Lesson 19

The external surfaces in radiologic orientation show upper, middle, and lower lobes on the right and upper and lower lobes on the left (right lung at left of left panel). In the right panel the cross-section of normal right lung shows minimal posterior and inferior congestion. There is minimal anthracotic pigment from dust in the air breathed in, scavenged by pulmonary macrophages, and transferred to pleural lymphatics to make them appear grayish black.

The delicate alveolar walls of the lung are seen here at high magnification. The attenuated cytoplasm of the alveolar type I epithelial cells cannot easily be distinguished from the endo-thelial cells of the capillaries that are present within the alveolar walls. These thin alveolar walls provide for efficient gas exchange so that the alveolar-arterial (A-a) oxygen gradient is typically less than 15mmHg in young, healthy individuals, although the A-a gradient may increase to greater than 20mmHg in elderly individuals. Occasional alveolar macrophages can be found within the alveoli. The type II pneumocytes produce surfactant that reduces surface tension to increase lung compliance and help keep the alveoli expanded. 

At low magnification (right panel) all alveoli are filled with fibrin-rich edema fluid and inflammatory cells (noncardiogenic edema from alveolar injury) from damage to endothelial and epithelial cells. At medium magnification (left panel) the alveolar walls are congested and expanded from inflam-mation with acute DAD, a form of acute lung injury (ALI). Oxygenation is impaired from reduced alveolar ventilation and diffusion block. ALI and DAD may be part of multiorgan failure. 

On the left are lighter areas () that appear to be raised on cut surfaces from the surrounding lung. Bronchopneumonia (lobular pneumonia) has patchy areas of pulmonary consolidation. The PA chest radiograph on the right shows extensive bilateral patchy brighter infiltrates () that are composed primarily of alveolar exudates. The infiltrates seen here are made even denser through hemorrhage from vascular damage by infection with the bacterial organism Pseudomonas aeruginosa. 

This is a lobar pneumonia with consolidation of the entire left upper lobe (), as seen on the left. This pattern is much less com-mon than the bronchopneumonia pattern. Most lobar pneumonias are caused by community-acquired Streptococcus pneumoniae(pneumococcus) infection. The PA chest radiograph on the right shows complete right upper lobe consolidation, consistent with a lobar pneumonia. The mediastinal and right heart borders are obscured by this process. Fever and cough productive of sputum are commonly present. Microscopic examination of the sputum shows numerous neutrophils, and a gram stain often shows a pre-dominance of one bacterial organism. 

On the left, the alveoli are filled with a neutrophilic exudate that corresponds to the areas of grossly apparent consolidation with bronchopneumonia. This contrasts with the aerated lung on the right. The pattern matches the patchy radiographic distribution of bronchopneumonia. The consoli-dated areas may match the distribution pattern of lung lobules—hence the term lobular pneumo-nia. Bronchopneumonia is classically a hospital-acquired pneumonia seen in patients already ill. Typical causative bacterial organisms include Staphylococcus aureus, Klebsiella pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Escherichia coli, and Pseudomonas aeruginosa. 

These alveolar exudates are composed mainly of neutrophils. The surrounding alveolar walls have congested capillaries (dilated and filled with RBCs). This exudative process is typical for bacterial infection. The exudate gives rise to a productive cough of purulent yellow sputum often seen with bacterial pneumonias. The alveolar architecture is still maintained, which is why even an extensive pneumonia often resolves with minimal residual destruction or damage to the pulmonary parenchyma. In patients with compro-mised lung function from underlying obstructive or restrictive lung disease or cardiac disease, however, even limited pneumonic consolidation can be life-threatening. 

This bronchopneumonia has several abscesses () with irregular, rough-surfaced walls within areas of tan consolidation. If large enough, abscesses contain liquefied necrotic material and purulent exudate that often results in an air-fluid level on chest radiograph or CT scan. An abscess is typically a complication of severe pneumonia, most often from virulent organisms such as Staphylococ-cus aureus, some pneumococci, and Klebsiella pneumoniae. Abscesses often complicate aspiration, particularly in patients with neurologic diseases, in whom they appear more frequently in the right posterior lung. Abscesses can continue to be a source of septicemia and are difficult to treat 

This pleural surface shows a thick, yellow-tan purulent exudate and adjacent unaffected lung at the far right. A collection of pus in the pleural space is an empyema. Pneumonia may spread within the lung and may be complicated by pleuritis with chest pain. Initially there may be only an effusion with a transudate into the pleural space. There may also be exudation of blood proteins to form a fibrinous pleuritis. Bacterial infections in the lung can spread to the pleura to produce a purulent pleuritis. A thoracentesis yields cloudy fluid characteristic of an exudate, with a high protein and a high white blood cell count, mainly neutrophils. 

