1 What are the most important diseases of the respiratory system?

Collapse of the alveoli (atelectasis) and pneumothorax

Circulatory disturbances, such as pulmonary edema and chronic passive congestion, and adult respiratory distress syndrome

Infections such as rhinitis, laryngitis, bronchitis, and pneumonia

Immunologically mediated diseases, such as asthma

Environmentally induced diseases, such as pneumoconioses, asbestosis, and silicosis

Tumors

2 Define atelectasis

Atelectasis refers to incomplete expansion of the lungs or the collapse of previously inflated lung substance (Fig. 10-1). It is a pathologic condition that produces areas of relatively airless pulmonary parenchyma. Severe atelectasis significantly reduces oxygenation and predisposes to infection. Acquired atelectasis is generally encountered in adults and may be divided into the following categories:

Obstruction (or resorption) atelectasis

Compression atelectasis

Patchy atelectasis

Contraction atelectasis

Figure 10-1 Atelectasis. Four types of atelectasis are illustrated. Left to right: Obstruction atelectasis involves parts of the lung distal to an obstructed bronchus. Compression atelectasis usually involves the entire lung. The pleural space is filled with fluid compressing the lung, which has retracted toward the hilus. Similar findings can be produced by pneumothorax, except in this case the lung collapses because of entry of air into the pleural space. Patchy atelectasis involves small segments of all lobes. Airless patches of lung parenchyma, which have collapsed because of a deficiency of surfactant, are distributed irregularly and usually are found in both lungs. Contraction atelectasis usually occurs in subpleural areas and is typically caused by interstitial fibrosis, which prevents the expansion of the parenchyma.

Atelectasis is a reversible disorder (except that caused by contraction).

3 What are the main characteristics of obstruction atelectasis?

Obstruction (or resorption) atelectasis results from complete obstruction of an airway and, in time, it causes resorption of the oxygen trapped in the dependent alveoli.

The mediastinum may shift toward the atelectatic lung.

It is most often found in bronchial asthma, chronic bronchitis, bronchiectasis, postoperative states, and with aspiration of foreign bodies; bronchial neoplasms may also cause it.

4 What are the main characteristics of compression, patchy, and contraction atelectasis?

Compression atelectasis ensues whenever the pleural cavity is partially (or completely) filled by fluid exudate, tumor, blood, or air (pneumothorax) or, in the case of tension pneumothorax, when the entry of air into the pleural cavity causes pulmonary collapse. It is most commonly found in patients with cardiac failure who develop pleural effusions as well as in patients experiencing malignant effusions within the pleural cavities; abnormal elevation of the diaphragm (peritonitis and subdiaphragmatic abscesses) induces basal atelectasis. With compression atelectasis, the mediastinum shifts away from the affected lung.

Patchy atelectasis develops when there is loss of pulmonary surfactant, as in neonatal and adult respiratory distress syndrome.

Contraction atelectasis occurs when local or generalized fibrotic changes in the lung or pleura prevent full expansion of the lung.

5 What are the main causes of pulmonary edema?

Hemodynamic disturbances

The most common mechanism is the one attributable to increased hydrostatic pressure, as occurs in left-sided congestive heart failure.

It can also occur as a consequence of decreased plasma oncotic pressure.

Direct increase in capillary permeability

The most common causes are infectious agents, inhaled gases, liquid aspiration, and drugs.

The edema results from primary injury to the vascular endothelium or damage to alveolar epithelial cells (with secondary microvascular injury).

Lymphatic insufficiency

Lymphangitic carcinomatosis

Fibrosing lymphangitis (e.g., silicosis)

6 What are the pathologic features of pulmonary congestion and edema?

Macroscopic features

Pulmonary congestion and edema are macroscopically characterized by heavy, wet lungs.

Long-standing pulmonary congestion causes brown induration of the lungs (the lungs are firm and brown), which predisposes to infection.

Histologic features

The alveolar capillaries are engorged.

Proteinaceous material is located within the alveoli; it appears pink in the hematoxylin and eosin-stained specimens.

In long-standing cases of pulmonary congestion, numerous heart failure cells, as well as fibrosis and thickening of the alveolar walls, appear.

