כשהשעון הביולוגי מזייף יעקב סיון

Transcription

1 כשהשעון הביולוגי מזייף יעקב סיון מכון ריאות, בי"ח "ספרא" לילדים, המרכז הרפואי שיבא חיפ"פ, גליליון,

2 Adjustment insomnia Paradoxical insomnia Insomnia due to medical cond. Insomnia due to drugs Childhood insomnia Psychophysiologic isomnia Inadequate sleep hygiene 9% Insomnia Snoring (8-10%) OSAS (2-3%) CSAS 70% Sleep Related Breathing Disorders Idiopathic Hypersomnia Narcolepsy (0.05%) Kleine-Levine synd. 7% Hypersomnia sleep disorders Parasomnia 4% Disorders of Arousal Sleepwalking (5%) Sleeptalking Night Terrors (2-5%) REM associated Circadian Rhythm Sleep Disorders 8% Delayed sleep phase syndrome (7% teens) Advanced sleep phase syndrome Jet lag, Shift shift work Free running Sleep Related Movement Disorders 2% Rhythmic movement dis. (3-15%) Periodic Limb Movement Syn.

3 Average hours of night sleep by country - adults France 8:24 Finland 8:12 UK 8:11 Hungary 8:08 Belgium 8.01 Denmark 8:00 Estonia 7:52 USA 7:00 Israel 6:30

4 The use of Electricity for lighting is in no way harmful to health, nor does it affect soundness of sleep.

5 The 1879 revolution

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7 Circadian physiologic alterations Lowest pain sensitivity Reduced daytime alertness Max. HR & metabolism Asthma attacks Acute MI Menopausal hot flashes independent of light exposure

8 cortisol melatonin The sleep-wake pattern has only a minimal effect on pattern of secretion

9 Diurnal variation Chronotherapy adjustment of meds to the activity of metabolizing or activating enzymes

10 Chronobiology International 2010 Bedtime chronotherapy for hypertension reduces cardiovascular risk compared to conventional therapy

11 Relative risks (with 95% confidence intervals) of CVD events (adjusted by age, sex, and diabetes) as a function of time-of-day of hypertension treatment

12 The circadian rhythm is independent of light ( self sustained ) ל ו י ו ו ו חו חי ו יי ח ו יו י י

13 Biological clock endogenous pacemaker master clock Biological clock - suprachiasmatic nucleus (anterior hypothalamus, 1972) Hypothalamus, destruction causes loss of many CRs including sleep-wake. Melatonin melatonin receptors in all body organs

14 Biological master clock - synchronization Entrainment, synchronizers: Morning light Noise Food, meals time Daily activity, social interactions Specific stimuli ~ 24 h. + Temperature: phase shift but not circadian change (temperature compensation)

15 Peripheral clocks synchronization 24 h. not synchronized by light same machinary central master clock ~ 24 h. HR, BP Endocrine Renal synchronization Liver pancreas Phase shift Desynchronized meals

16 circadian desynchrony at the cellular, tissue, and behavioral levels may play much more widespread roles in human medical and psychiatric pathologies % of the human (and animals) genes display circadian behavior. Hence, protein, enzymes (and lipids) levels show circadian levels. Examples: insulin, leptin, ghrelin, adiponectin, CS, glucose, TG, cholesterol, HDL

17 9 genes responsible for intracellular mechanisms of the circadian oscillator. This molecular circadian clock machinary exists and can produce circadian rhythms in most or all body cells. Transcription-translation loop Takes +24h. positive feedback negative feedback

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19 Sleep homeostasis Sleep homeostat accumulation and dissipation of sleep pressure (adenosine = neuromodulator) Propensity to be awake (aroused, alert) Ability to stay awake: Duration of prior wakefulness Internal body time (circadian clock) Propensity to be asleep (sleep pressure) Circadian cycle/clock regulates the daily arousal / sleep propensity. Arousal increases throughout the day, maximal immediately before plasma melatonin increase (circadian power overcomes accumulated aleep homeostatic load).

20 Actigraphy

21 normal 10:00 16:00 22:00 4:00 10:00

22 Non-24 sleep-wake syn. (free runner)

23 Sleep disorders associated with circadian rhythm abnormalities Delayed sleep phase syndrome Advanced sleep phase syndrome Non-24 h. sleep-wake syndrome Jet lag Shift workers Blind individuals Irregular sleep-wake pattern Aging

24 Delayed Sleep Phase Syndrome, DSPS 15 M sleep onset and wake times that are usually delayed 3 to 6 hours. most alert in the late evening -night people. 7% in adolescents and young adults.

25 melatonin onset Enforced conventional wake times result in chronically insufficient sleep and excessive daytime sleepiness.

26 Delayed Sleep Phase Syndrome - Pathophysiology Genetic autosomal dominant, polymorphism in circadian genes. Behavioral induced late activities, evening exposure to light, late wake-up and late exposure to morning entrainment. "All illnesses have some hereditary contribution. Genetics loads the gun and environment pulls the trigger" (Francis Collins,Director, National Human Genome Research Institute)

27 ולטן ל ו ב ל ו כחול י ל ופסין גי ל חו nm( ) כ י י לטו ין LCD computer and phone screens emit a higher percentage of melatonin-blocking blue wavelengths than most light bulbs. Light from electronic screens decreases melatonin levels may cause insomnia and daytime sleepiness.

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29 Many people cannot switch to amber lights at night, because they work a night shift or spend their evenings on a computer. Blue-blocking glasses filter out up to 99% of the blue wavelengths. Late night computer users are able to fall asleep an average of 43 minutes earlier when wearing blue blocking glasses.

30 Delayed Sleep Phase Syndrome - Treatment sleep hygiene Behavioral sleep hygiene, avoidance of evening arousing activities and caffeine Light morning entrainment 5,000 10,000 lux Blue light restriction evening Melatonin Treatment results in both wake-sleep time and physiologic changes (temp.)

31 Jet lag > 5 time zones Inability to sleep, premature awakening Inappropriate sleepiness Adaptation to time zone at different rates: Asymmetry effect (east vs. west) age

32 Gradual reentrainement 2 h./day influenced by light intensity

33 Jet Lag Treatment Zolpidem (Ambien, Stilnox) before eastbound transatlantic nighttime flight and/or at bedtime in the new time zone Prevention treatment (light + early awakening + melatonin timing)

34 SHIFT-WORK SLEEP DISORDER Definition: 10% of shift workers Insomnia (after night shift) or excessive sleepiness (during night work) temporally associated with a work period that occurs during the habitual sleep phase. Most night shift workers do not adapt: Light-dark cycle opposes their adaption Most night-shift workers revert to daytime wakefulness and nighttime sleep on days off Total sleep time decreases

35 SHIFT-WORK SLEEP DISORDER fall asleep 34 min. faster Sleep efficiency 4.6% higher Sleep fragmentation 4.2% lower Cardiovascular morbidity Depression Type II diabetes Overweight / obesity / metabolic dysregulation Malignency

36 ליל טוב כ ס עי טוב י