Chapter ____ Respiration Hypoventilation means that ventilation of the lungs is inadequate to remove carbon dioxide that has

diffused from the blood into the alveoli. Ventilation requires an adequate minute ventilation, which is defined as the respiratory rate (breaths per minute) times the tidal volume (liters per breath) expressed in liters per minute. Normally, ventilation removes carbon dioxide at a steady pace so that the amount of CO2 in arterial blood (PaCO2) remains stable at about 40 mm Hg. However, a decrease in minute ventilation will reduce the ability of the lungs to expel CO2. A decrease in minute ventilation can occur in any disorder that causes a decrease in respiratory rate and/or tidal volume. If CO2 is not "blown off" from the alveoli, then the concentration gradient from blood to alveoli for CO2 is lost, and the PaCO2 increases. This is called hypercapnia and results in a fall in pH (respiratory acidosis). Hyperventilation means that minute ventilation exceeds that necessary to remove carbon dioxide from the alveoli and blood. This is usually a result of an increase in respiratory rate. Hypocapnia (low PaCO2) and a respiratory alkalosis result." When hemoglobin becomes desaturated due to hypoxemia, it causes central cyanosis, a bluish coloration of skin and mucous membranes. Cyanosis is easily detected in infants but can be difficult to see in adults (look at buccal mucosa and lips). Central cyanosis can result from any pulmonary or cardiac condition that causes acute or chronic hypoxemia. Peripheral cyanosis is bluish coloration of the digits due to poor circulation. It can occur as a result of intense vasoconstriction, obstruction of distal blood vessels, or heart failure. The best place to look for peripheral cyanosis is in the nail beds. Clubbing is bulbous enlargement of the distal digits due to hypertrophy of the nail bed. It results from conditions that cause chronic hypoxemia, such as bronchiectasis, cystic fibrosis, heart failure, pulmonary fibrosis, and congenital heart disease. It can occasionally be seen with lung tumors (hypertrophic osteoarthropathy). Cyanosis indicates the need for emergent evaluation and treatment; clubbing, however, indicates a more chronic condition. Hypercapnia is caused by many diseases and conditions that are associated with alveolar hypoventilation. Hypercapniaoccurs when there is a fall in minute ventilation due to a decreased drive to breathe (as evidenced by a decreased respiratory rate) or poor ability to respond to ventilatory stimulation (as evidenced by a decrease in tidal volume). Many conditions can contribute to a decreased respiratory rate or tidal volume, Individuals with underlying pulmonary diseases are at risk to develop hypoventilation as a result of many medical interventions including surgery, anesthesia, pain medications, sleeping medications, electrolyte disorders, and pain. A decrease in respiratory rate is easy to recognize clinically; however, a decrease in tidal volume can be very subtle. The best way to document hypercapnia is through the use of arterial blood gas measurement. Hypercapnia causes a respiratory acidosis. Other complications include electrolyte abnormalities, somnolence, and arrhythmias. Alveolar hypoventilation and associated hypercapnia limit the amount of oxygen available for diffusion into the blood and thus cause secondary hypoxemia. Proceed through the Hypercapnia Algorithm. Hypoxemia is another condition that is caused by pulmonary disease or injury. It results from:

1. Decreased oxygen delivery to the alveoli a. Decreased oxygen content of the inspired air (FIO2) b. Decreased minute ventilation with accumulation of CO2 in the alveoli 2. Decreased diffusion of oxygen from the alveoli into the blood 1. Imbalance between alveolar ventilation and perfusion ( 2. Diffusion barrier at the alveolocapillary barrier Decreased pulmonary perfusion 0. Intracardiac defects with right-to-left shunting 1. Intrapulmonary arteriovenous malformations mismatching is one of the most important causes of hypoxemia mismatch)

Acute Respiratory Failure

The term acute respiratory failure refers to the condition in which hypercapnia, hypoxemia, or both are severe enough to threaten survival. This is commonly defined as when:

y Arterial carbon dioxide levels (PaCO2) 50 mm Hg and pH is 7.25; or when y Arterial oxygen levels (PaO2) 50 mm Hg.
Individuals with chronic pulmonary disorders can partially compensate for respiratory failure and tolerate hypoxemia and hypercapnia that would be life-threatening if they occurred acutely. When assessing an individual with significant pulmonary dysfunction, it is imperative that ventilation as well as oxygenation are evaluated promptly. Because the signs and symptoms of acute respiratory failure can be subtle, obtaining arterial blood gases is essential in adequately assessing the patient and in determining appropriate interventions. Remember that hypercapnic respiratory failure requires ventilation (bag mask, noninvasive positive pressure ventilation, or intubation with mechanical ventilation), while hypoxemic respiratory failure requires oxygenation. Many individuals with severe lung disease suffer from both hypercapnia and hypoxemia and require both ventilation and oxygenation.

Disorders of the Chest Wall and Pleura

Disorders of the chest wall and pleura restrict lung expansion and can therefore limit tidal volume. Thus individuals with these disorders will generally present with increased respiratory rate in order to prevent hypercapnia from developing. In addition, space-occupying conditions such as pneumothorax and pleural effusions cause ventilation and perfusion mismatching with resultant hypoxemia. Recognition and prompt initiation of appropriate interventions for individuals with disorders of the chest wall and pleura is essential Chest wall restriction is caused by any disorder that impairs the ability of the chest wall to expand. As discussed on the last screen, this limits tidal volume and respiratory rate must increase in order to maintain minute ventilation. If respiratory rate can no longer compensate for the fall in tidal volume, then hypercapnia and respiratory acidosis will develop. Perhaps one of the most common causes of limited chest expansion is pain. Other causes of chest wall restriction include the following:

y Trauma or surgery to the ribs or muscles y Skeletal deformity (e.g., kyphoscoliosis, pectusexcavatum, ankylosing spondylitis)

y Neuromuscular diseases (e.g., polio, amyotrophic lateralizing sclerosis, myasthenia gravis,

muscular dystrophy, Guillain-Barr syndrome).

y Obesity
Individuals with any of these underlying conditions are at increased risk for acute respiratory failure, especially if undergoing medical interventions that increase chest wall pain or decrease the drive to breathe (e.g., anesthetic agents). The amount of chest wall restriction can be quantified by performing pulmonary function tests. Disorders that restrict the chest wall result in a decrease in the forced vital capacity (FVC). Unlike restrictive disease of the lung, restriction that is confined to the chest wall does not interfere with diffusion of gases and usually results in hypercapnia without hypoxemia. Management includes reversal of the underlying disorder, if possible, and supportive ventilation. One of the most dramatic examples of chest wall restriction is flail chest. In flail chest, multiple rib fractures result in instability of a portion of the chest wall. This results in paradoxical movement of the injured portion of the thoracic cage (injured area moves out with inspiration and in with expiration) and thus ineffective ventilation. Management requires rapid intubation and management of underlying pleural and pulmonary injury.

