26
ALTERATIONS OF
PULMONARY FUNCTION
Valentina L. Brashers
CHAPTER OUTLINE
Clinical Manifestations of Pulmonary
Alterations, 714
Signs and Symptoms of Pulmonary Disease, 714
Conditions Caused by Pulmonary Disease
or Injury, 717
Pulmonary Disorders, 723
Restrictive Lung Diseases, 723
Obstructive Lung Diseases, 726
Respiratory Tract Infections, 732
Pulmonary Vascular Disease, 736
Respiratory Tract Malignancies, 739
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P
ulmonary disease is often classified as acute or
chronic, obstructive or restrictive, or infectious or
noninfectious and is caused by alteration in the lung
or heart. Because skillful and knowledgeable clinical care
plays a major role in decreasing respiratory mortality and
morbidity, the clinician who has a clear understanding of
the pathophysiology of common respiratory problems can
greatly affect the outcome for each individual.
The lungs, with their large surface area, are constantly
exposed to the external environment. Therefore, lung disease is greatly influenced by conditions of the environment,
occupation, and personal and social habits. Symptoms of
lung disease are common and associated not only with primary lung disorders but also with diseases of other organ
systems.
714
CLINICAL MANIFESTATIONS OF
PULMONARY ALTERATIONS
Signs and Symptoms of
Pulmonary Disease
Pulmonary disease is associated with many signs and symptoms, the most common of which are cough and dyspnea.
Others include chest pain, abnormal sputum, hemoptysis,
altered breathing patterns, cyanosis, and fever.
Dyspnea
Dyspnea is the subjective sensation of uncomfortable
breathing, the feeling of being unable to get enough air. It
is often described as breathlessness, air hunger, shortness
of breath, labored breathing, and preoccupation with
breathing.
Dyspnea can be caused by diffuse or focal pulmonary
disease. Disturbances of ventilation, gas exchange, or ventilation-perfusion relationships can cause dyspnea, as can
increased work of breathing or any disease that damages
lung tissue (lung parenchyma). One proposed mechanism
for dyspnea is a mismatch between sensory and motor
input from the respiratory center such that there is more
urge to breathe than there is response by the respiratory
muscles. Other causes of dyspnea include stimulation of
central and peripheral chemoreceptors, and stimulation of
afferent receptors in the lung and chest wall.1,2
The signs of dyspnea include flaring of the nostrils, use
of accessory muscles of respiration, and retraction (pulling
back) of the intercostal spaces. In dyspnea caused by parenchymal disease (e.g., pneumonia), retractions of tissue
between the ribs (subcostal and intercostal retractions)
may be observed, although retractions are more common
in children than in adults. In upper airwary obstruction,
supercostal retractions (retractions of tissues above the ribs)
predominate. Dyspnea can be quantified by the use of both
ordinal rating scales and visual analog scales and is frequently associated with significant anxiety.3
Dyspnea can occur transiently or can become chronic.
Often the first episode occurs with exercise and is called
dyspnea on exertion. This type of dyspnea is common to
many pulmonary disorders. One cause of dyspnea is pulmonary congestion usually resulting from heart disease.
Pulmonary congestion tends to cause dyspnea when the
individual is lying down (orthopnea). The horizontal
Alterations of Pulmonary Function
position redistributes body water, causes the abdominal
contents to exert pressure on the diaphragm, and decreases
the efficiency of the respiratory muscles. Sitting up in a
forward-leaning posture or supporting the upper body on
several pillows generally relieves orthopnea. Some individuals with pulmonary or cardiac disease wake up at night
gasping for air and have to sit up or stand to relieve the
dyspnea (paroxysmal nocturnal dyspnea [PND]).
Abnormal breathing patterns
Normal breathing (eupnea) is rhythmic and effortless. The
resting ventilatory rate is 8 to 16 breaths per minute, and
tidal volume ranges from 400 to 800 ml. A short expiratory
pause occurs with each breath, and the individual takes an
occasional deeper breath, or sighs. Sigh breaths, which help
to maintain normal lung function, are usually 1n to 2 times
the normal tidal volume and occur approximately 10 to 12
times per hour.
The rate, depth, regularity, and effort of breathing
undergo characteristic alterations in response to physiologic
and pathophysiologic conditions. Patterns of breathing
automatically adjust to minimize the work of respiratory
muscles. Strenuous exercise or metabolic acidosis induces
Kussmaul respiration (hyperpnea), which is characterized
by a slightly increased ventilatory rate, very large tidal
volumes, and no expiratory pause.
Labored breathing occurs whenever there is an increased
work of breathing, especially if the airways are obstructed.
If the large airways are obstructed, a slow ventilatory rate,
large tidal volume, increased effort, prolonged inspiration
and expiration and stridor or audible wheezing (depending
on the site of obstruction) are typical. In small airway
obstruction like that seen in asthma and chronic obstructive
pulmonary disease, a rapid ventilatory rate, small tidal volume, increased effort, and prolonged expiration are often
present.
Restricted breathing is commonly caused by disorders
such as pulmonary fibrosis that stiffen the lungs or chest
wall and decrease compliance. Small tidal volumes, rapid
ventilatory rate (tachypnea), and rapid expiration are
characteristic.
Shock and severe cerebral hypoxia (insufficient oxygen
in the brain) contribute to gasping respirations that consist
of irregular, quick inspirations with an expiratory pause.
Anxiety can cause sighing respirations, which consist of
irregular breathing characterized by frequent, deep sighing
inspirations.
Cheyne-Stokes respirations are characterized by alternating periods of deep and shallow breathing. Apnea lasting
from 15 to 60 seconds is followed by ventilations that
increase in volume until a peak is reached; then ventilation
(tidal volume) decreases again to apnea. Cheyne-Stokes
respirations result from any condition that slows the blood
flow to the brain stem, which in turn slows impulses sending information to the respiratory centers of the brain
stem. Neurologic impairment above the brain stem is also
a contributing factor.
Chapter 26
715
Hypoventilation/hyperventilation
Hypoventilation is inadequate alveolar ventilation in relation to metabolic demands. Hypoventilation occurs when
minute volume (tidal volume times respiratory rate) is
reduced. It is caused by alterations in pulmonary mechanics
or in the neurologic control of breathing. When alveolar
ventilation is normal, carbon dioxide (CO2) is removed
from the lungs at the same rate as that produced by cellular
metabolism; therefore, arterial and alveolar PCO2 values
remain at normal levels (40 mm Hg). With hypoventilation, CO2 removal does not keep up with CO2 production
and the level of CO2 in the arterial blood (PaCO2)
increases, causing hypercapnia (PaCO2 more than
44 mm Hg) (see Table 25-2 for a definition of gas partial
pressures and other pulmonary abbreviations). This results
in respiratory acidosis that can affect the function of many
tissues throughout the body. Hypoventilation is often overlooked until it is severe because breathing pattern and ventilatory rate may appear to be normal and changes in tidal
volume can be difficult to detect clinically. Blood gas analysis (i.e., measurement of the PaCO2 of arterial blood)
reveals the hypoventilation. Pronounced hypoventilation
can cause somnolence or disorientation.
Hyperventilation is alveolar ventilation exceeding metabolic demands. The lungs remove CO2 faster than it is produced by cellular metabolism, resulting in decreased
PaCO2, or hypocapnia (PaCO2 less than 36 mm Hg).
Hypocapnia results in a respiratory alkalosis that also can
interfere with tissue function. Like hypoventilation, hyperventilation can be determined by arterial blood gas analysis.
Increased respiratory rate or tidal volume can occur with
severe anxiety, acute head injury, pain, and in response to
conditions that cause insufficient oxygenation of the blood.
Cyanosis
Cyanosis is a bluish discoloration of the skin and mucous
membranes caused by increasing amounts of desaturated
or reduced hemoglobin (which is bluish) in the blood. It
generally develops when 5 g of hemoglobin is desaturated,
regardless of hemoglobin concentration.
Cyanosis can be caused by decreased arterial oxygenation (low PaO2), pulmonary or cardiac right-to-left shunts,
decreased cardiac output, cold environment, or anxiety.
Lack of cyanosis does not necessarily indicate that oxygenation is normal. In adults, cyanosis is not evident until severe
hypoxemia is present and, therefore, is an insensitive indication of respiratory failure. Severe anemia (inadequate
hemoglobin concentration) and carbon monoxide poisoning (in which hemoglobin binds to carbon monoxide
instead of to oxygen) can cause inadequate oxygenation of
tissues without causing cyanosis. Individuals with polycythemia (an abnormal increase in numbers of red blood
cells), however, may have cyanosis when oxygenation is
adequate. Therefore, cyanosis must be interpreted in relation to the underlying pathophysiology. If cyanosis is suggested, the PaO2 should be measured. Central cyanosis
(decreased oxygen saturation of hemoglobin in arterial
716
Unit 8
The Pulmonary System
Clubbing is the selective bulbous enlargement of the end
(distal segment) of a digit (finger or toe) (Figure 26-1).
Usually it is painless. Clubbing is commonly associated
with diseases that cause chronic hypoxemia, such as lung
cancer, bronchiectasis, cystic fibrosis, pulmonary fibrosis,
lung abscess, and congenital heart disease. It can sometimes
be seen in individuals with lung cancer even without
hypoxemia.
Acute cough is cough that resolves within 2 to 3 weeks of
the onset of illness or resolves with treatment of the underlying condition. It is most commonly the result of upper
respiratory infections, allergic rhinitis, acute bronchitis,
pneumonia, congestive heart failure, pulmonary embolus,
or aspiration. Chronic cough is defined as cough that has
persisted for more than 3 weeks. In nonsmokers, chronic
cough is almost always the result of postnasal drainage
syndrome, asthma, or gastroesophageal reflux disease. In
smokers, chronic bronchitis is the most common cause of
chronic cough, although lung cancer must always be considered.4 Chronic cough can result in a significantly decreased
quality of life.5
Cough
Hemoptysis
A cough is a protective reflex that cleanses the lower airways by an explosive expiration. Inhaled particles, accumulated mucus, inflammation, or the presence of a foreign
body initiates the cough reflex by stimulating the irritant
receptors in the airway. There are few such receptors in
the most distal bronchi and the alveoli, thus it is possible
for significant amounts of secretions to accumulate in the
distal respiratory tree without cough being initiated. The
cough consists of inspiration, closure of the glottis and
vocal cords, contraction of the expiratory muscles, and
reopening of the glottis, causing a sudden, forceful expiration that removes the offending matter. The effectiveness
of the cough depends on the depth of the inspiration and
the degree to which the airways narrow, increasing the
velocity of expiratory gas flow. Cough occurs frequently in
healthy individuals.
Hemoptysis is the coughing up of blood or bloody secretions. This is sometimes confused with hematemesis, which
is the vomiting of blood. Blood that is coughed up is usually
bright red, has an alkaline pH, and is mixed with frothy
sputum, whereas blood that is vomited is dark, has an
acidic pH, and is mixed with food particles.
Hemoptysis indicates a localized abnormality, usually
infection or inflammation that damages the bronchi
(bronchitis, bronchiectasis) or the lung parenchyma (tuberculosis, lung abscess). Other causes include cancer and pulmonary infarction. The amount and duration of bleeding
provide important clues about its source. Bronchoscopy,
combined with chest computed tomography (CT) is used
to confirm the site of bleeding.
blood) is best seen in buccal mucous membranes and lips.
Peripheral cyanosis (slow blood circulation in fingers and
toes) is best seen in nail beds.
Clubbing
Clubbing — early
Abnormal sputum
Changes in the amount and consistency of sputum provide
information about progression of disease and effectiveness
of therapy. The gross and microscopic appearances of sputum enable the clinician to identify cellular debris or microorganisms, which aids in diagnosis and choice of therapy.
Pain
Clubbing — moderate
Clubbing — severe
Figure 26-1 n Clubbing of Fingers Caused by Chronic
Hypoxemia. (Modified from Seidel HM et al: Mosby’s guide to
physical examination, ed 5, St Louis, 2003, Mosby.)
Pain caused by pulmonary disorders originates in the pleurae, airways, or chest wall. Infection and inflammation of
the parietal pleura (pleurodynia) cause sharp or stabbing
pain when the pleura stretches during inspiration. The pain
is usually localized to a portion of the chest wall, where a
unique breath sound called a pleural friction rub may be
heard over the painful area. Laughing or coughing makes
pleural pain worse. Pleural pain is common with pulmonary infarction (tissue death) caused by pulmonary embolism and emanates from the area around the infarction.
Pulmonary pain is central chest pain that is pronounced
after coughing and occurs in individuals with infection and
inflammation of the trachea or bronchi (tracheitis or
tracheobronchitis). It can be difficult to differentiate from
cardiac pain. High blood pressure in the pulmonary circulation (pulmonary hypertension) can cause pain during
exercise that is often mistaken for cardiac pain (angina pectoris).
Pain in the chest wall is muscle pain or rib pain. Excessive coughing (which makes the muscles sore) and rib
Alterations of Pulmonary Function
fractures produce such pain. Inflammation of the costochondral junction (costochondritis) also can cause chest
wall pain. Chest wall pain can often be reproduced by
pressing on the sternum or ribs.
Conditions Caused by Pulmonary
Disease or Injury
Hypercapnia
Hypercapnia, or increased carbon dioxide in the arterial
blood (increased PaCO2), is caused by hypoventilation of
the alveoli. As discussed in Chapter 25, carbon dioxide is
easily diffused from the blood into the alveolar space; thus,
minute volume (respiratory rate times tidal volume) determines not only alveolar ventilation but also PaCO2. Hypoventilation is often overlooked because the breathing
pattern and ventilatory rate may appear to be normal;
therefore, it is important to obtain blood gas analysis to
determine the severity of hypercapnia and resultant respiratory acidosis (acid-base balance is described in Chapter 4).
There are many causes of hypercapnia. Most are a result
of decreased drive to breathe or an inadequate ability to
respond to ventilatory stimulation. Some of these causes
include (1) depression of the respiratory center by drugs;
(2) diseases of the medulla, including infections of the central nervous system or trauma; (3) abnormalities of the spinal conducting pathways, as in spinal cord disruption or
poliomyelitis; (4) diseases of the neuromuscular junction
or of the respiratory muscles themselves, as in myasthenia
gravis or muscular dystrophy; (5) thoracic cage abnormalities, as in chest injury or congenital deformity; (6) large
airway obstruction, as in tumors or sleep apnea; and
(7) increased work of breathing or physiologic dead space,
as in emphysema.
Hypercapnia and the associated respiratory acidosis
result in electrolyte abnormalities that may cause dysrhythmias. Individuals also may present with somnolence and
even coma because of changes in intracranial pressure associated with high levels of arterial carbon dioxide, which
causes cerebral vasodilation. Alveolar hypoventilation with
increased alveolar CO2 limits the amount of oxygen available for diffusion into the blood, thereby leading to secondary hypoxemia.
Hypoxemia
Hypoxemia, or reduced oxygenation of arterial blood
(reduced PaO2), is caused by respiratory alterations, whereas hypoxia, or reduced oxygenation of cells in tissues, may
be caused by alterations of other systems as well. Although
hypoxemia can lead to tissue hypoxia, tissue hypoxia can
result from other abnormalities unrelated to alterations of
pulmonary function, such as low cardiac output or cyanide
poisoning.
Hypoxemia results from problems with one or more of
the major mechanisms of oxygenation:
1. Oxygen delivery to the alveoli
a. Oxygen content of the inspired air (FiO2)
b. Ventilation of the alveoli
Chapter 26
717
2. Diffusion of oxygen from the alveoli into the blood
a. Balance between alveolar ventilation and perfusion
_ Q_ match)
(V/
b. Diffusion of oxygen across the alveolar capillary
barrier
3. Perfusion of pulmonary capillaries.
The amount of oxygen in the alveoli is called the PAO2
and is dependent on two factors. The first factor is the presence of adequate oxygen content of the inspired air. The
amount of oxygen in inspired air is expressed as the percentage or fraction of air that is composed of oxygen called
the FiO2. The FiO2 of air at sea level is approximately 21%
or 0.21. Anything that decreases the FiO2 (such as high altitude) decreases the PAO2. The second factor is the amount
of alveolar minute volume (tidal volume times respiratory
rate). Hypoventilation results in an increase in PACO2
and a decrease in PAO2 such that there is less oxygen available in the alveoli for diffusion into the blood. This type of
hypoxemia can be completely corrected if alveolar ventilation is improved by increases in the rate and depth of
breathing. Hypoventilation causes hypoxemia in unconscious persons; in persons with neurologic, muscular, or
bone diseases that restrict chest expansion; and in individuals who have chronic obstructive pulmonary disease.
