Pulmonary disease is often classified as acute or ALTERATIONS PULMONARY FUNCTION

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1 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 ELECTRONIC RESOURCES Companion CD Review Questions and Answers Animations Website Quick Check Answers Key Terms Exercises Critical Thinking Questions with Answers Algorithm Completion Exercises WebLinks Pulmonary 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

2 Alterations of Pulmonary Function Chapter 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. 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 (CO 2 ) is removed from the lungs at the same rate as that produced by cellular metabolism; therefore, arterial and alveolar PCO 2 values remain at normal levels (40 mm Hg). With hypoventilation, CO 2 removal does not keep up with CO 2 production and the level of CO 2 in the arterial blood (PaCO 2 ) increases, causing hypercapnia (PaCO 2 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 PaCO 2 of arterial blood) reveals the hypoventilation. Pronounced hypoventilation can cause somnolence or disorientation. Hyperventilation is alveolar ventilation exceeding metabolic demands. The lungs remove CO 2 faster than it is produced by cellular metabolism, resulting in decreased PaCO 2, or hypocapnia (PaCO 2 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 PaO 2 ), 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 PaO 2 should be measured. Central cyanosis (decreased oxygen saturation of hemoglobin in arterial

3 716 Unit 8 The Pulmonary System 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 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. Cough 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. Clubbing early 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.) 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 Hemoptysis 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. 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 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

4 Alterations of Pulmonary Function Chapter 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 PaCO 2 ), 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 PaCO 2. 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 CO 2 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 PaO 2 ), 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 (FiO 2 ) b. Ventilation of the alveoli 2. Diffusion of oxygen from the alveoli into the blood a. Balance between alveolar ventilation and perfusion ( _V/ _Q match) b. Diffusion of oxygen across the alveolar capillary barrier 3. Perfusion of pulmonary capillaries. The amount of oxygen in the alveoli is called the PAO 2 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 FiO 2. The FiO 2 of air at sea level is approximately 21% or Anything that decreases the FiO 2 (such as high altitude) decreases the PAO 2. The second factor is the amount of alveolar minute volume (tidal volume times respiratory rate). Hypoventilation results in an increase in PACO 2 and a decrease in PAO 2 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 between the amount of air getting into alveoli ( _V) and the amount of blood perfusing the capillaries around the alveoli ( _Q) An abnormal ventilation-perfusion ratio ( _V/ _Q) is the most common cause of hypoxemia (Figure 26-2). Normally, alveolocapillary lung units receive almost equal amounts of ventilation and perfusion. The normal _V/ _Q is 0.8 to 0.9 because perfusion is somewhat greater than ventilation in the lung bases and because some blood is normally shunted to the bronchial circulation. _V/ _Q mismatch refers to an From pulmonary artery Alveolocapillary membrane Normal V/Q Airway Alveolus To pulmonary vein Low V/Q Blocked ventilation Collapsed alveolus Hypoxemia Shunt (very low) V/Q Impaired perfusion High V/Q Impaired ventilation Hypoxemia Alveolar dead space Hypoxemia Figure 26-2 n Ventilation-Perfusion ( _ V/ _ Q) Abnormalities.

5 718 Unit 8 The Pulmonary System abnormal distribution of ventilation and perfusion. Hypoxemia can be caused by inadequate ventilation of well-perfused areas of the lung (low _V/ _Q). Mismatching of this 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 PaO 2 and hypoxemia. Hypoxemia also can be caused by poor perfusion of well-ventilated portions of the lung (high _V/ _Q), resulting in wasted ventilation. The most common cause of high _V/ _Q is a pulmonary 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 PO 2 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 PaCO 2 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 List the primary signs and symptoms of pulmonary disease. 2. What abnormal breathing patterns are seen with pulmonary disease? 3. What mechanisms produce hypercapnia? 4. What mechanisms produce hypoxemia? Acute respiratory failure Respiratory failure is defined as inadequate gas exchange such that PaO 2 50 mm Hg or PaCO 2 50 mm Hg with ph 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 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,

6 Alterations of Pulmonary Function Chapter 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 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 PaCO 2 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

7 720 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 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 26-4). 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 Inspired air Normal alveolus Mucus plug Closed pore of Kohn Atelectatic alveolus Mucus plug Open pore of Kohn A Low inspiratory volume (shallow breathing) High inspiratory volume (deep breathing) 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. B

8 Alterations of Pulmonary Function Chapter 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 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 Normal lung Outside air enters because of disruption of chest wall and parietal pleura 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.