A viral pulmonary infection is characterized by interstitial lymphocytic infiltrates without an alveolar exudate and without a productive cough. The most common causes are influenza virus types A and B, parainfluenza virus, adenovirus, human metapneumovirus, and respiratory syncy-tial virus (RSV), which occurs mostly in children. Cytomegalovirus infection is most common in immunocompromised hosts. Some strains of coronavirus can cause severe acute respiratory syndrome. Viral cultures of sputum or bronchoal-veolar lavage fluid may be performed. Alterna-tively, serologic testing may reveal the causative agent. 

RSV pneumonia in a child is shown. Note the giant cells, which are a consequence of the viral cytopathic effect. The inset shows a typical multinucleated giant cell with a prominent round, pink intracytoplasmic inclusion. RSV accounts for many cases of pneumonia in children younger than 2 years and can be a cause of death in in-fants 1 to 6 months old or older. RSV often leads to bronchiolitis and manifests with low-grade fever, cough, and wheezing. If severe there can be retractions and cyanosis. Most patients recover with supportive care. 

Note the very large cells that have large violet in-tranuclear inclusions surrounded by a small clear halo. Basophilic stippling () can be seen in the cytoplasm of these cytomegalic cells. This is an infection typically seen in immunocompromised patients, such as patients with HIV infection. Endothelial and epithelial cells can become infected. There are no characteristic gross or microscopic features of cytomegalovirus pneu-monia. Though infection may begin in the lungs, dissemination to other organs is common. 

The two major types of emphysema are centri-lobular (centriacinar) and panlobular (panacinar). The former involves primarily the upper lobes, as shown here, whereas the latter involves all lung fields, particularly the bases. The central lobular loss of lung tissue with intense black anthracotic pigmentation () is apparent here. In contrast to increased risk for lung cancer, which diminishes when a smoker stops smoking, the lung tissue loss with emphysema is permanent. Centriacinar emphysema mainly involves loss of the respiratory bronchioles in the proximal portion of the acinus, with sparing of distal alveoli. This type is most typical for cigarette smokers. 

Panacinar emphysema occurs with loss of all portions of the acinus from the respiratory bronchiole to the alveoli. This pattern is typical for α1-antitrypsin deficiency. The bullae seen here are most prominent in the lower lobe on the left. The typical chest radiographic appearance of panlobular emphysema, with increased lung volume and diaphragmatic flattening, is shown on the right. 

This more localized form of emphysema can follow focal scarring of the peripheral lung paren-chyma. Paraseptal emphysema is not related to smoking. Because this process is focal, pulmonary function is not seriously affected, but the peripheral location of the bullae, which can be 2cm in size or more, along septa may lead to rupture into the pleural space, causing spontaneous pneumothorax. This is most likely to occur in young adults, with sudden onset of dyspnea. Two small bullae () are seen here just beneath the pleural surface. 

There is loss of distal airspaces: bronchioles, alveolar ducts, and alveoli. The remaining air-spaces become dilated as shown here; overall, there is less surface area for gas exchange. Emphysema leads to loss of lung parenchyma, loss of elastic recoil with increased lung compli-ance, and increased pulmonary residual volume with increased total lung capacity. There is decreased diaphragmatic excursion and increased use of accessory muscles for breath-ing. Over time, with reduced ventilation and air trapping, the Pao2 decreases, the Paco2increases, and respiratory acidosis ensues. 

Note increased numbers of chronic inflamma-tory cells in the submucosal region. Chronic bronchitis does not have characteristic pathologic findings but is defined clinically as a persistent productive cough for at least 3 consecutive months in at least 2 consecutive years. Most patients are smokers, but inhaled air pollutants can exacerbate chronic bronchitis. Often there is parenchymal destruction with features of emphy-sema as well, and there is often overlap between pulmonary emphysema and chronic bronchitis, with patients having elements of both. Secondary infections are common and worsen pulmonary function further. 

These are the hyperinflated lungs of a patient who died with status asthmaticus. The two major clinical forms of asthma can overlap and symp-tomatically present similarly. With atopic (extrinsic) asthma there is typically an association with ato-py (allergies) IgE-mediated type I hypersensitivity; asthmatic attacks are precipitated by contact with inhaled allergens. This form begins most often in childhood. In nonatopic (intrinsic) asthma, more likely to occur in adults with hyper-reactive airways, asthmatic attacks are precipi-tated by a variety of stimuli such as respiratory infections and exposure to cold, exercise, stress, inhaled irritants, and drugs such as aspirin. 

