kidney failure have with high creatine have uremia are at risk for RLS

Answer 60

1. dopamine agonists (ropinirole or pramipexole) 2. gabapentin anti-convulsive medication that acts on Ca+2 and blocks it which prevents NT release 3. opioid for severe cases