Sleep Cycle Pathophysiology Flashcards
Define Sleep
Unconsciousness from which a person can be aroused by sensory or other stimuli
Define Coma
Unconsciousness from which a person cannot be aroused
For those 65 y.o or olders,
80% report sleep-related disturbances
Electroencephalogram
Monitors state of sleep
Uses scalp electrodes to monitor electrical signals produced by the surface of the brain
If they stimulate the ascending activating system,
You wake up
If they stimulate the thalamus,
You fall asleep
What happens during sleep?
Brain cleans itself
Waste products of brain metabolism are removed from the interstitial space among brain cell where they accumulate
- Faster clearance during sleep as compare to awake
What happens if you don’t sleep?
Potentially toxic metabolites that are there as a result of a working brain won’t be cleared
Phases of Sleep
First Non-Rapid Eye Movement sleep (NREM) and then shift to REM sleep
- Typically 4-6 cycles of REM and NREM (each night with each cycle lasting 90 minutes)
Define REM
Active or desynchronized sleep
Define NREM
Quiet, restful, or slow wave sleep
- Dreamless sleep
*Stage 1 of NREM
Between the state of awake and sleep
Background theta waves
- Where you get the falling sensation
*Stage 2 of NREM
Background theta waves superimposed with burst of sleep spindles and K complexes
- Longest portion
*Stage 3 of NREM
*Slow wave or delta sleep
Reduction in brain and body temperature
*Eye movements are absent and muscle tone is very low
Reduced BP, HR, RR, cortisol and thyroid hormone levels, increased growth hormone
REM Sleep last for how long
5-30 minutes
25% of total sleep
REM Sleep is characterized by:
Low amplitude, mixed frequency, desynchronized EEG activity (similar to awake state)
Brain is activated
*Burst of bilateral eye movements, active dreaming and fluctuations in RR and HR
Gets longer throughout the night
Sleep in Newborns
18-20 hours of sleep per day with poor segregation between REM and NREM
Start in REM and NREM is only ~50 minutes
By 3 years old, sleep
Segregate sleep and wakefulness into distinct periods
Sleep in Adolescence
Reduced slow wave delta sleep
Sleep in Older age
Reduction in length of sleep and increase in number or awakenings
Reduced slow wave delta sleep
Fall asleep earlier and wake up earlier
Ascending Reticular Activating System (ARAS) involves what neurotransmitters?
Adrenergic (NE)
5HT
DA
Histamin
ARAS promotes:
Wakefulness and arousal through inhibition of cholinergic cells that promote REM sleep through NE and 5HT
Ventrolateral Preoptic Area (VLPO) involves what neutrotransmitters?
GABA
VLPO promotes
Sleep through neuron firing that decreases ARAS activity
Orexin/Hypocretin Peptide System promotes:
smooth transition from awake to sleep or vice versa
- Located in the lateral hypothalamus (LAT)
How does NREM sleep get initiated?
Driven by VLPO GABAergic neurons which are active during sleep and inhibit TMN histaminergic neurons and (NE, DA, 5HT)
Sleep and Wake Promoters
When the TMN is active and histamine is released, the wake promoter is on and sleep promoter is inhibited
When VLP is active and GABA is released in TMN, the sleep promoter is on and the wake promoter is inhibited
How is REM sleep initiated?
During NREM sleep, VLPO neurons start to inhibit orexin neurons (which normally excites REM-off NE and 5HT cells)
So, VLPO inhibits REM-off monoamineric cells which disinhibits REM-on cholinergic cells of the pontine tegmentum
Pontine tegmentum cholinergic cells also:
Project to medulla and spinal cord to initiate many of the physical manifestations of REM sleep (muscle atonia, eye movement)
**What cells promote REM-on and are inhibited during wakefulness?
Pontine tegmentum (PPT and LDT) Cholinergic Cells
Sleep + homeostatic drive?
Partially controlled
Related to the length of prior wakefulness
Drive increases throughout the day
MOA is poorly understood but involves adensosine**
Adenosine function
May modulate the sleep generating effect
Carreine and methylxanthines function
Block adenosine receptors to promote activity and attention
Circadian Rhythm Function and how it does it?
Sleep regulation
Controlled by Suprachiasmatic nucleus (SCN)
What is the SCN and how does it work?
Primary pacemaker of neuroendocrine phythms
Direct neural input from the retina to the SCN allows the SCN to be closely linked to light and dark cycles
Circadian + Homeostatic
Circadian: wake drive comes from input (light, melatonin, activity) to the SCN
Homeostatic: sleep drive increases the longer one is awake and decreases with sleep
- As the day progress, circadian wake drive diminishes and homeostatic sleep drive increases until the VLPO sleep promtor triggers the release of GABA and TMN inhibits wakefulness
Excessive arousal during the day leads to
Hyper-vigilance during the night which leads to insomnia
Deficient arousal during the day leads to
Excessive sleepiness and sleep attacks
Cortico-Thalamic Circuit does what?
Thalamus has a critical role in regulating arousal by controlling amount of sensory input that reaches the cortex
Sleep/wake disorders = problem with:
Thalamic filters -
Insomnia + Thalamic FIlters
Filters fail to filter out sensory input in the cortex at night
- Boost the filter with GABA-enhancing agents
Daytime sedation + Thalamic FIlter
Filters filter out too much sensory input to the cortex during the day
- Reduce the filter with DA agents or stimulants
