Adv Physiol Educ 32: 196 202, 2008;

doi:10.1152/advan.90137.2008.

Refresher Course

Using the pathophysiology of obstructive sleep apnea to teach

cardiopulmonary integration
Michael G. Levitzky
Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, Louisiana
Submitted 16 April 2008; accepted in final form 10 June 2008

mechanics of breathing; alveolar hypoventilation; pulmonary hypertension; systemic hypertension

OBSTRUCTIVE SLEEP APNEA (OSA) is a common disorder characterized by numerous brief occlusions of the upper airway that
occur during sleep. These occlusions, which occur during
inspiratory efforts, result in alveolar hypoventilation that leads
to decreased arterial PO2 and increased arterial PCO2. Stimulation of arterial chemoreceptors by these altered blood gases
causes repeated arousal responses that disturb sleep architecture and may result in hypersomnolence during daily activity.
Chronic intermittent alveolar and systemic arterial hypoxiahypercapnia can cause pulmonary and systemic hypertension,
with effects on the right and left ventricles, and even affect the
renal system. The pathophysiology of OSA can therefore be
used to review and integrate many aspects of pulmonary and
cardiovascular physiology in the context of problem-based
learning, a guided discussion, or a formal lecture. The common
symptoms and signs of OSA can be related to the effects of the
disorder on the mechanics of breathing in the upper airway; the
effects of alveolar hypoventilation on arterial blood gases,
oxygen and carbon dioxide transport by the blood, and acidbase status; pulmonary blood flow and hypoxic pulmonary

Address for reprint requests and other correspondence: M. G. Levitzky,

Dept. of Physiology, Box P7-3, Louisiana State Univ. Health Sciences
Center, 1901 Perdido St., New Orleans, LA 70112-1393 (e-mail: mlevit
@lsuhsc.edu).
196

vasoconstriction; the control of breathing and how normal

sleep affects the control of breathing and respiratory muscles;
and the effects of repeated episodes of hypoventilation on
pulmonary and systemic blood vessels, right and left ventricular mechanics, the electrocardiogram, and cardiac effects on
urine formation. OSA can also be used to review the physiology of sleep and the electroencephalogram, but they are outside the scope of this article (and the authors knowledge).
OSA Case Scenario
A 61-yr-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 ft 7 in.
tall and weighs 250 lb. His heart rate is 80 beats/min, his blood
pressure is 135/95 mmHg, and his respiratory rate is 15 breaths/
min. His electrocardiogram, chest radiograph, and echocardiogram strongly suggest pulmonary hypertension.
Definition and Epidemiology of OSA
OSA is usually defined as 15 or more apneas (and/or hypopneas)
per hour during sleep, caused by collapse of the upper airway
(21, 25). An apnea is usually defined in this context as 10 s or
more without airflow (12, 21, 25). It is important to note that as
much as 40 70% of the resistance to airflow normally resides
in the upper airway, even when a person is awake. Note that
unlike central sleep apnea, obstruction occurs in OSA despite
the central drive to breathe and inspiratory muscle activity
(12). OSA occurs in 9% of middle-aged men and 4% of
middle-aged women in the United States, although estimates of
its prevalence have a very wide range; one source stated that
85% of people with OSA are undiagnosed (21, 26). The
prevalence of OSA increases with age and body weight; it is
increased among pregnant women. There is also a high prevalence in 3- to 5-yr-old children, among whom it may be as
high as 5% (26).
Symptoms and Signs of OSA
A symptom is usually defined as a problem reported by the
patient, yet people with OSA may be unaware that they show
many of the most common symptoms (1, 12) of the disorder
and may not know (or be willing to acknowledge) that there is
The costs of publication of this article were defrayed in part by the payment
of page charges. The article must therefore be hereby marked advertisement
in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1043-4046/08 $8.00 Copyright 2008 The American Physiological Society