9 722 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 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) Exudate Pus (empyema) Watery fluid that diffuses out of capillaries beneath the pleura (i.e., capillaries in lung or chest wall) Fluid rich in cells and proteins (leukocytes, plasma proteins of all kinds; see Chapter 5) that migrates out of the capillaries Debris of infection (microorganisms, leukocytes, cellular debris) dumped into the pleural space by blocked lymphatic vessels 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) Hemorrhage into the pleural space Traumatic injury, surgery, rupture, or malignancy that damages blood vessels 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, 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

10 Alterations of Pulmonary Function Chapter 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 C 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 Describe pulmonary edema, and list two causes. 2. Contrast atelectasis and bronchiectasis. 3. How does pneumothorax differ from pleural effusion? 4. What causes empyema? 5. 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 B D

11 724 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 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. 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 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. Acute respiratory distress syndrome 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. 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

12 Alterations of Pulmonary Function Chapter 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 leads to worsening _V/ _Q mismatching and hypoxemia. 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

13 726 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 What are some of the causes of pulmonary fibrosis? 2. What symptoms are produced by inhalation of toxic gases? 3. Describe pneumoconiosis, and give two examples. 4. 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 (FEV 1 ). 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

14 Alterations of Pulmonary Function Chapter Mast cell Parasympathetic nerve Smooth muscle Bronchioles Pulmonary artery Cartilage Submucosal gland Basement membrane Respiratory bronchioles Epithelium Goblet cell Alveoli Normal alveoli A B Enlarged submucosal gland Degranulation of mast cell Mucus accumulation Smooth muscle constriction Mucus plug Hyperinflation of alveoli Inflammation of epithelium Mucus plug Hyperinflation of alveoli Mucus accumulation C 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.) D 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 PaCO 2 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), CO 2 retention, and respiratory acidosis. Respiratory acidosis signals respiratory failure. CLINICAL MANIFESTATIONS Between attacks, individuals 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

15 728 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 Autonomic dysregulation Release of toxic neuropeptides Bronchial hyperresponsiveness Airway obstruction 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 PaCO 2 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 PaCO 2 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 FEV 1 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 FEV 1 ). 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 b 2 - agonists 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

16 Alterations of Pulmonary Function Chapter 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: , 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): , 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 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 ,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 common 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 Late in course with infection Dyspnea Late in Common course Wheezing Intermittent Common History of smoking Common Common Barrel chest Occasionally Classic Prolonged Always Always present expiration present Cyanosis Common Uncommon Chronic Common Late in course hypoventilation Polycythemia Common Late in course Cor pulmonale Common Late in course

17 730 Unit 8 The Pulmonary System Tobacco smoke Air pollution Inflammation of the airway epithelium Inherited 1 -antitrypsin deficiency Systemic effects (muscle weakness, weight loss) Infiltration of inflammatory cells and release of cytokines (neutrophils, macrophages, lymphocytes, leukotrienes, interleukins) 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 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.

18 Alterations of Pulmonary Function Chapter Air movement during INSPIRATION Mucus plug Muscle Alveolar walls Air movement during EXPIRATION Bronchial walls collapse Figure 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 a 1 -antitrypsin, a major component of a 1 -globulin, a plasma protein. 34 Normally a 1 - antitrypsin inhibits the action of many proteolytic enzymes, therefore a 1 -antitrypsin deficiency (an autosomal recessive trait) produces an increased likelihood of developing emphysema because proteolysis in lung tissues is not inhibited. a 1 -Antitrypsin deficiency is suggested in individuals 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 in significant ventilation-perfusion ( _V/ _Q) mismatching and 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) 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 a 1 -antitrypsin deficiency. CLINICAL MANIFESTATIONS The clinical manifestations of emphysema are listed in Table 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 FEV 1 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 b 2 -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