Pleural Abnormalities

Pleural abnormalities fall into two major categories: pneumothorax and pleural effusions. The visceral and parietal pleura normally are separated by only a very small amount of fluid, and their adherence to one another is what allows chest wall expansion to inflate the underlying lung during inspiration. Thus pleural abnormalities can lead to partial lung collapse, decreased ventilation, and resultant hypercapnia. In addition, air or fluid in the pleural space compresses the underlying lung leading to mismatching and hypoxemia. Pneumothorax refers to the condition in which air has leaked into the pleural space, and pleural effusion refers to the condition in which fluid has leaked into the pleural space.

Animation: Open Pneumothorax vs. Tension Pneumothorax

Pneumothorax occurs when the visceral or parietal pleura rupture and air leaks into the space between these layers. Pneumothorax can occur spontaneously due to rupture of a bleb (as is found in COPD or in some tall healthy men), or secondary to trauma. Open pneumothorax occurs if the pleural tear remains open to either the outside of the chest or to the bronchi; air then enters the pleura during inspiration and is expelled during expiration (two-way valve). The lung on that side of the thorax will tend to collapse partially. Tension pneumothorax occurs if the communication with the pleural rupture closes during expiration (one-way valve). In this situation, air is sucked into the pleural space during inspiration and is unable to escape during expiration. This results in increasing pressure in the pleural space and thorax with complete collapse of the lung on the affected side. In addition, this increased intrathoracic pressure can put pressure on the other lung, rendering the patient unable to ventilate and causing decreased venous return into the thorax, which leads to hypotension and shock. Most individuals with pneumothorax will complain of sharp chest pain and dyspnea, and physical examination will reveal decreased breath sounds and hyperresonance (tympany) over the affected lung. Although small pneumothoraces will resolve spontaneously, most will require the placement of a chest tube (tube thoracostomy) to decompress the lung and allow for the pleural tear to heal.

Pleural Effusion

Fluid in the pleural space is called a pleural effusion. It most commonly results from a shift of fluid and blood components from nearby capillaries into the pleura. Pleural effusions can be one of five major types:

y Transudative watery fluid with few cells and little protein that is edema fluid from
increased pulmonary capillary hydrostatic pressure or decreased oncotic pressure. This type of effusion is managed by treating the underlying condition (e.g., heart failure or liver failure).

y Exudative inflammatory or malignant process resulting in breakdown of the capillary

barrier, allowing leakage of fluid, cells, and proteins into the pleural space. An exudative effusion is treated by addressing the underlying malignant or inflammatory condition, but also may require placement of a thoracostomy tube (commonly termed a "chest tube") to drain the fluid. y Empyema exudative pleural effusion that contains bacteria. This type of pleural effusion requires administration of antibiotics and placement of a thoracostomy tube to drain the fluid. y Hemothorax - blood in the pleural space, usually resulting from trauma. This almost always requires placement of a thoracostomy tube. y Chylothorax lymph fluid in the pleural space due to malignancy or trauma involving the thoracic duct. Most individuals with pleural effusion complain of dyspnea and chest pain. If there is infection, fever may also be present. Depending on its size, a pleural effusion can exert pressure on the lung, creating ventilation/perfusion mismatching and hypoxemia; it also can limit lung expansion and cause hypoventilation and hypercapnia. Diagnosis is made by chest X-ray and thoracentesis.

Pulmonary DisordersRestrictive Lung Disorders

Disorders that affect the lung itself can be divided into two pathophysiologic categories: restrictive lung disorders and obstructive lung disorders. These conditions almost always cause some mismatch and hypoxemia, and several can also cause decreased ventilation and hypercapnia. The fundamental difference between restrictive and obstructive lung disorders is that in lung restriction, there is decreased compliance of lung tissue which increases the work of breathing during inspiration. This can be quantified by using pulmonary function testing to measure a decrease in the forced vital capacity (FVC). In obstructive lung disorders, the primary problem is a decrease in the rate of expiration from the lungs causing hyperexpansion, which also increases the work of breathing. The amount of airway obstruction can be quantified by measuring the forced expiratory volume in one second (FEV1). In this section, we will focus on the restrictive lung disorders including aspiration, atelectasis, bronchiectasis, bronchiolitis, pulmonary fibrosis, pulmonary edema, and the acute respiratory distress syndrome.

Aspiration and Atelectasis

Aspiration is the passage of fluid and/or solid particles into the lung, usually due to abnormal swallowing or ineffective cough. Individuals receiving sedation or anesthesia and residents of longterm facilities are at greatest risk. Common causes are disorders that affect the central nervous system, neuromuscular diseases, structural defects in the esophagus and trachea, and nasogastric feeding. Aspiration of acidic gastrointestinal contents can lead to severe pulmonary inflammation and infection (aspiration pneumonia). Patient positioning, careful feeding, and oral care are important nursing interventions that can reduce the risk of aspiration. Atelectasis can be the result of compression of lung tissue by tumors or pleural disease, absorption of alveolar air trapped behind an endobronchial obstruction, or surfactant impairment. Absorption atelectasis is especially common in hospitalized patients whose breathing is shallow, such as those that are confined to bed rest, are in pain, or have muscle weakness. Deep breathing and coughing, incentive spirometry, and chest physical therapy all can help to prevent and treat atelectasis.

Bronchiectasis and Bronchiolitis

Bronchiectasis is a secondary pulmonary disorder in which there is abnormal dilation of the bronchi. It results from pulmonary lung diseases that cause persistent bronchial wall inflammation (for example, cystic fibrosis or infection). Bronchiectasis is also associated with systemic disorders such as rheumatologic diseases, inflammatory bowel diseases, and immunodeficiency syndromes. There are three forms: cylindrical (symmetrical bronchial dilation); saccular (balloon-like dilation); and varicose (bronchial constriction and dilation are both present). Clinical manifestations of bronchiectasis often begin in childhood, with frequent lower respiratory tract infections and high-volume purulent sputum production. Clubbing and hemoptysis are common. Pulmonary function tests show evidence of both restrictive and obstructive changes including decreased forced vital capacity (FVC) and decreased expiratory flow rates (FEV1). Increasing hypoxemia and corpulmonale develop as the disease advances. Treatment involves the use of antibiotics and possible surgical resection of affected portions of the lung. Bronchiolitis is a diffuse obstructive inflammatory disorder of the bronchioles. In childhood, the most common cause is respiratory syncytial virus (RSV), a relatively common illness. In adults, it is associated with chronic bronchitis secondary to smoking or inhalation of toxic gases. Pathophysiologic events involve bronchiolar inflammation and obstruction of the bronchioles distal to the inflammatory lesions. Bronchiolitis obliterans is a fibrotic process that occurs primarily after lung transplantation associated bronchiolitis. As this process progresses, alveoli and bronchioles become increasingly blocked by scar tissue causing bronchiolitis obliterans organizing pneumonia (BOOP). BOOP can also be associated with infections, radiation, and medications. Corticosteroids and immunosuppressive agents are used to slow the process. Clinical manifestations of bronchiolitis include tachypnea, use of accessory muscles, chest hyperinflation, and a low-grade fever with a non-productive (dry) cough.