Downloaded from http://advan.physiology.org/ by 10.220.33.5 on January 9, 2017

Levitzky MG. Using the pathophysiology of obstructive sleep

apnea to teach cardiopulmonary integration. Adv Physiol Educ 32:
196 202, 2008; doi:10.1152/advan.90137.2008.Obstructive sleep
apnea (OSA) is a common disorder of upper airway obstruction
during sleep. The effects of intermittent upper airway obstruction
include alveolar hypoventilation, altered arterial blood gases and
acid-base status, and stimulation of the arterial chemoreceptors, which
leads to frequent arousals. These arousals disturb sleep architecture
and cause hypersomnolence. Chronic intermittent alveolar and systemic arterial hypoxia-hypercapnia can cause pulmonary and systemic
hypertension, with effects on the right and left ventricles, and even the
renal system. The pathophysiology of OSA can therefore be used to
review and integrate many topics in pulmonary and cardiovascular
physiology in the context of problem-based learning, a guided discussion, or a formal lecture. The discussion begins with a case
scenario, followed by a definition of the disorder, the common
symptoms and signs of OSA, and a description of an apneic event.
These are related to the physiology of the upper airway in OSA,
normal alterations in the respiratory system during sleep, the effects of
apnea on gas exchange and arterial blood gases, and the cardiovascular
consequences of alterations in alveolar and systemic arterial PO2 and
PCO2. The treatment of OSA, particularly how the use of continuous
positive airway pressure relates to the pathophysiology of the disorder, is
discussed briefly.

Refresher Course
PATHOPHYSIOLOGY OF OBSTRUCTIVE SLEEP APNEA

197

Description of a Sleep Apnea Event

Several factors predispose to obstruction of the upper airway
during sleep. Altered body position, decreased tone of the
pharyngeal muscles, depression of the respiratory drive, and
depression of respiratory protective reflexes all occur in normal
people during normal nonrapid eye movement (NREM) sleep,
as discussed in greater detail below. Incomplete intermittent
obstruction of the upper airway, usually involving the soft
palate, results in snoring; periods of complete obstruction
lasting 10 s or more are considered a sleep apnea. As shown in
Fig. 1, an apnea of 10 s or more will result in a significant
increase in arterial PCO2 and a significant decrease in arterial
PO2 (16). Even small increases in arterial PCO2 stimulate
increased activity in arterial chemoreceptors, as shown in Fig. 2,
and eventually in central chemoreceptors; much larger decreases in PCO2 are necessary to stimulate increased activity.
Increased arterial chemoreceptor activity results in increased
respiratory drive and inspiratory muscle activity, but, as discussed below, this is likely to exacerbate the obstruction of the

Fig. 1. Estimated changes in arterial PO2 and PCO2 during 30 s of apnea. Slopes
of changes were modeled after the breathhold data of Lanphier and Rahn (16)
but start at an arterial PO2 of 100 mmHg and a PCO2 of 40 mmHg instead of
after hyperventilation as in the original. A patient with obstructive sleep apnea
(OSA) is likely to begin the apneic period at a lower arterial PO2 and a higher
arterial PCO2 than those shown.

Fig. 2. Estimated effects of changes in arterial PO2 and PCO2 on carotid body
activity. Carotid bodies are much more sensitive to changes in PCO2 than PO2
near the normal range.