Between the bronchial cartilage on the right and the bronchial lumen filled with mucus on the left is a submucosa widened by smooth muscle hypertrophy, edema, and an inflam-matory infiltrate with many eosinophils. These are changes of bronchial asthma, more specifically, atopic asthma from type I hypersensitivity to aller-gens. Sensitization to inhaled allergens promotes a subtype 2 helper T-cell (TH2) immune response with release of IL-4 and IL-5 promoting B-cell IgE production and eosinophil infiltration and activa-tion. The peripheral blood eosinophil count and/or sputum eosinophils can be increased. 

At high magnification, the numerous eosinophils are prominent from their bright-red cytoplas-mic granules in this case of bronchial asthma. The two major clinical forms of asthma, atopic and nonatopic, can overlap in symptoms and pathologic findings. In the early phase of an acute atopic asthmatic attack, there is cross-linking by allergens of IgE bound to mast cells, causing degranulation with release of biogenic amines and cytokines producing an immediate response in minutes with bronchoconstriction, edema, and mucus production. A late phase develops over hours from leukocyte infiltration with continued edema and mucus production. 

Sputum analysis with an acute asthmatic episode may reveal Charcot-Leiden crystals derived from breakdown of eosinophil granules. Pharma-cologic therapies used emergently to treat asth-ma include short-acting β-adrenergic agonists, such as albuterol, and longer-acting agents such as salmeterol. Theophylline, a methylxanthine, promotes bronchodilation by increasing cyclic adenosine monophosphate (cAMP), whereas anticholinergics, such as tiotropium, also produce bronchodilation. Long-term asthma control includes use of glucocorticoids, leukotriene inhibi-tors such as zileuton, receptor antagonists such as montelukast, and mast cell–stabilizing agents such as cromolyn sodium. 

This focal area of dilated bronchi is typical of a less common form of obstructive lung disease. Bronchiectasis tends to be a localized process associated with diseases such as pulmonary neoplasms and aspirated foreign bodies that block a portion of the airways, leading to obstruc-tion with distal airway distention mediated by inflammation and airway destruction. Widespread bronchiectasis is more typical in patients with cystic fibrosis, who have recurrent infections and obstruction of airways by mucus plugs throughout the lungs. A rare cause is primary ciliary dyskinesia, seen with Kartagener syndrome. 

The mid and lower portion of this photomicrograph shows a dilated bronchus in which the mucosa and bronchial wall are not seen clearly because of the necrotizing inflammation with tissue destruction. Bronchiectasis is not a specific disease, but a consequence of another disease process that destroys airways. Innate immune defense from normal structure and function is compromised. 

Regardless of the cause of restrictive lung diseas-es, many eventually lead to extensive pulmonary interstitial fibrosis. The gross appearance shown here in a patient with organizing DAD is known as “honeycomb lung” because of the appearance of the irregular residual small dilated airspaces between bands of dense fibrous interstitial con-nective tissue. The lung compliance is markedly diminished so that patients receiving mechani-cal ventilation require increasing positive end-expiratory pressure (PEEP), predisposing them to airway rupture and development of interstitial emphysema. 

There is dense fibrous connective tissue surrounding residual airspaces filled with pink proteinaceous fluid. These remaining airspaces have become dilated and lined with metaplastic bronchiolar epithelium as shown here. This pro-duces marked diffusion block to gas exchange. Vital capacity as well as residual volume both become diminished with this restrictive, interstitial lung disease. 

Anthracotic pigment deposition in the lung is common but ordinarily is not fibrogenic because the amount of inhaled carbonaceous dusts from environmental air pollution is not large. Smokers have more anthracotic pigmentation because of tobacco smoke tar but still do not have signifi-cant disease from the carbonaceous pigment. Massive amounts of inhaled particles (as in black lung disease in coal miners), elicit a fibrogenic response to produce coal worker’s pneumoco-niosis with the coal macule seen here, accompa-nied by progressive massive fibrosis. There is no increased risk for lung cancer. 

The most common pneumoconiosis is silicosis. There is an interstitial pattern of disease with eventual development of larger silicotic nodules () that can become confluent. The silicotic nodules shown here are composed mainly of bundles of interlacing pale pink collagen, and there is a surrounding inflammatory reaction. A greater degree of exposure to silica and an increasing length of exposure determine the amount of silicotic nodule formation and the degree of restrictive lung disease, which is progressive and irreversible. Silicosis increases the risk for lung carcinoma about twofold.