Diffusion of oxygen from the alveoli into the blood is
also dependent on two factors. The first is the balance
_ and the
between the amount of air getting into alveoli (V)
amount of blood perfusing the capillaries around the alveoli
_ An abnormal ventilation-perfusion ratio (V/
_ is the
_ Q)
(Q)
most common cause of hypoxemia (Figure 26-2). Normally,
alveolocapillary lung units receive almost equal amounts of
_ is 0.8 to 0.9
_ Q
ventilation and perfusion. The normal V/
because perfusion is somewhat greater than ventilation in
the lung bases and because some blood is normally shunted
_ mismatch refers to an
_ Q
to the bronchial circulation. V/
From
pulmonary
artery
Airway
Impaired
ventilation
Alveolus
Alveolocapillary
membrane
To
Normal V/Q pulmonary vein Low V/Q
Blocked
ventilation
Hypoxemia
Impaired
perfusion
Collapsed
alveolus
Hypoxemia
Shunt (very low) V/Q
High V/Q
Alveolar
dead space
Hypoxemia
_ Abnormalities.
_ Q)
Figure 26-2 n Ventilation-Perfusion (V/
718
Unit 8
The Pulmonary System
abnormal distribution of ventilation and perfusion. Hypoxemia can be caused by inadequate ventilation of well-per_ Mismatching of this
_ Q).
fused areas of the lung (low V/
type, called shunting, occurs in atelectasis, in asthma as a
result of bronchoconstriction, and in pulmonary edema
and pneumonia when alveoli are filled with fluid. When
blood passes through portions of the pulmonary capillary
bed that receive no ventilation, right-to-left shunt occurs,
resulting in decreased systemic PaO2 and hypoxemia. Hypoxemia also can be caused by poor perfusion of well-venti_ resulting in wasted
_ Q),
lated portions of the lung (high V/
_ is a pul_ Q
ventilation. The most common cause of high V/
monary embolus that impairs blood flow to a segment of
the lung. An area where alveoli are ventilated but not perfused is termed alveolar dead space.
The second factor affecting diffusion of oxygen from the
alveoli into the blood is the alveolocapillary barrier. Diffusion of oxygen through the alveolocapillary membrane is
impaired if the membrane is thickened or the surface area
available for diffusion is decreased. Thickened alveolocapillary membranes, as occur with edema (tissue swelling) and
fibrosis (formation of fibrous lesions), increase the time
required for oxygen to diffuse from the alveoli into the
capillaries. If diffusion is slowed enough, the PO2 of alveolar gas and capillary blood do not have time to equilibrate
during the fraction of a second that blood remains in
the capillary. Destruction of alveoli, as in emphysema,
decreases the surface area available for diffusion. Hypercapnia is seldom produced by impaired diffusion because carbon dioxide diffuses so easily from capillary to alveolus
that the individual with impaired diffusion would die from
hypoxemia before hypercapnia could occur.
Finally, hypoxemia can result from blood flow bypassing
the lungs. This can occur because of intracardiac defects
that cause right to left shunting or because of intrapulmonary arteriovenous malformations.
Hypoxemia is often associated with a compensatory
hyperventilation and the resultant respiratory alkalosis
(i.e., decreased PaCO2 and increased pH). However, in individuals with associated ventilatory difficulties, hypoxemia
may be complicated by hypercapnia and respiratory acidosis. Hypoxemia results in widespread tissue dysfunction
and, when severe, can lead to organ infarction. In addition,
hypoxic pulmonary vasoconstriction can contribute to
increased pressures in the pulmonary artery and lead to
right heart failure or cor pulmonale. Clinical manifestations
of acute hypoxemia may include cyanosis, confusion, tachycardia, edema, and decreased renal output.
QUICK CHECK 26-1
1.
2.
3.
4.
List the primary signs and symptoms of pulmonary
disease.
What abnormal breathing patterns are seen with
pulmonary disease?
What mechanisms produce hypercapnia?
What mechanisms produce hypoxemia?
Acute respiratory failure
Respiratory failure is defined as inadequate gas exchange
such that PaO2 50 mm Hg or PaCO2 50 mm Hg with
pH 7.25. Respiratory failure can result from direct injury
to the lungs, airways, or chest wall or indirectly because of
injury to another body system, such as the brain or spinal
cord. It can occur in individuals who have an otherwise
normal respiratory system or in those with underlying
chronic pulmonary disease. Most pulmonary diseases can
cause episodes of acute respiratory failure. If the respiratory
failure is primarily hypercapnic, it is the result of inadequate alveolar ventilation and the individual must receive
ventilatory support, such as with a bag-valve mask or
mechanical ventilator. If the respiratory failure is primarily
hypoxemic, it is the result of inadequate exchange of oxygen between the alveoli and the capillaries and the individual must receive supplemental oxygen therapy. Many
people will have combined hypercapnic and hypoxemic
respiratory failure and will require both kinds of support.
Respiratory failure is an important potential complication of any major surgical procedure, especially those that
involve the central nervous system, thorax, or upper abdomen. The most common postoperative pulmonary problems are atelectasis, pneumonia, pulmonary edema, and
pulmonary emboli. Smokers are at risk, particularly if they
have preexisting lung disease. Limited cardiac reserve, chronic renal failure, chronic hepatic disease, and infection also
increase the tendency to develop postoperative respiratory
failure.
Prevention of postoperative respiratory failure includes
frequent turning, deep breathing, and early ambulation to
prevent atelectasis and accumulation of secretions. Humidification of inspired air can help loosen secretions. Incentive
spirometry gives individuals immediate feedback about
tidal volumes, which encourages them to breathe deeply.
Supplemental oxygen is given for hypoxemia, and antibiotics are given as appropriate to treat infection. If respiratory
failure develops, the individual may require mechanical
ventilation for a time.
Pulmonary edema
Pulmonary edema is excess water in the lung. The normal
lung is kept dry by lymphatic drainage and a balance
among capillary hydrostatic pressure, capillary oncotic
pressure, and capillary permeability. In addition, surfactant
lining the alveoli repels water, keeping fluid from entering
the alveoli. Predisposing factors for pulmonary edema
include heart disease, acute respiratory distress syndrome,
and inhalation of toxic gases. The pathogenesis of pulmonary edema is shown in Figure 26-3.
The most common cause of pulmonary edema is heart
disease. When the left ventricle fails, filling pressures on
the left side of the heart increase and vascular volume redistributes into the lungs, subsequently causing an increase in
pulmonary capillary hydrostatic pressure.6 When the
hydrostatic pressure exceeds oncotic pressure (which holds
fluid in the capillary), fluid moves out into the interstitium,
Alterations of Pulmonary Function
Chapter 26
Valvular dysfunction
Coronary artery
disease
Left ventricular
dysfunction
Injury to capillary
endothelium
Blockage of
lymphatic vessels
Increased left
atrial pressure
Increased capillary
permeability and
disruption of surfactant
production by alveoli
Inability to remove
excess fluid from
interstitial space
Increased pulmonary
capillary hydrostatic
pressure
Movement of fluid and plasma
proteins from capillary to
interstitial space (alveolar
septum) and alveoli
Accumulation of fluid
in interstitial space
719
Pulmonary edema
Figure 26-3 n Pathogenesis of Pulmonary Edema.
or interstitial space (the space within the alveolar septum
between alveolus and capillary). When the flow of fluid
out of the capillaries exceeds the lymphatic system’s ability
to remove it, pulmonary edema develops.
Another cause of pulmonary edema is capillary injury
that increases capillary permeability, as in cases of acute
respiratory distress syndrome or inhalation of toxic gases,
such as ammonia. Capillary injury causes water and plasma
proteins to leak out of the capillary and move into the interstitium, increasing the interstitial oncotic pressure, which is
usually very low. As the interstitial oncotic pressure begins
to equal capillary oncotic pressure, water moves out of the
capillary and into the lung. (This phenomenon is discussed
in Chapter 4, Figures 4-1 and 4-2.)
Pulmonary edema also can result from obstruction of
the lymphatic system. Drainage can be blocked by compression of lymphatic vessels by edema, tumors, and fibrotic tissue and by increased systemic venous pressure.
Clinical manifestations of pulmonary edema include
dyspnea, hypoxemia, and increased work of breathing.
Physical examination may reveal inspiratory crackles (rales)
and dullness to percussion over the lung bases. In severe
edema, pink frothy sputum is expectorated and PaCO2
increases.
The treatment of pulmonary edema depends on its
cause. If the edema is caused by increased hydrostatic pressure that results from heart failure, therapy is geared toward
improving cardiac output with diuretics, vasodilators, and
drugs that improve the contraction of the heart muscle. If
edema is the result of increased capillary permeability
resulting from injury, the treatment is focused on removing
the offending agent and supportive therapy to maintain
adequate ventilation and circulation. Individuals with either
type of pulmonary edema require supplemental oxygen.
Positive-pressure mechanical ventilation may be needed if
edema significantly impairs ventilation and oxygenation.
Aspiration
Aspiration is the passage of fluid and solid particles into
the lung. It tends to occur in individuals whose normal
swallowing mechanism and cough reflex are impaired by
central or peripheral nervous system abnormalities. Predisposing factors include an altered level of consciousness
caused by substance abuse, sedation, or anesthesia; seizure
disorders; cerebrovascular accident; and neuromuscular disorders that cause dysphagia. The right lung, particularly the
right lower lobe, is more susceptible to aspiration than the
left lung because the branching angle of the right main stem
bronchus is straighter than the branching angle of the left
main stem bronchus.
The aspiration of large food particles or foreign bodies
can obstruct a bronchus, resulting in bronchial inflammation and collapse of airways distal to the obstruction. Clinical manifestations include the sudden onset of choking,
cough, vomiting, dyspnea, and wheezing. If the aspirated
solid is not identified and removed by bronchoscopy, a
chronic, local inflammation develops that may lead to
recurrent infection and bronchiectasis (permanent dilation
of the bronchus). Once the pathologic process has progressed to bronchiectasis, surgical resection of the affected
area is usually required.
Aspiration of acidic gastric fluid (pH <2.5) may cause
severe pneumonitis (lung inflammation). Bronchial damage
includes inflammation, loss of ciliary function, and bronchospasm. In the alveoli, acidic fluid damages the alveolocapillary membrane, allowing plasma and blood cells to
720
Unit 8
The Pulmonary System
move from capillaries into the alveoli, resulting in hemorrhagic pneumonitis. The lung becomes stiff and noncompliant as surfactant production is disrupted, leading to further
edema and collapse.
Preventive measures for individuals at risk are more
effective than treatment of known aspiration. The most
important preventive measures include the semirecumbent
position, the surveillance of enteral feeding, the use of promotility agents, and the avoidance of excessive sedation.7
Nasogastric tubes, which are often used to remove stomach
contents, are used to prevent aspiration but also can cause
aspiration if fluid and particulate matter are regurgitated
as the tube is being placed. Treatment of aspiration includes
supplemental oxygen and mechanical ventilation with positive end-expiratory pressure (PEEP), fluid restriction, and
steroids. Bacterial pneumonia may develop as a complication of aspiration pneumonitis and must be treated with
broad-spectrum antimicrobials.
Atelectasis
Atelectasis is the collapse of lung tissue. There are two
types of atelectasis:
1. Compression atelectasis is caused by external pressure
exerted by tumor, fluid, or air in pleural space or by
abdominal distention pressing on a portion of lung,
causing alveoli to collapse.
2. Absorption atelectasis results from removal of air from
obstructed or hypoventilated alveoli or from inhalation
of concentrated oxygen or anesthetic agents.
Clinical manifestations of atelectasis are similar to those
of pulmonary infection including dyspnea, cough, fever,
and leukocytosis.
Atelectasis tends to occur after surgery.8 Postoperative
patients may have received supplemental oxygen or inhaled
Inspired air
Mucus plug
Normal
alveolus
anesthetics, and they are usually in pain, breathe shallowly,
are reluctant to change position, and produce viscous
secretions that tend to pool in dependent portions of the
lung. Prevention and treatment of postoperative atelectasis
usually include deep breathing, frequent position changes,
and early ambulation. Deep breathing and the use of an
incentive spirometer helps open connections between patent and collapsed alveoli, called pores of Kohn (Figure 264). This allows air to flow into the collapsed alveoli (collateral ventilation) and aids in the expulsion of intrabronchial
obstructions.
Bronchiectasis
Bronchiectasis is persistent abnormal dilation of the bronchi. It usually occurs in conjunction with other respiratory
conditions and can be caused by obstruction of an airway
with mucus plugs, atelectasis, aspiration of a foreign body,
infection, cystic fibrosis, tuberculosis, congenital weakness
of the bronchial wall, or impaired defense mechanisms.
Bronchiectasis is often associated with inflammation of
the bronchi (bronchitis) and has similar symptoms (see p.
735).
The symptoms of bronchiectasis may date back to a
childhood illness or infection. The disease is commonly
associated with recurrent lower respiratory tract infections
and expectoration of voluminous amounts of purulent sputum (measured in cupfuls). If the individual is not receiving
antibiotics, the sputum has a foul odor. Hemoptysis and clubbing of the fingers are common. Pulmonary function studies
show decreased vital capacity (VC) and expiratory flow
rates. Bronchiectasis is often associated with bronchitis and
atelectasis. Hypoxemia eventually leads to cor pulmonale
(see p. 738).
Inspired air
Mucus plug
Closed pore
of Kohn
Open pore
of Kohn
Atelectatic
alveolus
A
Low inspiratory volume
(shallow breathing)
High inspiratory volume
(deep breathing)
B
Figure 26-4 n Pores of Kohn. A, Absorption atelectasis caused by lack of collateral ventilation through pores of Kohn. B, Restoration
of collateral ventilation during deep breathing.
Alterations of Pulmonary Function
Bronchiolitis
Bronchiolitis is an inflammatory obstruction of the small
airways or bronchioles, occurring most commonly in children. In adults, it usually accompanies chronic bronchitis
but can occur in otherwise healthy individuals in association with an upper or lower respiratory infection or inhalation of toxic gases. Bronchiolitis is also a serious
complication of lung transplantation. Atelectasis or emphysematous destruction of the alveoli may develop distal to
the inflammatory lesion. Bronchiolitis is usually diffuse.
Bronchiolitis obliterans is a fibrotic process that occludes
airways and causes permanent scarring of the lungs. This
process can occur in all causes of bronchiolitis but is most
common after lung transplantation. Bronchiolitis obliterans
can be further complicated by the development of organizing pneumonia (BOOP). Bronchiolitis frequently presents
with a rapid ventilatory rate; marked use of accessory
muscles; low-grade fever; dry, nonproductive cough; and
hyperinflated chest. A decrease in the ventilation-perfusion
ratio results in hypoxemia. Bronchiolitis is treated with
appropriate antibiotics, steroids, and chest physical therapy
(humidified air, coughing and deep breathing, postural
drainage) as indicated by the underlying cause.
Pleural abnormalities
Pneumothorax
Pneumothorax is the presence of air or gas in the pleural
space caused by a rupture in the visceral pleura (which surrounds the lungs) or the parietal pleura and chest wall. As
air separates the visceral and parietal pleurae, it destroys
Chapter 26
721
the negative pressure of the pleural space and disrupts the
equilibrium between elastic recoil forces of the lung and
chest wall. The lung then tends to recoil by collapsing
toward the hilum (Figure 26-5).
Spontaneous pneumothorax, which occurs unexpectedly
in healthy individuals (usually men) between 20 and 40
years of age, is caused by the spontaneous rupture of blebs
(blister-like formations) on the visceral pleura. Bleb rupture
can occur during sleep, rest, or exercise. The ruptured bleb
or blebs are usually located in the apexes of the lungs. The
cause of bleb formation is not known.
A secondary or traumatic pneumothorax can be caused
by chest trauma (such as a rib fracture or stab and bullet
wounds that tear the pleura; rupture of a bleb or bulla
[larger vesicle], as occurs in chronic obstructive pulmonary
disease; or mechanical ventilation, particularly if it includes
positive end-expiratory pressure [PEEP]).
