Respiratory Physiology In Sleep

1
Respiratory Physiology In Sleep

• Ritu Grewal, MD

2
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

3
Electrographic State Determination

• Wake
• NREM
• REM

• EEG - Desynchronized
• EMG - Variable
• EEG - Synchronized
• EMG - Attenuated but present
• EEG - Desynchronized
• EMG - Absent (active paralysis)

4
Normal Sleep Histogram
5
Stage REM

• Rapid eye movements
• Mixed frequency EEG
• Low tonic submental EMG

6
Overview of Sleep and Respiratory Physiology
I. CNS Ventilatory Control II. Respiratory
Control of the Upper Airway III. Obstructive
Sleep Apnea
7
Ventilatory pump and its central neural control
8
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.

9
Influences on Respiration in Wake State

• Metabolic control /Automatic control
• Maintain blood gases
• Voluntary control/behavioral
• Phonation, swallowing
• (wakefulness stimulus to breathing)

10
Respiration during sleep

• Metabolic control/automatic control
• Controlled by the medulla
• on the respiratory muscles
• Maintain pCO2 and pO2

11
(No Transcript)
12
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

13
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

14
Chemosensitivity and Sleep
15
Chemosensitivity and Sleep
16
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

17
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

18
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)

19
Overview of Sleep and Respiratory Physiology
I. CNS Ventilatory Control II. Respiratory
Control of the Upper Airway III. Obstructive
Sleep Apnea
20
Anatomy of the Upper Airway
The Upper Airway is a Continuation of the
Respiratory System
20
21
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
22
Collapsible Pharynx Challengesthe 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
23
Components of the Upper Airway

• Nose
• Nasopharynx
• Oropharynx
• Laryngopharynx
• Larynx

23
24
Anatomy of the Upper Airway

• Alae nasi (widens nares)
• Levator palatini (elevates palate)
• Tensor palatini (stiffens palate)

24
25
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
26
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
27
Respiratory pump muscles generate airflow
Upper airway muscles modulate airflow

• Primary Respiratory Muscles (e.g., Diaphragm,
  Intercostals)
• Contraction generates airflow into lungs
• Secondary Respiratory Muscles (e.g., Genioglossus
  of tongue)
• Contraction does not generate airflow but
  modulates resistance

Upper Airway (collapsible tube)
Respiratory Pump
28
Sleep and respiratory muscle activity
Sleep reduces upper airway muscle activity more
than diaphragm activity
29
Tendency for upper airway collapse in sleep
The pharynx is a collapsible tube vulnerable to
closure in sleep especially when supine
30
Determinants of pharyngeal muscle activity
Tonic and respiratory inputs summate to determine
pharyngeal muscle activity
31
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
32
Airway anatomy and vulnerability to closure
The airway is narrowest in the region posterior
to the soft palate
Redrawn from Horner et al., Eur Resp J, 1989
33
Upper airway size varies with the breathing cycle
Retropalatal Airspace
Glossopharyngeal Airspace
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
34
Upper airway size varies with the breathing cycle
The upper airway is narrowest at end-expiration
and so vulnerable to collapse on inspiration
Glossopharyngeal Airspace
Retropalatal Airspace
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
35
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
36
Determinants of upper airway collapsibility
Mechanics of the upper airway and influences on
collapsibility
Redrawn from Smith and Schwartz, Sleep Apnea
Pathogenesis, Diagnosis and Treatment, 2002
37
Influences on upper airway collapsibility
Mechanics of the upper airway influences airway
collapsibility
Redrawn from Smith and Schwartz, Sleep Apnea
Pathogenesis, Diagnosis and Treatment, 2002
38
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
39
Reflex responses to sub-atmospheric pressure
Sub-atmospheric airway pressures cause reflex
pharyngeal muscle activation
0
Suction Pressure (cmH2O)
-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
40
Afferents mediating reflex response
Major contribution of nasal and laryngeal
afferents to negative pressure reflex in humans
Anesthesia of nasal afferents
Anesthesia of laryngeal afferents
From Horner, Personal data archive
41
Upper airway reflex and clinical relevance
Upper airway trauma may impair responses to
negative pressure and predispose to OSA
Redrawn from Horner, Sleep, 1996
42
Responses to hypercapnia in sleep
Chemoreceptor stimulation cause reflex pharyngeal
muscle activation
Chemoreceptor stimulation increases genioglossus
muscle activity Reflex is reduced in sleep,
especially REM sleep
Modified from Horner, J Appl Physiol, 2002
43
Overview of Sleep and Respiratory Physiology
I. CNS Ventilatory Control II. Respiratory
Control of the Upper Airway III. Obstructive
Sleep Apnea
44
Obstructive Sleep Apnea (OSA) Syndrome
State-dependent respiratory disorders - OSA

• 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).

45
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.

46
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
47
Site of obstruction in OSA
The site of obstruction varies within and between
patients with obstructive sleep apnea
48
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.

49
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).

50
Summary

• Increased upper airway resistance-OSAS
• Circadian changes in airway muscle tone
• Reduced ventilation
• COPD
• Neuromuscular diseases
• Interstitial lung disease

51
COPD

• Hyperinflated diaphragm(reduced efficiency)
• ABGs deteriorate during sleep
• Coexisting OSAS-severe hypoxemia
• Pulmonary hypertension

52
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.
53
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.

54
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