PhysiologyNeurophysiologySleep physiology

MMed Phase I · Neurophysiology · Lesson 19

Sleep is not one state.
It is two, alternating all night, and they are opposites.

01

Orientation

Rapid review

Estimated study time

About 50 minutes

Plus the time it takes to redraw this lesson’s figures from memory, which is the fastest way to find out what you have not understood.

Why it matters

Where this shows up

Sleep physiology is the direct route into obstructive sleep apnoea, postoperative respiratory risk and delirium — three of the commonest perioperative problems in an ageing surgical population.

Learning outcomes

By the end of this lesson you should be able to:

  1. Describe the EEG signature of each non-REM stage and of REM sleep, and name the features unique to stage 2.
  2. Draw a normal adult hypnogram and state how cycle length and stage proportions change across the night.
  3. Compare non-REM and REM sleep across the cardiovascular, respiratory, thermoregulatory, muscular and endocrine systems.
  4. Explain the two-process model of sleep regulation and name the neural structures behind each process.
  5. State the similarities and the crucial differences between sleep and general anaesthesia.
  6. Explain why obstructive sleep apnoea worsens in REM sleep and in the postoperative period, and describe postoperative sleep architecture.

Together these settle one syllabus objective: Sleep architecture and its regulation. Tick it on the Physiology objective list once you can do all of the above without notes.

The minimum high-yield framework

  1. Two types. Non-REM in three stages (N1, N2, N3) and REM.
  2. Non-REM = quiet brain, movable body. EEG slows and grows, metabolism falls, tone is reduced but present.
  3. REM = active brain, paralysed body. Desynchronised EEG resembling wakefulness, dreaming, and near-complete skeletal muscle atonia.
  4. Cycle length about 90 minutes, four to six cycles a night. Slow-wave sleep dominates the first third; REM periods lengthen towards morning.
  5. Adult proportions — approximately N1 5%, N2 45%, N3 25%, REM 25%.
  6. Stage 2 signature: sleep spindles and K complexes.
  7. REM is autonomically unstable — irregular heart rate, blood pressure and respiration, and the loss of accessory and upper airway muscle tone that makes obstructive apnoea worst here.
  8. Two-process regulation: homeostatic sleep pressure (process S, adenosine) and circadian drive (process C, suprachiasmatic nucleus).
02

The state

Defining sleep

Two features distinguish it from every other state of reduced responsiveness, and both are required.
03

Architecture

The stages of sleep

Four stages, each with an EEG signature, and one of them defined by two named waveforms.
StageEEGEye movementMuscle toneNotes
Awake, eyes closedAlpha (8-13 Hz), occipitalSlow rovingNormalAlpha is abolished by opening the eyes
N1Low-voltage mixed frequency, theta (4-7 Hz); alpha disappearsSlow rollingSlightly reducedThe transition to sleep. Around 5% of total sleep time; easily woken, and subjects often deny having slept
N2Theta background with sleep spindles (11-16 Hz bursts) and K complexesAbsentReducedThe largest single stage, around 45%. The spindles are generated by the thalamic reticular nucleus
N3 (slow-wave sleep)High-voltage delta (0.5-4 Hz, over 75 µV) occupying more than 20% of the epochAbsentReducedAround 25%. The deepest stage, hardest to rouse from, and the stage of night terrors, sleepwalking and enuresis. Growth hormone is secreted here
REMLow-voltage, desynchronised, fast — resembling wakefulness, hence 'paradoxical sleep'Rapid, conjugate, burstsAtonia, apart from diaphragm and extraocular musclesAround 25%. Vivid dreaming, penile or clitoral tumescence, and autonomic instability
04

The night

The hypnogram

One diagram that carries the cycle length, the ordering of the stages and the change across the night.
Original teaching diagram · representative night

A normal young-adult hypnogram

Four features to be able to draw. Sleep is entered through non-REM stage 1, never directly into REM. The first descent is the deepest, with the long block of slow-wave sleep in the first third of the night. The cycle repeats at roughly 90-minute intervals, giving four to six REM periods a night. And the balance shifts across the night: slow-wave sleep dominates early and REM periods lengthen towards morning, so the last REM period is the longest and often ends in waking.

Brief arousals are normal and are drawn. In an adult, REM occupies about a quarter of total sleep time — half in the full-term neonate, and falling again in old age. This is a representative night: no source publishes a per-minute trace, so the shape encodes the stated timings rather than measured data.

