Download Upper Airway

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
• EEG - Desynchronized
• EMG - Variable
• NREM
• EEG - Synchronized
• EMG - Attenuated but present
• REM
• EEG - Desynchronized
• EMG - Absent (active paralysis)
Normal Sleep Histogram
Stage REM
• Rapid eye movements
• Mixed frequency EEG
• Low tonic submental EMG
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
Main pontomedullary respiratory neurons
 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 pons
integrate many peripheral and central
respiratory and non-respiratory inputs
and modulate the cells of the medullary
rhythm and pattern generator.
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 sleep
• Decrease in Minute Ventilation (Ve)(0.5-1.5
l/min)
• Decrease in Tidal Volume)
• Respiratory Rate unchanged
• ↑ UA resistance (reduced activity of pharyngeal
dilator muscle activity)
• Reduction of VCO2 and VO2 (reduced
metabolism)
• Absence of the tonic influences of wakefulness
• Reduced chemosensitivity
Changes in Blood Bases
• Decrease in CO2 production (less than
decrease in Ve)
• Increase in pCO2 3-5 mm Hg
• Decrease in pO2 by 5-8 mm Hg
• O2 saturation decreases by less than 2%
Chemosensitivity and Sleep
Chemosensitivity and Sleep
Metabolism
• Metabolism slows at sleep onset
• Increases during the early hours of the
morning when REM sleep is at its
maximum
• Ventilation is worse in REM sleep
REM sleep
• Worse in REM sleep
• Hypotonia of Intercostal muscles and
accessory muscles of respiration
• Increased upper airway resistance
• Diaphragm is preserved
• Breathing rate is erratic
Arousal responses in sleep
• Reduced in REM compared to NonREM
• Hypercapnia is a stronger stimulus to
arousal than hypoxemia
– Increase in pCO2 of 6-15 mmHg causes
arousal
– SaO2 has to decrease to below 75%
• Cough reflex in response to laryngeal
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
Respiratory Control of the Upper Airway
Pharyngeal Muscles are Activated during
Breathing
Mechanical Properties and Collapsibility of
Upper Airway
Reflexes Maintaining an Open Airway and
Effects of Sleep
Respiratory pump muscles generate airflow
Upper airway muscles modulate airflow
1. Primary Respiratory Muscles (e.g., Diaphragm, Intercostals)
Contraction generates airflow into lungs
2. Secondary Respiratory Muscles (e.g., Genioglossus of tongue)
Contraction does not generate airflow but modulates resistance
Upper Airway
(collapsible tube)
Respiratory
Pump
Sleep and respiratory muscle activity
Sleep reduces upper airway muscle activity more
than diaphragm activity
Awake
Non-REM
Genioglossus
+++
Intercostals
+++
Diaphragm
+++
Consequences:
Clinical Relevance:
REM
++
+
+
++
++
++
 Lung ventilation in sleep caused by both
 Upper airway resistance (major
contributor) and  pump muscle activity
Airway narrowing in sleep
(potential for hypopneas and obstructions)
Tendency for upper airway collapse in sleep
The pharynx is a collapsible tube vulnerable to
closure in sleep – especially when supine
Awake
Sleep
Genioglossus
+++
Diaphragm
+++
Genioglossus
+
Diaphragm
++
Tongue
movement
Tendency for Airway Collapse:
Reduced muscle activation in sleep
Weight of tongue
Weight of neck - worse with obesity
Worse when supine
Clinical Relevance:
Snoring
Airflow limitation (hypopneas)
Obstructive Sleep Apnea (OSA)
Determinants of pharyngeal muscle activity
Tonic and respiratory inputs summate to determine
pharyngeal muscle activity
Genioglossus muscle:
Respiratory-related activity
superimposed upon
background tonic activity
Tensor veli palatini (palatal muscle):
Mainly tonic activity
Enhances stiffness in the airspace
behind the palate
Overview of Sleep and Respiratory Physiology
Pharyngeal Muscles are Activated during
Breathing
Mechanical Properties and Collapsibility of
Upper Airway
Reflexes Maintaining an Open Airway and
Effects of Sleep
Airway anatomy and vulnerability to closure
The airway is narrowest in the region
posterior to the soft palate
Retropalatal
Airspace
Glossopharyngeal
Airspace
Redrawn from Horner et al., Eur Resp J, 1989
Upper airway size varies with the breathing cycle
Retropalatal Airspace
Glossopharyngeal Airspace
Normal
Normal
Expiration
OSA
OSA
Inspiration
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)
Redrawn from Schwab, Am Rev Respir Dis, 1993
Upper airway size varies with the breathing cycle
The upper airway is narrowest at end-expiration and so
vulnerable to collapse on inspiration
Retropalatal Airspace
Glossopharyngeal Airspace
Normal
Normal
OSA
OSA
Upper airway at end-expiration is most vulnerable to collapse on inspiration
Tonic muscle activity sets baseline airway size and stiffness ( in sleep)
Any factor that  airway size makes the airway more vulnerable to collapse
Redrawn from Schwab et al., Am Rev Respir Dis, 1993
Fat deposits around the upper airspace
OSA patients have larger retropalatal fat deposits
and narrower airways
Fat
deposit
Retropalatal
airspace
Magnetic resonance image showing large fat deposits lateral to the airspace
These fat deposits are larger in OSA patients compared to weight matched controls
Weight loss decreases size of fat deposits and increases airway size
From Horner, Personal data archive
Determinants of upper airway collapsibility
Mechanics of the upper airway and
influences on collapsibility
●
VMAX
PCRIT
V MAX (ml/sec)
PN RN
●
500
400
RN = 1/slope
300
200
PCRIT
100
0
Lungs
-8
-4
0
4
8
PN (cmH2O)
The upper airway has been modeled as
a ●collapsible tube with maximum flow
(VMAX) determined by upstream nasal
pressure (PN) and resistance (RN).
