Post on 16-Dec-2015
Respiratory Physiology In Sleep
Ritu Grewal, MD
States of Mammalian Being
• Wake
• Non-REM sleep
– brain is regulating bodily functions in a movable body
• REM sleep:
- highly activated brain in a paralyzed body
Electrographic State Determination
• Wake
• NREM
• REM
• EEG - Desynchronized• EMG - Variable
• EEG - Synchronized• EMG - Attenuated but present
• EEG - Desynchronized• EMG - Absent (active paralysis)
Normal Sleep Histogram
• Rapid eye movements
• Mixed frequency EEG
• Low tonic submental EMG
Stage REM
Overview of Sleep and Respiratory Physiology
I. CNS Ventilatory Control
II. Respiratory Control of the Upper Airway
III. Obstructive Sleep Apnea
Ventilatory pump and its central neural control
Dorsal view of the brainstem and upper spinal cord showing the medullary origin of the descending inspiratory and expiratory pathways that control major respiratory pump muscles, such as the diaphragm and intercostals.
Central respiratory neurons form a network that ensures reciprocal activation and inhibition among the cells to be active during different phases of the respiratory cycle.
Respiratory-modulated cells in the ponsintegrate many peripheral and centralrespiratory and non-respiratory inputsand modulate the cells of the medullary rhythm and pattern generator.
Main pontomedullary respiratory neurons
Influences on Respiration in Wake State
• Metabolic control /Automatic control– Maintain blood gases
• Voluntary control/behavioral – Phonation, swallowing
(wakefulness stimulus to breathing)
Respiration during sleep
• Metabolic control/automatic control– Controlled by the medulla
• on the respiratory muscles
– Maintain pCO2 and pO2
Changes in Ventilation in sleepChanges in Ventilation in sleep
• Decrease in Minute Ventilation (Ve)(0.5-1.5 Decrease in Minute Ventilation (Ve)(0.5-1.5 l/min)l/min)
• Decrease in Tidal Volume)Decrease in Tidal Volume)• Respiratory Rate unchangedRespiratory Rate unchanged
• ↑↑ UA resistance (reduced activity of pharyngeal UA resistance (reduced activity of pharyngeal dilator muscle activity)dilator muscle activity)
• Reduction of VCO2 and VO2 (reduced Reduction of VCO2 and VO2 (reduced metabolism)metabolism)
• Absence of the tonic influences of wakefulnessAbsence of the tonic influences of wakefulness• Reduced chemosensitivityReduced chemosensitivity
Changes in Blood BasesChanges in Blood Bases
• Decrease in CO2 production (less than Decrease in CO2 production (less than decrease in Ve)decrease in Ve)
• Increase in pCO2 3-5 mm HgIncrease in pCO2 3-5 mm Hg
• Decrease in pO2 by 5-8 mm HgDecrease in pO2 by 5-8 mm Hg
• O2 saturation decreases by less than 2%O2 saturation decreases by less than 2%
Chemosensitivity and SleepChemosensitivity and Sleep
Chemosensitivity and SleepChemosensitivity and Sleep
MetabolismMetabolism
• Metabolism slows at sleep onsetMetabolism slows at sleep onset
• Increases during the early hours of the Increases during the early hours of the morning when REM sleep is at its morning when REM sleep is at its maximummaximum
• Ventilation is worse in REM sleep Ventilation is worse in REM sleep
REM sleepREM sleep
• Worse in REM sleepWorse in REM sleep
• Hypotonia of Intercostal muscles and Hypotonia of Intercostal muscles and accessory muscles of respirationaccessory muscles of respiration
• Increased upper airway resistanceIncreased upper airway resistance
• Diaphragm is preservedDiaphragm is preserved
• Breathing rate is erraticBreathing rate is erratic
Arousal responses in sleepArousal responses in sleep
• Reduced in REM compared to NonREMReduced in REM compared to NonREM
• Hypercapnia is a stronger stimulus to Hypercapnia is a stronger stimulus to arousal than hypoxemiaarousal than hypoxemia– Increase in pCO2 of 6-15 mmHg causes Increase in pCO2 of 6-15 mmHg causes
arousal arousal – SaO2 has to decrease to below 75%SaO2 has to decrease to below 75%
• Cough reflex in response to laryngeal Cough reflex in response to laryngeal stimulation reduced (aspiration)stimulation reduced (aspiration)
Overview of Sleep and Respiratory Physiology
I. CNS Ventilatory Control
II. Respiratory Control of the Upper Airway
III. Obstructive Sleep Apnea
Anatomy of the Upper Airway
The Upper Airway is a Continuation of the Respiratory System
20
The Upper Airway is a Multipurpose Passage
• It transmits air, liquids and solids.