upper airway. Chemoreceptor stimulation, probably mainly

due to increased arterial PCO2, and possibly stimulation of
mechanoreceptors in the upper airway, lead to arousal from
sleep, resulting in a nearly immediate decrease in upper airway
resistance and restoration of airflow. The arousal response has
not been well defined, but it does not usually cause complete
awakening (the person with OSA is usually unaware of it). The
increased respiratory drive that occurs during the apneic period
may result in a brief period of hyperventilation after airway
patency is restored.
Diagnosis of OSA: Polysomnography
Polysomnography is a diagnostic test used in the evaluation
of sleep disorders (4, 7, 12). Various physiological sensors are
connected to the patient, and data are collected while the
patient sleeps. The tests are usually done overnight in a
dedicated sleep laboratory, and the data are displayed simultaneously on a polysomnogram or polysomnograph. Physiological data that may be collected during a sleep study of a
person suspected of having OSA include electroencephalograms and electrooculograms, to monitor the persons sleep
state; electromyograms of muscles involved in breathing; airflow at the nose or mouth, usually determined with a thermistor; end-tidal carbon dioxide, as an indicator of alveolar
ventilation; chest and abdominal motion, usually determined
by impedance plethysmography; electrocardiograms and blood
pressure; and pulse oximetry. Esophageal pressure (as an
indicator of intrapleural pressure) and autonomic nervous system activity, as determined by a finger tonometer, are collected
far less commonly. Figure 3 shows an idealized normal polysomnogram; Fig. 4 shows an idealized polysomnogram from a
person with OSA.
In the normal polysomnogram (Fig. 3), chest and abdominal
motion are in phase and hemoglobin oxygen saturation, as
determined by a pulse oximeter, is nearly constant as airflow is
normal. There are no changes in heart rate or blood pressure.

Advances in Physiology Education VOL

32 SEPTEMBER 2008

Downloaded from http://advan.physiology.org/ by 10.220.33.5 on January 9, 2017

anything wrong (25). The most frequently occurring symptom,

loud snoring, is often reported by the persons bed partner,
especially if the bed partner is aware of the periods of obstructive apnea indicated by no snoring and the gasping that accompanies arousals. Snoring is almost always a feature of OSA, but
not everyone who snores has OSA. Hypersomnolence (also
known as excessive daytime sleepiness) is usually a symptom,
often accompanied by depressed mentation. Changes in personality may be noted by people close to the person with OSA.
People with OSA often have headaches upon waking and
frequently report nocturia. The signs of OSA include systemic
hypertension; polycythemia; right axis deviation on the electrocardiogram, indicating right ventricular hypertrophy secondary to pulmonary hypertension; and signs of cor pulmonale.
Bradycardia may occur during the apneic event, with tachycardia after airflow is restored. There is usually no respiratory
abnormality while the person with OSA is awake, but the
arterial blood gases may show metabolic alkalosis.

Refresher Course
198

PATHOPHYSIOLOGY OF OBSTRUCTIVE SLEEP APNEA

Fig. 3. Representation of a normal polysomnogram. EEG, electroencephalogram; EMG, electromyogram; ECG, electrocardiogram; BP, arterial blood
pressure; Abd, abdominal motion; Chest, rib cage motion; Vt, air flow. Note
that abdominal and rib cage motion are in phase during breathing.

There are two sleep apnea events in the polysomnogram drawn

to represent one from a person with OSA (Fig. 4). Oxygen
saturation decreases as each apnea continues, while blood
pressure increases and heart rate decreases. Respiratory efforts
continue during the apneas, but there is no airflow. (In people
with central sleep apnea there is no drive to breathe during the
apneas, so there is no chest or abdominal motion.) Chest and
abdominal motion are not in phase. After arousal, airflow is
restored, oxygen saturation increases, blood pressure falls, and
heart rate increases.
Pathophysiology of OSA
During normal eupneic inspiration, air moves from the
external environment through the resistance of the airways into
the alveoli because alveolar pressure is made less than the
atmospheric pressure (by convention, 0 cmH2O) by the actions
of inspiratory muscles. Because there is a gradient from the
negative (0cmH2O) pressure in the alveoli to the atmospheric
pressure at the nose or mouth, the pressure in the upper airway
must be negative during inspiration (15). During normal quiet
breathing, alveolar pressure may be only 1 or 2 cmH2O,
but it can be much more negative with a greater inspiratory
effort, as shown in Fig. 5. During a Mueller maneuver, intrapleural pressure can fall as low as 30 cmH2O (2); pressures as low as 80 cmH2O during episodes of complete
airway obstruction in OSA are possible. Negative pressure in
the upper airway during a large inspiratory effort can easily be
demonstrated by a strong rapid inspiration through the nose;
the nose is pulled inward and resistance to airflow increases.
Small reinforced adhesive butterfly bandages to place over the
nose to prevent collapse during inspiration are sold in drug
stores. They can often be seen on athletes during sporting
events. The most common causes of upper airway collapse
during inspiration appear to be the tongue or the soft palate
adhering to the wall of the pharynx, as shown in Fig. 6 (4, 7,
22, 25). As the airway begins to collapse because of negative
pressure in the upper airway, the person with OSA makes
greater inspiratory efforts, thus making upper airway pressure

