Using the Pathophysiology of Obstructive Sleep Apnea OSA to Teach Cardiopulmonary Integration

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Using the Pathophysiology of Obstructive Sleep
Apnea (OSA) to Teach Cardiopulmonary Integration

• Michael G. Levitzky, Ph.D.
• Department of Physiology
• Louisiana State University Health Sciences Center
• 1901 Perdido Street
• New Orleans, Louisiana 70112-1393
•  
• Phone  [phone]
• Fax     [phone]
• E-mail mlevit_at_lsuhsc.edu

2
Outline

• I. Introduction Clinical Aspects of OSA
• A. Case scenario
• B. Definition and epidemiology
• C. Symptoms and signs
• D. Description of sleep apnea event
• E. Diagnosis polysomnography
• II. Pathophysiology of OSA
• A. Mechanical/Anatomic
• B. Pulmonary
• 1. Mechanics of breathing in OSA
• 2. Effects of obstruction/apnea on gas exchange
• C. Cardiovascular effects of OSA
• 1. Effects on the pulmonary circulation
• 2. Effects on the systemic circulation
• D. Disturbances in sleep architecture and
  hypersomnolence
• III. Treatment of OSA CPAP
• IV. References

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Case Scenario

• A 61 year old professor comes to the family
  physician because he feels tired all the time. He
  often falls asleep when he attends lectures,
  seminars, or boring meetings. Although he says he
  sleeps through the night (except to get up to
  urinate), his wife says he snores loudly and
  often seems to stop breathing and gasp for
  breath. He is restless and thrashes around in
  bed. He almost always wakes up with a headache
  and for the past year he has been having trouble
  remembering things. He is 5 feet 7 inches tall
  and weighs 250 pounds. His heart rate is 80/min,
  blood pressure is 135/95 mmHg and his respiratory
  rate is 15/min. His electrocardiogram, chest
  radiograph, and echocardiogram strongly suggest
  pulmonary hypertension.
• Diagnosis Obstructive Sleep Apnea

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Obstructive Sleep Apnea (OSA) Definition and
Epidemiology

• Definition 15 apneas (gt 10 sec) and/or
  hypopneas per hour of sleep because of
  sleep-related collapse of the upper airway (Note
  that as much as 40-70 of resistance to airflow
  is normally in upper airway)
• Associated with snoring, but not everyone who
  snores has OSA
• May occur in 9 of middle-aged men and 4 of
  middle-aged women in US estimates in the
  literature have a very wide rangeone source
  stated that 85 of people with OSA are
  undiagnosed
• Prevalence increases with age, body weight,
  pregnancy
• High prevalence in 3- to 5-year old children may
  be as high as 5

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Symptoms of Obstructive Sleep Apnea

• (In descending order of approximate incidence)
• Loud snoring
• Hypersomnolence (Excessive Daytime Sleepiness)
• Depressed mentation
• Altered personality
• Impotence
• Headaches upon waking
• Nocturia

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Signs of Obstructive Sleep Apnea

• Systemic hypertension
• Pulmonary hypertension (right axis deviation on
  ECG)
• Polycythemia
• Cor pulmonale
• Bradycardia during apneic event
• Tachycardia after airflow restored
• Typically no respiratory abnormality while awake
• Arterial blood gasses while awake may show
  metabolic alkalosis

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Description of Sleep Apnea Event

• Upper airway obstruction
• Intermittent obstruction snoring
• Complete obstruction
• Decreased alveolar ventilation
• Decreased alveolar PO2 increased alveolar PCO2
• Decreased arterial PO2 increased arterial PCO2
• Stimulation of arterial chemoreceptors central
  chemoreceptors
• Arousal
• Secondary hyperventilation?

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Effects of Breathhold on Arterial PO2 and PCO2
O2
100
80
Arterial Partial Pressure (mmHg)
60
40
CO2
20
10
20
30
Time (sec)
All figures created by Betsy Giaimo
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Effects of Arterial PO2 and PCO2 on Carotid Body
Activity
20
40
60
80
100
120
140
Carotid Body Activity
10
20
30
40
50
60
, torr
Pa
CO
2
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Diagnosis Polysomnography

• Variables that may be determined include
• EEG and electrooculogram (for sleep state) EMG
• Airflow at nose or mouth (thermistor,
  pneumotachograph)
• End-tidal CO2
• Chest and abdominal motion (impedance
  plethysmography)
• ECG
• Blood pressure
• Pulse oximetry
• Esophageal pressure (intrapleural pressure)
• Autonomic nervous system activity (finger
  tonometer)