Idiopathic Pulmonary Fibrosis

Pulmonary fibrosis is an excessive amount of fibrous or connective tissue in the lung (i.e., lung scarring). Almost any severe pulmonary inflammatory or autoimmune condition and many inhalational exposures can lead to pulmonary fibrosis; however, idiopathic pulmonary fibrosis (IPF) is most common. Fibrosis of the alveolar capillary membrane leads to decreased diffusion of oxygen and hypoxemia. Fibrosis also causes decreased lung compliance which restricts lung expansion and therefore increases the work of breathing. IPF is more common in men than in women and usually presents in the 5th and 6th decades of life. It develops relatively rapidly (6 months) or more slowly (over several years). Dyspnea on exertion is the most common complaint. Diagnosis is confirmed by high-resolution computed tomography or biopsy. Management includes supplemental oxygen and a trial of corticosteroids, but there is usually a gradual progression to respiratory failure.

Pulmonary Fibrosis and Exposure to Toxic Gases

Inhalation of several kinds of gases can cause inflammation and scarring of the lung. Industrial agents such as ammonia, hydrogen chloride, sulfur dioxide, and many others can injure the lung. Oxygen toxicity is a special form of inhalational injury. Oxygen toxicity is most often the result of mechanical ventilation or the use of hyperbaric oxygen as a treatment modality.

y Exposure to high concentrations of oxygen (fraction of inspired oxygen (FIO2) > 50%-75%)
for more than 24 hours has been associated with severe inflammation and scarring due to the production of toxic oxygen radicals in the pulmonary tissue. y These oxygen radicals contribute to alveolar permeability and the breakdown of surfactant.

Oxygen toxicity can also affect the central nervous system and the eyes, especially in infants. Avoidance of oxygen toxicity requires reduction in oxygen concentrations as soon as possible.

Pulmonary Fibrosis and Pneumoconiosis

The term pneumoconiosis is used to describe any fibrosing lung condition that results from inhalation of inorganic dust particles. The most prevalent causes are inhalation of sand or silica (silicosis), asbestos, or coal dust (coal worker's pneumoconiosis, or "black lung"). These inorganic particles lodge in the lung and cause acute and chronic inflammation with fibrosis of the lung. Diagnosis is made by history of exposure, chest X-ray, and lung biopsy. Pneumoconiosis is a chronic, progressive disease process, and treatment is usually supportive.

Pulmonary Fibrosis and Allergic Alveolitis

Allergic alveolitis (also called hypersensitivity pneumonitis) is inflammation of the lung due to inhalation of organic dusts such as grains, silage, bird droppings, wood, cork, and many other inhalants. This results in an allergic reaction in susceptible individuals with production of autoantibodies and inflammation. This disorder can be acute, with patients developing fever, cough, and dyspnea within hours of exposure, or it can be chronic, presenting with fibrosis and eventual pulmonary failure. Diagnosis is made by obtaining an exposure history, antibody testing, chest X-ray, and biopsy.

Systemic Causes of Pulmonary Fibrosis

Systemic disorders can affect any part of the respiratory system. Fibrosis, vasculitis, hemorrhage, and granuloma formation are common sequelae of systemic disorders that affect the lung. Most of these disorders are idiopathic and autoimmune in nature; for example, many of the collagen-vascular (rheumatologic) diseases can affect the lung (see Module 19). One of the more common systemic causes of pulmonary fibrosis is sarcoidosis. Sarcoidosis is an idiopathic disorder that is most common in blacks in the 2nd and 3rd decades of life. It is characterized by granulomatous inflammation (see Module 4) that can be followed by significant pulmonary fibrosis in approximately 10% of cases. Individuals with sarcoidosis present with dyspnea, cough, and atypical chest pain. The diagnosis is confirmed by chest X-ray, high-resolution computed tomography, and biopsy. Management is based on the stage of disease progression and includes corticosteroids and cytotoxic drugs.

Pulmonary Edema

Pulmonary edema is excess water in the interstitium and alveoli of the lungs. It is a common manifestation of a variety of pulmonary diseases and insults. Edema, no matter where it occurs in the body, results from:

y an increase in intravascular hydrostatic pressure (fluid pushes out of the vessel and into the
tissues);

y a decrease in intravascular oncotic or osmotic pressure (as in severe anemia or

hypoalbuminemia);

y increased capillary permeability; and/or y blockage of lymphatic vessels.

The relationship underlying the mechanisms above is referred to as Starling's relationship (click on Plasma-Interstitial Fluid Exchange for a more detailed discussion). In the lungs, pulmonary edema can result from any of these four mechanisms, but it is usually caused by increased intravascular hydrostatic pressure due to left ventricular heart failure (see Module 15: Alterations of Cardiovascular Function). When the left ventricle fails, pressure builds up in the ventricle and is then reflected back to the left atrium. Pulmonary capillaries and water are then pushed from the capillaries into the alveoli. This is referred to as cardiogenic pulmonary edema. Another important cause of pulmonary edema is inflammation of the alveolar-capillary barrier, which causes water to leak from the capillary into the lung. This is called noncardiogenic pulmonary edema and is also known as acute respiratory distress syndrome (ARDS). ARDS is discussed later in this module. Pulmonary edema causes mismatch with resultant hypoxemia. Patients with this condition present with tachypnea, tachycardia, inspiratory crackles, and dullness to percussion over the lung bases. Evidence of underlying heart disease or pulmonary insult also may be evident. Treatment depends on the cause of the pulmonary edema, but supportive therapy usually includes oxygen administration.

Acute Respiratory Distress Syndrome (ARDS)

Almost a quarter of a million people in the United States develop ARDS each year. It is one of the most frequent and difficult syndromes encountered in intensive care. By far the most common causes of ARDS are sepsis and multiple trauma, although many other systemic insults have been associated with this syndrome. ARDS is a severe form of acute lung injury (ALI). These two terms are defined as: Acute lung injury (ALI) a syndrome of acute and persistent lung inflammation with increased vascular permeability. ALI is characterized by three clinical features:

y Bilateral radiographic infiltrates y A ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2/FiO2)
between 201 and 300 mm Hg, regardless of the level of positive end-expiratory pressure (PEEP) y No clinical evidence for an elevated left atrial pressure; if measured, the pulmonary capillary wedge pressure is 18 mm Hg or less. Acute respiratory distress syndrome (ARDS) The definition of ARDS is the same as acute lung injury, except that the hypoxia is worse, requiring a PaO2/FiO2 ratio of 200 mm Hg or less, regardless of the level of PEEP.