WAwakeREMN1Non-REM 1N2Non-REM 2N3Non-REM 3 (slow wave)012345678Hours from sleep onsetSlow-wave sleep is front-loaded; REM periods lengthen towards morning.
  1. Sleep is entered through non-REM, descending N1 → N2 → N3. Entering sleep directly into REM in an adult is abnormal and is a diagnostic feature of narcolepsy.
  2. The cycle is approximately 90 minutes, giving four to six cycles in a normal night.
  3. Slow-wave sleep is concentrated in the first third of the night and may be absent altogether from the last cycles.
  4. REM periods lengthen progressively, so the longest REM period is the last one before waking — which is why dreams are usually recalled from the early morning.
  5. Brief arousals to wakefulness are normal and are usually not remembered.
AgeTotal sleepREM proportionSlow-wave sleep
Neonate16-18 hAbout 50%, and sleep may be entered through REMPresent, and cycles are shorter — about 50-60 minutes
Child10-12 hFalling towards adult valuesAbundant
Young adult7-8 hAbout 25%About 25%
ElderlyReduced, and fragmentedApproximately preserved as a proportionMarkedly reduced, with more frequent nocturnal arousals
05

Systems

Physiological changes in sleep

Work through this system by system, and let the non-REM against REM contrast carry the structure.
SystemNon-REMREM
CerebralMetabolic rate and blood flow fall, by up to about 25% in slow-wave sleep. EEG synchronisedMetabolic rate and blood flow equal or exceed the awake value. EEG desynchronised
CardiovascularHeart rate, blood pressure and cardiac output fall steadily; vagal tone predominates. StableMarked variability — irregular heart rate and blood pressure, with surges. Sympathetic bursts. The period of greatest risk for myocardial ischaemia and arrhythmia
RespiratoryRate and tidal volume fall; minute ventilation falls by around 10-15%; PaCO₂ rises by about 0.5-1 kPa (roughly 3-8 mmHg). Chemoreceptor sensitivity reduced. Breathing is regularBreathing is irregular in rate and depth. Chemoreceptor and load responses are further blunted. Accessory and intercostal muscle contribution is lost — ventilation becomes diaphragm-dependent
Upper airwayPharyngeal dilator tone reduced but presentPharyngeal dilator tone markedly reduced or lost — obstructive events are longest and desaturation deepest
Muscle toneReduced; posture is maintained and movement occursAtonia, apart from diaphragm and extraocular muscles
ThermoregulationMaintained, around a lower set point. Shivering and sweating both occurEffectively suspended — poikilothermic. Neither shivering nor sweating occurs, so core temperature drifts with the environment
EndocrineGrowth hormone secretion peaks in slow-wave sleep, early in the night. Prolactin rises; cortisol is at its nadirCortisol rises towards the morning peak; testosterone peaks
Renal and gastrointestinalUrine output falls; gastric acid secretion continuesReduced gut motility; swallowing and salivation are reduced
06

Control

The regulation of sleep

Two independent processes, and a flip-flop switch between the nuclei that execute them.
Process S — homeostaticProcess C — circadian
DriveSleep pressure accumulating with time awakeAn intrinsic near-24-hour rhythm, independent of prior sleep
SubstrateAccumulation of adenosine in the basal forebrain during wakefulness, inhibiting arousal neuronsThe suprachiasmatic nucleus of the hypothalamus, entrained to light by the retinohypothalamic tract
BehaviourRises during wakefulness, discharges during sleep — hence the rebound after deprivationOscillates regardless of sleep, producing the mid-afternoon dip and the early-morning trough
PharmacologyCaffeine is an adenosine antagonist, which is precisely why it opposes sleep pressureMelatonin from the pineal gland, secreted in darkness under suprachiasmatic control, is the output signal and can be given to shift the rhythm

The two processes act on a switch. The ventrolateral preoptic nucleus of the hypothalamus is sleep-promoting and GABAergic; it inhibits the arousal nuclei of lesson 17 — tuberomammillary, locus coeruleus and raphe — and they inhibit it in return. Mutual inhibition of this kind behaves as a flip-flop switch, which is why transitions between sleep and wakefulness are rapid and complete rather than gradual. Orexin from the lateral hypothalamus stabilises the switch in the waking position, and its loss produces the abrupt, involuntary state transitions of narcolepsy and cataplexy.

Within sleep, the alternation between non-REM and REM is generated by a second reciprocal circuit in the pons: cholinergic REM-on neurons in the pedunculopontine and laterodorsal tegmental nuclei against monoaminergic REM-off neurons in the locus coeruleus and raphe. This explains a clinical observation — drugs that raise monoamine levels, such as antidepressants, suppress REM sleep.