Factors That May Contribute to the Development of OSA

Many factors can contribute to the development of OSA in
different patients (4, 14, 22, 25). Although the disorder is
usually associated with middle-aged and older obese men, as
discussed previously, it is not limited to them. People with
short thick necks (especially when the neck is flexed or they are
in the supine position); people with nasal congestion, obstruction, or polyps; people with enlarged tonsils and adenoids
(especially in 3- to 5-yr-old children) or uvulas; people with
large tongues (macroglossia), short jaws (retrognathia), or craniofacial abnormalities; people with very compliant (floppy) pharynxes or soft palates; and people with fat deposition or submucosal edema in the lateral walls of the pharynx or pharyngeal dilator muscles may be prone to the development of OSA.
Decreased function of the pharyngeal dilator muscles, decreased effectiveness of the pharyngeal dilator reflex, decreased chemoreceptor response, or an impaired arousal response may lead to OSA; all of these may be impaired by the

Fig. 4. Representation of a polysomnogram from a person with OSA. Shown

are two sleep apnea events during which oxygen saturation decreases, blood
pressure increases, and heart rate decreases. Respiratory efforts continue
during the apneas, but there is no airflow. Rib cage and abdominal motion are
not in phase. After arousal, airflow is restored, oxygen saturation increases,
blood pressure falls, and heart rate increases.

Advances in Physiology Education VOL

32 SEPTEMBER 2008

Downloaded from http://advan.physiology.org/ by 10.220.33.5 on January 9, 2017

even more negative, exacerbating the problem until arousal

occurs (see Fig. 4).
Collapse of the upper airway during normal inspiration is
believed to be prevented by contraction of the pharyngeal
dilator muscles (4). As many as 20 muscles may be included in
the pharyngeal dilator group, including the genioglossis, which
pulls the tongue forward to prevent upper airway obstruction;
the geniohyoid, sternohyoid, and thyrohyoid, which move the
hyoid bone forward to enlarge and stabilize the pharyngeal
airway; and the tensor palatini, which pulls the palate away
from the posterior wall of the pharynx (2, 4). (Similarly, the
alae nasi muscles dilate the anterior nares during inspiration.)
The activity of all of these dilator muscles appears to be
centrally coordinated with the activity of the diaphragm. It is
also known that experimentally induced negative pressure in
the upper airway causes a reflex contraction of the pharyngeal
dilator muscles (pharyngeal dilator reflex).

Refresher Course
PATHOPHYSIOLOGY OF OBSTRUCTIVE SLEEP APNEA

199

Fig. 5. Representation of alveolar, intrapleural, and upper airway pressure at end expiration (left) and during a strong inspiratory
effort (right). Note the potential collapse of
the upper airway during the strong inspiratory
effort.

Why Obstruction Occurs During Sleep

Significant changes in the mechanics and control of breathing occur during normal sleep in people that do not have OSA
(23). The most obvious is a result of altered body position.

When a person is in the supine position gravity pulls the tongue

toward the back wall of the pharynx, as shown in Fig. 6. The
control of breathing is altered during NREM sleep by removal
of the component of respiratory drive known as the wakefulness drive (23). Minute volume decreases by 16% and
arterial PCO2 increases by 4 6 mmHg; arterial oxygen saturation decreases by as much as 2% (2, 23). The tone of the
pharyngeal muscles is decreased and the pharyngeal dilator

Fig. 6. Common sites of upper airway obstruction during OSA events (right).
Advances in Physiology Education VOL

32 SEPTEMBER 2008

Downloaded from http://advan.physiology.org/ by 10.220.33.5 on January 9, 2017

persons use of ethanol or depressant drugs. Central sleep

apnea and OSA are often mixed, so a depressed central drive
may also be present in a person with OSA.

