12 - Sleep Pathophysiology Flashcards
What three parts of the brain regulate sleep and wake? What results from lesions in each location?
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)
What two things contribute to the sleep-wake cycle?
The circadian rhythm and sleep-wake homeostasis (both of which are influnced by genes)
What is the homeostatic process that regulates sleep and wakefulness?
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).
What are the three components of the sleep promoting system?
- Gamma-Aminobutyric acid (GABA)
- Ventrolateral preoptic area (VLPO)
- Median preoptic nucleus (MnPN)
Adenosine build up results in us becoming more sleepy throughout the day.
Describe the circadian process that regulates sleep and wakefulness?
It goes through ebs and flows; you’re most alert right before you fall asleep.
What are a few components of the arousal/wake system?
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).
What impacts your circadian rhythym?
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
What is the master clock of hte circadian rhythm? What provides it input and what does it send output to?
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).
What is the strongest non-photic input to the human SCN? What does it bind to?
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.
How does non-REM sleep differ from REM sleep?
In Non-REM sleep:
- Fewer motor events
- Body repositioning
What occurs during REM sleep?
Paralysis: postsynaptic inhibition of motorneurons, hyperpolarization of motorneuron membranes
Phasic movements: rapid eye movements and muscle twitches.
Dreams occur in REM sleep.
What percent of sleep is REM vs. Non-REM?
REM is 20% of sleep, Non-REM is 80% of sleep.
How does brain activity, HR, BP, and blood flow to the brain differ in deep NREM compared to REM?
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.
How does respiration, body temperature, and sexual arousal differ in deep NREM compared to REM?
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.
How much are adults supposed to sleep? What percentage of their sleep is REM? Describe their sleep cycles.
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
How much are children supposed to sleep? What percentage of their sleep is REM? Describe their sleep cycles.
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
What are two factors that sleep directly influences?
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.
What are two things that are influenced by the circadian rhythm?
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.
What are the reasons why we sleep?
- Energy conservation
- Hormone synthesis and release
- Brain plasticity (memory consolidation)
- Immune function
What happens to GH and prolactin levels when you’re sleep deprived?
The levels decrease and the levels become flattened.
What happens to cortisol and TSH levels when you’re sleep deprived?
Cortisol gets increased from sustained wakefulness
Jacks up TSH - stress hormones (cortisol and thyroid)
What are some examples of circadian rhythm disorders?
- 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)
What happens on the cellular level in narcolepsy with cataplexy?
Hypocretin (Orexin) cell loss in the hypothalamus occurs. Once these are gone, you can’t get them back.
How does the hypothalamus regulate sleep?
Hypocretin modifies the switch between sleep and wakefulness.
Without hypocretin, you can have fast oscillations between states.
What is the differene btween obstructive and central sleep apnea patterns?
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).
What occurs in the vicous cycle of obstructive sleep apnea?
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.
What effects does obstructive sleep apnea have on the heart?
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
Who is at risk for Cheyne-stokes respiration (type of central sleep apnea)? What causes this type of sleep apnea?
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
What are the three main problems that occur with cheyne-stoke respiration (central apnea)?
- 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
When and how should sleep apnea be treated?
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.