7 What is adult respiratory distress syndrome (ARDS)?

ARDS has many synonyms, such as diffuse alveolar damage, adult respiratory failure, shock lungs, acute alveolar injury, and traumatic wet lungs.

Its clinical features are the rapid onset of life-threatening respiratory insufficiency, cyanosis, and severe arterial hypoxemia that is refractory to oxygen therapy and sometimes progresses to extrapulmonary multisystem organ failure.

It is almost always associated with evidence of severe pulmonary edema (often called noncardiogenic, low-pressure, or high-permeability pulmonary edema).

8 Which conditions are associated with the development of ARDS?

Direct lung injuries

Diffuse pulmonary infections

Oxygen toxicity

Inhalation of toxins and other irritants

Aspiration of gastric contents

Systemic conditions

Septic shock

Shock associated with trauma

Hemorrhagic pancreatitis

Burns

Complicated abdominal surgery

Narcotic overdose and other drug reactions

9 What are the pathologic features of ARDS?

Macroscopic findings: The lungs are heavy, filled with fluid, firm, red, and boggy.

Microscopic findings in acute stage: There is congestion, interstitial and intraalveolar edema, inflammation, and fibrin deposition along the inside of alveoli in form of hyaline membranes.

Healing stage: It is characterized by the organization of fibrin exudate, with resultant intraalveolar fibrosis and marked thickening of the alveolar septa.

Fatal cases: These often exhibit superimposed bronchopneumonia.

10 Describe the pathogenesis of ARDS

ARDS is the end result of acute alveolar injury caused by a variety of insults, whereas the respiratory distress syndrome of newborns is caused by deficiency in pulmonary surfactant.

In ARDS, the initial injury affects capillary endothelium (most frequently) or alveolar epithelium (occasionally), but in the end both are clearly affected.

Increased capillary permeability is caused by an action of leukocytes on the endothelium.

Increased capillary permeability is followed by interstitial and then intraalveolar edema, fibrin exudation, and formation of hyaline membranes.

The exudates and diffuse tissue destruction cannot be easily resolved, and the result is organization with scarring, in contrast to the transudate of cardiogenic pulmonary edema, which usually resolves.

11 What is the clinical course of ARDS?

Initially, patients may have no pulmonary symptoms. ARDS is heralded by profound dyspnea and tachypnea, but the chest radiograph is initially normal. Subsequently, progressive cyanosis and hypoxemia develop, followed by respiratory failure and the appearance of diffuse bilateral infiltrates on x-ray examination. Hypoxemia can then become unresponsive to oxygen therapy, sometimes resulting in respiratory acidosis. Patients’ lungs can be divided into areas that are infiltrated, consolidated, or collapsed (and thus poorly aerated and poorly compliant) and regions that have almost normal levels of compliance and ventilation.

Therapy of ARDS is extremely demanding, and the disorder is frequently fatal (60%). High concentrations of oxygen, required in therapy for ARDS, can contribute to perpetuation of the damage (oxygen toxicity).

12 What are the main differences between obstructive and restrictive lung diseases?

Obstructive diseases (or airway diseases) are characterized by an increase in resistance to airflow due to partial or complete obstruction from the trachea and larger bronchi to the terminal and respiratory bronchioles. Pulmonary function tests in patients with obstructive lung disease always show a decrease in expiratory flow rates. The major obstructive disorders (excluding tumor or inhalation of a foreign body) are:

Emphysema

Chronic bronchitis

Bronchiectasis

Asthma

Restrictive diseases are characterized by reduced expansion of lung parenchyma, with decreased total lung capacity. The hallmark of the restrictive pattern of disease is a decrease in lung volumes. Restrictive diseases occur in the following conditions:

Chest wall disorders in the presence of normal lungs

Neuromuscular diseases (poliomyelitis)

Severe obesity

Pleural diseases

Kyphoscoliosis

Interstitial and infiltrative lung disease

Acute ARDS

Chronic pneumoconiosis and most of the infiltrative conditions

13 Define chronic obstructive pulmonary disease (COPD)

The term COPD includes a group of conditions that share one major symptom—dyspnea—and are accompanied by chronic or recurrent obstruction to airflow within the lung.