Refresher Course
200

PATHOPHYSIOLOGY OF OBSTRUCTIVE SLEEP APNEA

reflex, as well as other protective respiratory reflexes, is depressed. The response to arterial hypoxia is depressed as well.
REM sleep decreases the tone of the intercostal and accessory
muscles, but it has less effect on diaphragm. The depression of
minute volume and the increase in arterial PCO2 are not as great
as occur during NREM sleep, but the depression of the response to arterial hypoxia is greater. These changes in the
mechanics and control of breathing that occur during sleep in
people that do not have OSA predispose those with OSA to
obstruction during sleep.
Pathophysiology of Other Symptoms and Signs of OSA

Fig. 7. Representation of hypoxic pulmonary vasoconstriction in response to

alveolar hypoventilation. Decreased alveolar PO2 and increased alveolar PCO2
cause constriction of the pulmonary vessel supplying the alveolus with blood
flow. HPV, hypoxic pulmonary vasoconstriction.

Fig. 8. Representation of the effect of hematocrit on blood viscosity.

crease the afterload of the right ventricle, producing right

ventricular hypertrophy, which can be seen as a right-axis
deviation in the electrocardiogram. As the pulmonary hypertension and increased viscosity progress, the hypertrophied
right ventricle may not be able to meet the increased work load,
leading to cor pulmonale, which is defined as right ventricular
failure secondary to pulmonary hypertension (10, 17).
Systemic hypertension. Repeated increases in sympathetic
tone and systemic blood pressure during arousals may cause
vascular remodeling and changes in endothelial function, causing systemic hypertension that may persist when the patient is
awake with no upper airway obstruction (2, 6, 20).
Morning headache. Arterial hypoxemia and hypercapnia
during episodes of upper airway obstruction cause increased
cerebral blood flow, presumably caused by dilatation of cerebral blood vessels (5, 8). Figure 9 shows that the effect of
hypercapnia is much greater near the normal range for arterial
PCO2 than is the effect of hypoxemia near the normal range for

Fig. 9. Representation of the effects of arterial PO2 and PCO2 on cerebral blood
flow. Cerebral blood vessels are much more sensitive to changes in arterial
PCO2 than arterial PO2 near the normal range.

Advances in Physiology Education VOL

32 SEPTEMBER 2008

Downloaded from http://advan.physiology.org/ by 10.220.33.5 on January 9, 2017

Metabolic alkalosis when the patient is awake. Chronic

repeated upper airway obstructions during sleep cause carbon
dioxide retention and therefore respiratory acidosis. This leads
to the compensatory renal retention of bicarbonate ions and
excretion of hydrogen ions. The upper airway is not obstructed
when the patient is awake and arterial PCO2 may return to
normal levels. The elevated bicarbonate levels cause a metabolic alkalosis (19).
Pulmonary hypertension, polycythemia, right ventricular
hypertrophy, right-axis deviation, and cor pulmonale. Upper
airway obstructions during sleep cause alveolar hypoxia and
hypercapnia. Hypoxic pulmonary vasoconstriction occurs in
response to the hypoxia and hypercapnia, as shown in Fig. 7.
This constriction of pulmonary blood vessels in response to
alveolar hypoxia increases pulmonary vascular resistance and
causes pulmonary hypertension (10). Repeated episodes of
pulmonary hypertension due to obstruction-induced hypoxic
pulmonary vasoconstriction may lead to vascular remodeling,
resulting in chronic pulmonary hypertension that persists even
during unobstructed awake states. Chronic alveolar hypoxia
during the episodes of upper airway obstruction leads to
hypoxemia (low arterial PO2), which causes renal release of
erythropoietin. Erythropoietin acts on the bone marrow to
produce more red blood cells, which may eventually increase
the hematocrit. As the hematocrit increases, the viscosity of the
blood increases, as shown in Fig. 8. The increased pulmonary
artery pressure and increased blood viscosity chronically in-