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
Redrawn from Smith and Schwartz,
Sleep Apnea: Pathogenesis, Diagnosis and Treatment, 2002
Influences on upper airway collapsibility
Mechanics of the upper airway influences
airway collapsibility
V MAX
(ml/sec)
V MAX (ml/sec)
●
Normal
Snorer
Hypopnea
OSA
500
●
0
-15 -10 -5
0
500
400
●
 V MAX
 PCRIT
Active Upper Airway
300
Passive Upper Airway
200
100
0
5
10
15
-8
-4
0
4
8
PN (cmH2O)
PN (cmH2O)
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.
Redrawn from Smith and Schwartz,
Sleep Apnea: Pathogenesis, Diagnosis and Treatment, 2002
Overview of Sleep and Respiratory Physiology
Pharyngeal Muscles are Activated during
Breathing
Mechanical Properties and Collapsibility of
Upper Airway
Reflexes Maintaining an Open Airway and
Effects of Sleep
Reflex responses to sub-atmospheric pressure
Sub-atmospheric airway pressures cause reflex
pharyngeal muscle activation
Suction
Pressure
(cmH2O)
0
-25
Genioglossus
Electromyogram
100 msec
Sub-atmospheric airway pressures cause short latency (reflex) genioglossus
muscle activation in humans
Reflex thought to protect the upper airway from suction collapse during inspiration
Reflex is reduced in non-REM sleep and inhibited in REM sleep
From Horner, Personal data archive
Afferents mediating reflex response
Major contribution of nasal and laryngeal afferents to
negative pressure reflex in humans
Suction
Pressure
(cmH2O)
0
-25
Genioglossus
Electromyogram
Normal response
100 msec
Anesthesia of nasal
afferents
Anesthesia of
laryngeal afferents
From Horner, Personal data archive
Upper airway reflex and clinical relevance
Upper airway trauma may impair responses to negative pressure
and predispose to OSA
Sleeping normal subject
Structural (e.g., obesity, position)
Narrower than normal airway
 muscle activity (e.g., alcohol)
Exaggerated negative airway pressure
Reflex pharyngeal dilator muscle
activation (e.g., genioglossus)
Big responder
Small responder
Snoring, hypopneas
and occasional OSA
Any decrement in reflex
No change in reflex
e.g., age, alcohol
Remain normal
Decrement in upper airway
mucosal sensation to pressure
Decrement in upper
airway reflex
Worsening snoring
and OSA
Redrawn from Horner, Sleep, 1996
Responses to hypercapnia in sleep
Respiratory-Related
Genioglossus Activity (mV)
Chemoreceptor stimulation cause reflex
pharyngeal muscle activation
Wakefulness
Non-REM sleep
REM sleep
Inspired CO2 (%)
Chemoreceptor stimulation increases genioglossus muscle activity
Reflex is reduced in sleep, especially REM 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
State-dependent respiratory disorders - OSA
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.
Polysomnographic tracings in 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
Redrawn from Thompson et al., Adv Physiol Educ, 2001
Site of obstruction in OSA
The site of obstruction varies within and
between patients with obstructive sleep apnea
REM: Obstruction
extends caudally
All patients obstruct
at level of soft palate
~50% of patients: obstruction
behind tongue in non-REM
State-dependent respiratory disorders - 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).
Summary
• Increased upper airway resistance-OSAS
• Circadian changes in airway muscle tone
• Reduced ventilation
– COPD
– Neuromuscular diseases
– Interstitial lung disease
COPD
• Hyperinflated diaphragm(reduced
efficiency)
• ABG’s deteriorate during sleep
• Coexisting OSAS-severe hypoxemia
• Pulmonary 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