Algorithm: Pathophysiology of ARDS

As can be seen from the algorithm in Figure 33-8 of your textbook, the pathophysiology of ARDS is very complicated. In summary, an insult to the body that results in the systemic release of high levels of inflammatory cytokines (especially tumor necrosis factor alpha [TNF-alpha], interleukin 1 [IL-1], and platelet activating factor [PAF]) can result in breakdown of the alveolar-capillary barrier with flooding of the alveoli with proteinaceous fluid and cells. This is complicated by loss of surfactant, causing atelectasis, and by clotting and vasoconstriction of the alveolar capillaries. The resultant mismatch is usually very severe, and the associated hypoxemia is refractory (non-responsive) to the administration of supplemental oxygen. As the lungs become stiffer with fluid and atelectasis (decreasing lung compliance), hypoventilation and hypercapnia follow.

Management of ARDS

Patients frequently present with the symptoms of the original insult, followed in 24-48 hours by increasing dyspnea. This may progress to complete respiratory failure and death. Treatment is largely supportive and usually requires mechanical ventilation with positive end expiratory pressure (PEEP), which may cause its own set of complications, such as infection and hemodynamic instability. The administration of activated protein C and lowdose steroids to selected ARDS patients has shown positive results.Pulmonary DisordersObstructive Pulmonary Disease

Obstructive lung diseases are characterized by airway obstruction that is worse with expiration. There are two major problems associated with airway obstruction:

y Airway obstruction leads to uneven ventilation of alveoli, causing

mismatch and hypoxemia. y Expiratory airway obstruction requires that expiration either be more forceful (increased work of breathing with use of the accessory muscles) or more prolonged. Individuals with expiratory airway obstruction trap air in the lungs, causing a gradual increase in lung size (hyperexpansion), which stretches the chest wall and puts the respiratory muscles at a mechanical disadvantage. This increases the work of breathing and leads to a decrease in tidal volume which can result in hypercapnia.

The most common symptom for all obstructive diseases is dyspnea, and the most common physical sign is wheezing that is worse with expiration. Pulmonary function testing reveals a decrease in peak flow (PF) and a decrease in forced expiratory volume in one second (FEV1). The major obstructive lung diseases in adults are asthma and chronic obstructive pulmonary disease (COPD).

Animations: Expiratory Airflow Obstruction

Understanding the process of normalinspiration and expiration is important as you prepare to learn how airway obstruction interferes with this process. During inspiration, the lungs expand, and airways are stretched open. During normal expiration, the airways decrease in size but remain patent due to the lack of significant mucus accumulation and the elasticity of bronchial walls in healthy lungs. Listen to the auscultatory sounds of inspiration and expiration. In obstructive lung diseases, the inspiratory stretch of the bronchi allows air to enter the alveoli, but bronchial obstruction occurs during expiration due to mucus accumulation and/or loss of the normal elasticity of the airways with resultant expiratory bronchial collapse. Air becomes trapped in the alveoli, and expiration must be more forceful and prolonged.

Definition of Asthma

The National Asthma Education and Prevention Program (NAEPP) of the National Heart, Lung, and Blood Institute of the National Institutes of Health definesasthma as: "A chronic disorder of the airways that involves a complex interaction of airway obstruction, bronchial hyperresponsiveness, and an underlying inflammation." The definition also includes the following information: "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, sub-basement fibrosis may occur in some patients with asthma and those changes contribute to persistent abnormalities in "lung function." Asthma has a complex pathophysiology that combines the effects of allergy (type I hypersensitivity) and obstructive airway disease. (See Module 06: Alterations in Immunity and Inflammation.) Asthma occurs in individuals with a genetic predisposition to respond immunologically to certain environmental antigens (allergens) so that high levels of IL-4 and IgE are produced. More than 100 gene polymorphisms have been associated with an increased risk for asthma and allergy. Furthermore, environmental exposure to allergens, pollutants, and certain airway infections can increase the risk of asthma. It has been postulated that children who have high allergen exposure and little exposure to common childhood infections are at greater risk for asthma because they tend to produce more of the immune cytokines (interleukins) that stimulate the production of IgE antibodies (called the Hygiene Hypothesis).

Algorithm: Asthma's Effects on Respiration

As was seen in the allergy animation, asthma causes two kinds of problems for respiratory function.

y First, airway narrowing and mucus production result in uneven ventilation, which results in
mismatch and hypoxemia. Individuals will frequently complain of dyspnea and chest tightness, and will often be mildly hypoxemic. y Second, as the airway obstruction worsens, it results in expiratory airway obstruction that is greater than inspiratory obstruction, which means that it is harder to get air out than in. Air is trapped in the lungs, which causes hyperexpansion of the chest, putting the respiratory muscles at a mechanical disadvantage and causing increased work of breathing. As air trapping progresses, tidal volume begins to fall until increasing respiratory rate can no longer compensate, and minute ventilation begins to fall. When this happens, hypoventilation

causes hypercapnia and respiratory acidosis. Respiratory acidosis is an ominous sign in asthma patients and may indicate impending respiratory failure. In addition, persistent airway inflammation that results from inadequately treated asthma can lead to airway scarring and fibrosis that becomes irreversible over time. History: Physical Exam: Positive for allergies such as hay fever, family history of allergies/asthma, wheezing or coughing, exercise limitation, episodic dyspnea, or chest tightness 1. Normal pulmonary assessment between episodes 2. With episodes: o Tripod positioning (see image) o Use of accessory muscles o Tachypnea, tachycardia o Expiratory wheezing/prolonged expiratory phase o Increased pulsusparadoxus

Laboratory:

1. Decreased peak flow and FEV1 on pulmonary function testing during acute attacks which improve with bronchodilator treatment 2. Sputum eosinophilia

Asthma Classification
In 2007, the National Heart, Lung, and Blood Institute and the National Asthma Education and Prevention Program reclassified asthma according to its severity. This classification scheme allows the clinician to provide "stepwise" therapyin other words, the types and amounts of medication and other management interventions that can be introduced to patients in direct relationship to the severity of their illness. It also allows the clinician to better assess the success of treatment in achieving asthma control for a given individual. A necessary feature of the classification scheme and its use in the clinical setting is:

y A careful history of the patient's symptoms and y The ability of both the provider and the patient to objectively measure airway obstruction

using pulmonary function testing with monitoring of the forced expiratory airway volume in one second (FEV1) and measurement of peak flow.