Refresher Course
PATHOPHYSIOLOGY OF OBSTRUCTIVE SLEEP APNEA

Hypersomnolence or excessive daytime sleepiness. The repeated arousals precipitated by upper airway obstruction,
which may occur as many as hundreds of times per night,
interfere with normal sleep architecture, especially REM sleep.
Abnormal sleep architecture leads to daytime somnolence,
decreased attentiveness, blunted mentation, depression, and
personality changes; hypersomnolence greatly increases the
risk of motor vehicle accidents (9, 11, 13, 25).
Ethanol consumption exacerbates OSA. Ethanol depresses
the respiratory responses to hypoxia and hypercapnia as well as
depressing the activity and tone of the genioglossal and pharyngeal dilator muscles (10). Ethanol also depresses other
protective respiratory reflexes, which can lead to aspiration and
other problems not directly related to OSA. Ethanol consumption may also interfere with normal sleep architecture.
Treatment of OSA
OSA can be treated a number of ways, depending on the
cause and severity of the problem in the individual patient and
whether or not the patient is compliant with the treatment.
Lifestyle changes. Because the supine position predisposes
upper airway obstruction, changing to another body position
during sleep may decrease or eliminate obstructions. Simple
solutions such as sewing a tennis ball into the back of the
patients pajama top, body belts that make the supine position
uncomfortable, or the use of special pillows may prevent
patients from assuming the supine position during sleep.
Weight loss can help patients for whom adipose tissue around
the upper airway is a contributing factor to upper airway
obstruction during sleep. Decreased consumption of ethanol
will help many OSA patients for the reasons described above.

Fig. 10. Representation of the effects of continuous positive airway pressure (CPAP) in opposing upper airway obstruction in OSA.
Advances in Physiology Education VOL

32 SEPTEMBER 2008

Downloaded from http://advan.physiology.org/ by 10.220.33.5 on January 9, 2017

arterial PO2. The repeated dilatations of cerebral blood vessels

during sleep are the likely cause of the morning headaches
commonly experienced by people with OSA.
Bradycardia during obstruction and tachycardia after airflow is restored. Stimulation of arterial chemoreceptors usually
increases heart rate because it increases tidal volume. This
increase in heart rate is believed to be a reflex initiated by
stimulation of stretch receptors in the small airways, possibly
the same receptors involved in the Hering-Breuer inflation
reflex. The afferent pathway of this lung inflation reflex includes the vagus nerves. On the other hand, stimulation of
arterial chemoreceptors when tidal volume cannot increase, for
example, in a patient on a mechanical ventilator, causes bradycardia (2, 18). During the episodes of obstruction, inspiratory efforts against the obstructed airway do not result in much
of an increase in lung volume even though the arterial chemoreceptors are stimulated. After arousal leads to the restoration
of airflow, large tidal volumes stretch the lungs and cause
tachycardia via the lung inflation reflex. The person with OSA
may hyperventilate immediately after arousal and then hypoventilate until arterial PCO2 is restored to levels sufficient to
stimulate arterial chemoreceptors again.
Nocturia. As noted above, hypoxic pulmonary vasoconstriction, increased blood viscosity, and pulmonary hypertension
increase the right ventricular afterload. The increased afterload
leads to increased right ventricular end-diastolic pressure and
volume. The increased right ventricular end-diastolic pressure
and volume lead to increased right atrial volume, which increases the secretion of atrial natriuretic peptide from atrial
myocytes, increasing sodium excretion. The increased atrial
volume also stretches receptors that suppress antidiuretic hormone secretion from the posterior pituitary gland and increases
urine volume (6).

