12 - Sleep Pathophysiology Flashcards

1
Q

What three parts of the brain regulate sleep and wake? What results from lesions in each location?

A

Basal forbrain and anterior hypothalamus: lessions cause insomnia

Lateral hypothalamus: lesions result in narcolepsy

Juncture of the midbrain and posterior hypothalamus: lesions result in hypersomnolence (excessive daytime sleepiness)

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2
Q

What two things contribute to the sleep-wake cycle?

A

The circadian rhythm and sleep-wake homeostasis (both of which are influnced by genes)

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3
Q

What is the homeostatic process that regulates sleep and wakefulness?

A

The homeostatic drive for sleep is the pressure to sleep that builds up throughout the day (thought to be a result of adenosine build up).

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4
Q

What are the three components of the sleep promoting system?

A
  • Gamma-Aminobutyric acid (GABA)
  • Ventrolateral preoptic area (VLPO)
  • Median preoptic nucleus (MnPN)

Adenosine build up results in us becoming more sleepy throughout the day.

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5
Q

Describe the circadian process that regulates sleep and wakefulness?

A

It goes through ebs and flows; you’re most alert right before you fall asleep.

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6
Q

What are a few components of the arousal/wake system?

A

There are many components, but the ones emphasized in class are:

  • Histamine (His) from the tubero mammillary nucleus
  • Orexin (ORX) lateralhypothalamus (LH)

(It was emphasized that we do NOT need to know everything in the attached image).

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7
Q

What impacts your circadian rhythym?

A

Your genes! The master clock is the master clock superchiastmatic nucleus.

  • Cellular clocks keep near-24-hour biological time via a classic negative feedback loop.

Peripheral clocks:

Clock genes: Per 1-3, Cry 1-2, Bmal1, Clock

Proteins: PER 1-3, CRY, 1-2 BMAL1, CLOCK

Enzymes: CKIe

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8
Q

What is the master clock of hte circadian rhythm? What provides it input and what does it send output to?

A

Retinal photoreceptors (rods and cones) send info to the intrinsically photoreceptive melanopsin containing retinal ganglion cells (ipRGCs) send input to the superchiasmatic nucleus (master clock).

This sends output that controls physiology and behavior and entrain peripheral clocks (feeding, cortisol, temperature, melatonin).

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9
Q

What is the strongest non-photic input to the human SCN? What does it bind to?

A

Melatonin binds to MT1 and MT2 receptors on the SCN.

Melatonin then directly affects the transcription and translation of the clock genes and their protein products.

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10
Q

How does non-REM sleep differ from REM sleep?

A

In Non-REM sleep:

  • Fewer motor events
  • Body repositioning
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11
Q

What occurs during REM sleep?

A

Paralysis: postsynaptic inhibition of motorneurons, hyperpolarization of motorneuron membranes

Phasic movements: rapid eye movements and muscle twitches.

Dreams occur in REM sleep.

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12
Q

What percent of sleep is REM vs. Non-REM?

A

REM is 20% of sleep, Non-REM is 80% of sleep.

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13
Q

How does brain activity, HR, BP, and blood flow to the brain differ in deep NREM compared to REM?

A

Brain activity: decreased from wake in NRAM; increase motor and sensory similar to wake in REM.

HR: Decreased from wake in NREM; increased from NREM in REM.

BP: Decreased from wake in NREM; increased from NREM in REM.

Blood flow to the brain: No change from wake in NREM; increased from NREM in REM.

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14
Q

How does respiration, body temperature, and sexual arousal differ in deep NREM compared to REM?

A

Respiration: decreased from wake in NREM; variable and increased from NREM in REM.

Body temperature: slightly decreased from wake and shiver less in NRAM; not regulated and no shiver in REM.

Sexual arousal: rare in NREM; increased from NREM in REM.

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15
Q

How much are adults supposed to sleep? What percentage of their sleep is REM? Describe their sleep cycles.

A

Most sleep at night; a total of 6.5-8.5 hours, 25% of which is REM sleep.

  • First REM occurs after 90 minutes.
  • They have decreased stage 3/4 sleep (delta sleep which is associated with growth hormones - adults don’t need to grow anymore)
  • Wake easily
  • Frequent stage shifts
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16
Q

How much are children supposed to sleep? What percentage of their sleep is REM? Describe their sleep cycles.

A

Sleep some during the day, more at night. Total of 10-14 hours, more REM with the first 3-5 years of life.

  • First REM of the night earlier than the 90 minutes seen in adults.
  • Move stage 3/4 sleep (delta sleep - associated with growth hormone)
  • Hard to wake
  • Less stage shifts
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17
Q

What are two factors that sleep directly influences?