Management of Asthma

The basics of asthma management include: Patient education

y Patients and their families need to understand the risks and allergen exposures for their
asthma and how to prevent and manage attacks.

y An asthma "Action Plan" allows patients and families to objectively assess the severity of an
asthma attack and respond appropriately. Evaluation and care planning

y Individuals with asthma need comprehensive evaluation and care planning by a team of health
professionals.

y Periodic peak flow measurements can help monitor for response to treatments y Allergy testing and avoidance of allergens and triggers are key to decreasing the severity of
asthma symptoms and preventing both acute and chronic complications Drug therapy

y Anti-inflammatory drugs (usually inhaled steroids or leukotriene inhibitors) y Bronchodilators (inhaled long- and short-acting beta agonists) y Other drugs, including cromolyn sodium, ipratropium, and oral steroids (oral steroids only as a
last resort)

y Anti-IgE antibodies (omalizumab) y

Chronic Obstructive Pulmonary Disease (COPD)

y y

Chronic obstructive pulmonary disease (COPD) has been defined as the pathologic lung changes consistent with emphysema or chronic bronchitis. The Global Initiative for Chronic Obstructive Lung Disease (GOLD defines COPD 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." COPD is the fourth leading cause of death in the United States and is the sixth leading cause of death worldwide. COPD is primarily caused by cigarette smoke and both active and passive smoking have been implicated. Other risks include occupational exposures, indoor and outdoor air pollution, and history of severe childhood respiratory infections. Genetic susceptibilities have been identified including polymorphisms of genes that code for tumor necrosis factor, surfactant, proteases, and anti-proteases. An inherited mutation in the alpha-1 anti-trypsin gene results in the development of COPD at an early age, even in nonsmokers. COPD is characterized by expiratory airway obstruction. Patients frequently present with dyspnea, cough, and wheezing. On pulmonary function testing, FEV1 is reduced and does not respond significantly to bronchodilator therapy.

COPD Pathophysiology of Chronic Bronchitis

Chronic bronchitis results from inhalation of irritants that cause inflammation and hyperplasia of the mucus-producing goblet cells of the bronchial epithelium. Large amounts of mucus in the airways facilitate the colonization and growth of bacteria, which further contributes to airway inflammation, bronchospasm, and eventual scarring. Narrowed airways cause mismatching and expiratory airway obstruction with air trapping. Individuals with chronic bronchitis cough up large amounts of sputum and suffer from both hypoxemia and hypercapnia. The chronic bronchitis pathophysiologic sequence of events is as follows: 1. 2. 3. 4. Hypersecretion of bronchial mucus, which leads to Recurrent respiratory infections, which lead to Airway inflammation, which leads to Bronchospasm and irreversible airway obstruction.

COPDPathophysiology of Emphysema

Emphysema results from inhalation of irritants that cause an imbalance between lung proteases (break down lung tissue, e.g., elastin) and antiproteases (preserve lung tissue, e.g., alpha1antitrypsin) so that the alveoli and bronchial walls are destroyed. Alveolar destruction causes decreased surface area for gas exchange leading to hypoxemia. Alveolar destruction causes decreased surface area for gas exchange leading to hypoxemia. Bronchial wall damage leads to expiratory airway collapse, air trapping, hypoventilation, and hypercapnia. The following algorithm will take you through the steps of the pathophysiology of chronic bronchitis and emphysema.

COPDAlpha1-Antitrypsin Deficiency

Primary emphysema refers to the 1% to 3% of cases of emphysema linked to an inherited deficiency of the enzyme 1-antitirypsin. This enzyme is essential for balancing the effects of the protease enzymes in the lung; thus, when deficient, alveolar and bronchial wall destruction develops. Individuals homozygous for this autosomal recessive trait have a 70% to 80% likelihood of developing emphysema even if they do not smoke, often before the age of 40. In addition to emphysema, in some individuals this disorder affects the liver, causing cirrhosis and an increased risk for cancer. At one time, 1-antitirypsin deficiency was considered untreatable and had a very poor prognosis. Now however, purified human 1-antitrypsin can be given intravenously to stop the progression of disease, and lung transplantation may be an option for those in whom the disease has already progressed to respiratory failure.

COPDClinical Manifestations of Chronic Bronchitis and Emphysema

When comparing and contrasting the clinical presentations of individuals with chronic obstructive pulmonary disease (COPD), those who primarily have chronic bronchitis have different historical and physical findings than those who primarily have emphysema. Chronic Bronchitis History Productive cough of purulent sputum present on most days, progressive dyspnea, recurrent infections Prolonged expiratory phase, wheezing, edema Emphysema Cough only in morning, often of scant white sputum, progressive dyspnea, weight loss Barrel chest, thin body habitus, prolonged expiratory phase

Physical Exam

Diagnosis and Classification of COPD

Diagnosis The history and physical exam, as discussed in the previous screen, can suggest the diagnosis of COPD in a smoker; however, further evaluation is needed. Spirometry, which assesses airway obstruction (forced expiratory volume in one second, or FEV1) and lung expansion (forced vital capacity, or FVC), is the primary way of confirming the diagnosis of COPD and for classifying COPD severity. In COPD, FEV1 is decreased and is not improved significantly with the use of bronchodilators. Chest X-ray, sputum samples, and computed tomography may also be used in evaluating suspected COPD. Classification The GOLD program (Global Initiative for Chronic Obstructive Lung Disease) provides a classification system for severity of COPD that is based on spirometric values (FEV1 and FVC) and associated symptoms (e.g., cough, dyspnea, sputum). Such a classification system is helpful in planning stepwise therapy.

Management of COPD
The use of bronchodilators (e.g., ipratropium, beta agonists) is central to the management of the symptoms of COPD, but without other interventions, such as smoking cessation, the disease will progress until the patient develops respiratory failure. Treatment steps are based on severity of disease. New therapies are emerging and are discussed in your textbook. Other modalities beyond drugs are necessary to enhance the lifestyle of the patient. Patient education

y Smoking cessation
Evaluation of disease progression and response to therapy

y Pulmonary function testing

Drug and oxygen therapy

y Bronchodilators as needed (e.g., ipratropium, beta agonists) y Prompt treatment of infections y Oxygen for severe hypoxemia
Supportive treatments

y Pulmonary rehabilitation exercises y Nutritional support y y

Respiratory Tract Infections

Upper airway respiratory tract infections, like the common cold, are usually short-term disabilities. However, lower respiratory tract infections, such as pneumonia, are associated with increased morbidity and mortality. Lower respiratory tract infections can be caused by bacteria (including tuberculosis), viruses, and opportunistic organisms (such as fungi and parasites).

Pneumonia

Pneumonia is one of the most common diseases in the world. It continues to be a leading cause of death even in industrialized nations. Risk factors for pneumonia are those that compromise the normal respiratory defense mechanisms and include:

y y y y y y y y

Extremes of age Smoking Immunocompromise Alcoholism Altered consciousness Malnutrition Mechanical ventilation Immobilization

These risk factors are common to hospitalized patients, so pneumonia can not only cause hospitalization, it can also be a complication of hospitalization for other reasons.