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Normal Polysomnograph
EEG
EMG
ECG
BP
Abd
Chest
Vt (air flow)
Pulse Oxygen Saturation
Time (minutes)
20 sec
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Obstructive Sleep Apnea
EEG
ECG
BP
Abd
Chest


Vt (air flow)
Time (minutes)
20 sec
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Pathophysiology of Obstructive Sleep Apnea

• Mechanical
• Short, thick neck
• Neck flexion, supine position
• Nasal obstruction, congestion, polyps
• Surface tension of upper airway lining fluid

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Pathophysiology of Obstructive Sleep Apnea
(continued)

• Anatomic
• Enlarged tonsils and adenoids (esp. ages 3-5),
  enlarged uvula
• Macroglossia
• Retrognathia, craniofacial abnormalities
• Compliant (floppy) pharynx, especially soft
  palate
• Fat deposition in lateral walls of pharynx,
  pharyngeal dilator muscles (obesity)
• Submucosal edema in lateral walls of pharynx

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Pathophysiology of Obstructive Sleep Apnea
(continued)

• Physiologic
• Decreased function of upper airway dilator
  muscles (more than 20 skeletal muscles normally
  involved)
• Decreased pharyngeal dilator reflex response
• Decreased chemoreceptor drive/central drive
  (mixed with central sleep apnea)
• Impaired arousal response
• Alcohol, depressant drugs

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Eupneic Inspiration
(Revised from Fig. 2-1 in Levitzkys Pulmonary
Physiology)
Atmospheric Pressure 0 cm H2O
Atmospheric Pressure 0 cm H2O
Flow in
No flow
Inspiratory force
Outward recoil of chest wall
Alveolar pressure 0 cm H2O
Alveolar pressure 0 cm H2O
Alveolar pressure -1 cm H2O
Inward recoil of alveoli
Intrapleural pressure -5 cmH2O
Intrapleural pressure -8 cmH2O
Transmural pressure -1 cmH2O - (-8cmH2O) 7
cmH2O
Transmural pressure 0 cmH2O - (-5cmH2O) 5
cmH2O
DURING INSPIRATION
END EXPIRATION
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Forced Inspiration
(Revised from Fig. 4-10C in Levitzkys Pulmonary
Physiology)
END EXPIRATION
DURING INSPIRATION
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Mechanics of Breathing in Obstructive Sleep Apnea

• Does negative pressure in the upper airway cause
  obstruction or does obstruction cause negative
  pressure in the upper airway?
• Forced inhalation through the nose causes
  increased nasal resistance to airflow
• Mueller maneuver causes intrapleural pressure to
  fall to approximately -30 cm H2O as low as -80
  cm H2O during episodes of obstructive sleep apnea?

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Obstructive Sleep Apnea
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Obstructive Sleep Apnea
Upper airway anatomy
Sites of obstruction during sleep apnea
Hard Palate
Tongue
Tongue
Hyoid bone
Larynx
Soft Palate
Nasopharynx
Oropharynx
Laryngopharynx
Epiglottis
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Why Obstruction Occurs During Sleep

• Supine position
• Control of breathing during normal non-rapid eye
  movement sleep
• Lack of wakefulness drive
• Minute volume decreases about 16
• PaCO2 increases 4-6 mmHg
• SaO2 decreases as much as 2
• Decreased tone of pharyngeal muscles
• Depressed reflexes, including pharyngeal dilator
• Depressed response to hypoxia in men
• REM sleep decreases tone of intercostal and
  accessory muscles, less effect on diaphragm
  depression of minute volume, increase in CO2 not
  as great, depression of response to hypoxia
  greater

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Possible Explanation for Metabolic Alkalosis When
Patient is Awake

• Chronic repeated obstructions cause carbon
  dioxide retention and therefore respiratory
  acidosis
• Compensatory renal retention of bicarbonate and
  excretion of hydrogen ions leads to metabolic
  alkalosis when PaCO2 is normal during awake state

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Effects of Obstruction on Pulmonary Circulation
and Right Ventricle

• Hypoxic and hypercapnic pulmonary
  vasoconstriction cause pulmonary hypertension
• Chronic nighttime hypoxia may cause
  erythropoiesis and polycythemia
• Increased hematocrit increases blood viscosity
• Hypoxic pulmonary vasoconstriction (HPV),
  increased blood viscosity, pulmonary hypertension
  increase right ventricular afterload
• Increased right ventricular afterload may lead to
  right ventricular hypertrophy and eventually cor
  pulmonale