Both spontaneous and secondary pneumothorax can
present as either open or tension. In open pneumothorax
(communicating pneumothorax), air pressure in the pleural space equals barometric pressure because air that is
drawn into the pleural space during inspiration (through
the damaged chest wall and parietal pleura or through the
lungs and damaged visceral pleura) is forced back out during expiration. In tension pneumothorax, however, the site
of pleural rupture acts as a one-way valve, permitting air to
enter on inspiration but preventing its escape by closing up
during expiration. As more and more air enters the pleural
space, air pressure in the pneumothorax begins to exceed
barometric pressure. The pathophysiologic effects of tension pneumothorax are life threatening. Air pressure in
Outside air enters
because of disruption
of chest wall and
parietal pleura
Normal
lung
Chest
wall
Mediastinum
Lung air enters
because of disruption of
visceral pleura
Pleural
space
Diaphragm
Figure 26-5 n Pneumothorax. Air in the pleural space causes the lung to collapse around the hilus and may push mediastinal contents (heart and great vessels) toward the other lung.
722
Unit 8
The Pulmonary System
the pleural space pushes against the already recoiled lung,
causing compression atelectasis, and against the mediastinum, compressing and displacing the heart and great
vessels.
Clinical manifestations of spontaneous or secondary
pneumothorax begin with sudden pleural pain, tachypnea,
and dyspnea. The manifestations depend on the size of
the pneumothorax. Physical examination may reveal absent
or decreased breath sounds and hyperresonance to percussion on the affected side. Tension pneumothorax may be
complicated by severe hypoxemia, tracheal deviation away
from the affected lung, and hypotension (low blood pressure). Deterioration occurs rapidly and immediate treatment is required. Diagnosis of pneumothorax is made
with chest radiographs and computed tomography (CT).
Pneumothorax is treated with insertion of a chest tube that
is attached to a water-seal drainage system with suction.
After the pneumothorax is evacuated and the pleural rupture is healed, the chest tube is removed.
Pleural effusion
Pleural effusion is the presence of fluid in the pleural
space. The most common mechanism of pleural effusion
is migration of fluids and other blood components through
the walls of intact capillaries bordering the pleura. Pleural
effusions that enter the pleural space from the intact blood
vessels can be transudative (watery) or exudative (high
concentrations of white blood cells and plasma proteins).
Other types of pleural effusion characterized by the presence of pus (empyema), blood (hemothorax), or chyle (chylothorax). Mechanisms of pleural effusion are summarized
in Table 26-1.
Small collections of fluid normally can be drained away
by the lymphatics. Dyspnea, compression atelectasis with
impaired ventilation, and mediastinal shift occur with large
effusions. Pleural pain is present if the pleura is inflamed,
and cardiovascular manifestations occur in a large, rapidly
developing effusion. Physical exam reveals decreased breath
sounds and dullness to percussion on the affected side.
A pleural friction rub can be heard over areas of extensive
effusion.
Diagnosis is confirmed by chest x-ray and thoracentesis
(needle aspiration), which can determine the type of effusion and provide symptomatic relief. If the effusion is large,
drainage usually requires the placement of a chest tube.
Empyema
Empyema (infected pleural effusion) is the presence of
pus in the pleural space. It is thought to develop when the
pulmonary lymphatics become blocked, leading to an outpouring of contaminated lymphatic fluid into the pleural
space. Empyema occurs most commonly in older adults
and children and usually develops as a complication of
pneumonia, surgery, trauma, or bronchial obstruction from
a tumor.9 Commonly documented infectious organisms
include Staphylococcus aureus, Escherichia coli, anaerobic
bacteria, and Klebsiella pneumoniae.
Individuals with empyema present clinically with cyanosis, fever, tachycardia (rapid heart rate), cough, and pleural
pain. Breath sounds are decreased directly over the empyema. Diagnosis is made by chest radiographs, thoracentesis,
and sputum culture.
The treatment for empyema includes the administration
of appropriate antimicrobials and drainage of the pleural
TABLE 26-1
Mechanism of Pleural Effusion
Type of Fluid/Effusion
Source of Accumulation
Primary or Associated Disorder
Transudate (hydrothorax)
Watery fluid that diffuses out of capillaries
beneath the pleura (i.e., capillaries in lung or
chest wall)
Exudate
Fluid rich in cells and proteins (leukocytes,
plasma proteins of all kinds; see Chapter 5)
that migrates out of the capillaries
Pus (empyema)
Debris of infection (microorganisms,
leukocytes, cellular debris) dumped into the
pleural space by blocked lymphatic vessels
Hemorrhage into the pleural space
Cardiovascular disease that causes high
pulmonary capillary pressures; liver or kidney
disease that disrupts plasma protein
production, causing hypoproteinemia
(decreased oncotic pressure in the blood
vessels)
Infection, inflammation, or malignancy of the
pleura that stimulates mast cells to release
biochemical mediators that increase capillary
permeability
Pulmonary infections, such as pneumonia; lung
abscesses; infected wounds
Blood (hemothorax)
Chyle (chylothorax)
Chyle (milky fluid containing lymph and fat
droplets) that is dumped by lymphatic vessels
into the pleural space instead of passing from
the gastrointestinal tract to the thoracic duct
Traumatic injury, surgery, rupture, or
malignancy that damages blood vessels
Traumatic injury, infection, or disorder that
disrupts lymphatic transport
The principles of diffusion are described in Chapter 1; mechanisms that increase capillary permeability and cause exudation of cells and proteins
are discussed in Chapter 5
Alterations of Pulmonary Function
Chapter 26
723
space with a chest tube. In severe cases, instillation of
fibrinolytic agents or deoxyribonuclease (DNase) into the
pleural space is needed for adequate drainage.
Chest wall restriction
If the chest wall is deformed, traumatized, immobilized, or
made heavy by fat, the work of breathing increases and ventilation may be compromised because of a decrease in tidal
volume. The degree of ventilatory impairment depends on
the severity of the chest wall abnormality. Grossly obese
individuals are often dyspneic on exertion or when recumbent. Individuals with severe kyphoscoliosis (lateral bending and rotation of the spinal column, with distortion of
the thoracic cage) often present with dyspnea on exertion
that can progress to respiratory failure. Such individuals
are also susceptible to lower respiratory tract infections.
Both obesity and kyphoscoliosis are risk factors for respiratory disease in hospital patients admitted for other problems, particularly those who require surgery. Other
musculoskeletal abnormalities that can impair ventilation
are ankylosing spondylitis (rheumatoid arthritis of the
spine; see Chapter 37) and pectus excavatum, or funnel
chest (a deformity characterized by depression of the
sternum).
Impairment of respiratory muscle function caused by
neuromuscular disease also can restrict the chest wall and
impair pulmonary function. Muscle weakness can result in
hypoventilation, inability to remove secretions, and hypoxemia. Respiratory difficulty is the most common cause of
hospital admission for individuals with neuromuscular diseases such as poliomyelitis, muscular dystrophy, myasthenia gravis, and Guillain-Barré syndrome. (See Unit 4 for a
more complete discussion of these disorders.)
Chest wall restriction results in a decrease in tidal volume. An increase in respiratory rate can compensate for
small decreases in tidal volume, but many patients will
progress to hypercapnic respiratory failure. Diagnosis of
chest restriction is made by pulmonary function testing
(reduction in forced vital capacity [FVC]), arterial blood
gas measurement (hypercapnia), and radiographs. Treatment is aimed at any reversible underlying cause but is otherwise supportive. In severe cases, mechanical ventilation
may be indicated.
Flail chest
Flail chest results from the fracture of several consecutive
ribs in more than one place or the fracture of the sternum
plus several consecutive ribs. These multiple fractures result
in instability of a portion of the chest wall, causing paradoxic movement of the chest with breathing. During inspiration the unstable portion of the chest wall moves inward,
and during expiration it moves outward, impairing movement of gas in and out of the lungs (Figure 26-6).
The clinical manifestations of flail chest are pain,
dyspnea, unequal chest expansion, hypoventilation, and
hypoxemia. Treatment is internal fixation by controlled
mechanical ventilation until the chest wall can be stabilized
surgically.
A
B
C
D
Figure 26-6 n Flail Chest. Normal respiration: A, inspiration;
B, expiration. Paradoxical motion: C, inspiration, area of lung
underlying unstable chest wall sucks in on inspiration; D, expiration, unstable area balloons out. Note movement of mediastinum toward opposite lung during inspiration.
QUICK CHECK 26-2
1.
2.
3.
4.
5.
Describe pulmonary edema, and list two causes.
Contrast atelectasis and bronchiectasis.
How does pneumothorax differ from pleural effusion?
What causes empyema?
How does chest wall restriction affect ventilation?
PULMONARY DISORDERS
Restrictive Lung Diseases
Restrictive lung diseases are characterized by decreased
compliance of the lung tissue and resultant increased work
of breathing. Individuals with lung restriction complain of
dyspnea and have an increased respiratory rate and
decreased tidal volume. Pulmonary function testing reveals
a decrease in forced vital capacity (FVC). Restrictive lung
diseases commonly affect the alveolocapillary membrane
and cause decreased diffusion of oxygen from the alveoli
into the blood resulting in hypoxemia. Some of the most
common restrictive lung diseases in adults are pulmonary
fibrosis, inhalational disorders, pneumoconiosis, allergic
alveolitis, and the acute respiratory distress syndrome.
Pulmonary fibrosis
Pulmonary fibrosis is an excessive amount of fibrous or
connective tissue in the lung. The most common form of
pulmonary fibrosis has no known cause and therefore is
called idiopathic pulmonary fibrosis. Pulmonary fibrosis
also can be caused by formation of scar tissue after
active pulmonary disease (e.g., acute respiratory distress
724
Unit 8
The Pulmonary System
syndrome, tuberculosis), in association with a variety of
autoimmune disorders (e.g., rheumatoid arthritis, progressive systemic sclerosis, sarcoidosis), or by inhalation of
harmful substances (e.g., coal dust, asbestos).
Fibrosis causes a marked loss of lung compliance.
The lung becomes stiff and difficult to ventilate, and the
diffusing capacity of the alveolocapillary membrane may
decrease, causing hypoxemia. Diffuse pulmonary fibrosis
has a poor prognosis.
Inhalation disorders
Treatment is usually palliative and focuses on preventing
further exposure, particularly in the workplace.
Allergic alveolitis
Inhalation of organic dusts can result in an allergic inflammatory response called extrinsic allergic alveolitis, or
hypersensitivity pneumonitis. Many allergens can cause
this disorder, including grains, silage, bird droppings or
feathers, wood dust (particularly redwood and maple), cork
dust, animal pelts, coffee beans, fish meal, mushroom compost, and molds that grow on sugarcane, barley, and straw.
The lung inflammation, or pneumonitis, occurs after
repeated, prolonged exposure to the allergen.
Allergic alveolitis can be acute, subacute, or chronic. The
acute form causes a fever, cough, and chills a few hours
after exposure. In the subacute form, coughing and dyspnea
are common and sometimes necessitate hospital care.
Recovery is complete if the offending agent can be avoided
in the future. With continued exposure, the disease
becomes chronic and pulmonary fibrosis develops.
Exposure to toxic gases
Inhalation of gaseous irritants can cause significant respiratory dysfunction. Commonly encountered toxic gases
include smoke, ammonia, hydrogen chloride, sulfur dioxide, chlorine, phosgene, and nitrogen dioxide. Inhalation
of a toxic gas results in severe inflammation of the airways,
alveolar and capillary damage, and pulmonary edema. Initial symptoms include burning of the eyes, nose, and throat;
coughing; chest tightness; and dyspnea. Hypoxemia is common. Treatment includes supplemental oxygen, mechanical
ventilation with PEEP, and support of the cardiovascular
system. Steroids are sometimes used, although their effectiveness has not been well documented. Most individuals
respond quickly to therapy. Some, however, may improve
initially and then deteriorate as a result of bronchiectasis
or bronchiolitis (inflammation of the bronchioles).
Prolonged exposure to high concentrations of supplemental oxygen can result in a relatively rare condition
known as oxygen toxicity. The basic underlying mechanism of injury is a severe inflammatory response mediated
primarily by oxygen radicals. Toxicity is often undetected
because it occurs in individuals who are already in acute
respiratory failure. Treatment involves ventilatory support
and a reduction of inspired oxygen concentration to less
than 60% as soon as the individual can tolerate this change.
Acute respiratory distress syndrome (ARDS) is characterized by acute lung inflammation and diffuse alveolocapillary injury. In the United States, over 30% of ICU
admissions are complicated by this syndrome. Advances
in therapy have decreased overall mortality in people younger than 60 years to approximately 40%, although mortality
in older adults and those with severe infections remains
much higher.12 The most common predisposing factors
are sepsis and multiple trauma; however, there are many
other causes, including pneumonia, burns, aspiration, cardiopulmonary bypass surgery, pancreatitis, blood transfusions, drug overdose, inhalation of smoke or noxious
gases, fat emboli, high concentrations of supplemental oxygen, radiation therapy, and disseminated intravascular
coagulation.
Pneumoconiosis
Pneumoconiosis represents any change in the lung caused
by inhalation of inorganic dust particles, usually in the
workplace. As in all cases of environmentally acquired lung
disease, the individual’s history of exposure is important in
determining the diagnosis. Pneumoconiosis often occurs
after years of exposure to the offending dust, with progressive fibrosis of lung tissue.
The dusts of silica, asbestos, and coal are the most common causes of pneumoconiosis. Others include talc, fiberglass, clays, mica, slate, cement, cadmium, beryllium,
tungsten, cobalt, aluminum, and iron. Deposition of these
materials in the lungs leads to chronic inflammation with
scarring of the alveolar capillary membrane leading to pulmonary fibrosis (see p. 723).10 These dust deposits are permanent and lead to progressive pulmonary deterioration.
Clinical manifestations with advancement of disease
include cough, chronic sputum production, dyspnea,
decreased lung volumes, and hypoxemia. Diagnosis is confirmed by chest x-ray and computed tomography (CT).11
PATHOPHYSIOLOGY All disorders causing ARDS cause
massive pulmonary inflammation that injures the alveolocapillary membrane and produces severe pulmonary edema, shunting, and hypoxemia (Figure 26-7). The damage
can occur directly, as with the aspiration of highly acidic
gastric contents or the inhalation of toxic gases, or indirectly
from chemical mediators released in response to systemic
disorders such as sepsis. Injury to the pulmonary capillary
endothelium stimulates platelet aggregation and intravascular thrombus formation. Endothelial damage also initiates
the complement cascade, stimulating neutrophil and macrophage activity and the inflammatory response.13
Once activated, macrophages produce toxic mediators
such as tumor necrosis factor (TNF) and interleukin
1 (IL-1). The role of neutrophils is central to the development of ARDS. Activated neutrophils release a battery of
inflammatory mediators, including proteolytic enzymes,
toxic oxygen products, arachidonic acid metabolites (prostaglandins, thromboxanes, leukotrienes), and plateletactivating factor.13 These mediators extensively damage
Acute respiratory distress syndrome
Alterations of Pulmonary Function
Chapter 26
725
Acute insult
(e.g., pneumonia, aspiration, smoke inhalation)
Release of cytokines
(e.g., IL-1␤, TNF)
Influx of inflammatory cells to lung
(i.e., neutrophils, macrophages, activated platelets)
Release of ROS and cytokines
Activation of complement system
Damage to type II
pneumocytes
Disruption of alveolarcapillary membrane
Microthrombi in
pulmonary circulation
Release of fibroblast growth
factors (e.g., TGF-␤, PDGF)
Atelectasis and decreased
lung compliance
Noncardiogenic pulmonary
edema and intrapulmonary
shunting
Pulmonary hypertension
Pulmonary fibrosis
Figure 26-7 n Proposed Mechanisms for the Pathogenesis of Acute Respiratory Distress Syndrome (ARDS). IL-1-b, Interleukin-1-b;
TNF, tumor necrosis factor; ROS, reactive oxygen species; TGF-b, transforming growth factor-b; PDGF, platelet derived growth factor.
(From Soubani AO, Pieroni R: Acute respiratory distress syndrome: a clinical update, South Med J 92[5]:452, 1999.)
the alveolocapillary membrane and greatly increase capillary membrane permeability. This allows fluids, proteins,
and blood cells to leak from the capillary bed into the pulmonary interstitium and alveoli. The resulting pulmonary
edema severely reduces lung compliance and impairs alveolar ventilation. Mediators released by neutrophils and
macrophages also cause pulmonary vasoconstriction, which
_ mismatching and hypoxemia.