Pneumonia Classification

Pneumonia can be classified by where it is acquired and by the immune status of the individual. These categories allow the healthcare provider to better predict the likely causative organisms. The major categories of pneumonia are:

y Community acquired pneumonia (CAP) most commonly caused by viruses (e.g.,

influenza) or by bacteria (e.g., Streptococcus pneumoniae, Mycoplasma pneumoniae).

y Nosocomial if a hospitalized patient contracts pneumonia (nosocomial infection), it is often

with a dangerous organism that is difficult to treat (e.g., Pseudomonas aeruginosa).

y Immunocompromised individuals individuals with human immunodeficiency virus (HIV)

infection, those on chemotherapy, and those on chronic immunosuppressive medications, such as prednisone, are at risk for opportunistic infections. Opportunistic infections are caused by organisms that do not normally cause disease in healthy individuals, but can become pathogenic in those who lack normal immune defense mechanisms. Important causes of opportunistic pneumonia are the fungus Pneumoncystisjiroveci and cytomegalovirus.

Algorithm: Pathophysiology of Pneumococcal Pneumonia

Now that you have completed the textbook reading on pneumonia, let's focus on the pathophysiology of pneumonia caused by the most common etiologic bacteria of CAP, the pneumococcus. Streptococcus pneumoniae is a gram-positive diplococcus that is encapsulated (see Module 7). The capsules resists phagocytosis until it can be opsonized by complement and antibodies (see Modules 4 and 5). This allows the organism to evade the body's early defenses and multiply until there are

enough bacteria in the lower respiratory tract to overwhelm the initial responses of the alveolar macrophages. Thus individuals with pneumococcal pneumonia frequently become quite ill and the mortality of this disease is quite high, especially in the elderly and in those who are immunocompromised. View the Pathophysiology of Pneumococcal Pneumonia Algorithm. As you view the algorithm, take careful note of each stage: 1. Organisms enter the respiratory tract, most commonly due to failure of normal upper airway defense mechanisms, by aspiration of infected oral secretions. 2. These organisms overwhelm the alveolar macrophages and set off an intense immunologic and inflammatory response. 3. Inflammatory cytokines, white blood cells, and edema fluid flood the alveoli and bronchi. 4. Ventilation/perfusion ( ) mismatching occurs, with resultant hypoxemia. 5. The infection may spread to the bloodstream (bacteremia and sepsis), pleura (empyema), or other organs (e.g., meningitis).

6. Viral Pneumonia

7. 8. Viruses cause many cases of community acquired pneumonia, and most of these are mild and self limited. However, immunocompromised individuals can become seriously ill even with common viral pathogens and are at risk for acquiring opportunistic viral pathogens, such as cytomegalovirus, that can be deadly. 9. Some viruses are capable of causing serious illness and pneumonia even in healthy immunocompetent individuals. The most important group of these viruses is the influenza viruses. Seasonal influenza causes serious illness in thousands of individuals in the United States each year. Most of these viruses are categorized as influenza A or B, but there are many subcategories of influenza organisms. In 2009, the H1N1 virus spread across the U.S. resulting in a public health emergency. A vaccine to prevent even more widespread morbidity and mortality is being developed.

10.

Emerging Viral Infections that Cause Pneumonia

11. 12. In 2009, the H1N1 influenza virus spread across the U.S. and the world, resulting in a public health emergency. This virus caused many deaths, especially in Mexico, but appears to cause less morbidity as it spreads throughout the world. A vaccine to prevent even more

widespread morbidity and mortality is being developed, and currently available antivirals are effective in treating the disease if given early. 13. Another severe influenza infection is caused by the H5N1 influenza virus which causes avian influenza. Also called "bird flu," this flu infects both wild and domestic birds. Currently, the virus is transmitted to humans only upon close contact with infected birds. This form of influenza causes severe respiratory illness and carries a significant mortality risk. There is great concern that the virus will mutate to a form that can be easily transmitted from person to person. Fears of a pandemic have sparked worldwide efforts to control the spread of the virus in the bird population. 14. Yet another emerging viral infection is the coronavirus that causes the severe acute respiratory distress syndrome (SARS). First reported in China, the infection appears to be spread by close contact with infected individuals by inhalation of droplet nuclei containing the organism or by contact with infected body fluids. Many cases have occurred in healthcare workers who did not take adequate infection control and isolation precautions. Fortunately SARS has not yet spread into a serious pandemic because it has a very high mortality and does not respond well to antiviral medication.

Activity: Clinical Manifestations and Treatment of Pneumonia

The clinical manifestations and treatment of pneumonia depend on the underlying health of the individual and the causative organism. Clinical manifestations

y Fever, cough, and dyspnea are common to most types of pneumonia. y Physical examination may reveal fine crackles with associated egophony and increased tactile
fremitus (consistent with pulmonary consolidation). Evaluation

y Blood work may reveal a leukocytosis with an increase in neutrophils in bacterial pneumonia,
and an increase in lymphocytes in viral pneumonia.

y Chest X-ray will reveal lobar consolidation in most bacterial pneumonias, while an interstitial
pattern is common in viral pneumonia.

y Sputum Gram stain may reveal numerous neutrophils and bacteria or may be nonspecific.
Sputum and blood cultures can help confirm the diagnosis.

Treatment

y Patients should be placed on isolation precautions until the causative organism can be
identified.

y Bacterial pneumonia is treated with antibiotics; severe cases of influenza are treated with
antivirals.

y Other important interventions include hydration, deep breathing and cough, and, in some
cases, chest physical therapy.

Tuberculosis

y y

Tuberculosis (TB) is one of the most common serious infections in the world. In the United States, tuberculosis usually occurs in patients who are immunocompromised (e.g., someone with AIDS). Mycobacterium tuberculosis is transmitted through the inhalation of droplet nuclei containing the microorganism. This form of transmission means that TB is highly contagious, and close contacts of individuals with active TB are at high risk for becoming infected. The droplet nuclei travel easily down the bronchial tree and are eventually phagocytosed by alveolar macrophages. The macrophages release a large number of inflammatory and chemotactic cytokines that result in the formation of a protective shell of phagocytes around the organism called a granuloma (tubercle). In an immunocompetent individual, this results in the organism being walled off from the rest of the body, and the tuberculosis is considered "latent." Individuals who are immunocompromised (e.g., individuals with AIDS, chemotherapy recipients, infants, and uncontrolled diabetics) may develop active TB either on initial contact with the organism or through reactivation of a previously latent infection. This results in the spreading of the organism throughout the lungs, and often to extrapulmonary sites such as bone and the genitourinary tract.

Clinical Manifestations, Evaluation, and Treatment of TB

Clinical Manifestations

y Latent infection with TB is asymptomatic and requires laboratory testing to detect.

