Download Sleep Pulmonology

Respiratory Pathophysiology: Introduction to Sleep and Sleep Medicine
INTRODUCTION:
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Importance of Diagnosing Sleep Disorders:
Associated with:
o Impaired quality of life
o Increased motor vehicle accidents
o Cardiovascular morbidity
o Increased health care costs
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Underdiagnosis of Sleep Disorders:
One of the most common medical complaints in our society
Underdiagnosed due to:
o Lack of sleep education in medical curriculm
o Patient underreporting of sleep symptoms
SLEEP:
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Definition: gradual sensory perception shut down by the brain
Mediated by active processes in the:
o Brainstem
o Thalamus
o Subcortical regions
o Cortical regions
ACTIVE (not passive) process
Sleep Regulation:
Homeostatic Mechanisms:
o Sleep need accumulates the longer one is away
o Sleep need can only be met by sleeping
o The more one sleeps, the less the need to sleep
Circadian Influences (Biologic Clock):
o ‘On’ biologic clock opposes homeostatic drive to sleep and allows for consolidated wake time
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On approximately 16 hours per day
o ‘Off’ biologic clock no longer opposes sleep and allows for consolidated sleep to occur
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Off approximately 8 hours per day
Opponent Sleep Processes:
o Homeostatic Sleep Drive:
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Proportional to the amount of previous wake and sleep debt
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Sleep debt builds throughout the day
o Altering Effects of Biologic Clock:
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Opposes the homeostatic drive
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Allows for consolidated wake during the subjective day
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Mid-day dip in alerting activity of clock occurs
Determinants of Sleep:
o Homeostatic sleep drive
o Biologic clock
o Social/external factors
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Sleep environment (noise, light, safety)
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Emotional (fear, anxiety, stress, elation, sadness(
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Effects of others (co-sleepers, infants/children)
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Drugs/medications
o Intrinsic illness:
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Psychiatric disorders (depression)
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Neurologic disorders (dementia)
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Medical disorders (pain, asthma, GERD, heart failure)
Normal Sleep:
NREM (Non-Rapid Eye Movement Sleep):
o Characteristics:
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Decreased metabolic rate
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Reduced minute ventilation (reduced tidal volume; no change in breathing frequency)
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Decreased HR and BP (parasympathetic predominance)
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Normal thermoregulation
3 Stages:
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Stage N1:
 Transition between wakefulness and sleep
 Often perceive you are still away
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Stage N2:
 True sleep
 Thoughts are now fragmented and short
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Stage N3:
 Slow wave sleep
 Little or no mentation
REM (Rapid Eye Movement Sleep):
o Characteristics:
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Dreaming
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Rapid eye movements
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Muscle atonia (except diaphragm)
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Instability of cardiopulmonary system
 Minute ventilation, HR and BP remain below wake values and fluctuate widely in
relation to rapid eye movements
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Poikilothermic state (do not shiver or sweat)
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Penile erection
o Function: unclear
Sleep Architecture:
o Definition: refers to overall structure of the sleep stages during the night
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Organization depends on age, although some generalities can be made
o General Features:
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NREM Sleep:
 Stages N1 and N2 predominate during the night and are the first stages seen during
the night
 Slow wave sleep (N3) predominates early in the night
o Amount of SWS during the night decreases with age
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REM Sleep:
 First appears about 90-110 minutes after sleep onset
 REM periods then cycle with NREM periods ~every 90 minutes
 First REM period is short, and they become longer during the later part of sleep
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Sleep in Childhood:
 Longer total sleep time
 Increased SWS (N3)
 Increased REM sleep
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Sleep in Elderly:
 Decreased sleep efficiency
 Daytime napping
 Decreased SWS (N3)
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Normal Sleep Time:
 Number of hours a person needs to feel alert/awake throughout the day
 Generally 7-8 hours
Effects of Sleep Deprivation:
Alertness and vigilance become unstable and unreliable
Cognitive slowing occurs and time pressure increases errors