_ Q
leads to worsening V/
The initial lung injury also damages the alveolar epithelium. This type II alveolar cell injury increases alveolocapillary permeability, increases susceptibility to bacterial
infection and pneumonia, and decreases surfactant production.13 Alveoli and respiratory bronchioles fill with fluid or
collapse. The lungs become less compliant, ventilation of
alveoli decreases, and pulmonary blood flow is shunted
right to left. The work of breathing increases. The end
result is acute respiratory failure.
Twenty-four to 48 hours after the acute phase of ARDS,
hyaline membranes form, and after approximately 7 days,
fibrosis progressively obliterates the alveoli, respiratory
bronchioles, and interstitium (fibrosing alveolitis). Functional residual capacity declines, and more severe right-toleft shunting is evident.
The chemical mediators responsible for the alveolocapillary damage of ARDS often cause widespread inflammation, endothelial damage, and capillary permeability
throughout the body resulting in the systemic inflammatory
response syndrome (SIRS), which then leads to multiple
organ dysfunction syndrome (MODS). In fact, death may
not be caused by respiratory failure alone but by MODS
associated with ARDS. (MODS is discussed in Chapter 23.)
CLINICAL MANIFESTATIONS The classic signs and
symptoms of ARDS are marked dyspnea; rapid, shallow
breathing; inspiratory crackles; respiratory alkalosis;
decreased lung compliance; hypoxemia unresponsive to
oxygen therapy (refractory hypoxemia); and diffuse alveolar
infiltrates seen on chest radiographs, without evidence of
cardiac disease. Symptoms develop progressively, as follows:
Hyperventilation
#
Respiatory alkalosis
#
Dyspnea and hypoxemia
#
Metabolic acidosis
#
Hypoventilation
#
Respiratory acidosis
#:
Further hypoxemia
#
Hypotension; decreased cardiac output; death
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Unit 8
The Pulmonary System
EVALUATION AND TREATMENT Diagnosis is based on
physical examination, analysis of blood gases, and radiologic examination. Treatment is based on early detection,
supportive therapy, and prevention of complications. Supportive therapy is focused on maintaining adequate oxygenation and ventilation while preventing infection. This
often requires alternative modes of mechanical ventilation.13,14 Surfactant can be given to improve lung compliance. Many studies are under way that investigate new
ways to prevent or treat ARDS. Anticoagulant therapy with
recombinant human-activated protein C improves outcomes in sepsis associated with ARDS and continues to be
evaluated.14,15
QUICK CHECK 26-3
1.
2.
3.
4.
What are some of the causes of pulmonary fibrosis?
What symptoms are produced by inhalation of toxic
gases?
Describe pneumoconiosis, and give two examples.
Briefly describe the role of neutrophils in the acute
respiratory distress syndrome (ARDS).
Obstructive Lung Diseases
Obstructive lung disease is characterized by airway obstruction that is worse with expiration. More force (i.e., use of
accessory muscles of expiration) is required to expire a given
volume of air, or emptying of the lungs is slowed, or both. In
adults, the major obstructive lung diseases are asthma,
chronic bronchitis, and emphysema. Asthma is one of the
most common lung disorders in the U.S. and is one of the
few that is increasing in prevalence. Because many individuals have both chronic bronchitis and emphysema, these
diseases together are often called chronic obstructive pulmonary disease (COPD). Asthma is more acute and intermittent
than COPD, even though it can be chronic (Figure 26-8). The
unifying symptom of obstructive lung diseases is dyspnea,
and the unifying sign is wheezing. Individuals have an
increased work of breathing, ventilation/perfusion mismatching, and a decreased forced expiratory volume in one
second (FEV1).
Asthma
Asthma is defined as follows:
A chronic inflammatory disorder of the airways in which many
cells and cellular elements play a role, in particular, mast cells,
eosinophils, T lymphocytes, macrophages, neutrophils, and
epithelial cells. In susceptible individuals, this inflammation
causes recurrent episodes of wheezing, breathlessness, chest
tightness, and coughing, particularly at night or in the early
morning. These episodes are usually associated with widespread but variable airflow obstruction that is often reversible,
either spontaneously or with treatment. The inflammation also
causes an associated increase in the existing bronchial hyperresponsiveness to a variety of stimuli. Subbasement membrane
fibrosis may occur in some patients with asthma, and these
changes contribute to persistent abnormalities of lung
function.16
Asthma occurs at all ages, with approximately half of all
cases developing during childhood and another third before
age 40. In the United States, more than 5% of children under
the age of 18 report having asthma attacks.16 Mortality rates
have declined since 1995, but the incidence of asthma has
increased since the 1980s, especially in urban areas.16
Asthma is a familial disorder, and over 20 genes have
been identified that may play a role in the susceptibility
and pathogenesis of asthma, including those that influence
the production of interleukins 4 and 5, IgE, eosinophils,
mast cells, beta adrenergic receptors, and bronchial hyperresponsiveness.17,18 Risk factors for asthma, in addition to
family history, include allergen exposure, urban residence,
exposure to air pollution and cigarette smoke, recurrent
respiratory viral infections, and other allergic diseases, such
as allergic rhinitis.17,19 There is considerable evidence that
exposure to high levels of certain allergens during childhood
increases the risk for asthma. Furthermore, decreased exposure to certain infectious organisms appears to create an
immunologic imbalance that favors the development of
allergy and asthma. This complex relationship has been
called the hygiene hypothesis.20,21 Urban exposure to pollution and cockroaches and decreased exercise by young
people also play a role in the increasing prevalence of
asthma.19,21
PATHOPHYSIOLOGY Inflammation resulting in hyperresponsiveness of the airways is the major pathologic feature of asthma. It is initiated by a Type I hypersensitivity
reaction (see Chapter 7). Exposure to allergens (with
subsequent immunologic activation in the atopic individual
with production IL-4 and IgE) or irritants results in a cascade of events beginning with mast cell degranulation and
the release of multiple inflammatory mediators (Figure
26-9). Some of the most important mediators that are
released during an asthma attack are histamine, interleukins,
prostaglandins, leukotrienes, and nitric oxide. Vasoactive
effects of these cytokines include vasodilation and increased
capillary permeability. Chemotactic factors are produced
that result in bronchial infiltration by neutrophils, eosinophils, and lymphocytes. Eosinophils release a variety of toxic
chemicals that contribute to inflammation and tissue damage. The resulting inflammatory process produces bronchial
smooth muscle spasm, vascular congestion, edema formation, production of thick mucus, impaired mucociliary function (see Figure 26-8), thickening of airway walls, and
increased bronchial hyperresponsiveness. In addition, the
autonomic control of bronchial smooth muscle is dysregulated because of production of toxic neuropeptides leading
to acetylcholine-mediated bronchospasm. These changes,
combined with epithelial cell damage caused by eosinophil
infiltration, produce airway hyperresponsiveness and
obstruction and, untreated, can lead to long-term airway
damage that is irreversible.22,23
Airway obstruction increases resistance to airflow and
decreases flow rates, primarily expiratory flow. Impaired
expiration causes air trapping and hyperinflation distal to
Alterations of Pulmonary Function
Chapter 26
727
Pulmonary artery
Cartilage Submucosal
gland
Mast cell
Parasympathetic
nerve
Smooth
muscle
Basement
membrane
Bronchioles
Epithelium
Respiratory
bronchioles
Goblet cell
Alveoli
A
Normal
alveoli
B
Enlarged
submucosal
gland
Degranulation
of mast cell
Mucus
accumulation
Smooth muscle
constriction
Mucus
plug
Mucus
plug
Inflammation
of epithelium
Hyperinflation
of alveoli
C
Hyperinflation
of alveoli
Mucus
accumulation
D
Figure 26-8 n Airway Obstruction Caused by Emphysema, Chronic Bronchitis, and Asthma. A, The normal lung. B, Emphysema:
enlargement and destruction of alveolar walls with loss of elasticity and trapping of air; (left) panlobular emphysema showing abnormal weakening and enlargement of all air spaces distal to the terminal bronchioles (normal alveoli shown for comparison only); (right)
centrilobular emphysema showing abnormal weakening and enlargement of the respiratory bronchioles in the proximal portion of the
acinus. C, Chronic bronchitis: inflammation and thickening of mucous membrane with accumulation of mucus and pus leading to
obstruction; characterized by cough. D, Bronchial asthma: thick mucus, mucosal edema, and smooth muscle spasm causing obstruction of small airways; breathing becomes labored, and expiration is difficult. (Modified from Des Jardins T, Burton GG: Clinical manifestations and assessment of respiratory disease, ed 5, St Louis, 2006, Mosby.)
obstructions and increases the work of breathing. Intrapleural and alveolar gas pressures rise and cause decreased
perfusion of the alveoli. These changes lead to uneven
ventilation-perfusion relationships causing hypoxemia.
Hyperventilation is triggered by lung receptors responding
to hyperinflation and causes decreased PaCO2 and
increased pH (respiratory alkalosis). As the obstruction
becomes more severe, however, the number of alveoli being
adequately ventilated and perfused decreases. Air trapping
continues to worsen and the work of breathing increases
further, leading to hypoventilation (decreased tidal volume), CO2 retention, and respiratory acidosis. Respiratory
acidosis signals respiratory failure.
CLINICAL MANIFESTATIONS Between attacks, indi-
viduals are asymptomatic and pulmonary function tests
are normal. At the beginning of an attack, the individual
experiences chest constriction, expiratory wheezing, dyspnea, nonproductive coughing, prolonged expiration,
tachycardia, and tachypnea. Severe attacks involve the
accessory muscles of respiration and wheezing is heard during inspiration and expiration. A pulsus paradoxus
(decrease in systolic blood pressure during inspiration of
more than 10 mm Hg) may be noted. Peak flow measurements should be obtained. Because the severity of blood
gas alterations is difficult to evaluate by clinical signs alone,
arterial blood gas tensions should be measured if oxygen
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Unit 8
The Pulmonary System
Allergen or irritant exposure
Immune activation
(IL-4, IgE production)
Mast cell degranulation
Vasoactive mediators
Chemotactic mediators
Vasodilation
Increased capillary permeability
Cellular infiltration
(neutrophils, lymphocytes, eosinophils)
Bronchospasm
Vascular congestion
Mucus secretion
Impaired mucociliary function
Thickening of airway walls
Increased contractile response of
bronchial smooth muscle
Bronchial hyperresponsiveness
Airway obstruction
Autonomic
dysregulation
Release of toxic
neuropeptides
Epithelial desquamation
and fibrosis
Figure 26-9 n Pathophysiology of Asthma. Allergen or irritant exposure results in a cascade of inflammatory events leading to acute
and chronic airway dysfunction.
saturation falls below 90%. Usual findings are hypoxemia
with an associated respiratory alkalosis.
If bronchospasm is not reversed by usual measures, the
individual is considered to have severe bronchospasm or
status asthmaticus. If status asthmaticus continues, hypoxemia worsens, expiratory flows and volumes decrease further, and effective ventilation decreases. Acidosis develops
as PaCO2 begins to rise. Asthma becomes life threatening
at this point if treatment does not reverse this process
quickly. A silent chest (no audible air movement) and a
PaCO2 over 70 mm Hg are ominous signs of impending
death.
EVALUATION AND TREATMENT Between attacks, the
diagnosis of asthma is supported by a history of allergies
and recurrent episodes of breathlessness or exercise intolerance. Further evaluation includes spirometry, which may
document reversible decreases in FEV1 during an induced
attack. Gastroesophageal reflux disease may contribute to
asthma severity and should be investigated.
Management of asthma begins with avoidance of allergens and irritants and patient education. Individuals with
asthma tend to underestimate the severity of their illness
and should be taught the use of a home peak-flowmeter.
Acute attacks are treated with oral corticosteroids and
inhaled beta-agonists. Staging of asthma (mild intermittent,
mild persistent, moderate persistent, severe persistent) is
based on the frequency and severity of symptoms as well as
pulmonary function tests (decreases in FEV1).16,17 Chronic
management is based on the stage of asthma and includes
the regular use of anti-inflammatory medications such as
inhaled corticosteroids, cromolyn sodium, or leukotriene
inhibitors.16,17,24 Inhaled bronchodilators such as b2agonists and ipratropium are added to supplement symptom
control. Immune therapies such as allergy shots and monoclonal antibodies to IgE have been found to be extremely
helpful in allergic individuals.16,17,24–26
Chronic obstructive pulmonary
disease
Chronic obstructive pulmonary disease (COPD) is a syndrome that includes the pathologic lung changes consistent
with emphysema or chronic bronchitis. It is characterized
by abnormal tests of expiratory airflow that do not change
markedly over time nor exhibit major reversibility in
response to pharmacologic agents. A 2006 update of the
Global Strategy for the Diagnosis, Management, and Prevention of COPD consensus report (GOLD) defines COPD
Alterations of Pulmonary Function
as “a preventable and treatable disease with some significant extrapulmonary effects that may contribute to the
severity in individual patients. Its pulmonary component
is characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lung
to noxious particles or gases.”27 It is currently the fourth
leading cause of death in the United States and is one of
the few causes of death that have increased in incidence
since the 1970s.28 COPD is primarily caused by cigarette
smoke, and both active and passive smoking have been
implicated. Other risks include occupational exposures
and air pollution. Genetic susceptibilities also have been
identified.29
HEALTH ALERT
Monoclonal Antibodies to IgE for
Treatment of Asthma
In genetically predisposed individuals, exposure to inhaled
allergens can lead to an allergic response that is manifested clinically as asthma. This immunologic response is
a type I hypersensitivity reaction (see Chapter 7) and
results from a complex interaction of macrophages, T lymphocytes, antibodies, mast cells, and eosinophils. The
immune response leads to a profound inflammatory
response, with resultant bronchospasm, mucus formation,
and mucosal edema in the airways. Allergen avoidance
and immunotherapy (allergy shots) can be effective in preventing this type I hypersensitivity reaction. Omalizumab
(Xolair) is humanized monoclonal anti-immunoglobulin E
(IgE) antibody that is indicated for individuals with moderate or severe asthma who do not respond to standard
therapy. Omalizumab can improve symptoms, reduce hospitalizations, and limit the need for systemic corticosteroid
therapy.
Data from Mathur SK, Busse WW: Asthma: diagnosis and
management, Med Clin North Am 90(1):39–60, 2006; Davydov L:
Omalizumab (Xolair) for treatment of asthma, Am Family Phys
71:341–342, 2005; Marcus P, Practice Management Committee,
American College of Chest Physicians: Incorporating anti-IgE
(omalizumab) therapy into pulmonary medicine practice: practice
management implications, Chest 129(2):466–474, 2006.
Chronic bronchitis
Chronic bronchitis is defined as hypersecretion of mucus
and chronic productive cough for at least 3 months of the
year (usually the winter months) for at least 2 consecutive
years. It is almost always caused by cigarette smoking and
by exposure to air pollution.
PATHOPHYSIOLOGY Inspired irritants result in airway
inflammation with infiltration of neutrophils, macrophages,
and lymphocytes into the bronchial wall. Continual bronchial inflammation causes bronchial edema and increases
the size and number of mucous glands and goblet cells in
Chapter 26
729
the airway epithelium.30 Thick, tenacious mucus is produced and cannot be cleared because of impaired ciliary
function. The lung’s defense mechanisms are, therefore,
compromised, increasing susceptibility to pulmonary infection and injury. Frequent infectious exacerbations are complicated by bronchospasm with dyspnea and productive
cough.31 The pathogenesis of chronic bronchitis is shown
in Figure 26-10.28,30
Initially this process affects only the larger bronchi, but
eventually all airways are involved. As the airways become
increasingly narrowed, expiratory airway obstruction results
(Figure 26-11). The airways collapse early in expiration,
trapping gas in the distal portions of the lung. Eventually
ventilation-perfusion mismatch and hypoxemia occurs.
Extensive air trapping puts the respiratory muscles at a
mechanical disadvantage, resulting in hypoventilation and
hypercapnia.
CLINICAL MANIFESTATIONS Table 26-2 lists the com-
mon clinical manifestations of chronic obstructive lung disease including chronic bronchitis.