• It is a common pathway for respiratory, digestive and phonation functions.
21
Collapsible Pharynx Challenges
the Respiratory System• Airflow requires a patent upper airway.
• Nose vs. mouth breathing must be regulated.
• State of consciousness is a major determinant of pharyngeal patency.
22
Components of the Upper Airway
• Nose
• Nasopharynx
• Oropharynx
• Laryngopharynx
• Larynx
23
Anatomy of the Upper Airway• Alae nasi
(widens nares)
• Levator palatini (elevates palate)
• Tensor palatini (stiffens palate)
24
Anatomy of the Upper Airway
• Genioglossus (protrudes tongue)
• Geniohyoid (displaces hyoid arch anterior)
• Sternohyoid (displaces hyoid arch anterior)
• Pharyngeal constrictors (form lateral pharyngeal walls)
25
Pharyngeal Muscles are Activated during Breathing
Mechanical Properties and Collapsibility of Upper Airway
Reflexes Maintaining an Open Airway and Effects of Sleep
Respiratory Control of the Upper Airway
Upper airway muscles modulate airflow1. Primary Respiratory Muscles (e.g., Diaphragm, Intercostals)
Contraction generates airflow into lungs2. Secondary Respiratory Muscles (e.g., Genioglossus of tongue)
Contraction does not generate airflow but modulates resistance
Upper Airway(collapsible tube)
Respiratory Pump
Respiratory pump muscles generate airflow
Awake
Genioglossus+++
Intercostals+++
Diaphragm+++
Non-REM
++
++
++
REM
++
+
+
Consequences: Lung ventilation in sleep caused by both Upper airway resistance (major contributor) and pump muscle activity
Clinical Relevance: Airway narrowing in sleep (potential for hypopneas and obstructions)
Sleep reduces upper airway muscle activity more than diaphragm activity
Sleep and respiratory muscle activity
The pharynx is a collapsible tube vulnerable to closure in sleep – especially when supine
Tendency for Airway Collapse:Reduced muscle activation in sleepWeight of tongueWeight of neck - worse with obesityWorse when supine
+Diaphragm
++
Sleep
GenioglossusGenioglossus
Diaphragm+++
+++
Awake
Tongue movement
Clinical Relevance:SnoringAirflow limitation (hypopneas)Obstructive Sleep Apnea (OSA)
Tendency for upper airway collapse in sleep
Tonic and respiratory inputs summate to determine pharyngeal muscle activity
Hypoglossal Motoneuron
Tonic Inputs Inspiratory Drive
GenioglossusEMG
Lung Volume
Inspiratory pre-activationof genioglossus
Trigeminal Motoneuron
Tonic Inputs
Tensor veli palatini EMG
Inspiratory Drive
Insp. Lung Volume
Insp.
Hypoglossal Motoneuron
Tonic Inputs Inspiratory Drive
GenioglossusEMG
Lung Volume
Inspiratory pre-activationof genioglossus
Trigeminal Motoneuron
Tonic Inputs
Tensor veli palatini EMG
Inspiratory Drive
Insp. Lung Volume
Insp.
Genioglossus muscle: Respiratory-related activity
superimposed upon background tonic activity
Tensor veli palatini (palatal muscle): Mainly tonic activityEnhances stiffness in the airspace
behind the palate
Determinants of pharyngeal muscle activity
Pharyngeal Muscles are Activated during Breathing
Mechanical Properties and Collapsibility of Upper Airway
Reflexes Maintaining an Open Airway and Effects of Sleep
Overview of Sleep and Respiratory Physiology
The airway is narrowest in the region posterior to the soft palate
RetropalatalAirspace
GlossopharyngealAirspace
Airway anatomy and vulnerability to closure
Redrawn from Horner et al., Eur Resp J, 1989
Retropalatal Airspace Glossopharyngeal Airspace
Normal
Normal
OSA
OSA
InspirationExpiration
The upper airway is:(1) Narrowest in the retropalatal airspace(2) Narrower in obstructive sleep apnea (OSA) patients vs. controls(3) Varies during the breathing cycle (narrowest at end-expiration)
Upper airway size varies with the breathing cycle
Redrawn from Schwab, Am Rev Respir Dis, 1993
The upper airway is narrowest at end-expiration and so vulnerable to collapse on inspiration
Upper airway at end-expiration is most vulnerable to collapse on inspirationTonic muscle activity sets baseline airway size and stiffness ( in sleep)Any factor that airway size makes the airway more vulnerable to collapse
Retropalatal Airspace Glossopharyngeal Airspace
Normal
Normal
OSA
OSA
Upper airway size varies with the breathing cycle
Redrawn from Schwab et al., Am Rev Respir Dis, 1993
OSA patients have larger retropalatal fat depositsand narrower airways
Fatdeposit
Magnetic resonance image showing large fat deposits lateral to the airspace These fat deposits are larger in OSA patients compared to weight matched controlsWeight loss decreases size of fat deposits and increases airway size
Retropalatalairspace
Fat deposits around the upper airspace
From Horner, Personal data archive
Mechanics of the upper airway and influences on collapsibility
The upper airway has been modeled as a collapsible tube with maximum flow (VMAX) determined by upstream nasal pressure (PN) and resistance (RN).