Individuals with latent TB are at risk for reactivation TB if their immune systems become compromised, so they are treated with antituberculous drugs over a course of several months. y Active infection is associated with common symptoms of fever, night sweats, dyspnea, productive cough (sometimes with hemoptysis), and weight loss. It has a significant morbidity and mortality and must be treated promptly. Evaluation

y The individual should be isolated as soon as active TB is suspected. y The most commonly used test to diagnose tuberculosis is the purified protein derivative, or
PPD. The PPD does not differentiate between active or latent TB and is also positive in

individuals who have never had TB but who have been previously vaccinated with bacilleCalmette-Guerin (BCG). y Chest X-ray and sputum stains (Ziehl-Neelsen) and cultures are used to document active infection. y Immunoassays such as the enzyme-linked immunospot are sensitive and specific for both latent and active TB and do not provide false positives for TB in those who have had BCG vaccination. Treatment Tuberculosis is very difficult to treat, and the choice of therapy and duration of treatment depend on the individual case. Isolation should be continued for up to 2 months of therapy until the sputum cultures become negative. Treatment often requires as many as four different types of antituberculous drugs in order to treat the disease quickly and effectively and to avoid drug resistance. Common antituberculous drugs used for active infection include isoniazid, rifampicin, rifapentine, pyrazinamide, streptomycin, and ethambutol. Individuals who have been exposed to active TB must be evaluated and may need prophylactic treatment to prevent infection.

Atypical Pneumonias
Although bacterial pneumonias like those caused by Streptococcus pneumoniae and tuberculosis and those caused by viruses are common, a significant number of pneumonias are caused by atypical organisms. Immunocompromised individuals are at risk for opportunistic infections. Atypical pneumonias are commonly acquired in the community and include those caused by Mycoplasma pneumoniae and Chlamydia pneumoniae. These infections often cause a dry cough and an interstitial pattern on chest X-ray. They generally respond well to antibiotics. Opportunistic infections that can cause pneumonia in immunocompromised individuals include fungi (e.g. Pneumocystis jiroveci), viruses (e.g., cytomegalovirus), protozoa, and parasites. These kinds of infections can be very serious and have high mortality rates. Abscesses involving the lung are circumscribed cavities filled with pus. This usually occurs after pneumonia, especially involving destructive organisms such as Klebsiella or Staphylococcus organisms.

y Clinical manifestations Individuals present with high fever, cough, pleural pain, and may
produce purulent sputum.

y Treatment Antibiotics and postural drainage may be adequate, but in some cases
bronchoscopic or surgical drainage is required.

Acute Bronchitis
Acute bronchitis is infection or inflammation of the bronchi. In most individuals this is a self-limiting disorder caused by viruses. Clinical manifestations include either a dry cough or, in the case of some bacterial infections, cough productive of discolored sputum.

Unlike pneumonia, most individuals with acute bronchitis will not have high fevers and will have only scattered coarse wheezes on examination without evidence of pulmonary consolidation. Chest X-ray is usually normal.

Pulmonary Vascular Disease

y y

Pulmonary vascular diseases can be acute (e.g., pulmonary embolus, acute pulmonary hypertension) or chronic (e.g., chronic pulmonary hypertension, corpulmonale) and may be life-threatening.

Pulmonary Embolism

y y

There are three categories of pathologic risks for thrombus formation (Virchow triad), including venous stasis (e.g., immobility, prolonged bed rest); hypercoagulability (e.g., coagulation disorders, oral contraceptive use, malignancy); and endothelial cell injury (e.g., vascular trauma, recent surgery). These thrombi usually form in the leg and are called deep venous thrombosis. When a portion of a clot from a leg DVT travels through the systemic venous circulation, it goes through the right heart and lodges in the pulmonary arterial circulation. This causes a sudden blockage of flow into the affected portion of the lungs with immediate mismatch, hypoxemia, and increased pulmonary artery pressures. If the embolus is small, collateral circulation from the bronchial arteries may prevent lung infarction. However, many pulmonary emboli are large enough to cause at least some infarction of lung tissue with associated hypoxic vasoconstriction, atelectasis, and loss of functional lung tissue. Large emboli with blockage of significant pulmonary artery flow can result in pulmonary hypertension, right heart failure, shock, and death.

Clinical Manifestations, Diagnosis, and Management of Pulmonary Embolism

The clinical manifestations of pulmonary embolism (PE) can resemble many other pulmonary conditions. Thus the clinician must have a high index of suspicion in patients who have risk factors for thrombosis. The classic symptoms of sudden dyspnea, pleuritic chest pain, and hemoptysis do not occur in all patients. DVT is often asymptomatic and difficult to document on physical examination, making the recognition of PE even more difficult. Diagnostic tests for PE include serum D-dimer levels (elevated), chest X-ray (atelectasis or infarcts), and helical computed tomography (helical CT). Some medical centers continue to use ventilation perfusion ( ) scanning, although it is less sensitive and less specific than helical CT.

Management includes initiation of anticoagulant therapy with thrombolytics or heparin. Long-term anticoagulation with warfarin is usually indicated, and every attempt should be made to reverse the underlying risk factors that led to the development of the DVT and associated PE. In patients who cannot receive anticoagulation, placement of a venous filter may be indicated.

Hypoxic Pulmonary Vasoconstriction, Pulmonary Hypertension, and CorPulmonale

Pulmonary hypertension is simply defined as a sustained mean pulmonary artery pressure above 20 mm Hg.

y Primary pulmonary hypertension (PAH) is a rare idiopathic disorder involving the

precapillary pulmonary arterioles. Decreased endogenous vasodilators, increased vasoconstrictors, and vascular remodeling combine to cause vasoconstriction and fibrotic changes in the vessel walls. y Secondary pulmonary hypertension results from direct damage to pulmonary vessels by inflammatory or immune disorders, or more commonly from hypoxic pulmonary vasoconstriction. In either case, narrowing of the vessels increases resistance to pulmonary artery inflow to the lungs; thus pulmonary artery pressures rise, creating significant afterload to the right ventricle. This results in right ventricular hypertrophy that usually progresses to right heart failure, which is called corpulmonale. Pressures then back up into the systemic venous circulation. Most instances of pulmonary hypertension and corpulmonale are secondary due to severe diffuse pulmonary parenchymal diseases that result in significant hypoxic vasoconstriction and marked increases in pulmonary artery pressure. The following animation will help you understand the pathophysiology of secondary pulmonary hypertension and corpulmonale that results from hypoxic pulmonary vasoconstriction.

Clinical Manifestations and Treatment of Pulmonary Hypertension and CorPulmonale

The primary clinical manifestations of corpulmonale are those of the underlying lung disease (e.g., dyspnea, cough, crackles, etc.), plus evidence of right heart failure with possible right ventricular heave, jugular venous distension, loud second heart sound, and peripheral edema. Treatment for PAH is challenging and includes oxygen, diuretics, anticoagulants, and vasodilators such as prostacyclin analogs, endothelin blockers, and nitric oxide. Lung transplantation may become necessary. Treatment of secondary pulmonary hypertension and corpulmonale relies on the administration of supplemental oxygen while working to improve the underlying lung disease.