Tasks may begin well but performance declines with increasing rapidity
Growing neglect of activities judged to be nonessential (loss of situational awareness)
Loss of perceptive abilities
Involuntary sleep attacks begin to occur
Risks of accidents and crashes increase
Sleep Hygiene:
Definition: refers to daily activities and habits that are consistent with and/or promote the maintenance of good
quality sleep and full daytime alertness
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Good Sleep Hygiene:
o Develop regular sleep habits
o Slow down and unwind before bed
o Bedroom should be dark, cool and quiet
o Daily exercise (best in late afternoon)
o Light snack before bedtime
Bad Sleep Hygiene:
o Napping during the day
o Forcing yourself to sleep
o Taking problems to bed
o Strenuous mental and physical activities just before bedtime
o Use of caffeine, alcohol or tobacco just before bedtime
o Reading, eating or watching TV in bed
SLEEP DISORDERS:
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Classification:
Insomnias: disorders that manifest as either difficulty initiating or maintaining sleep and are NOT secondary to
other medical/psychiatric disorders
o Examples:
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Adjustment sleep disorder
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Pyschophysiologic insomnia
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Childhood behavioral insomnias
 Limit-setting sleep disorder
 Sleep-onset association disorder
Sleep-Related Breathing Disorders: characterized by abnormal breathing at night
o Examples:
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Obstructive sleep apnea
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Central sleep apnea
Hypersomnias (Not Related to Breathing Disorder): characterized by excessive daytime sleepiness without
evidence of a breathing disorder
o Examples:
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Narcolepsy
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Insufficient Sleep Syndrome
Circadian Rhythm Disorders: characterized by misalignment of the patient’s sleep pattern from that which is
desired or regarded as the norm
o Examples:
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Shift work sleep disorder
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Time zone change syndrome
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Delayed sleep phase syndrome
Parasomnias: clinical disorders that are undesirable phenomena that occur during sleep
o More often disruptive to a bed partner than to the patient
o Many predominate in childhood
o Examples:
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Associated with NREM Sleep (often at the beginning of the night):
 Sleep walking
 Night terrors
 Confusional arousal
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Associated with REM Sleep (often at the end of the night):
 Nightmares
 Sleep paralysis
 REM behavior disorder (ie. act out dreams)
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Other:
 Sleep enuresis (bed wetting)
 Sleep related eating disorder
Sleep-Related Movement Disorders: characterized by abnormal movements during sleep
o Examples:
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Restless Leg Syndrome
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Bruxism
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Diagnosis:
Screening: starts with primary care physician
o All patients should be asked the following:
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How many hours of sleep do you get per night?
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Do you have trouble falling asleep or staying asleep during the night?
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Are you excessively sleepy during the day?
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Do you snore?
Polysomnography: overnight study that monitors multiple body functions simultaneously
o EEG: electrodes placed on scalp to monitor brain electrical activity and stage sleep
o EOG: monitors eye movements and used to stage sleep
o EMG:
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Chin: helps stage sleep
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Anterior Tibilalis: allows for diagnosis of movement disorders
o ECG: diagnose arrhythmias during the night
o Airflow at nose and/or mouth: diagnose hypopneas/apneas
o Respiratory movements: differentiation of apneas
o Pulse oximetry: measure oxygen saturation during the night
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INSOMNIA:
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Basics:
Refers to persistent difficulty initiating or maintaining sleep
Can be both of the following:
o A symptom (not a cause) of a condition that interferes with sleep
o A primary disorder (no other associated medical condition)
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Types:
Transient Insomnia (Adjustment Sleep Disorder):
o Usually <1 week
o Precipitated by anxiety/emotion producing life event
Short-Term Insomnia:
o Up to several weeks
o Temporary stressful experiences of inability to adjust sleep-wake cycle to new needs
Chronic Insomnia:
o Months to years
o Many possible causes
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Epidemiology:
35% of Americans complain of insomnia in a given year
o 10% complain of chronic, daily insomnia
o More likely in women and the elderly
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Common Causes of Chronic Insomnia:
Sleep Related Disorders:
o Inadequate sleep hygiene
o Disruptive or irregular sleep-wake schedule
o Obstructive sleep apnea
o Restless Leg Syndrome
Medication/Drug-Related:
o Extended use of sleep medications or other medications that interfere with sleep
o Excessive use of alcohol or other drugs of abuse
Medical Disorders:
o Chronic pain syndromes
o GERD
o Asthma
Psychiatric Disorders:
o Particularly mood and anxiety disorders
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Symptoms:
Nocturnal Complaints:
o Delayed sleep onset
o Early morning awakening
o Multiple, frequently prolonged awakenings
o Insufficient sleep time
Daytime Complaints: these need to present in order for insomnia to be a disorder rather than a complaint*
o Being unrefreshed in the morning and/or throughout the day
o Feeling fatigued or sleepy during the day but with the inability to nap
o Poor concentration, attentiveness and memory
Consequences:
Impairments in daytime function
Poor school/job performance
Impairments in interpersonal relationships
Impaired driving skills
Self-medication
Determinants of Primary Insomnia:
General: usually the result of an interaction of biological, physical, psychological and environmental factors
o Physiological Factors:
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Heightened autonomic arousal
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Increased metabolic rate
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HPA dysregulation
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Immune dysfunction
o Psychological Factors:
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Anxiety
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Dysphoria
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Overresponsiveness to stress
o Behavioral Factors:
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Conditioned arousals
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Poor sleep hygiene
o Cognitive Factors:
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Excessive cognitive activity
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Excessive problem solving
Hyperarousal Theory:
o Insomniacs have a generalized disorder of hyperarousability
o Poor sleep is the nighttime manifestation of this disorder (not necessarily the cause of daytime
dysfunction)
o Compared to normals:
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Have higher rates of depression and anxiety
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Score higher on scales of arousal
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Have more night-to-night variability in sleep
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Have more beta EEG activity at sleep onset (seen during memory processing/performing tasts)
Cognitive Theory:
o Insomniacs are prone to rumination and worry
o Increased problem solving leads to sleeplessness
o If insomnia becomes chronic, worry about sleep all day
Behavioral Theory:
o Stimulus Control Mode: normal cues associated with sleep become associated with wakefulness
o Chronic Insomnia:
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All insomniacs have predisposing factors
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Insomnia begins with a precipitating factor
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Insomnia becomes chronic with onset of perpetuating factors and conditioned arousals (these
are the target of CBT in the management of insomnia)
Psychophysiologic Insomnia:
General: most common primary insomnia
Description:
o Disorder of somatized tension and learned sleep-preventing associations
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Stimuli surrounding bed time become conditioned triggers to arousal
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Patient makes effort to fall asleep unaware of the effect of this effort on causing arousal
Key Details in History:
o Sleepy until the start of bedtime
o Frequent racing thoughts once in bed
o Tries to force self asleep but feels tense in bed
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Worries about getting to sleep all day
Sleeps better on a couch or away from home (ie. in a hotel)
EXCESSIVE DAYTIME SLEEPINESS (EDS):
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Definition: no exact definition
Feeling sleepy at times of the day other than after lunch and early evening (normal to feel sleepy at these times)
Feeling sleepy during situations in which alterness is warranted (meetings, driving etc.)
Implies that the patient is SLEEPY; not just fatigued, lacking in energy or depressed
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Physiologic Sleep Tendency:
Definition: tendency for sleep to occur in the absence of alerting factors
o How much you need to sleep, particularly if you strip away factors keeping you awake
Determinants of Physiological Sleepiness:
o Quantity of sleep
o Quality of sleep
o Circadian rhythm
o Drugs
o CNS
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Manifest Sleep Tendency:
Definition: how sleepy you are after introduction of motivating factors (ie. light, noise, motivation)
o Has a longer sleep latency (time to fall asleep) than physiologic sleepiness
o Approaches physiologic sleepiness as you strip away motivating factors
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Epidemiology of EDS:
38% of Americans report EDS that interferes with daily activities at least a few days a month
19% report EDS interfering with activities at least a few days per week
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Consequences of EDS:
Problems in vigilance, cognitive function, memory/concentration and mood
Lead to deterioration in:
o School/job performance
o Social relationships and family life
o Driving skills