EVALUATION AND TREATMENT Diagnosis is based on
physical examination, chest radiograph, pulmonary function tests, and blood gas analyses; these tests reflect the progressive nature of the disease. The best “treatment” for
chronic bronchitis is prevention, because pathologic
changes are not reversible. By the time an individual seeks
medical care for symptoms, considerable airway damage is
present. If the individual stops smoking, disease progression
can be halted. If smoking is stopped before symptoms
occur, the risk of chronic bronchitis decreases considerably.
Bronchodilators, expectorants, and chest physical
therapy are employed as needed to control cough and
reduce dyspnea.32 Teaching of individuals includes nutritional counseling, respiratory hygiene, recognition of the
TABLE 26-2
Clinical Manifestations of Chronic
Obstructive Lung Disease
Clinical
Manifestations
Bronchitis Emphysema
Productive cough
Classic sign
Dyspnea
Late in
course
Intermittent
Common
Occasionally
Always
present
Common
Common
Wheezing
History of smoking
Barrel chest
Prolonged
expiration
Cyanosis
Chronic
hypoventilation
Polycythemia
Cor pulmonale
Common
Common
Late in course with
infection
Common
Common
Common
Classic
Always present
Uncommon
Late in course
Late in course
Late in course
730
Unit 8
The Pulmonary System
Tobacco smoke
Air pollution
Inherited
␣1-antitrypsin deficiency
Inflammation of the
airway epithelium
Infiltration of inflammatory
cells and release of cytokines
(neutrophils, macrophages,
lymphocytes, leukotrienes,
interleukins)
Systemic effects
(muscle weakness, weight loss)
Inhibition of normal
endogenous antiproteases
Continuous bronchial
irritation and inflammation
Increased protease activity
with breakdown of elastin
in connective tissue of lungs
(elastases, cathepsins, etc.)
Chronic bronchitis
(bronchial edema, hypersecretion of
mucus, bacterial colonization of airways)
Emphysema
(destruction of alveolar septa and
loss of elastic recoil of bronchial walls)
Airway obstruction
Air trapping
Loss of surface area for gas exchange
Frequent exacerbations
(infections, bronchospasm)
Dyspnea
Cough
Hypoxemia
Hypercapnia
Cor pulmonale
Figure 26-10 n Pathogenesis of Chronic Bronchitis and Emphysema (Chronic Obstructive Pulmonary Disease [COPD]).
HEALTH ALERT
Nutrition and Chronic Obstructive Pulmonary Disease
Malnutrition is a major concern for individuals with chronic
obstructive pulmonary disease (COPD) because they have
increased energy expenditure, decreased energy intake, and
impaired oxygenation. The disproportionate muscle wasting
is similar to what occurs with other chronic diseases, such
as cancer, heart failure, and AIDS. Systemic inflammatory
mediators may impair appetite and contribute to hypermetabolism. Malnutrition (1) adversely affects exercise tolerance
by limiting skeletal and respiratory muscle strength and aerobic capacity, (2) limits surfactant production, (3) reduces cellmediated immune responses, (4) reduces protein synthesis,
and (5) increases morbidity and mortality. The medical nutrition therapy goal is to maintain an acceptable and stable
weight for the person. This can be accomplished by including
foods of high energy density, frequent snacking, soft foods
and beverages, assistance with shopping, and meal preparation. Increasing omega-3 fatty acids and antioxidant intake
may modulate the effects of systemic inflammation. Protein
intake should be maintained at 1.0 to 1.5 g/kg of body weight,
and a daily vitamin C supplement should be added to the diet
if the individual is still smoking.
Alterations of Pulmonary Function
Air movement
during INSPIRATION
Mucus
plug
Muscle
Air movement
during EXPIRATION
Bronchial
walls
collapse
Alveolar walls
Figure 26-11 n Mechanisms of Air Trapping in COPD. Mucus
plugs and narrowed airways cause air trapping and hyperinflation on expiration. During inspiration, the airways are pulled
open allowing gas to flow past the obstruction. During expiration, decreased elastic recoil of the bronchial walls results in
collapse of the airways and prevents normal expiratory airflow.
early signs of infection, and techniques that relieve dyspnea,
such as pursed-lip breathing. During acute exacerbations
(infection and bronchospasm), individuals require treatment with antibiotics and steroids and may need mechanical ventilation.33 Chronic oral steroids may be needed late
in the course of the disease but should be considered a last
resort. Individuals with severe hypoxemia will require home
oxygen therapy.
Emphysema
Emphysema is abnormal permanent enlargement of gasexchange airways (acini) accompanied by destruction of
alveolar walls without obvious fibrosis. Obstruction results
from changes in lung tissues, rather than mucus production
and inflammation as in chronic bronchitis. The major
mechanism of airflow limitation is loss of elastic recoil
(see Figure 26-11).30 The major cause of emphysema by
far is cigarette smoking, although air pollution and childhood respiratory infections are known to be contributing
factors.
Primary emphysema, which accounts for 1% to 3% of all
cases of emphysema, is commonly linked to an inherited
deficiency of the enzyme a1-antitrypsin, a major component of a1-globulin, a plasma protein.34 Normally a1antitrypsin inhibits the action of many proteolytic enzymes,
therefore a1-antitrypsin deficiency (an autosomal recessive
trait) produces an increased likelihood of developing
emphysema because proteolysis in lung tissues is not inhibited. a1-Antitrypsin deficiency is suggested in individuals
Chapter 26
731
who develop emphysema before 40 years of age and in nonsmokers who develop the disease.
PATHOPHYSIOLOGY Emphysema begins with destruction of alveolar septa, which eliminates portions of the pulmonary capillary bed and increases the volume of air in the
acinus. It is postulated that inhaled oxidants in tobacco
smoke and air pollution inhibit the activity of endogenous
antiproteases and stimulate inflammation with increased
activity of the proteases (e.g., elastase). Thus, the balance
is tipped toward alveolar destruction and loss of the normal
elastic recoil of the bronchi (see Figure 26-10). Alveolar
destruction produces large air spaces within the lung parenchyma (bullae) and air spaces adjacent to pleurae (blebs).
Bullae and blebs are not effective in gas exchange and result
_ mismatching and
_ Q)
in significant ventilation-perfusion (V/
hypoxemia. Expiration becomes difficult because loss of
elastic recoil reduces the volume of air that can be expired
passively and air is trapped in the lungs (see Figure
26-11). Air trapping causes hyperexpansion of the chest,
which puts the muscles of respiration at a mechanical
disadvantage. This results in increased workload of breathing, so that late in the course of disease, many individuals
will develop hypoventilation and hypercapnia.
Emphysema can be centriacinar (centrilobular) or panacinar (panlobular), depending on the site of involvement
(Figure 26-12).30
1. Centriacinar emphysema. Septal destruction occurs in
the respiratory bronchioles and alveolar ducts, causing
inflammation in bronchioles. Alveolar sac is intact.
Tends to occur in persons who smoke and persons with
chronic bronchitis.
2. Panacinar emphysema. Involves entire acinus, with
damage more randomly distributed and involving lower
lobes of lung. Tends to occur in elderly persons and
persons with a1-antitrypsin deficiency.
CLINICAL MANIFESTATIONS The clinical manifesta-
tions of emphysema are listed in Table 26-2.
EVALUATION AND TREATMENT Pulmonary function
testing, chest x-ray, high-resolution computed tomograph
(CT), and arterial blood gas measurement are used to diagnose emphysema.27,35 Pulmonary function measurements,
especially FEV1 values, also are helpful in determining the
stage of disease, appropriate treatment, and prognosis.27
Treatment for emphysema is similar to that for chronic
bronchitis and includes smoking cessation, bronchodilating
drugs, nutrition, breathing retraining, relaxation exercises,
anti-inflammatory medications, and antibiotics for acute
infections. The most recent recommendations for the management of chronic symptoms of COPD are based on the
four stages of severity of airflow limitation and include
bronchodilators, such as ipratropium and b2-agonists.27,36
Treatment of severe COPD may require the use of methylxanthines, inhaled or oral steroids, and home oxygen.27,36,37
A new class of drugs called phosphodiesterase E4 (PDE4)
inhibitors are proving to be effective in selected patients
732
Unit 8
The Pulmonary System
Distended
respiratory
bronchiole
A
Alveoli
Distended
alveolus
B
Figure 26-12 n Types of Emphysema. A, Centriacinar emphysema. B, Panacinar emphysema. (Micrographs from Damjanov I,
Linder J, editors: Anderson’s pathology, ed 10, St Louis, 1996, Mosby.)
with severe COPD.38 Selected individuals with severe
emphysema can benefit from lung reduction surgery or
lung transplantation.
QUICK CHECK 26-4
1.
2.
3.
What mechanisms cause obstruction in asthma?
How does emphysema affect oxygenation and
ventilation?
Define chronic bronchitis.
Respiratory Tract Infections
Respiratory tract infections are the most common cause of
short-term disability in the United States. Most of these
infections—the common cold, pharyngitis (sore throat),
and laryngitis—involve only the upper airways. Although
the lungs have direct contact with the atmosphere, they
usually remain sterile. Infections of the lower respiratory
tract occur most often in individuals whose normal defense
mechanisms are impaired.
Pneumonia
Pneumonia is infection of the lower respiratory tract
caused by bacteria, viruses, fungi, protozoa, or parasites. It
is the sixth leading cause of death in the United States.
The incidence and mortality of pneumonia are highest in
the elderly. Risk factors for pneumonia include advanced
age, immunocompromise, underlying lung disease, alcoholism, altered consciousness, smoking, endotracheal intubation, malnutrition, and immobilization. The causative
microorganism influences how the individual presents
clinically, how the pneumonia should be treated, and the
prognosis. Community-acquired pneumonia (CAP) tends
to be caused by different microorganisms as compared with
those infections acquired in the hospital (nosocomial). In
addition, the characteristics of the individual are important
in determining which etiologic microorganism is likely; for
example, immunocompromised individuals tend to be susceptible to opportunistic infections that are uncommon in
normal adults. In general, nosocomial infections and those
affecting immunocompromised individuals have a higher
mortality than CAPs. Some of the most common causal
microorganisms include the following39-41:
Community-Acquired
Pneumonia (CAP)
Nosocomial
Pneumonia
Immunocompromised
Individuals
Streptococcus pneumoniae
Pseudomonas
aeruginosa
Staphylococcus
aureus
Klebsiella
pneumoniae
Escherichia coli
Pneumocystis jiroveci
Mycoplasma pneumoniae
Haemophilus influenza
Oral anaerobic bacteria
Influenza virus
Legionella pneumophila
Chlamydia pneumoniae
Moraxella catarrhalis
Mycobacterium
tuberculosis
Atypical mycobacteria
Fungi
Respiratory viruses
Protozoa
Parasites
The most common community-acquired pneumonia is
caused by Streptococcus pneumoniae (also known as the
pneumococcus), which has a relatively high mortality in
the elderly.42 Mycoplasma pneumoniae is a common cause
Alterations of Pulmonary Function
of pneumonia in young people, especially those living in
group housing such as dormitories and army barracks.43
Influenza is the most common viral community-acquired
pneumonia in adults; in children, respiratory syncytial virus
and parainfluenza virus are common etiologic microorganisms.44 Legionella species is an important cause of community-acquired pneumonia, and Legionnaire’s disease has
increased in incidence since it was first described in the
1976 incident at the American Legion Convention in Philadelphia.45 Pseudomonas aeruginosa, other gram-negative
microorganisms, and Staphylococcus aureus are the most
common etiologic agents in nosocomial pneumonia.40
Immunocompromised patients (HIV, transplant) are especially susceptible to Pneumocystis jiroveci (formerly called
P. carinii), mycobacterial infections, and fungal infections
of the respiratory tract.41,46 These infections can be difficult
to treat and have a high mortality.
PATHOPHYSIOLOGY Aspiration
of oropharyngeal
secretions is the most common route of lower respiratory
tract infection; thus, the nasopharynx and oropharynx constitute the first line of defense for most infectious agents.
Another route of infection is through the inhalation of
microorganisms that have been released into the air when
an infected individual coughs, sneezes, or talks, or from
aerosolized water such as that from contaminated respiratory therapy equipment. This route of infection is most
important in viral and mycobacterial pneumonias and in
Legionella outbreaks. Pneumonia also can occur when bacteria are spread to the lung in the blood from bacteremia
that can result from infection elsewhere in the body or from
IV drug abuse.
In healthy individuals, pathogens that reach the lungs
are expelled or held in check by mechanisms of self-defense
(see Chapters 5, 6, and 7). If a microorganism gets past the
upper airway defense mechanisms, such as the cough reflex
and mucociliary clearance, the next line of defense is the
alveolar macrophage. This phagocyte is capable of removing most infectious agents without setting off significant
inflammatory or immune responses. However, if the microorganism is virulent or present in large enough numbers, it
can overwhelm the alveolar macrophage. This results in a
full-scale activation of the body’s defense mechanisms,
including the release of multiple inflammatory mediators,
cellular infiltration, and immune activation.47,48 These
inflammatory mediators and immune complexes can damage bronchial mucous membranes and alveolocapillary
membranes causing the acini and terminal bronchioles to
fill with infectious debris and exudate. In addition, some
microorganisms release toxins from their cell walls that can
cause further lung damage. The accumulation of exudate in
_ Q_ mismatching and
the acinus leads to dyspnea and to V/
hypoxemia.
Pneumococcal pneumonia
In pneumococcal pneumonia, S. pneumoniae microorganisms initiate the inflammatory response, and inflammatory
Chapter 26
733
exudate causes alveolar edema, which leads to the other
changes shown in Figure 26-13.48
Viral pneumonia
Although viral pneumonia can be severe (see Health Alert:
Avian Influenza), it is usually mild and self-limiting but can
set the stage for a secondary bacterial infection by providing
an ideal environment for bacterial growth and by damaging
ciliated epithelial cells, which normally prevent pathogens
from reaching the lower airways. Viral pneumonia can be
a primary infection or a complication of another viral illness, such as chickenpox or measles (spread from the
blood). The virus not only destroys the ciliated epithelial
cells but also invades the goblet cells and bronchial mucous
glands. Sloughing of destroyed bronchial epithelium occurs
throughout the respiratory tract, preventing mucociliary
clearance. Bronchial walls become edematous and infiltrated with leukocytes. In severe cases, the alveoli are
involved with decreased compliance and increased work
of breathing.
HEALTH ALERT
Avian Influenza
A highly pathogenic virus called H5N1 influenza virus has
been causing massive infections in poultry in Asia and
was first found to infect humans in 1997. So far, most
human infections have occurred only in those individuals
who have been in close contact with infected birds. However, there has been at least one instance in which several
cases of flu were documented within an extended family.
This raises concerns that the virus is mutating to a form
that can be passed from human to human. The H5N1 virus
can be carried by migratory birds and is expected to
spread to the United States and throughout the world.
Human infection with avian influenza results in symptoms
of fever, cough, sore throat, and muscle aches, eye
infections (conjunctivitis), pneumonia, acute respiratory
distress, and other severe and life-threatening complications. As of March 2007, a total of 279 cases and 169 deaths
have been attibuted to avian influenza worldwide, most
were reported in Indonesia and Vietnam. In preparation
for possible viral mutation and potential human pandemic,
stockpiles of two effective antivirals (oseltamivir and zanamivir) are being created. In February 2007, the WHO
announced that several new vaccines have been developed that are demonstrating significant immune effectiveness and appear to be safe even in the elderly and in
children. Extensive research on vaccine development is
continuing.
Data from the Centers for Disease Control and Prevention, available
at www.cdc.gov/flu/avian/gen-info/avian-flu-humans.htm; and the
World Health Organization, available at www.who.int/csr/disease/
avian_influenza/en/index.html
CLINICAL MANIFESTATIONS Many cases of pneumo-
nia are preceded by an upper respiratory infection, which is
often viral. Individuals then develop fever, chills, productive
734
Unit 8
The Pulmonary System
Aspiration of Streptococcus pneumoniae
Adherence to
alveolar macrophages:
exposure of cell wall
components
Inflammatory response:
attraction of neutrophils;
release of inflammatory mediators;
accumulation of fibrinous exudate,
red blood cells, and bacteria
Red hepatization
and consolidation
of lung parenchyma
Leukocyte infiltration
(neutrophils and
macrophages)
Gray hepatization and
deposition of fibrin on
pleural surfaces;
phagocytosis in alveoli
Resolution of infection:
macrophages in alveoli ingest
and remove degenerated neutrophils,
fibrin, and bacteria
Figure 26-13 n Pathophysiologic Course of Pneumococcal Pneumonia.
or dry cough, malaise, pleural pain, and sometimes dyspnea
and hemoptysis. Physical examination may reveal signs of
pulmonary consolidation, such as dullness to percussion,
inspiratory crackles, increased tactile fremitus, egophony,
and whispered pectoriloquy. Individuals also may demonstrate symptoms and signs of underlying systemic disease
or sepsis.