201

Refresher Course
202

PATHOPHYSIOLOGY OF OBSTRUCTIVE SLEEP APNEA

Summary
OSA is a common disorder of upper airway obstruction
during sleep. Discussion and explanation of the pathophysiology of the disorder and its symptoms and signs involves many
aspects of pulmonary and cardiovascular physiology and can
be used to demonstrate the integration of the cardiovascular
and respiratory systems. Topics that can be discussed include
the mechanics of breathing, alveolar ventilation, pulmonary
blood flow, oxygen transport by the blood, acid-base balance,
control of breathing, systemic and pulmonary hypertension,
right ventricular hypertrophy, and cor pulmonale. Sleep physiology, renal physiology, interpretation of electrocardiograms,
and lifestyle and social issues can be added to the discussion,
particularly in the context of problem-based learning.
ACKNOWLEDGMENTS
The author thanks Betsy Giaimo for preparing the figures in this article.
REFERENCES
1. Barton C. Respiratory abnormalities with sleep disorders. In: Pulmonary
Pathophysiology (2nd ed.), edited by Ali J, Summer W, Levitzky M. New
York: Lange/McGraw-Hill, 2005, p. 213231.

2. Caples SM, Gami AS, Somers VK. Obstructive sleep apnea. Ann Intern
Med 142: 187197, 2005.
3. Chan ASL, Lee RWW, Cistulli PA. Non-positive airway pressure
modalities: mandibular advancement devices/positional therapy. Proc Am
Thorac Soc 5: 179 184, 2008.
4. Deegen PC, McNicholas WT. Pathophysiology of obstructive sleep
apnoea. Eur Respir J 8: 11611178, 1995.
5. Dripps RD, Comroe JH Jr. The respiratory and circulatory response of
normal man to inhalation of 7.6 and 10.4 per cent CO2 with a comparison
of the maximal ventilation produced by severe muscular exercise, inhalation of CO2, and maximal voluntary ventilation. Am J Physiol 149:4351,
1947.
6. Eaton DC, Pooler JP. Vanders Renal Physiology (6th ed). New York:
Lange/McGraw-Hill, 2004, p. 118 124.
7. Eckert D, Malhotra A. Pathophysiology of adult obstructive sleep apnea.
Proc Am Thorac Soc 5: 144 153, 2008.
8. Edvinsson L, MacKenzie ET, McCulloch J. Cerebral Blood Flow and
Metabolism. New York: Raven, 1993, p. 537 and 544.
9. Fuentes-Pradera MA, Botebol G, Sanchez-Armengol A, Carmona C,
Garcia-Fernandez A, Castillo-Gomez J, Capote-Gil F. Effect of snoring and obstructive respiratory events on sleep architecture in adolescents.
Arch Pediatr Adolesc Med 157: 649 654, 2003.
10. Golbin JM, Somers VK, Caples SM. Obstructive sleep apnea, cardiovascular disease, and pulmonary hypertension. Proc Am Thorac Soc 5:
200 206, 2008.
11. Goncalves MA, Paiva T, Ramos E, Guilleminault C. Obstructive sleep
apnea syndrome, sleepiness, and quality of life. Chest 125: 20912096,
2004.
12. Guilleminault C, Tilkian A, Dement WC. The sleep apnea syndromes.
Annu Rev Med 27: 465 484, 1976.
13. Ingbar DH, Gee JBL. Pathophysiology and treatment of sleep apnea.
Annu Rev Med 36: 369 395, 1985.
14. Kirkness JP, Krishnan V, Patil SP, Schneider H. Upper airway obstruction in snoring and upper airway resistance syndrome. In: Sleep
Apnea, edited by Randerath WJ, Sanner BM, Somers VK. Basel: Karger,
2006, p. 79 89.
15. Kirkness JP, Schwartz AR, Schneider H, Punjabi NM, Maly JJ,
Laffan AM, McGinley BM, Magnuson T, Schweitzer M, Smith PL,
Patil SP. Contribution of male sex, age, and obesity to mechanical
instability of the upper airway during sleep. J Appl Physiol 104: 1618
1624, 2008.
16. Lanphier EH, Rahn H. Alveolar gas exchange during breath-hold diving.
J Appl Physiol 18: 471 477, 1963.
17. Lawrence EC, Brigham KL. Chronic cor pulmonale. In: Hursts The
Heart (12th ed.), edited by Fuster V, ORourke RA. New York: McGrawHill, 2008, p. 16731688.
18. Levy MN, Pappano AJ. Cardiovascular Physiology (9th ed.). Philadelphia, PA: Mosby, 2007, p. 89 91.
19. Malley WJ. Clinical Blood Gases (2nd ed.). St. Louis, MO: Elsevier/
Saunders, 2005, p. 355.
20. Parish JM, Somers VK. Obstructive sleep apnea and cardiovascular
disease. Mayo Clin Proc 79: 1036 1046, 2004.
21. Punjabi NM. The epidemiology of adult obstructive sleep apnea. Proc Am
Thorac Soc 5: 136 143, 2008.
22. Ryan CM, Bradley TD. Pathogenesis of obstructive sleep apnea. J Appl
Physiol 99: 2440 2450, 2005.
23. Schaefer T. Physiology of breathing during sleep. In: Sleep Apnea, edited
by Randerath WJ, Sanner BM, Somers VK. Basel: Karger, 2006, p. 2128.
24. Won CHJ, Li KK, Guilleminault C. Surgical treatment of obstructive
sleep apnea: upper airway and maxillomandibular surgery. Proc Am
Thorac Soc 5: 193199, 2008.
25. Yim S, Jordan A, Malhotra A. Obstructive sleep apnea: clinical presentation, diagnosis and treatment. In: Sleep Apnea, edited by Randerath WJ,
Sanner BM, Somers VK. Basel: Karger, 2006, p. 119 136.
26. Young T, Peppard PE, Gottlieb DJ. Epidemiology of obstructive sleep
apnea: a population health perspective. Am J Respir Crit Care Med 165:
12171239, 2002.