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Diagnosis:
Multiple Sleep Latency Test (MSLT): objective test of sleepiness that measures the tendency to fall asleep while
lying in a quiet, dark room at 4 times during the day
o Based on assumption that sleeping is a physiological need that leads to a tendency to fall asleep
o Normal well rested adults:
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Daytime sleep latency is >15 minutes
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There should be no REM sleep during the 20 minute nap
Epworth Sleepiness Scale (ESS): questionnaire designed to measure the general level of excessive daytime
sleepiness or sleep propensity in adults (quantifies subjective sleepiness)
o Measures the chance of dozing off in 8 situations that most adults have found themselves in during the
last month
o Scores ≤10 considered normal
o Higher scores associated with higher likelihood of falling asleep on MSLT, but does not necessarily
correlate with falling asleep faster (ie. having more severe sleepiness)
o Useful for tracking patient’s symptoms (score generally decreases with treatment)
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Differential Diagnosis:
Behaviorally induced insufficient sleep
Obstructive sleep apnea
Narcolepsy
Restless Leg Syndrome/Periodic Leg Movement Disorder
Disorders of sleep-wake cycle (shift work, sleep phase delay, jet lag)
Drug effect (antihistamines, narcotics, anti-seizure meds, neuroleptics, sedative-hypnotics)
BREATHING DURING SLEEP:
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Ventilatory Response: response to both CO2 and O2 decreased during NREM and REM sleep
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Apneic Threshold: PaCO2 level below which a subject will become apneic during NREM sleep
Does not occur during wakefulness
Infrequently observed during REM sleep
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Higher threshold indicates greater propensity to sleep-disordered breathing
o Men have higher apneic threshold than women
o Subjects with sleep apnea have higher threshold than controls
Ventilatory Patterns During Sleep:
Stage N1: can be irregular with periodic breathing
Stage N2: regular breathing
REM: irregular breathing associated with rapid eye movements
Summary:
o Tidal volume and minute ventiltation decrease with no change in breathing frequency
o Decreased metabolic rate
o Increased PaCO2
Upper Airway During Sleep:
Decreased upper airway dilator activity and response to negative pressure during sleep (particularly REM)
Decreased upper airway caliber results in:
o Increased upper airway resistance
o Increased compliance and collapsibility
OBSTRUCTIVE SLEEP APNEA:
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Definition:
Characterized by recurrent episodes of upper airway collapse and obstruction during sleep
Episodes of obstruction associated with recurrent oxyHb desaturations and arousals from sleep
If associated with daytime sequelae, termed “Obstructive Sleep Apnea Syndrome” (OSAS)
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Diagnosis:
Polysomnography: identify apneas and hypopneas by combining airflow and respiratory movements
o Apnea: complete cessation of airflow for 10 seconds
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Obstructive: persistent ventilatory effort seen
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Central: no ventilatory effort
o Hypopnea: 20-50% reduction in airflow associated with either an arousal or a 2-4% drop in oxygen
saturation
Apnea-Hypopnea Index (AHI): for the whole night, the total number of apneas and hypopneas are divided by the
total sleep time
o Normal AHI for the night is <5 events per hour of sleep
o Abnormal AHI:
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Mild: 5-15
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Moderate: 16-30
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Severe: >30
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Epidemiology of Obstructive Sleep Apnea:
More common in men:
o 9-25% of men aged 30-60 (prevalence is 4%)
o 4-9% of women same age (prevalence is 2%)
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However, prevalence increases after menopause
o Ratio of men:women is ~2-3:1
African Americans:
o Prevalence in 30-60 age range similar to whites, but severity is thought to be higher
o Prevalence in younger (<25) and older (>65) populations higher in blacks
Age:
o Prevalence increases with age
o Prevalence in children unknown (estimated at ~6%)
Familial Forms:
o There is evidence of familial tendencies for OSA, independent of family history of obesity
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Associated Conditions:
Obesity (most important)*
Adenotonsillar hyperplasia (particularly in children and young adults)
Hypothyroidism
Craniofacial skeletal abnormalities (retrognathia, micrognathia)
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Pathophysiology:
Upper Airway Anatomy:
o Smaller upper airway
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Increased volume of tongue, lateral pharyngeal walls and total soft tissue
Increased length of the soft palate
Inferiorly placed hyoid bone
Surround pressure from:
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Tonsils
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Tongue
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Pharyngeal fat
Central Control of Breathing:
o Abnormal control of breathing during sleep
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Increased propensity to develop central apnea (increased apneic threshold)
Consequences:
Excessive Daytime Sleepiness:
o Clear link
o Automobile accidents more prevalent in patients with OSA
CV Morbidity:
o HTN: independently associated with OSA (after correction for confounding factors)
o Metabolic Syndrome: primarily increased insulin resistance
o Heart Disease: OSA associated with left ventricular hypertrophy and diastolic dysfunction
o Cerebrovascular Disease: increased risk of stroke
o Pulmonary HTN and Right Sided Heart Failure: uncommon in OSA patients
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Unless there is evidence of lung disease or daytime hypoxemia
Mortality: higher in patients with untreated OSA
Symptoms:
While Asleep:
o Snoring (habitual, loud, irregular, bothersome to others)
o Gasping or snorting
o Witnessed apneas
o Sudden or jerky body movements
o Restless sleep
While Awake:
o Wake up feeling unrefreshed
o Morning headache
o Morning dry and sore throat
o Excessive daytime sleepiness
o Personality changes
o Problems with memory/concentration
Treatment:
Conservative Measures:
o Weight loss: minimum of 10-15% drop in current body weight
o Alcohol avoidance: for at least 4-6 hours prior to bed
o Sleeping on side: apnea is worse on back
o Treatment of sinus symptoms
Continuous Positive Airway Pressure (CPAP):
o Splints upper airway to prevent it from collapsing
o Improves EDS, cognitive performance and quality of life
o Modifies inflammatory/metabolic abnormalities associated with metabolic syndrome
o Long-term compliance is an issue
Dental Devices:
o Move tongue/mandible forward
o Effective in patients with AHI <40/hr (although exact role in treatment of OSA unclear)
o Compliance may be better than CPAP
Surgery:
o Indicated for patients with surgically correctable abnormality (ie. adenotonsillar hyperplasia)
o Otherwise considered a 2nd or 3rd option due to overall low success rates
NARCOLEPSY:
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Definition: condition characterized by
Irresistible episodes of sleep of short duration
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Inappropriate intrusion of REM sleep into a person’s waking hours
Epidemiology:
Incidence: 1/1000
Prevalence: 100,000-200,000 Americans (both sexes affected equally)
Age of Onset: 15-25 years of age
Pathophysiology:
Closely associated with HLA DQB1*0602 (but minimal evidence that it is an autoimmune disease)
Associated with loss of hypocretin (orexin) neurons in the hypothalamus
o Control/coordinate other wake centers in the brain
Symptoms:
Excessive Daytime Sleepiness: irresistible and unwanted sleep attacks that are usually followed by a refractory
period
Cataplexy: sudden brief loss of muscle control that is usually precipitated by strong emotions (ie. laugher,
surprise, anger)
o Pathognomonic of narcolepsy: seen in 80% of patients (ie. if you have cataplexy, you have narcolepsy;
but you do not have to have cataplexy to have narcolepsy)
Sleep Paralysis: feeling totally paralyzed even though awake
Hypnagogic Hallucinations: extremely vivid dreams as falling asleep
Automatic Behavior: wake up and realize that you have been actively doing something (ie. driving, cooking)
Diagnosis:
Polysomnography:
o Latency time to REM sleep is characteristically less than 60 minutes
o Sleep is often poor with frequent awakenings for no apparent reason
Multiple Sleep Latency Test:
o Mean sleep latency <7 minutes
o Two or more naps have REM period within 10 minutes of sleep onset
Treatment:
o EDS: usually treated with stimulants
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Modafinil
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Armodafinil
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Methylphenidate
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Dextroamphetamine
o Cataplexy:
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TCAs (protryptyline, imipramine)
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SSRIs (fluoxetine, sertraline)
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Sodium oxybate
o Behavioral:
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Avoidance of triggers
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Short, scheduled naps
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Optimize nocturnal sleep hygiene
RESTLESS LEG SYNDROME:
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General:
Often presents as insomnia, but can present as EDS
Prevalence of ~4-5% (increases with age)
Underdiagnosed and frequently misdiagnosed
May be associated with ADHD in children and adolescents
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Characteristic Features:
Urge to move, usually due to uncomfortable sensations (creeping/crawling/aching), primarily in the legs
Motor restlessness expressed as activity (ie. walking) that can relieve the urge to move
Worsening of symptoms by relaxation; improved if legs are moved
Day to day variability but generally worse in the evening/early in the night
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Supportive Features:
Family history in ~50% of cases (earlier onset in these cases)
o Increased prevalence in first degree relatives
o Autosomal dominant trait with incomplete penetrance
Presence of periodic limb movements during sleep
Response to dopaminergic therapy
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Associated Conditions:
Iron deficiency (particularly ferritin <50; DA synthesis requires iron)
Renal insufficiency
Pregnancy
Parkinson’s Disease
Pharmacologic Management:
Dopamine agonists (ropirinole, pramipexole, levodopa)
Opiates (oxycodone, propoxyphene)
Anticonvulsants (gabapentin, enacarbil)
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