●
PN (cmH2O)
0
100
200
300
400
500
0 4 8-4-8
PCRIT
RN = 1/slope
V M
AX
(ml/s
ec)
●
Airflow ceases in the collapsible segment of the upper airway at a value of critical pressure (PCRIT). VMAX is determined by:
VMAX = (PN - PCRIT) / RN
●
●
Lungs
PN RN
PCRITVMAX
●
Determinants of upper airway collapsibility
Redrawn from Smith and Schwartz,Sleep Apnea: Pathogenesis, Diagnosis and Treatment, 2002
Mechanics of the upper airway influences airway collapsibility
PN (cmH2O)
V MAX
(ml/sec)
0
500
150 105-5-10-15
NormalSnorer
HypopneaOSA
●
PN (cmH2O)V
MA
X (m
l/se
c)
0
100
200
300
400
500
0 4 8-4-8
Passive Upper Airway
Active Upper Airway PCRIT
V MAX
●
●
PCRIT is more positive (more collapsible airway) from groups of normal subjects, to snorers, and patients with hypopneas and obstructive sleep apnea (OSA).
Increases in pharyngeal muscle activity (passive to active upper airway) increase VMAX and decrease PCRIT, i.e., make the airway less collapsible.
●
Influences on upper airway collapsibility
Redrawn from Smith and Schwartz,Sleep Apnea: Pathogenesis, Diagnosis and Treatment, 2002
Pharyngeal Muscles are Activated during Breathing
Mechanical Properties and Collapsibility of Upper Airway
Reflexes Maintaining an Open Airway and Effects of Sleep
Overview of Sleep and Respiratory Physiology
Sub-atmospheric airway pressures cause reflex pharyngeal muscle activation
Sub-atmospheric airway pressures cause short latency (reflex) genioglossus muscle activation in humansReflex thought to protect the upper airway from suction collapse during inspirationReflex is reduced in non-REM sleep and inhibited in REM sleep
Genioglossus Electromyogram
Suction Pressure(cmH2O)
0
-25
100 msec
Reflex responses to sub-atmospheric pressure
From Horner, Personal data archive
Major contribution of nasal and laryngeal afferents to negative pressure reflex in humans
0
Genioglossus Electromyogram
Suction Pressure(cmH2O) -25
100 msec
Normal response
Anesthesia of nasal afferents
Anesthesia of laryngeal afferents
Afferents mediating reflex response
From Horner, Personal data archive
Upper airway trauma may impair responses to negative pressure and predispose to OSA
Sleeping normal subject
Narrower than normal airwayStructural (e.g., obesity, position)
muscle activity (e.g., alcohol)
Exaggerated negative airway pressure
Reflex pharyngeal dilator muscle activation (e.g., genioglossus)
Small responder Big responder
Snoring, hypopneas and occasional OSA
Decrement in upper airwaymucosal sensation to pressure
Decrement in upper airway reflex
Worsening snoringand OSA
Any decrement in reflexe.g., age, alcohol
No change in reflex
Remain normal
Upper airway reflex and clinical relevance
Redrawn from Horner, Sleep, 1996
Chemoreceptor stimulation cause reflex pharyngeal muscle activation
Wakefulness
Non-REM sleep
REM sleepRes
pir
ato
ry-R
elat
edG
enio
glo
ssu
s A
ctiv
ity
(mV
)
Inspired CO2 (%)
Chemoreceptor stimulation increases genioglossus muscle activityReflex is reduced in sleep, especially REM sleep
Responses to hypercapnia in sleep
Modified from Horner, J Appl Physiol, 2002
Overview of Sleep and Respiratory Physiology
I. CNS Ventilatory Control
II. Respiratory Control of the Upper Airway
III. Obstructive Sleep Apnea
Obstructive Sleep Apnea (OSA) Syndrome
• Very common; affects 2-5% of middle-aged persons, both men and women.