EVALUATION AND TREATMENT Diagnosis is made on
the basis of physical examination, white blood cell count,
chest x-ray, stains and cultures of respiratory secretions,
and blood cultures.49 The white blood cell count is usually
elevated, although it may be low if the individual is debilitated or immunocompromised. Chest radiographs show
infiltrates that may involve a single lobe of the lung or
may be more diffuse. Once the diagnosis of pneumonia
has been made, the pathogen is identified by means of sputum characteristics (gram stain, color, odor) and cultures
or, if sputum is absent, blood cultures. Because many
pathogens exist in the normal oropharyngeal flora, the
specimen may be contaminated with pathogens from oral
secretions. If sputum studies fail to identify the pathogen,
the individual is immunocompromised, or the individual’s
condition worsens, further diagnostic studies may include
bronchoscopy or lung biopsy. Positive identification of
viruses can be difficult. Blood cultures often help to identify
the virus if systemic disease is present.
Antibiotics are used to treat bacterial pneumonia; however, resistant strains of pneumococcus are on the rise.50
Empiric antibiotics are chosen based on the likely causative
microorganism.49 Viral pneumonia is usually treated with
supportive therapy alone; however, antivirals may be needed
in severe cases. Infections with opportunistic microorganisms may be polymicrobial and require multiple drugs,
including antifungals. Adequate hydration and good pulmonary hygiene (e.g., deep breathing, coughing, chest physical
therapy) are important aspects of treatment for all types of
pneumonia.
Tuberculosis
Tuberculosis (TB) is an infection caused by Mycobacterium
tuberculosis, an acid-fast bacillus that usually affects the
lungs but may invade other body systems. Tuberculosis is
the leading cause of death from a curable infectious disease
in the world. TB cases increased greatly during the mid1990s as a result of the acquired immunodeficiency
syndrome (AIDS).51 In 2005, a total of 14,093 TB cases
were reported in the United States, representing a 3.8%
decline in the rate from 2004. This decline was the result
of more effective treatment of HIV-infected individuals.
Even so, individuals with AIDS are highly susceptible to
infection with multidrug resistant tuberculosis that is difficult to manage.52,53 Emigration of infected individuals from
high-prevalence countries, transmission in crowded institutional settings, homelessness, substance abuse, and lack of
access to medical care also have contributed to the spread
of TB.
Alterations of Pulmonary Function
HEALTH ALERT
Multidrug Resistant Tuberculosis in HIV
Infection
Tuberculosis is the leading cause of death from a curable
infectious disease in the world, with 8.8 million new cases
of tuberculosis documented in 2005. Although the total
number of cases continues to increase, the rate of new
TB cases appears to be leveling off for the first time. Africa
continues to have the highest estimated incidence rate, but
the majority of patients with tuberculosis live in the most
populous countries of Asia including Bangladesh, China,
India, Indonesia, and Pakistan. The incidence rate in these
countries is highest among young adults, and most cases
are the result of recent infection or reinfection. Much of
the increase in global tuberculosis incidence seen since
1980 is attributable to the spread of HIV, especially in
Africa. HIV infection is the most common identifiable risk
factor for progression from latent TB to active disease
(reactivation). Treatment of TB in HIV-infected persons is
characterized by relatively good short-term responses
(especially if rifampicin [rifampin] is used as a primary
drug) but becomes more difficult as both diseases progress and is associated with more adverse reactions to
the antituberculous medications. This scenario is made
even more challenging by the increasing prevalence of
multidrug resistant TB microorganisms.
Data from de Jong BC et al: Clinical management of tuberculosis in
the context of HIV infection, Annu Rev Med 55:283–301, 2004; Nunn
P et al: Tuberculosis control in the era of HIV, Nat Rev Immunol
5(10):819–826, 2005; and the World Health Organization at http://
www.who.int/tb/en/.
PATHOPHYSIOLOGY Tuberculosis is transmitted from
person to person in airborne droplets. Microorganisms
lodge in the lung periphery, usually in the upper lobe. Once
the bacilli are inspired into the lung, they multiply and
cause nonspecific pneumonitis (lung inflammation). Some
bacilli migrate through the lymphatics and become lodged
in the lymph nodes, where they encounter lymphocytes
and initiate the immune response.
Inflammation in the lung causes activation of alveolar
macrophages and neutrophils. These cells are phagocytes
that engulf the bacilli and begin the process by which the
body’s defense mechanisms isolate the bacilli, preventing
their spread. The neutrophils and macrophages seal off
the colonies of bacilli, forming a granulomatous lesion
called a tubercle (see Chapter 5). Infected tissues within
the tubercle die, forming cheeselike material called caseation necrosis.54,55 Collagenous scar tissue then grows
around the tubercle, completing isolation of the bacilli.
The immune response is complete after about 10 days, preventing further multiplication of the bacilli.
Once the bacilli are isolated in tubercles and immunity
develops, tuberculosis may remain dormant for life.54,55 If
the immune system is impaired, however, or if live bacilli
escape into the bronchi, active disease occurs and may
spread through the blood and lymphatics to other organs.
Chapter 26
735
Endogenous reactivation of dormant bacilli may be caused
by poor nutritional status, insulin-dependent diabetes,
long-term corticosteroid therapy, the use of antirejection
drugs, HIV infection, and other debilitating diseases.
CLINICAL MANIFESTATIONS In many infected indi-
viduals, tuberculosis is asymptomatic. In others, symptoms
develop so gradually that they are not noticed until the disease is advanced. Common clinical manifestations include
fatigue, weight loss, lethargy, anorexia (loss of appetite),
and a low-grade fever that usually occurs in the afternoon.
A cough that produces purulent sputum develops slowly
and becomes more frequent over several weeks or months.
Night sweats and general anxiety are often present. Dyspnea, chest pain, and hemoptysis may occur as the disease
progresses. Extrapulmonary TB disease is common in
HIV infected individuals and may cause neurologic deficits,
meningitis symptoms, bone pain, and urinary symptoms.56
EVALUATION AND TREATMENT Tuberculosis is usually
diagnosed by a positive tuberculin skin test, sputum culture,
and chest radiographs. Newer diagnostic tests include the
enzyme-linked immunospot and quantitative blood interferon-gamma assay that improve the sensitivity and specificity
of skin testing.57,58
Treatment consists of antibiotic therapy to control active
or dormant tuberculosis and prevent transmission. Today,
with the increased numbers of immunosuppressed individuals and drug-resistant bacilli, the recommended treatment
includes a combination of drugs to which the organism is
susceptible, including use of isoniazid, rifampin, pyrazinamide, ethambutol, and streptomycin. Treatment usually is
continued for a minimum of 3 months.58,59 Infection in
immunocompromised individuals often require the use of
newer drugs for longer periods of time.52,53,58,59
In the past, individuals with active tuberculosis were
isolated from the community and their families in sanitariums. Today, individuals remain at home or, rarely, in the
hospital, until sputum cultures show that the active bacilli
have been eliminated. This usually takes a few weeks to
2 months if antibiotics are taken conscientiously. Longacting antituberculous medications have improved adherence in outpatient clinical settings. If the individual’s cooperation is in question, it is advisable for the administration
of the drugs to be supervised by health care workers.
Acute bronchitis
Acute bronchitis is acute infection or inflammation of the
airways or bronchi and is usually self-limiting. In the vast
majority of cases, acute bronchitis is caused by viruses.60
Many clinical manifestations are similar to those of
pneumonia (i.e., fever, cough, chills, malaise), but chest
radiographs show no infiltrates. Individuals with viral bronchitis present with a nonproductive cough that often occurs
in paroxysms and is aggravated by cold, dry, or dusty air. In
some cases, purulent sputum is produced. Chest pain often
develops from the effort of coughing. Treatment consists of
736
Unit 8
The Pulmonary System
rest, aspirin, humidity, and a cough suppressant, such as
codeine.60
Bacterial bronchitis is rare in previously healthy adults
except after viral infection but is common in patients with
COPD. Although individuals with bronchitis do not have
signs of pulmonary consolidation on physical examination
(e.g., crackles, egophony), many will require chest x-ray
evaluation to exclude the diagnosis of pneumonia. Bacterial
bronchitis is treated with rest, antipyretics, humidity, and
antibiotics.
Abscess formation and cavitation
An abscess is a circumscribed area of suppuration and
destruction of lung parenchyma. Abscess formation follows
consolidation of lung tissue, in which inflammation causes
alveoli to fill with fluid, pus, and microorganisms. Necrosis
(death and decay) of consolidated tissue may progress
proximally until it communicates with a bronchus. Cavitation is the process of the abscess emptying into a bronchus
and cavity formation. The diagnosis is made by chest radiography.
Pneumonia caused by aspiration, Klebsiella, or Staphylococcus is the most common cause of abscess formation.
Aspiration abscess is usually associated with alcohol abuse,
seizure disorders, general anesthesia, and swallowing disorders. The clinical manifestations of abscess formation are
similar to those of pneumonitis: fever, cough, chills, sputum
production, and pleural pain. Abscess communication with
a bronchus causes a severe cough, copious amounts of often
foul-smelling sputum, and occasionally hemoptysis.
Treatment includes the administration of appropriate
antibiotics and chest physical therapy, including chest percussion and postural drainage. Sometimes bronchoscopy
is performed to drain the abscess.
QUICK CHECK 26-5
1.
2.
3.
Compare pneumococcal and viral pneumonia as to
severity of disease.
Describe the pathophysiologic features of tuberculosis.
How does lung abscess present clinically?
Pulmonary Vascular Disease
Blood flow through the lungs can be disrupted by disorders
that occlude the vessels, increase pulmonary vascular resistance, or destroy the vascular bed. Effects of altered pulmonary blood flow may range from insignificant dysfunction
to severe and life-threatening changes in ventilationperfusion ratios. Major disorders include pulmonary embolism, pulmonary hypertension, and cor pulmonale.
Pulmonary embolism
Pulmonary embolism is occlusion of a portion of the pulmonary vascular bed by an embolus, which can be a thrombus (blood clot), tissue fragment, lipids (fats), foreign body,
or an air bubble. More than 90% of pulmonary emboli
result from clots formed in the veins of the legs and pelvis.
Risk factors for pulmonary thromboembolism, or the
obstruction of a pulmonary vessel by a thrombus, include
conditions and disorders that promote blood clotting as a
result of venous stasis (slowing or stagnation of blood flow
through the veins), hypercoagulability (increased tendency
of the blood to form clots), and injuries to the endothelial
cells that line the vessels. Genetic risks include factor V Leiden, antithrombin II, protein S, protein C, and prothrombin gene mutations.49 No matter its source, a blood clot
becomes an embolus when all or part of it breaks away
from the site of formation and begins to travel in the bloodstream. (Thromboembolism is described further in Chapter
20.)
Although the overall incidence of pulmonary embolism
has declined, it remains an important cause of death, especially in elderly and hospitalized persons.50 Trauma, especially head injuries and fractures of the lower extremities,
spine, or pelvis, confers a high risk for venous thromboembolism.51
PATHOPHYSIOLOGY The impact or effect of the embolus depends on the extent of pulmonary blood flow obstruction, the size of the affected vessels, the nature of the
embolus, and the secondary effects. Pulmonary emboli
can occur as any of the following:
1. Massive occlusion: an embolus that occludes a major
portion of the pulmonary circulation (i.e., main pulmonary artery embolus)
2. Embolus with infarction: an embolus that is large
enough to cause infarction (death) of a portion of lung
tissue
3. Embolus without infarction: an embolus that is not
severe enough to cause permanent lung injury
4. Multiple pulmonary emboli: may be chronic or recurrent
The pathogenesis of pulmonary embolism caused by a
thrombus is summarized in Figure 26-14.
If the embolus does not cause infarction, the clot is dissolved by the fibrinolytic system and pulmonary function
returns to normal. If pulmonary infarction occurs, shrinking and scarring develop in the affected area of the lung.
CLINICAL MANIFESTATIONS In most cases, the clini-
cal manifestations of pulmonary embolism are nonspecific,
so evaluation of risk factors and predisposing factors is an
important aspect of diagnosis. Although most emboli originate from clots in the lower extremities, deep vein thrombosis is often asymptomatic, and clinical examination has
low sensitivity for the presence of clot, especially in the
thigh.
An individual with pulmonary embolism usually presents with the sudden onset of pleuritic chest pain, dyspnea,
tachypnea, tachycardia, and unexplained anxiety. Occasionally syncope (fainting) or hemoptysis occurs. With large
emboli, a pleural friction rub, pleural effusion, fever, and
leukocytosis may be noted. Recurrent small emboli may
Alterations of Pulmonary Function
Venous stasis
Vessel injury
Hypercoagulability
Thrombus formation
Dislodgement of portion of thrombus
Occlusion of part of pulmonary circulation
Hypoxic vasoconstriction
Decreased surfactant
Release of neurohumoral and inflammatory substances
Pulmonary edema
Atelectasis
Chapter 26
737
The ideal treatment for pulmonary embolism is prevention
through elimination of predisposing factors for individuals at
risk. Venous stasis in hospital patients is minimized by leg
elevation, bed exercises, position changes, early postoperative
ambulation, and pneumatic calf compression. Clot formation
is also prevented by prophylactic low-dose anticoagulant
therapy usually with low-molecular-weight heparin or warfarin. Newer medications such as the antithrombotics fondaparinux, idraparinux, and ximelagatran are superior to
standard prevention in high-risk individuals undergoing
orthopedic surgery.64
Anticoagulant therapy is the primary treatment for pulmonary embolism. Intravenous administration of heparin is
begun immediately and is followed by oral doses of coumarin. Studies suggest that low-molecular-weight heparins
(e.g., enoxaparin) are as safe and effective as standard heparin but are easier to administer.63,64 If a massive lifethreatening embolism occurs, a fibrinolytic agent, such as
streptokinase, is sometimes used, and some individuals will
require surgical thrombectomy.
Pulmonary hypertension
Tachypnea
Dyspnea
Chest pain
Increased dead space
• •
V/Q imbalances
Decreased PaO2
Pulmonary infarction
Pulmonary hypertension
Decreased cardiac output
Systemic hypotension
Shock
Figure 26-14 n Pathogenesis of Massive Pulmonary Embolism Caused by a Thrombus (Pulmonary Thromboembolism).
not be detected until progressive incapacitation, precordial
pain, anxiety, dyspnea, and right ventricular enlargement
are exhibited. Massive occlusion causes severe pulmonary
hypertension and shock.
Pulmonary hypertension is defined as a mean pulmonary
artery pressure 5 to 10 mm Hg above normal or above
20 mm Hg. Pulmonary hypertension is classified as primary
or secondary.
Primary pulmonary hypertension (PPH) is an idiopathic
form of pulmonary artery hypertension and is characterized
by pathologic changes in precapillary pulmonary
arteries.65,66 Primary pulmonary hypertension is rare, has
no known cause, usually occurs in women between the ages
of 20 and 40 years, and may be hereditary, although only
10% to 20% of those with a genetic predisposition actually
develop the disease. Risk factors for PPH include HIV
infection, collagen vascular diseases, and the use of appetite
suppressants.
Most pulmonary hypertension is called secondary pulmonary hypertension and results from diseases of the respiratory system that cause hypoxemia and are characterized
by pulmonary arteriolar vasoconstriction and arterial remodeling.65 In some cases, pulmonary hypertension is the
result of recurrent pulmonary emboli; however, this is relatively uncommon. Pulmonary venous hypertension is
caused by congestive heart failure and is discussed in Chapters 20 and 23.