The incidence of COPD has increased dramatically in the past few decades (largely because of cigarette smoking and environmental pollutants) and currently represents a major cause of activity-restricting or bed-confining disability in the United States.

14 What are the main differences between various types of COPD?

See Table 10-1.

TABLE 10-1 Major Differences in Various Types of Chronic Obstructive Pulmonary Disease

15 What is emphysema?

Emphysema is a condition of the lung in which abnormal permanent enlargement of the airspaces distal to the terminal bronchiole is accompanied by destruction of their walls, without obvious fibrosis. There are four main types of emphysema:

Centriacinar (centrilobular)

Panacinar (panlobular)

Paraseptal (distal acinar)

Irregular

Only the first two types cause clinically significant airflow obstruction. Centriacinar emphysema accounts for 95% of all cases and is far more common than the panacinar form or other rare forms of emphysema.

16 What are the main characteristics of different types of emphysema?

Centriacinar (centrilobular)

The central or proximal parts of acini, formed by respiratory bronchioles, are affected, whereas distal alveoli are spared.

The lesions are often localized and usually more severe in the upper lobes, particularly in the apical segments.

The walls of the emphysematous spaces often contain abundant black pigment.

It tends to occur in heavy smokers.

Panacinar (panlobular)

The acini are uniformly enlarged because the process affects all of the structures, from the respiratory bronchiole to the alveoli (the prefix pan refers to the entire acinus but not to the entire lung).

It tends to occur in the lower zones and in the anterior margins of the lung and is associated with a1-antitrypsin deficiency.

Paraseptal (distal acinar)

The proximal part of the acinus is normal, and the distal acinar portion is dominantly involved (more severe in the upper half of the lungs).

Irregular

It is almost invariably associated with scarring.

The acinus is irregularly involved.

17 Describe the main clinical symptoms of emphysema

The clinical manifestations of emphysema do not appear until at least one third of the functioning pulmonary parenchyma is incapacitated. Dyspnea is usually the first symptom, but in some patients the main complaints are cough or wheezing. Weight loss is common, and patients are barrel-chested and dyspneic, with an obviously prolonged expiration. Classically, patients sit bending forward in a hunched-over position, attempting to squeeze the air out of the lungs with each expiratory effort. Patients have a pinched face and breathe through pursed lips.

18 What is the difference in clinical presentation between patients with emphysema and those with chronic bronchitis?

In patients with severe emphysema, cough is often slight, but overdistention is severe. They exhibit low diffusing capacity, and blood gas values are relatively normal. Overventilation helps them remain well oxygenated (pink puffers).

Patients with chronic bronchitis often have a history of recurrent infection and abundant purulent sputum, followed by hypercapnia and severe hypoxemia (blue bloaters). The important complication in severe bronchitis, in addition to the respiratory difficulties, is the development of cor pulmonale and eventual congestive heart failure, associated with secondary pulmonary hypertension.

19 List the most frequent causes of death in patients with COPD

Respiratory insufficiency causing severe hypoxia, respiratory acidosis, and coma

Right-sided heart failure

Massive collapse of the lungs secondary to pneumothorax from ruptured bullae

20 What is chronic bronchitis?

Chronic bronchitis is defined clinically as persistent cough with sputum production for at least 3 months of the year, in at least 2 consecutive years. Clinically there are several forms of chronic bronchitis:

Simple chronic bronchitis: Patients experience a productive cough but have no evidence of airflow obstruction.

Chronic asthmatic bronchitis: Some patients may demonstrate severe dyspnea and wheezing in association with inhaled irritants or during respiratory infections due to hyperreactive airways.

Chronic obstructive bronchitis: Some patients, especially heavy smokers, develop chronic airflow obstruction, usually accompanied by emphysema.

21 List the factors important for the pathogenesis of chronic bronchitis

Chronic irritation by inhaled substances (cigarette smoking)

Infections

22 Discuss the pathologic characteristics of chronic bronchitis

Hyperemia, swelling, and bogginess of the mucous membranes are the main macroscopic features. They are frequently accompanied by excessive mucinous to mucopurulent secretions covering the epithelial surfaces. Heavy casts of secretions and pus occasionally fill the bronchi and bronchioles.