• The initial cause is a narrow and collapsible upper airway (due to fat deposits, predisposing cranial bony structure and/or hypertrophy of soft tissues surrounding the upper airway).
State-dependent respiratory disorders - OSA
•OSA patients have adequate ventilation during wakefulness because they develop a compensatory increase in the activity of their upper airway dilating muscles (e.g., contraction of the genioglossus, the main muscle of the tongue, effectively protects against upper airway collapse). However, the compensation is only partially preserved during SWS and absent during REMS. This causes repeated nocturnal upper airway obstructions which in most cases require awakening to resolve.
State-dependent respiratory disorders - OSA
OSA is characterized by cessation of oro-nasal airflow in the presence of attempted (but ineffective) respiratory efforts and is caused by upper airway closure in sleep
Hypopneas are caused by reductions in inspiratory airflow due to elevated upper airway resistance
100
80
15 sec
EEG (V) 100
200
200
EMG (V) 50
OxygenSaturation (%)
RibCage(ml)
Abdomen (ml)
Snoring Sound
Arousal Sleep Arousal
ObstructionObstruction
100
80
15 sec
EEG (V) 100
200
200
EMG (V) 50
OxygenSaturation (%)
RibCage(ml)
Abdomen (ml)
Snoring Sound
ArousalArousal Sleep ArousalArousal
ObstructionObstruction
Polysomnographic tracings in OSA
Redrawn from Thompson et al., Adv Physiol Educ, 2001
The site of obstruction varies within and between patients with obstructive sleep apnea
All patients obstruct at level of soft palate
~50% of patients: obstruction behind tongue in non-REM
REM: Obstruction extends caudally
Site of obstruction in OSA
• In severe OSA, 40-60 episodes of airway obstruction and subsequent awaking occur per hour; due to overwhelming sleepiness, the patient is often unaware of the nature of the problem.
• In light OSA, loud snoring is associated with periods of hypoventilation due to excessive airway narrowing.
State-dependent respiratory disorders - OSA
•Sleep loss, sleep fragmentation and recurring decrements of blood oxygen levels (intermittent hypoxia) have multiple adverse consequences for cognitive and affective functions, regulation of arterial blood pressure (hypertension), and metabolic regulation (insulin resistance, hyperlipidemia).
State-dependent respiratory disorders - OSA
SummarySummary
• Increased upper airway resistance-OSASIncreased upper airway resistance-OSAS
• Circadian changes in airway muscle toneCircadian changes in airway muscle tone
• Reduced ventilationReduced ventilation– COPDCOPD– Neuromuscular diseasesNeuromuscular diseases– Interstitial lung diseaseInterstitial lung disease
COPDCOPD
• Hyperinflated diaphragm(reduced Hyperinflated diaphragm(reduced efficiency)efficiency)
• ABG’s deteriorate during sleepABG’s deteriorate during sleep
• Coexisting OSAS-severe hypoxemiaCoexisting OSAS-severe hypoxemia
• Pulmonary hypertensionPulmonary hypertension
Decreased ventilatory responses to hypoxia, hypercapnia, and inspiratory resistance during sleep, particularly in REM sleep, permit REM hypoxemia in patients with chronic obstructive pulmonary disease, chest wall disease, and neuromuscular abnormalities affecting the respiratory muscles. They may also contribute to the development of the sleep apnea/hypopnea syndrome.
CNS Ventilatory Control – Summary 1
• The respiratory rhythm and pattern are generated centrally and modulated by a host of respiratory reflexes.
• The basic respiratory rhythm is generated by a network of pontomedullary neurons, of which some have pacemaker properties.
• The central controller is set to ensure ventilation that adequately meets demand for O2 supply and CO2 removal.
CNS Ventilatory Control – Summary 2
• Pharyngeal muscles are activated during breathing
• Upper airway size varies during breathing• Mechanical properties of the upper airway
influences collapsibility• Reflexes modulate pharyngeal muscle
activity, but reflexes are reduced in sleep• These mechanisms contribute to normal
maintenance of airway patency and are relevant to obstructive sleep apnea