Malignancies of the Respiratory Tract

Malignancies of the respiratory tract are some of the most common and deadly cancers. The three major cancers discussed in this section are lip cancer, laryngeal cancer, and lung cancer. To help you to understand the pathophysiology of cancer, review the carcinogenesis steps discussed in Module 08: Biology of Cancer.

Lip Cancer

Cancer of the lip is not a common cancer, but can have devastating effects on individuals because of its cosmetic effects and its potential to cause more serious disease if left untreated. Lip cancer is related to smoking and sun exposure and is usually of the squamous cell type. Metastases only occur if the primary tumor is left untreated for a long time. Treatment is surgical excision.

Laryngeal Cancer

Cancer of the larynx is most associated with the combination of smoking and drinking alcohol. It is also associated with human papillomavirus (HPV) infection. Squamous cell carcinoma can affect the vocal cords and surrounding structures, causing hoarseness and cough. Diagnosis is made by laryngoscopy with biopsy. Treatment is surgical or radiation therapy. Laryngectomy results in loss of voice, so efforts to preserve voice function are ongoing.

Lung Cancer

Lung cancer is the number one cancer killer in the world. In the U.S. there are over 200,000 cases and over 150,000 deaths annually from lung cancer. Although antismoking efforts have led to a levelling off of cancer death rates for men, it is still rising in women, and the overall 5-year survival once cancer is diagnosed is less than 20%. The primary risk factor for lung cancer is smoking. Radiation, air pollution, and some chemicals also contribute to cancer risk. Lung cancer develops when there is chronic irritation and inflammation of the bronchial mucosa.

The majority of lung cancers arise from the bronchial tissues and are caused by the carcinogenic properties of smoking. The process of inhaling tobacco and its associated chemicals into the lungs, and then exhaling those same products, allows for extensive contact with the bronchial passages.

y Every time cigarette smoke is inhaled, the delicate tissues of the bronchial passages are
irritated. Increasing irritation eventually triggers a change in cellular appearance.

y The most common respiratory tissues affected by smoking are the bronchial epithelial cells.
These are the cells that are exposed most frequently to the carcinogenic properties of smoke. y As the smoke continues to irritate the bronchial cells, they begin to structurally change from one cell type to another. This change is referred to as squamous metaplasia. o Metaplastic cells grow at a faster rate than normal cells. o Their size and shape become abnormal, and some of the metaplastic cells may have no nucleus. o At this early stage, if the person quits smoking, the bronchial cell changes are considered reversible and can regain normal structure. o However, if the person continues to smoke, the metaplastic cells can continue to alter and progress to anaplastic cells, or squamous cell carcinoma.

Types of Lung Cancer

Lung cancer is divided into two major categories: nonsmall cell carcinoma and small cell carcinoma. Nonsmall cell carcinoma can be further classified into:

Adenocarcinoma anaplasia of the ciliated and mucous cells that have a tendency to form irregular glands, hence the term adenocarcinoma. The prefix "aden(o)" refers to gland. This is the most common form of lung cancer and is caused most often by smoking; it tends to occur peripherally in the lung, which can result in pleural and thoracic wall involvement. The category of adenocarcinoma also includes a more rare form of lung cancer called bronchoalveolar carcinoma. Squamous cell carcinoma anaplasia of respiratory squamous epithelial cells. This tumor tends to occur centrally in the lung and cause blockage of bronchi. It is a slow-growing tumor that is late to metastasize but can be associated with metastases to the bone. Large cell carcinoma (undifferentiated) this is a poorly differentiated, highly anaplastic and aggressive tumor that grows rapidly and metastasizes early.

Small cell carcinoma is anaplasia of the neuroendocrine cells and is very aggressive and has a poor prognosis. It is frequently associated with the production of hormones. It has already metastasized widely in the body (bone marrow, brain, adrenal glands) in the majority of individuals by the time the diagnosis is made, and treatment is usually palliative rather than curative.

Lung Cancer Metastases

A major complication of lung cancer is that by the time it is diagnosed, a very high percentage of patients already have obvious metastases. Metastases occur when malignant cells from the cancerous organ travel to other sites in the body. Frequently, this occurs via the bloodstream or the lymph system, or by nearby organ transference. The photo above shows a tumor on a pleural surface. The location and number of metastases determines stage of the tumor and how it will be managed. Lung cancer has specific sites in the body to which it generally metastasizes. Complete the activity below to review the organs to which lung cancer most likely metastasizes.

Clinical Manifestations of Lung Cancer

The clinical manifestations of lung cancer are related to the location of the tumor, the type of tumor, and the stage of tumor growth and/or metastasis.

y Thoracic symptoms and signs are related to the tumor obstructing bronchi or impinging on

other thoracic structures like the heart, pleura, and chest wall. These manifestations frequently include dyspnea, cough, hoarseness, hemoptysis, and pleuritic chest pain. y Metastases from lung cancers can go anywhere in the body, but common sites include lymph nodes, bone, and brain. Thus symptoms and signs may include swelling of lymph nodes, bone pain, or neurologic deficits and seizures. y Paraneoplastic syndromes occur when some lung cancers secrete hormones that can cause symptoms of excess hormone production. When there are tumor-derived hormonal derangements, their manifestations are called paraneoplastic syndromes. Squamous cell cancers can secrete a parathyroid-like hormone that can cause bone damage and hypercalcemia. Small cell cancers arise from neuroendocrine cells and can cause several hormonal changes, most commonly the secretion of excess adrenocorticotropic hormone (Cushing syndrome).

Diagnosis and Management of Lung Cancer

y y y

Diagnosis Lung cancer is most commonly diagnosed by finding a mass on chest X-ray. Computed tomography (CT scan) and magnetic resonance imaging (MRI) provide more sensitive and specific evaluations of a pulmonary mass. Sputum may reveal abnormal cells when tested for

y y

y y

cytology. Bronchoscopy can be used to obtain secretions or tissue biopsies that may contain malignant cells. These cells can be used to confirm a preliminary diagnosis. Biopsies may also be performed using fine-needle aspiration or surgical excisions. Staging Lung cancer is staged in order to help choose the appropriate therapy. Nonsmall cell lung carcinoma is staged using the TNM (for Tumor Nodes Metastasis) system. This system combines the tumor size with the presence or absence of nodal involvement and metastases to help determine which therapy might result in the best outcome. Small cell carcinoma has usually metastasized by the time of diagnosis, so it is categorized simply as limited vs. extensive disease. In all patients, an extensive work-up is required to determine if metastasis has occurred. Treatment The primary treatment modality for the cure of lung cancer is complete surgical removal. For many individuals, however, the diagnosis is not made until the tumor is too advanced to allow for complete removal. Adjunctive chemotherapy and radiation are commonly used and may also be used along with bronchoscopic techniques for palliative care.