The typical histologic feature of chronic bronchitis is enlargement of the mucus-secreting glands of the trachea and bronchi. Increase in the size of the mucous glands is assessed by the ratio of the thickness of the mucous gland layer to the thickness of the wall between the epithelium and the cartilage (Reid index). The Reid index is normally 0.4. Marked narrowing of bronchioles caused by goblet cell metaplasia also occurs, as do mucous plugging, inflammation, and fibrosis. In the most severe cases, obliteration of lumens (bronchiolitis obliterans) further aggravates the patient’s condition.

23 What are the clinical features of chronic bronchitis?

There is a persistent cough productive of copious sputum.

When persistent for years, eventually dyspnea on exertion develops.

In time, and usually with continued smoking, hypercapnia, hypoxemia, and mild cyanosis with other elements of COPD may appear.

Long-standing severe chronic bronchitis often results in cor pulmonale with cardiac failure.

24 Define bronchial asthma and status asthmaticus

Bronchial asthma is a chronic relapsing inflammatory disorder presenting with hyperreactive airways that cause episodic, reversible bronchoconstriction. The reaction is the consequence of increased responsiveness of the tracheobronchial tree to various stimuli. Patients experience unpredictable disabling attacks of severe dyspnea, coughing, and wheezing triggered by sudden episodes of bronchospasm. Between the attacks, virtually no symptoms occur, but in some people, chronic bronchitis or cor pulmonale supervenes. In the most severe form of asthma, status asthmaticus, the severe acute paroxysm persists for days and even weeks, threatening the ventilatory function enough to cause severe cyanosis and even death.

25 What are the main differences between extrinsic and intrinsic asthma?

The extrinsic type is induced by exposure to an extrinsic antigen (type I hypersensitivity reaction). It comprises:

Atopic (allergic) asthma (the most common type)

Occupational asthma (fumes, organic and chemical dusts, gases, and other chemicals)

Allergic bronchopulmonary aspergillosis

The intrinsic (idiosyncratic) type is initiated by diverse, nonimmune mechanisms, including:

Ingestion of aspirin (drug-induced asthma)

Pulmonary infection, especially viral (most frequent cause of nonatopic asthma)

Cold

Inhaled irritants

Stress

Exercise

26 What is the pathogenesis of atopic asthma?

Atopic asthma usually begins in childhood, when it is triggered by environmental antigens, such as dusts, pollens, animal dander, and foods. Patients with this condition usually have a positive family history of atopy, and asthmatic attacks are often preceded by allergic rhinitis, urticaria, or eczema. It is a classic example of type I immunoglobulin E (IgE)-mediated hypersensitivity reaction. In the airways, inhaled antigens (allergens) initiate reactions, which eventually promote IgE production by B cells, growth of mast cells, and growth and activation of eosinophils.

27 Describe the main differences between acute and late-phase reactions in patients with bronchial asthma

Acute (immediate) response is caused by exposure of presensitized IgE-coated mast cells to the same or cross-reacting antigen and occurs within minutes after stimulation. Either directly or via neuronal reflexes, the mediators induce bronchoconstriction and increase vascular permeability (edema), mucus production, and, in extreme instances, hypotension. Mast cells also release cytokines that cause the influx of other leukocytes (particularly eosinophils).

Late-phase response is mediated by mediators released from leukocytes (neutrophils, monocytes, lymphocytes, basophils, and eosinophils), endothelium, and epithelial cells. It occurs 4 to 8 hours after exposure and may persist for 12 to 24 hour or more.

28 What are the major mediators responsible for bronchospasm in patients with bronchial asthma?

Leukotrienes C4, D4, and E4 cause prolonged bronchoconstriction, increased vascular permeability, and increased mucus secretion.

Acetylcholine causes smooth muscle constriction in the walls of airways.

Histamine is a potent bronchoconstrictive agent.

Prostaglandin D2 causes bronchoconstriction and vasodilatation.