EVALUATION AND TREATMENT Routine chest radio-
graphs and pulmonary function tests are not definitive for
pulmonary embolism. On chest radiographs, the infarcted
portion of the lung appears as a nonspecific infiltrate in a
classic wedge shape bordering the pleura. Arterial blood
gas analyses usually demonstrate hypoxemia and hyperventilation (respiratory alkalosis). A ventilation/perfusion scan
_ scan), in which lungs are scanned after injection
_ Q
(V/
and inhalation of a radioactive substances, may indicate
embolism; however, this test is rarely definitive. Today,
the diagnosis is made by measuring elevated levels of
D-dimer in the blood in combination with spiral computed
tomography (CT).61–63
PATHOPHYSIOLOGY PPH is considered an idiopathic
disorder characterized by endothelial dysfunction with
overproduction of vasoconstrictors, such as thromboxane
and endothelin, and decreased production of vasodilators,
such as prostacyclin.66 Vascular growth factors are released
that cause changes in the vascular smooth wall called remodeling. Angiotensin II, serotonin, electrolyte transporter
mechanisms, and nitric oxide also play a role in the pathogenesis of this disorder. Together, this results in pathologic
changes in the pulmonary vasculature characterized by
fibrosis and thickening of the vessel wall with luminal narrowing and abnormal vasoconstriction. These changes
738
Unit 8
The Pulmonary System
cause resistance to pulmonary artery blood flow, thus
increasing the pressure in the pulmonary arteries. As
resistance and pressure increase, the workload of the right
ventricle increases and subsequent right ventricular
hypertrophy, followed by failure, may occur (cor pulmonale).
This eventually results in the death of most individuals with
PPH.
Secondary pulmonary hypertension can often be
reversed if the primary disorder is resolved quickly. If
hypertension persists, hypertrophy occurs in the medial
smooth muscle layer of the arterioles. The larger arteries
stiffen, and hypertension progresses until pulmonary artery
pressure equals systemic blood pressure, causing right ventricular hypertrophy and eventually cor pulmonale. The
pathogenesis of pulmonary hypertension and cor pulmonale resulting from disease of the respiratory system is
shown in Figure 26-15.
CLINICAL MANIFESTATIONS Pulmonary hypertension
may not be detected until it is quite severe. The symptoms
are often masked by primary pulmonary or cardiovascular
disease. The first indication of pulmonary hypertension
may be an abnormality seen on a chest radiograph
(enlarged right heart border) or an electrocardiogram that
shows right ventricular hypertrophy. Manifestations of
fatigue, chest discomfort, tachypnea, and dyspnea, particularly with exercise, are common. Examination may reveal
peripheral edema, jugular venous distension, a precordial
heave, and accentuation of the pulmonary component of
the second heart sound.
EVALUATION AND TREATMENT Definitive diagnosis
of pulmonary hypertension can be made only with right
heart catheterization. The diagnosis of primary pulmonary
hypertension is made when all other causes of pulmonary
hypertension have been ruled out.
Currently, the most effective therapy for primary pulmonary hypertension is lung transplantation; however, prostacyclin analogs (epoprostenol, beraprost) and endothelinreceptor antagonists (sitaxsentan, bosentan) have been
shown to reduce pulmonary artery pressures and improve
symptoms.67-69 Supplemental oxygen, digitalis, and diuretics are used as palliatives. Other treatments that may be
helpful include vasodilators, anticoagulants, and nitric
oxide.67,68 The most effective treatment for secondary pulmonary hypertension is treatment of the primary disorder.
Treatment often includes supplemental oxygen to reverse
hypoxic vasoconstriction.
Cor pulmonale
COPD
Interstitial fibrosis
Obesity-hypoventilation syndrome
Chronic hypoxemia
Chronic acidosis
Pulmonary artery
vasoconstriction
Progression of pulmonary
hypertension can be
reversed at this point
with effective treatment
of primary or underlying
disease
Increased pulmonary
artery pressure
Intimal fibrosis and hypertrophy
of medial smooth muscle layer
of pulmonary arteries
Chronic pulmonary hypertension
Cor pulmonale (hypertrophy
and dilation of right ventricle)
Right heart failure
Figure 26-15 n Pathogenesis of Pulmonary Hypertension
and Cor Pulmonale.
Cor pulmonale, also called pulmonary heart disease, consists of right ventricular enlargement (hypertrophy, dilation, or both) and failure. It is caused by primary or
secondary pulmonary hypertension (see Figure 26-15).
PATHOPHYSIOLOGY Cor pulmonale develops as pulmonary hypertension creates chronic pressure overload in
the right ventricle, similar to that created in the left ventricle by systemic hypertension. (Systemic hypertension is discussed in Chapter 23.) Pressure overload increases the work
of the right ventricle and first causes hypertrophy of the
normally thin-walled heart muscle, but eventually leads to
dilation and failure of the ventricle. Acute hypoxemia, as
with pneumonia, can exaggerate pulmonary hypertension
and dilate the ventricle as well. The right ventricle usually
fails when pulmonary artery pressure equals systemic blood
pressure.
CLINICAL MANIFESTATIONS The clinical manifesta-
tions of cor pulmonale may be obscured by primary respiratory disease and appear only during exercise testing.
The heart may appear normal at rest, but with exercise, cardiac output falls. The electrocardiogram may show right
ventricular hypertrophy. The pulmonary component of
the second heart sound, which represents closure of the
pulmonic valve, may be accentuated, and a pulmonic valve
murmur also may be present. Tricuspid valve murmur may
accompany the development of right ventricular failure.
Increased pressures in the systemic venous circulation
cause jugular venous distension, hepatosplenomegaly, and
peripheral edema.
Alterations of Pulmonary Function
EVALUATION AND TREATMENT Diagnosis is based on
physical examination, radiologic examination, electrocardiogram, and echocardiography. The goal of treatment for
cor pulmonale is to decrease the workload of the right ventricle by lowering pulmonary artery pressure. Treatment is
the same as for pulmonary hypertension, and its success
depends on reversal of the underlying lung disease.
QUICK CHECK 26-6
1.
2.
3.
What factors influence the impact of an embolus?
List three causes of pulmonary hypertension.
What is cor pulmonale?
Respiratory Tract Malignancies
Chapter 26
739
recurrent scales that precede development of a bleeding
ulceration. Metastases to the cervical lymph nodes have a
low rate of occurrence (2% to 8%) and are more likely when
the primary lesion is larger and exists for a longer period.
EVALUATION AND TREATMENT Diagnosis is com-
monly made by clinical history and presentation of the
lesion. Biopsy confirms the presence of malignant cells.
The staging for lip cancer is summarized in Box 26-1. Surgical excision is effective for smaller lesions. A relatively
new surgical technique, called the Mohs micrographic surgery, has been found to be highly effective and is associated
with a low risk of local recurrence (8%). Larger lesions that
require extensive resection may be followed by cosmetic
surgeries. The prognosis for recovery is excellent, and
deaths are usually the result of inadequate treatment.
Lip cancer
Laryngeal cancer
Cancer of the lip is more prevalent in men, with 2000 new
cases per year.70 Long-term exposure to sun, wind, and cold
over a period of years results in dryness, chapping, hyperkeratosis, and predisposition to malignancy. In addition,
immunosuppression, such as that seen in individuals with
renal transplants, increases the risk for lip cancer. The lower
lip is the most common site.
Cancer of the larynx represents approximately 2% to 3% of
all cancers in the United States, and 11,300 new cases are
estimated for 2007.70 The risk of laryngeal cancer is
increased by the amount of tobacco smoked; risk is further
heightened with the combination of smoking and alcohol
consumption. More recently, the human papillomavirus
(HPV) has been implicated as a cause of laryngeal cancer.71
The highest incidence is in men between 50 and 75 years of
age.
PATHOPHYSIOLOGY The most common form of lower
lip cancer is termed exophytic. The lesion usually develops
in the outer part of the lip along the vermilion border.
The lip becomes thickened and evolves to an ulcerated center with a raised border (Figure 26-16). Verrucous-type
lesions are less common. They have an irregular surface,
follow cracks in the lip, and tend to extend toward the inner
surface. Squamous cell carcinoma is the most common cell
type. Basal cell carcinoma does not develop unless there is
extension from the mucous membrane or vermilion border
of the lip.
CLINICAL MANIFESTATIONS Malignant lesions are
often preceded by the development of a blister that evolves
into a superficial ulceration. There may be a history of
PATHOPHYSIOLOGY Carcinoma of the true vocal cords
(glottis) is more common than that of the supraglottic
structures (epiglottis, aryepiglottic folds, arytenoids, false
cords). Tumors of the subglottic area are rare. Squamous
cell carcinoma is the most common cell type, although
small cell carcinomas also occur (Figure 26-17). Metastasis
develops by spread to the draining lymph nodes, and distant metastasis, usually to the lung, is rare.
CLINICAL MANIFESTATIONS The presenting symp-
toms of laryngeal cancer include hoarseness, dyspnea, and
cough. Progressive hoarseness is the most significant symptom and can result in voice loss. Dyspnea is rare with
BOX 26-1
Staging of Lip Cancer
Stage I
Primary tumor less than 2 cm; no palpable nodes
Stage II
Primary tumor 2 to 4 cm; no palpable nodes
Stage III
Primary tumor over 4 cm; metastasis to lymph nodes
Figure 26-16 n Lip Cancer. Carcinoma of lower lip with central ulceration and raised, rolled borders. (From del Regato JA,
Spjut HJ, Cox JD: Ackerman and del Regato’s cancer, ed 2,
St Louis, 1985, Mosby.)
Stage IV
Large primary tumors; nodes fixed to mandible or distant
metastases
740
Unit 8
The Pulmonary System
A
B
R
L
Figure 26-17 n Laryngeal Cancer. A, Mirror view of carcinoma of the right false cord partially hiding the true cord. B, Lateral view.
(Redrawn from del Regato JA, Spjut HJ, Cox JD: Ackerman and del Regato’s cancer, ed 2, St Louis, 1985, Mosby.)
supraglottic tumors but can be severe in subglottic tumors.
Cough occurs less commonly and may follow swallowing.
Laryngeal pain or a sore throat is likely with supraglottic
lesions.
EVALUATION AND TREATMENT Evaluation of the lar-
ynx includes external inspection and palpation of the larynx
and the lymph nodes of the neck. Indirect laryngoscopy
provides a stereoscopic view of the structure and movement
of the larynx. A biopsy also can be obtained during this
procedure. Direct laryngoscopy provides specific visualization of the tumor. Plain films of the larynx and computed
tomography facilitate the identification of tumor boundaries and the degree of extension to surrounding tissue.
Radiation therapy has shown good results for early carcinoma of the vocal cords and is used as an adjunct to surgery in more advanced disease. Endoscopic laser for partial
laryngectomies is emerging as the preferred treatment for
small supraglottic and subglottic malignancies. Total laryngectomy is required when lesions are extensive and involve
the cartilage. Efforts to preserve voice function and improve
quality of life continue to be evaluated.72
Lung cancer
Lung cancers (bronchogenic carcinomas) arise from the
epithelium of the respiratory tract. Therefore, the term lung
cancer excludes other pulmonary tumors, including sarcomas, lymphomas, blastomas, hematomas, and mesotheliomas. Lung cancer is an epidemic in the United States,
with an estimated 213,380 new cases in 2007 (15% of all
cancer sites).70 It is the most common cause of cancer death
and is responsible for 29% of all deaths in the United States.
Deaths caused by lung cancer in men have declined, and
the death rate in women is approaching a plateau after a
long period of increase. One-year survival in individuals
with lung cancer increased from 37% to 42% since the early
1980s, but overall 5-year survival remains low at 16%.70
The most common cause of lung cancer is cigarette
smoking. Secondhand (environmental) smoke exposure
has also been identified as a risk for lung cancer. Smokers
with obstructive lung disease (low FEV1) are at even greater
risk. Genetic predisposition to developing lung cancer,
which is evident in analysis of pedigrees, also plays a role
in its pathophysiology. Other risk factors for lung cancer
include occupational exposures to certain workplace toxins,
radiation, air pollution, and tuberculosis.
Types of lung cancer
Primary lung cancers arise from the bronchi within the
lungs and are therefore called bronchogenic carcinomas.
Although there are many types of lung cancer, lung cancer
is divided into two major categories, non–small cell lung carcinoma (NSCLC, 75% to 85% of all lung cancers) and small
cell lung carcinoma (SCLC, 15% to 20% of all lung cancers).
The category of non–small cell carcinoma can be subdivided
into three common types of lung cancer: squamous cell carcinoma, adenocarcinoma, and large cell undifferentiated
carcinoma. Characteristics of these tumors, including clinical manifestations, are listed in Table 26-3. Many cancers
that arise in other organs of the body metastasize to the
lungs; however, these are not considered lung cancers and
are categorized by their primary site of origin.
Non–small cell lung cancer. Squamous cell carcinoma
accounts for about 30% of bronchogenic carcinomas, representing a sharp decline in incidence since the mid-1980s.
These tumors are typically located near the hilum and project into bronchi (Figure 26-18, A). Because of the location
in the central bronchi, obstructive manifestations are nonspecific and include nonproductive cough or hemoptysis.
Pneumonia and atelectasis are often associated with
Alterations of Pulmonary Function
Chapter 26
741
TABLE 26-3
Characteristics of Lung Cancers
Tumor Type
Growth
Rate
NON–SMALL CELL CARCINOMA
Squamous cell
Slow
carcinoma
Adenocarcinoma
Moderate
Large cell
carcinoma
Rapid
SMALL CELL CARCINOMA
Very rapid
Metastasis
Means of Diagnosis
Late; mostly to hilar
lymph nodes
Biopsy, sputum analysis,
bronchoscopy, electron
microscopy,
immunohistochemistry
Early; to lymph nodes,
pleura, bone, adrenal
glands and brain
Early and widespread
Radiography, fiber-optic
bronchoscopy, electron
microscopy
Sputum analysis,
bronchoscopy, electron
microscopy (by exclusion
of other cell types)
Very early; to
mediastinum, lymph
nodes, brain, bone
marrow
Radiography, sputum
analysis, bronchoscopy,
electron microscopy,
immunohistochemistry
Clinical Manifestations
and Treatment
Cough, hemoptysis, sputum
production, airway obstruction,
hypercalcemia; treated surgically,
chemotherapy and radiation as
adjunctive therapy
Pleural effusion; treated surgically,
chemotherapy as adjunctive
therapy
Chest wall pain, pleural effusion,
cough, sputum production,
hemoptysis, airway obstruction
resulting in pneumonia; treated
surgically
Cough, chest pain, dyspnea,
hemoptysis, localized wheezing,
airway obstruction, signs and
symptoms of excessive hormone
secretion; treated by chemotherapy
and ionizing radiation to thorax and
central nervous system
A
C
B
Figure 26-18 n Lung Cancer. A, Squamous cell carcinoma. This hilar tumor originates from the main bronchus. B, Peripheral
adenocarcinoma. The tumor shows prominent black pigmentation, suggestive of having evolved in an anthracotic scar. C, Small cell
carcinoma. The tumor forms confluent nodules. On cross section, the nodules have an encephaloid appearance. (From Damjanov
I, Linder J, editors: Anderson’s pathology, ed 10, St Louis, 1996, Mosby.)
742
Unit 8
The Pulmonary System
squamous cell carcinoma (see Figure 26-18, A). Chest pain is
a late symptom associated with large tumors. These tumors
can remain fairly well localized and tend not to metastasize
until late in the course of the disease. The preferred treatment
is surgical resection, although once metastasis has taken
place, total surgical resection is more difficult and survival
rates dramatically decrease.73,74 Adjunctive radiation and
chemotherapy improve outcomes in many individuals.75
Adenocarcinoma (tumor arising from glands) of the
lung constitutes 35% to 40% of all bronchogenic carcinomas
(Figure 26-18, B). The increase in incidence of adenocarcinoma has been ascribed to the increasing occurrence of lung
cancer in women, environmental and occupational carcinogens, and changes in the histologic criteria for diagnosis.
These tumors, which are usually smaller than 4 cm, more
commonly arise in the peripheral regions of the pulmonary
parenchyma. They may be asymptomatic and discovered
by routine chest roentgenogram in the early stages, or
the individual may present with pleuritic chest pain and
shortness of breath from pleural involvement by the tumor.
Included in the category of adenocarcinoma is bronchioloalveolar cell carcinoma. These tumors tend to arise from
the terminal bronchioles and alveoli. They are slow-growing tumors with an unpredictable pattern of metastasis.
Metastasis occurs through the pulmonary arterial system
and mediastinal lymph nodes. This cell type has the weakest association with smoking.