A

Growth hormone: tired directly to sleep and specifically to stage 3/4

Prolactin: linked to sleep

If you don’t get enough sleep, your growth hormone and prolactin will be low.

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18
Q

What are two things that are influenced by the circadian rhythm?

A

Thyroid hormone: diminished at sleep onset and decreased across sleep period

Corticol: is diminished by sleep onset; progressively increased to high levels toward the end of sleep.

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19
Q

What are the reasons why we sleep?

A
  • Energy conservation
  • Hormone synthesis and release
  • Brain plasticity (memory consolidation)
  • Immune function
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20
Q

How does sleep loss impact performace?

A
  • impaired attention
  • cognitive speed
  • visual search/decision making
  • executive functions / working memory
  • sleepiness
  • risk of accidents

After you’ve been awake for 24 hours, you’re worse than when you first woke up. This is the equivalent to beign drunk.

21
Q

What happens to GH and prolactin levels when you’re sleep deprived?

A

The levels decrease and the levels become flattened.

22
Q

What happens to cortisol and TSH levels when you’re sleep deprived?

A

Cortisol gets increased from sustained wakefulness

Jacks up TSH - stress hormones (cortisol and thyroid)

23
Q

What are the health consequences associated with inadequate or disturbed sleep?

A
  • Weight gain or obesity
  • Diabetes
  • Heart disease and stroke
  • Depression
  • Impaired performance and cognitive decline
  • Risk of accidents/drowsy driving crashes/falls
  • Cancer
  • Impaired immune function
  • Incresed pain

This is associated with getting <6-7 hours of sleep per night chronically. Long story short - adults should sleep 7 hours or more per night on a regular basis to promote optimal health.

24
Q

What are the categories of sleep disorders?

A
  • Circadian sleep/wake rhythm disorders
  • Hypersomnias
  • Sleep related breathing disorders
  • Sleep related movement disorders
  • Parasomnias
  • Insomnias
25
Q

What are circadian rhythm disorders?

A

Disorders that occur when the timing of sleep is in conflict with societal needs/demands.

26
Q

What are some examples of circadian rhythm disorders?

A
  • Jet lag
  • Shift work circadian sleep/wake disorder
  • Non-24 hour circadian sleep/wake disorder (retinal blindness)
  • Advanced sleep phase circadian sleep/wake disorder (early bird)
  • Delayed sleep phase circadian sleep/wake disorder (night owl)
  • Irregular sleep/wake (psych,dementia)
27
Q

What are two genetic circadian sleep/wake disorders?

A

Advanced: to bed early and up before the sun. 5% of the population. Complaint is usually early morning awakenings and sleepiness in the evening.

Delayed: To bed late and never up before the sun. 5% of the population. Complaint is usually that they oversleep and that sleepiness during the morning hours.

28
Q

What is the treatment for delayed sleep phase syndrome? Who can it commonly be seen in?

A

This may be more common in adolescence since there’s a slight shift to later bed time and rise time.

Most improve significantly by age 21.

Treatment is WORK (behavioral interventions). AM bright light, evening melatonin and a 365 ady schedule for wake and sleep.

29
Q

What are the five characteristics of narcolepsy with cataplexy?

A

Often presents in early adulthood with:

  • sleep attacks
  • inappropriate sleepiness
  • sleep paralysis (can’t move when you’re awake)
  • cataplexy (strong emotion or laughter causes collapse while remaining conscious)
  • vivid dreams (hypnogogic hallucinations)
30
Q

How common is narcolepsy with cataplexy (narcolepsy type 1)? What are most cases caused by?

A

Affects ~.1% of the population

Most cases are sporadic, 10% are familial

95% have very low levels of hypocretin (orexin) in CSF.

Environmental factors: antigen binding with HLA DQB1 *0602 (90% of cases)

31
Q

What role does genetics play in narcolepsy with cataplexy?

A

Increased autoantibodies against Tribbles homolog 2 (TRIB2) recently identified in patient with narcolepsy/cataplexy.

  • this protein is expressed in hypocretin cells and other neuronal cells
  • autoantibodies may be triggered by infection or other immune responses

This is uncommon in pts without cataplexy.

32
Q

What happens on the cellular level in narcolepsy with cataplexy?

A

Hypocretin (Orexin) cell loss in the hypothalamus occurs. Once these are gone, you can’t get them back.

33
Q

What is the main driver of non-REM sleep? What is the main driver of wakefulness?

A

Driver of Non-REM sleep: ventrolateral preoptic nucleus (VLPO)

Driver of wakefulness: hypocretin containing neurons in the lateral hypothalamus

34
Q

How does the hypothalamus regulate sleep?