19 732 Unit 8 The Pulmonary System Distended respiratory bronchiole Alveoli A Distended alveolus Figure 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.) B with severe COPD. 38 Selected individuals with severe emphysema can benefit from lung reduction surgery or lung transplantation. QUICK CHECK What mechanisms cause obstruction in asthma? 2. How does emphysema affect oxygenation and ventilation? 3. 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 following : Community-Acquired Pneumonia (CAP) Streptococcus pneumoniae Mycoplasma pneumoniae Haemophilus influenza Nosocomial Pneumonia Pseudomonas aeruginosa Staphylococcus aureus Klebsiella pneumoniae Immunocompromised Individuals Pneumocystis jiroveci Mycobacterium tuberculosis Atypical mycobacteria Oral anaerobic bacteria Escherichia coli Fungi Influenza virus Respiratory viruses Legionella pneumophila Protozoa Chlamydia pneumoniae Parasites Moraxella catarrhalis 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

20 Alterations of Pulmonary Function Chapter 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 the acinus leads to dyspnea and to _V/ _Q mismatching and hypoxemia. Pneumococcal pneumonia In pneumococcal pneumonia, S. pneumoniae microorganisms initiate the inflammatory response, and inflammatory exudate causes alveolar edema, which leads to the other changes shown in Figure 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 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 and the World Health Organization, available at avian_influenza/en/index.html CLINICAL MANIFESTATIONS Many cases of pneumonia are preceded by an upper respiratory infection, which is often viral. Individuals then develop fever, chills, productive

21 734 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 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 mid- 1990s 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 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.

22 Alterations of Pulmonary Function Chapter 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 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: , 2004; Nunn P et al: Tuberculosis control in the era of HIV, Nat Rev Immunol 5(10): , 2005; and the World Health Organization at 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. 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 individuals, 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

23 736 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 Compare pneumococcal and viral pneumonia as to severity of disease. 2. Describe the pathophysiologic features of tuberculosis. 3. 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 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 clinical 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

24 Alterations of Pulmonary Function Chapter 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 Tachypnea Dyspnea Chest pain Increased dead space V/Q imbalances Decreased PaO 2 Pulmonary infarction Pulmonary hypertension Decreased cardiac output Systemic hypotension Shock Figure 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. EVALUATION AND TREATMENT Routine chest radiographs 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 ( _V/ _Q scan), in which lungs are scanned after injection 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) 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 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. 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

25 738 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 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 Progression of pulmonary hypertension can be reversed at this point with effective treatment of primary or underlying disease COPD Interstitial fibrosis Obesity-hypoventilation syndrome Chronic hypoxemia Chronic acidosis Pulmonary artery vasoconstriction 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 n Pathogenesis of Pulmonary Hypertension and Cor Pulmonale. 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 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 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 manifestations 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.

26 Alterations of Pulmonary Function Chapter 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 What factors influence the impact of an embolus? 2. List three causes of pulmonary hypertension. 3. What is cor pulmonale? Respiratory Tract Malignancies Lip 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. 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 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 commonly 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 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. Laryngeal cancer Cancer of the larynx represents approximately 2% to 3% of all cancers in the United States, and 11,300 new cases are estimated for 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 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 symptoms 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 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

27 740 Unit 8 The Pulmonary System A B R L Figure 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 larynx 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 FEV 1 ) 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 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

28 Alterations of Pulmonary Function Chapter TABLE 26-3 Characteristics of Lung Cancers Tumor Type NON SMALL CELL CARCINOMA Squamous cell Slow carcinoma Growth Rate Metastasis Means of Diagnosis Late; mostly to hilar lymph nodes Adenocarcinoma Moderate Early; to lymph nodes, pleura, bone, adrenal glands and brain Large cell carcinoma Biopsy, sputum analysis, bronchoscopy, electron microscopy, immunohistochemistry Radiography, fiber-optic bronchoscopy, electron microscopy Rapid Early and widespread Sputum analysis, bronchoscopy, electron microscopy (by exclusion of other cell types) 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 SMALL CELL CARCINOMA Very rapid Very early; to mediastinum, lymph nodes, brain, bone marrow Radiography, sputum analysis, bronchoscopy, electron microscopy, immunohistochemistry 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 Figure 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.) B