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Hypoventilation with HPV
O2 150 torr CO2 0 torr
Decreased O2 Increased CO2
O2 40 torr CO2 45 torr
Decreased O2 Increased CO2
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Effects of Hematocrit on Human Blood Viscosity
8
6
Relative Viscosity
4
2
0.2
0.4
0.6
0.8
Hematocrit
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Possible Explanation for Systemic Hypertension

• Repeated increases in sympathetic tone and
  systemic blood pressure during arousals may cause
  vascular remodeling and changes in endothelial
  function

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Explanation for Morning Headaches

• Hypoxia and hypercapnia during obstruction cause
  dilatation of cerebral blood vessels

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Effects of Arterial PO2 and PCO2 on Cerebral
Blood Flow
Arterial PCO2 (mm Hg)
40
100
20
60
80
100
75
Cerebral Blood Flow (ml/100mg/min)
50
25
40
100
20
60
80
Arterial PO2 (mm Hg)
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Possible Explanations for Bradycardia During
Obstruction, Tachycardia after Airflow Restored

• Stimulation of arterial chemoreceptors usually
  increases heart rate because it increases tidal
  volume (lung inflation reflex)
• Stimulation of arterial chemoreceptors without
  stretching the lungs causes bradycardia
• After arousal leads to restoration of airflow,
  large tidal volumes stretch lungs and cause
  tachycardia
• May hyperventilate immediately after arousal,
  then hypoventilate until CO2 is restored

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Possible Explanation for Nocturia

• HPV, increased blood viscosity, pulmonary
  hypertension increase right ventricular afterload
• Increased afterload leads to increased right
  ventricular end diastolic pressure and volume
• Increased right ventricular end diastolic
  pressure and volume lead to increased right
  atrial volume
• Increased right atrial volume increases secretion
  of atrial natriuretic peptide from atrial
  myocytes, which increases sodium excretion, and
  stretches receptors that suppress ADH secretion
  from the posterior pituitary gland

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Explanation for Hypersomnolence or Excessive
Daytime Sleepiness

• Repeated arousals (may be hundreds per night)
  interfere with sleep architecture, especially
  rapid eye movement sleep
• Abnormal sleep architecture leads to daytime
  somnolence, decreased attentiveness, blunted
  mentation, depression, personality changes
• Hypersomnolence increases risk of motor vehicle
  accidents

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Ethanol Exacerbates Obstructive Sleep Apnea

• Ethanol depresses the responses to hypoxia and
  hypercapnia
• Ethanol depresses the activity and tone of the
  genioglossal and pharyngeal dilator muscles
• Ethanol depresses protective respiratory reflexes

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Treatment of OSA

• Lifestyle
• Body position during sleep
• Weight loss
• Decreased ethanol consumption
• Oral appliances
• Continuous Positive Airway Pressure (CPAP)
• Surgical
• Uvulopalatopharyngoplasty
• Tracheostomy

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CPAP Mask

• Photo of CPAP Mask

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Obstructive Sleep Apnea
Sites of obstruction during sleep apnea
With CPAP
Tongue
Tongue
Laryngopharynx
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Obstructive Sleep Apnea Web Sites

• http//www.aafp.org/afp/991115ap/2279.html
• http//www.sleepdisorderchannel.com/osa/

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References

• Caples SM, Gami AS, Somers, VK. Obstructive sleep
  apnea. Ann. Intern. Med. 142 187-197, 2005
• Guilleminault C, Tilkian A, Dement WC. The sleep
  apnea syndromes. Annu. Rev. Med. 27 465-484,
  1976
• Kirkness JP, Krishnan V, Patil SP, Schneider H.
  Upper airway obstruction in snoring and upper
  airway resistance syndrome. In Randerath WJ,
  Sanner BM, Somers VK (eds) Sleep Apnea. Prog.
  Respir. Res. Basel, Karger, 35 79-89, 2006
• Levitzky, Michael G. Pulmonary Physiology (7th
  ed.). 2007. New York McGraw Hill
• Ryan CM, Bradley TD. Pathogenesis of obstructive
  sleep apnea. J. Appl. Physiol. 99 2440-2450,
  2005
• Schaefer T. Physiology of breathing during sleep.
  In Randerath WJ, Sanner BM, Somers VK (eds)
  Sleep Apnea. Prog. Respir. Res. Basel, Karger,
  35 21-28, 2006