A

Hypocretin modifies the switch between sleep and wakefulness.

Without hypocretin, you can have fast oscillations between states.

35
Q

What test would diagnose narcolepsy type 1?

A

Checking CSF hypocretin levels (would be low in someone with narcolepsy with cataplexy).

36
Q

How would you treat narcolepsy with cataplexy?

A

Lifelong condition with no cure presently. Medications can improve control.

School should provide accomodations for lectures and testing environment. Working off hours/3rd shift is a significant disadvantage.

37
Q

What are two ways to diagnose sleep apnea?

A

Type 3 study (at home): records breathing pattern in sleep such as airflow, pulse oximetry, and chest belt.

In lab polysomnography: useful for obstructive sleep anpea and periodic limb movement disorder determination. Moniters brain waves. 10x more expensive than type 3 study.

38
Q

What is the differene btween obstructive and central sleep apnea patterns?

A

Obstructive “can’t breathe” : there’s adequate respiratory effort, but there’s diminished air flow.

Central “won’t breathe” : no respiratory effort resulting in no flow (ie the brain is not telling the body to breathe).

39
Q

What occurs in the vicous cycle of obstructive sleep apnea?

A

Loss of neuromuscular compensation causes decreased pharyngeal muscle activity. This results in airway collapse and apnea.

The apnea causes hypoxia and hypercapnea which ultimately causes the body to have incresed ventilatory effort.

The patient will arouse from sleep and their pharyngeal muscle activity will be restored. Their airwy will now be open, and they will hyperventilate to fix their hypoxia and hypercapnea.

They will then fall asleep and the cycle will repeat.

40
Q

What effects does obstructive sleep apnea have on the heart?

A

It causes a fall in intrathoracic pressure (as much as 80 mmHg - this is huge!)

  • rise in RV volume and pulmonary artery resistance
  • drop in LV filling
  • shift of the interventricular septum
  • rise in systemic resistance and drop in CO
41
Q

What are the five types of central sleep apnea (“won’t breathe”)? Which are temporary?

A
  1. Cheyne-Stokes respiration
  2. High altitude central apnea (temporary)
  3. Central apnea of infancy (temporary)
  4. Narcotic related central apnea (drug induced)
  5. Congenital hypoventilation syndrome (permanent)
42
Q

Who is at risk for Cheyne-stokes respiration (type of central sleep apnea)? What causes this type of sleep apnea?

A

People with class 3-4 CHF, CNS insult frmo stroke or coma, or those with uremia.

Disruption/dissynchrony of neural pathways regulating respiration causes increase sensitivity to CO2 centrally and prolonged lung to brain circulation time (CHF) that afftects peripheral chemosensor to brain response time.

  • this results in out of phase response
43
Q

What are the three main problems that occur with cheyne-stoke respiration (central apnea)?

A
  • Delayed central response to CO2
  • Higher ventilatory response to CO2 elevation (this causes an overshoot resulting in low CO2)
  • Lower pCO2 set point for triggering ventilation
44
Q

When and how should sleep apnea be treated?

A

When mild or more than mild. If left untreated, it will likely get worse over time.

First step is WEIGHT LOSS.

Continuous Positive Airway Pressure (CPAP) is first line for symptom treatment. It improves quality of life and reduces symptoms.

45
Q

What is parasomnia?

A

Means arising from sleep.

46
Q

What are examples of parasomnias that can occur during nonREM and REM sleep?

A

NonREM:

  • Night terrors
  • Sleep walking
  • Sleep talking
  • Sleep related eating
  • Sexomnia
  • Confusional arousal

REM: nightmares and REM behavior disorders

47
Q

What are characteristics of a non-REM night terror?

A
  • Unable to wake
  • Occurs in the first half of the night
  • Maybe injury
  • Stage 3 sleep
  • Unable to recal activity/dream
  • Maybe inherited
  • Equal genders, no age limit, common in young children
48
Q

What are characteristics of a REM behavior disorder?

A
  • Easy to wake
  • Occurs in the second half of the night
  • Usually injury occurs
  • REM sleep without atonia (without lack of tone)
  • Able to reemember what they dreamed about
  • Usually men (9:1) and age >50
  • Often associated with synucleinopathies - neurodegenerative diseases like Parkinsons disease.
49
Q

What are triggers to night terrors? How can you treat them?

A
  • Job or family stress
  • Change in sleep schedule
  • New/worsening health issues
  • Medication (new or increased)

Environmental safety (make sure they wont get hurt), sleep study if other symptoms, consider benzodiazepine in refractory cases.