07

The comparison

Sleep and anaesthesia

They share machinery, which is why the comparison is asked; they are not the same state, which is why it is worth marks.
SleepGeneral anaesthesia
ReversibilityBy sensory stimulation — the defining featureNot by stimulation. Only by elimination or reversal of the drug
Homeostatic drivePresent. Debt accumulates and is repaidAbsent. Anaesthesia does not discharge sleep debt, and may add to it
ArchitectureCyclical, with an orderly progression through defined stagesNo cycles or stages; depth follows drug concentration
EEGAlternates between synchronised non-REM and desynchronised REMProgressive dose-dependent slowing to burst suppression and isoelectricity
Airway reflexesLargely preservedProgressively obtunded — the basis of the aspiration risk
Ventilatory response to CO₂BluntedMarkedly depressed, and abolished at depth
MemoryPreserved for events at arousalAbolished — amnesia occurs at concentrations well below those causing unconsciousness
Shared machineryThe ventrolateral preoptic nucleus, the arousal nuclei and the thalamic gateAnaesthetics recruit those same nuclei — the bottom-up account of lesson 17
08

Clinical application

Sleep-disordered breathing and the postoperative period

Where this physiology is applied, and where it kills people.

Obstructive sleep apnoea

Airway patency depends on the balance between the collapsing force of inspiratory negative pressure and the dilating force of the pharyngeal dilator muscles, chiefly genioglossus. Sleep reduces dilator tone; REM sleep reduces it most. That is why obstructive events in REM are the longest and produce the deepest desaturation, and why an overnight study that samples little REM sleep can underestimate severity.

The perioperative consequences are direct and worth stating as a chain rather than a list. Opioids and sedatives reduce dilator tone further and blunt the arousal response that terminates an obstructive event — so the patient obstructs for longer and rouses less readily. Repeated hypoxaemia and hypercapnia with large negative intrathoracic pressure swings drive sympathetic activation, systemic and pulmonary hypertension, right ventricular strain and arrhythmia. These patients are additionally likely to be difficult to mask-ventilate and to intubate.

Postoperative sleep architecture

Surgery disrupts sleep in a characteristic and clinically important pattern:

  1. On the first one to two postoperative nights, REM and slow-wave sleep are suppressed or abolished, by pain, opioids, the surgical stress response and environmental disturbance.
  2. From about the third to the fifth night there is a REM rebound, with more REM sleep than normal and longer REM periods.
  3. Because REM carries atonia, autonomic instability and the worst upper airway obstruction, the rebound is associated with episodic hypoxaemia, haemodynamic instability and myocardial ischaemia — and this is a recognised contributor to the delayed timing of postoperative cardiorespiratory events, which cluster on the second to fourth nights rather than immediately.
  4. Sleep disruption also contributes to postoperative delirium, along with the fragmentation caused by the intensive care environment.

The implications follow: opioid-sparing multimodal analgesia, caution with sedatives, continuation of home CPAP, extended monitoring in patients with severe obstructive sleep apnoea, and deliberate attention to the night-time environment.

Previously examinedOctober 2013 — the stages of sleep and the physiological changes accompanying them. Worked answers in the library

09

Consolidation

The lesson in one paragraph

Sleep is a reversible state of reduced awareness and responsiveness, distinguished from coma and anaesthesia by reversibility with sensory stimulation and by homeostatic regulation, and it is actively generated rather than a passive loss of arousal. It comprises non-REM sleep, in stages N1 with theta activity, N2 defined by sleep spindles and K complexes, and N3 slow-wave sleep with high-voltage delta; and REM sleep, with a desynchronised EEG resembling wakefulness, rapid conjugate eye movements, dreaming and skeletal muscle atonia sparing the diaphragm and extraocular muscles. Sleep is entered through non-REM, cycles about every 90 minutes over four to six cycles, with slow-wave sleep concentrated in the first third and REM periods lengthening towards morning; adult proportions are roughly N1 5%, N2 45%, N3 25% and REM 25%. Non-REM is a quiet brain in a movable body — cerebral metabolism falls, cardiovascular and respiratory variables fall steadily and regularly, and thermoregulation is maintained at a lower set point. REM is an active brain in a paralysed body — cerebral metabolism equals or exceeds the awake value, heart rate, blood pressure and breathing are irregular with sympathetic surges, ventilation becomes diaphragm-dependent, and thermoregulation is suspended so the subject is poikilothermic. Regulation is by two processes: homeostatic sleep pressure through adenosine accumulation, and the circadian rhythm of the suprachiasmatic nucleus entrained by light and expressed through melatonin. These act on a flip-flop switch of mutual inhibition between the GABAergic ventrolateral preoptic nucleus and the monoaminergic arousal nuclei, stabilised by orexin. Clinically, loss of pharyngeal dilator tone makes obstructive apnoea worst in REM, and the postoperative suppression of REM followed by rebound on nights two to four accounts for the delayed clustering of hypoxaemic and ischaemic events after surgery.

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