Surgical resection is possible in a high proportion of
cases, but because metastasis occurs early, the 5-year survival
rate is less than 15%. Newer chemotherapy agents are resulting in increased survival rates in recent studies, although
benefits must be balanced with the considerable toxicities
of these drugs.75
Large cell carcinomas constitute 10% to15% of bronchogenic carcinomas. This cell type has lost all evidence
of differentiation and is therefore sometimes referred to as
undifferentiated large cell anaplastic cancer. Because large
cell carcinomas show none of the histologic findings of
squamous cell carcinoma or adenocarcinoma, they are diagnosed by a process of exclusion. The cells are large and contain darkly stained nuclei. These tumors commonly arise
centrally and can grow to distort the trachea and cause widening of the carina. Once metastasis has occurred, surgical
therapy is limited to palliative procedures (comfort measures) designed to relieve obstructive pneumonitis or prevent recurrence of pleural effusion.
Small cell lung cancer. Small cell carcinomas constitute 15% to 20% of bronchogenic carcinomas. Most of these
tumors are central in origin (Figure 26-18, C). Cell sizes
range from 6 to 8 mm. This cell type has the strongest correlation with cigarette smoking. Because these tumors show
a rapid rate of growth and tend to metastasize early and
widely, small cell carcinomas have the worst prognosis. Survival time for untreated small cell carcinoma is usually 1 to
3 months. Approximately 14% of treated individuals are
alive 2 years after diagnosis.
Small cell carcinoma is most often associated with
ectopic hormone production. Neuroendocrine cells (NE
cells) containing neurosecretory granules exist throughout
the tracheobronchial tree and may be associated with small
cell carcinoma.76 Ectopic hormone production is important
to the clinician because resulting signs and symptoms
(called paraneoplastic syndromes) may be the first manifestation of the underlying cancer. Small cell carcinomas most
commonly produce antidiuretic hormone from associated
neuroendocrine cells (the syndrome of inappropriate
antidiuretic hormone secretion [SIADH]). They also can
produce gastrin-releasing peptide, calcitonin, arginine vasopressin, and adrenocorticotropic hormone (ACTH). As a
result of ACTH secretion, individuals with lung cancer
secrete large quantities of 17-hydroxysteroids and 17-ketosteroids, leading to the development of an atypical Cushing
syndrome. Signs and symptoms related to this condition
include muscular weakness, facial edema, hypokalemia,
alkalosis, hyperglycemia, hypertension, and increased pigmentation. Treatment of small cell carcinoma is usually
palliative. More than 85% of tumors will have metastasized
by the time of diagnosis. Chemotherapy and radiation can
significantly prolong life and relieve symptoms, but relapse
is inevitable in most individuals.77
PATHOPHYSIOLOGY Tobacco smoke contains more
than 30 carcinogens and is responsible for causing 80% to
90% of lung cancers. These carcinogens, along with probable inherited genetic predisposition to cancers, result in
multiple genetic abnormalities in bronchial cells including
deletions of chromosomes, activation of oncogenes, and
inactivation of tumor suppressor genes.78 The most common genetic abnormality associated with lung cancer is loss
of the tumor suppressor gene p53; mutations in this gene
have been found in 50% to 60% of non–small cell lung cancers and 90% of small cell cancers.79 Once lung cancer is
initiated by these carcinogen-induced mutations, further
tumor development is promoted by growth factors such
as epidermal growth factor. Further cellular toxicity is
enhanced through smoke-induced toxic oxygen radical
production.
The bronchial mucosa suffers multiple carcinogenic
“hits” due to repetitive exposure to cigarette smoke, and
eventually epithelial cell changes begin to be visible on
biopsy. These changes progress from metaplasia to carcinoma in situ, and finally to invasive carcinoma. Further tumor
progression includes invasion of surrounding tissues and
finally metastasis to distant sites including the brain, bone
marrow, and liver.
CLINICAL MANIFESTATIONS Table 26-3 summarizes
the characteristic clinical manifestations according to tumor
type. By the time there are manifestations severe enough to
motivate the individual to seek medical advice, the disease
is usually advanced.
Alterations of Pulmonary Function
Chapter 26
743
EVALUATION AND TREATMENT Diagnostic tests for
HEALTH ALERT
the evaluation of lung cancer include chest x-ray, sputum
cytology, chest-computed tomography, fiberoptic bronchoscopy, and biopsy. Low-dose helical computed tomography is emerging as a sensitive and specific diagnostic test.
Biopsy determines the cell type, and the evaluation of
lymph nodes and other organ systems is used to determine
the stage of the cancer. The histologic cell type and the
stage of the disease are the major factors that influence
choice of therapy. The current accepted system for the
staging of non–small cell cancer is the TNM classification.
This system is a code in which T denotes the extent of the
primary tumor, N indicates the nodal involvement, and M
describes the extent of metastasis. Small cell carcinoma is
so rapidly progressive that its staging system consists of
only two stages: limited versus extensive disease.
The only proven way of reducing the risk for lung cancer
is the cessation of smoking, although chemopreventative
measures are being explored. To date, trials evaluating the
use of various early screening modalities such as chest
x-ray and computed tomography have not resulted in a
decrease in lung cancer mortality.80 The management of
lung cancer has been outlined here under each cell type,
but it generally is chosen on the basis of tumor stage and
patient functional status. Current modalities include combinations of surgical resection, chemotherapy, and radiation;
however, new genetic and immunologic therapies are being
explored81-85 (see Health Alert: Genetic and Immunologic
Breakthroughs in Lung Cancer Treatment).
Genetic and Immunologic Breakthroughs
in Lung Cancer Treatment
Although new chemotherapeutic agents have improved
outcomes slightly in the management of lung cancer, overall survival rates remain poor and toxicities of these regimens limit their use. New understandings of the genetic
and immunologic features of lung cancer cells have led
to new treatments. Gene therapy is emerging as a way of
restoring normal tumor suppressor gene function (e.g.,
p53) and increasing tumor responsiveness to chemoradiation. Immunologic therapies include antibodies to growth
factor receptors (e.g., epidermoid growth factor receptors
[EGFR]) and antiangiogenesis drugs. The effectiveness of
these strategies is still being evaluated, but new knowledge is leading to new opportunities for treatment.
Data from González G et al: Therapeutic vaccination with epidermal
growth factor (EGF) in advanced lung cancer: analysis of pooled
data from three clinical trials, Hum Vaccin 3(1):8–13, 2007; Ruttinger
D et al: Immunotherapy of lung cancer: an update, Onkologie 29(1–
2):33–38, 2006; Sandler AB: Targeting angiogenesis in lung cancer,
Sem Oncol 32(6 suppl 10):S16–S22, 2005; Toloza EM: Gene therapy
for lung cancer, Thorac Surg Clin 16(4):397–419, 2006.
QUICK CHECK 26-7
1.
2.
3.
What are the principal features of lip cancer?
Describe squamous cell carcinoma of the vocal cords.
Compare three types of lung cancer as to cause and
survival.
Did You Understand?
Clinical Manifestations of Pulmonary Alterations
1. Dyspnea is the feeling of breathlessness and
increased respiratory effort.
2. Abnormal breathing patterns are adjustments made
by the body to minimize the work of respiratory muscles. They include Kussmaul, obstructed, restricted,
gasping, Cheyne-Stokes respirations, and sighing.
3. Hypoventilation is decreased alveolar ventilation
caused by airway obstruction, chest wall restriction,
or altered neurologic control of breathing. Hypoventilation causes increased PaCO2.
4. Hyperventilation is increased alveolar ventilation produced by anxiety, head injury, or severe hypoxemia.
Hyperventilation causes decreased PaCO2.
5. Coughing is a protective reflex that expels secretions
and irritants from the lower airways.
6. Hemoptysis is expectoration of bloody mucus, which
can be caused by bronchitis, tuberculosis, abscess,
neoplasms, and other conditions that cause hemorrhage from damaged vessels.
7. Cyanosis is a bluish discoloration of the skin caused
by desaturation of hemoglobin, polycythemia, or
peripheral vasoconstriction.
8. Chest pain can result from inflamed pleurae, trachea,
bronchi, or respiratory muscles.
9. Clubbing of the fingertips is associated with diseases
that interfere with oxygenation of the tissues.
10. Hypercapnia is an increased PaCO2 caused by hypoventilation.
11. Hypoxemia is a reduced PaO2 caused by (a) decreased oxygen content of inspired gas, (b) hypoventilation, (c) diffusion abnormality, (d) ventilationperfusion mismatch, or (e) shunting.
12. Pulmonary edema is excess water in the lung caused
by disturbances of capillary hydrostatic pressure,
capillary oncotic pressure, or capillary permeability.
A common cause is left heart failure that increases
the hydrostatic pressure in the pulmonary circulation.
13. Atelectasis is the collapse of alveoli resulting from
compression of lung tissue or absorption of gas from
obstructed alveoli.
14. Bronchiectasis is abnormal dilation of the bronchi
secondary to another pulmonary disorder, usually
infection or inflammation.
15. Pneumothorax is the accumulation of air in the pleural space. It can be caused by spontaneous rupture of
weakened areas of a pleura, or it can be secondary to
pleural damage caused by disease, trauma, or
mechanical ventilation.
(Continued)
744
Unit 8
The Pulmonary System
Did You Understand?—Cont’d
16. Pneumothorax can be open, which means that the
lung will only partially collapse, or tension, which
means that pressure builds up in the pleural space
and can compress both the affected lung and the
mediastinum.
17. Pleural effusion is the accumulation of fluid in the
pleural space, usually resulting from disorders that
promote transudation or exudation from capillaries
underlying the pleura but occasionally resulting from
blockage or injury that causes lymphatic vessels to
drain into the pleural space.
18. Empyema is the presence of pus in the pleural space
(infected pleural effusion).
19. Chest wall compliance is diminished by obesity and
kyphoscoliosis, which compress the lungs, and by
neuromuscular diseases that impair chest wall muscle function.
20. Flail chest results from rib or sternal fractures that
disrupt the mechanics of breathing.
Pulmonary Disorders
1. Pulmonary fibrosis is an excessive amount of connective tissue in the lung. It diminishes lung compliance
and may be idiopathic or caused by disease.
2. Inhalation of noxious gases or prolonged exposure to
high concentrations of oxygen can damage the bronchial mucosa or alveolocapillary membrane and
cause inflammation or acute respiratory failure.
3. Pneumoconiosis, which is caused by inhalation of
dust particles in the workplace, can cause pulmonary
fibrosis, susceptibility to lower airway infection, and
tumor formation.
4. Allergic alveolitis is an allergic or hypersensitivity
reaction to many allergens.
5. Bronchiolitis is the inflammatory obstruction of small
airways. It is most common in children.
6. Acute respiratory distress syndrome (ARDS) results
from an acute, diffuse injury to the alveolocapillary
membrane and decreased surfactant production,
which increases membrane permeability and causes
edema and atelectasis.
7. Obstructive lung disease is characterized by airway
obstruction that causes difficult expiration. Obstructive disease can be acute or chronic in nature and
includes asthma, chronic bronchitis, and emphysema.
8. Asthma is the result of a type 1 hypersensitivity
immune response involving the activity lymphocytes,
IgE, mast cells, and eosinophils.
9. In asthma, obstruction is caused by episodic attacks
of bronchospasm, bronchial inflammation, mucosal
edema, and increased mucus production.
10. Dysregulation of the parasympathetic division of the
autonomic nervous system is thought to facilitate
bronchospasm in individuals with asthma.
11. Asthma staging is based on clinical severity from
mild intermittent to severe persistent and is used to
determine therapy.
12. Chronic bronchitis causes airway obstruction resulting from bronchial smooth muscle hypertrophy and
production of thick, tenacious mucus.
13. In emphysema, destruction of the alveolar septa and
loss of passive elastic recoil lead to airway collapse
and obstruct gas flow during expiration.
14. Chronic obstructive pulmonary disease (COPD) is the
coexistence of chronic bronchitis and emphysema.
15. COPD is an important cause of hypoxemic and hypercapnic respiratory failure.
16. Upper respiratory tract infections, which are the most
common cause of short-term disability in the United
States, include rhinitis (the common cold), pharyngitis, and laryngitis.
17. Serious lower respiratory tract infections occur most
often in the elderly and in individuals with impaired
immunity or underlying disease.
18. Pneumococcal pneumonia is an acute lung infection
resulting in an inflammatory response with four
phases: (a) consolidation, (b) red hepatization, (c)
gray hepatization, and (d) resolution.
19. Viral pneumonia can be severe, but is more often an
acute, self-limiting lung infection usually caused by
the influenza virus.
20. Tuberculosis is a lung infection caused by Mycobacterium tuberculosis (tubercle bacillus).
21. In tuberculosis, the inflammatory response proceeds to
isolate colonies of bacilli by enclosing them in tubercles and surrounding the tubercles with scar tissue.
22. Bacilli may remain dormant within the tubercles for
life or, if the immune system breaks down, cause
recurrence of active disease.
23. Pulmonary vascular diseases are caused by embolism or hypertension in the pulmonary circulation.
24. Pulmonary embolism is occlusion of a portion of the
pulmonary vascular bed by a thrombus (most common), tissue fragment, or air bubble. Depending on
its size and location, the embolus can cause hypoxic
vasoconstriction, pulmonary edema, atelectasis, pulmonary hypertension, shock, and even death.
25. Pulmonary hypertension (pulmonary artery pressure
5 to 10 mm Hg above normal) is caused by (a) elevated
left ventricular pressure, (b) increased blood flow
through the pulmonary circulation, (c) obliteration or
obstruction of the vascular bed, or (d) active constriction of the vascular bed produced by hypoxemia or
acidosis.
26. Cor pulmonale is right ventricular enlargement
caused by chronic pulmonary hypertension. Cor pulmonale progresses to right ventricular failure if the
pulmonary hypertension is not reversed.
27. Lip cancer is most common in men. In the most common cell type, squamous cell, metastasis is rare
when lesions are diagnosed and treated early.
28. Laryngeal cancer occurs primarily in men and represents 2% to 3% of all cancers. Squamous cell carcinoma of the true vocal cords is most common and
presents with a clinical symptom of progressive
hoarseness.
29. Lung cancer, the most common cause of cancer
death in the United States, is commonly caused by
cigarette smoking.
30. Cancer cell types include non–small cell carcinoma
(squamous cell, adenocarcinoma, and large cell) and
small cell carcinoma. Each type arises in a characteristic site or type of tissue, causes distinctive clinical
manifestations, and differs in likelihood of metastasis
and prognosis.
Alterations of Pulmonary Function
Chapter 26
745
Key Terms
Abscess, 736
Absorption atelectasis, 720
Acute bronchitis, 735
Acute respiratory distress syndrome
(ARDS), 724
Adenocarcinoma, 742
Alveolar dead space, 718
Aspiration, 719
Asthma, 726
Atelectasis, 720
Bronchiectasis, 720
Bronchiolitis, 721
Bronchiolitis obliterans, 721
Cavitation, 736
Centriacinar emphysema, 731
Cheyne-Stokes respirations, 715
Chronic bronchitis, 729
Chronic obstructive pulmonary disease
(COPD), 728
Clubbing, 716
Compression atelectasis, 720
Consolidation, 736
Cor pulmonale, 738
Cough, 716
Cyanosis, 715
Dyspnea, 714
Emphysema, 731
Empyema (infected pleural effusion), 722
Extrinsic allergic alveolitis (hypersensitivity
pneumonitis), 724
Exudative effusion, 722
Flail chest, 723
Hemoptysis, 716
Hypercapnia, 717
Hyperventilation, 715
Hypocapnia, 715
Hypoventilation, 715
Hypoxemia, 717
Hypoxia, 717
Kussmaul respiration (hyperpnea), 715
Large cell carcinoma, 742
Laryngeal cancer, 739
Lip cancer, 739
Lung cancer, 740
Open pneumothorax (communicating
pneumothorax), 721
Orthopnea, 714
Oxygen toxicity, 724
Panacinar emphysema, 731
Paroxysmal nocturnal dyspnea (PND), 715
Pleural effusion, 722
Pneumoconiosis, 724
Pneumonia, 732
Pneumothorax, 721
Pulmonary edema, 718
Pulmonary embolism, 736
Pulmonary fibrosis, 723
Pulmonary hypertension, 737
Pulmonary thromboembolism, 736
Pulsus paradoxus, 727
Shunting, 718
Small cell carcinoma, 742
Squamous cell carcinoma, 740
Status asthmaticus, 728
Tension pneumothorax, 721
TNM classification, 743
Transudative effusion, 722
Tuberculosis (TB), 734
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