Advances in Physiology Education VOL

32 SEPTEMBER 2008

Downloaded from http://advan.physiology.org/ by 10.220.33.5 on January 9, 2017

Oral appliances. Devices designed to be placed in the oral

cavity to maintain airway patency may be effective in patients
that can tolerate them (3). These include mandibular advancement devices that are custom made for the individual patient.
Continuous positive airway pressure. Continuous positive
airway pressure is positive pressure in the airway during both
inspiration and expiration administered to a spontaneously
breathing patient. Air is usually delivered to a mask covering
the nose via a tube from an electrically powered blower. The
mask, which is attached to the head by adjustable straps, has a
one-way valve to prevent exhaled air from being inhaled and to
allow air to flow though the mask so all of the air flow does not
enter the patients airway. The positive pressure prevents the
upper airway from collapsing during inspiration, as shown in
Fig. 10. Continuous positive airway pressure can be very
effective in preventing upper airway collapse during sleep, but
many patients cannot tolerate it because the mask may be
uncomfortable and may irritate the skin. Some patients say
they feel claustrophobic with the mask on or that it dries their
upper airway mucosa. Many report difficulty exhaling against
the positive pressure or that air is forced down the esophagus.
The apparatus may also be noisy and is cumbersome to bring
when traveling.
Surgery. Surgical treatment of patients with OSA who are
unable to alleviate sleep-related upper airway obstruction by
lifestyle change, oral appliances, or positive airway pressure is
aimed at removing anatomic sites of obstruction in the naso-,
oro-, or hypopharynx (24). Procedures include nasal reconstruction, tonsillectomy, uvulopalatopharyngoplasty (removing
the uvula and part of the posterior palate and reorienting the
anterior and posterior pharyngeal pillars), and other patientspecific corrective measures (24). Tracheotomy to completely
bypass the upper airway is considered a last resort.