DISEASES OF RESPIRATORY SYSTEM
ACUTE BACTERIAL INFECTIONS OF THE LUNGS
· Occur when normal lung or systemic protective mechanisms are impaired. Pulmonary protective mechanisms include nasal, tracheobronchial, and alveolar mechanisms to filter, neutralize, and clear inhaled organisms and particles.
· Important factors interfering with normal lung defenses are
1. Decreased cough reflex leading to aspiration (seen in coma, anesthesia, drug effects).
2. Injury to mucociliary apparatus (as with cigarette or other smoke / gaseous inhalations).
3. Decreased phagocytic /bactericidal function of the alveolar macrophage (as a result of alcohol, tobacco, oxygen toxicity).
4. Edema/congestion (CIHD).
5. Accumulation of secretions.
· There are a lot of diseases, of pulmonary system as well as the etiologic factors, which cause these diseases. Acute and chronic bronchitis, pneumonia, destructive processes (abscess and gangrene), bronchial asthma, chronic non-specific pulmonary diseases and cancer of lungs are the most common.
· Pathogenic organisms gain access to the lung through the airways, through the bloodstream, by traumatic implantation, or by direct spread across the diaphragm from the subphrenic source, probably through the lymphatics. The most common route is the airways.
· Pneumonia is acute inflammation of the respiratory tract with deposition of intraalveolar exudates.
· Etiologic classification of pneumonia:
1. Bacterial pneumonia.
2. Viral and mycoplasmal pneumonia.
3. Other types of pneumonias:
a) Pneumocystis carini pneumonia.
b) Legionella pneumonia.
c) Aspiration pneumonia.
d) Hypostatic pneumonia.
e) Lipid pneumonia.
· Clinical-morphological classification:
1. Lobar pneumonia.
2. Bronchopneumonia (lobular pneumonia).
3. Interstitial pneumonia.
· Synonyms: crupous, lobular, fibrinous, pleurapneumonia.
· Croupous pneumonia is infectious-allergic infection and involves a lobe of lung.
· Most lobar pneumonias are caused by pneumococci and Klebsiella pneumonia which enter the lungs via the airways.
· The pneumococcus continues to be responsible for 30% to 80% or more of community-acquired pneumonias.
· Groups at particular risk include the very young and very old, alcoholics, diabetics, spleenectomized subjects, and patients with multiple myeloma or circle cell disease.
· Hypersensivity of immediate type plays an important role in pathogenesis.
· Pleural involvement occurs commonly in lobar pneumonia Pneumococcal pneumonia typically presents the picture of lobar pneumonia. One or occasionally several lobes of the lung are involved. Fibrinous exudates in alveoli are presence.
· Traditionally the progress of the disease is divided into four stages:
1. Congestion and Edema predominates in the first 24 hours. The initial response to the organism is edema, which spreads throughout the lobe through pores of Kohn and bronchioles. At this stage an involved lobe appears distended, moist, and deep red of purple. The pleura are shiny, and fluid exudes from the cut surface.
2. Red hepatization (2 days) describes lung tissue with confluent acute exudate containing neutrophils and red cells, giving a red, firm. Lobe is liver-like.
3. Gray hepatization (4-6 days) follows, as the red cells disintegrate and the remaining fibrinous-suppurative exudates persist, giving a gray-brown gross appearance.
4. Resolution (9-11 days) is the favorable final stage in which consolidated exudates undergoes enzymatic and cellular degradation and clearance. Normal structure is restored.
1. Carnification is organization of fibrinoid exudate.
2. Abscess formation. Lung abscess results from the breakdown of alveolar walls.
3. Empyema (spread of infection to pleural cavity).
5. Bacteremic spread leads to purulent meningitis, bacterial endocarditis, arthritis, pericarditis and other organs.
· Causes of death are acute cardiac-respiratory insufficiency and purulent complications.
Bronchopneumonia (focal pneumonia)
· Bronchopneumonia is marked by patchy exudative consolidation of lung parenchyma
· Polyetiologic. The most often agents are bacterias: pneumococci, staphylococci, streptococci, hemophylus influenzae, pseudomonas aeruginosa, and coliform bacteria.
· Bronchopneumonia often arises due to autoinfection. Depending pathogenesis autoinfectional bronchopneumonia may be aspirationous, hypostatic, postoperative, immunodificiency.
· Bronchopneumonia often is a complication of others disease.
· According to extent may be acynous, lobular, segmental, and miliary.
· Initially bronchi are affected. Then, inflammation spreads to parenchyma of lungs with accumulation of exudates in the alveoli.
· Grossly, the lungs show dispersed, elevated, focal areas of palpable consolidation and suppuration.
· Histological features consist of acute (neutrophilic) suppurative, serous, hemorrhagic or mixed exudates filling airspaces and airways, usually about bronchi and bronchioles.
· Outcomes and complications: resolution of the exudates usually restores normal lung structure, but organization may occur and result in fibrous scarring in some cases. Aggressive disease may produce abscess, pleurisy, and empyema.
· Beta-hemolytic streptococci are an uncommon cause of pneumonia at the present time. In adults streptococcal pneumonia like other pneumonias usually occurs in elderly, severely debilitated patients. Diabetes is also a risk factor. Infections caused by this microbe in the newborn are discussed elsewhere.
· The lower lobe is usually the site of major involvement.
· The airways appear thickened and are filled with a hemorrhagic or purulent exudate.
· The pneumonia is lobular with consolidated patches clearly centered on terminal bronchioles. The distinctive microscopic feature of streptococcal pneumonia is greater interstitial involvement than in other bacterial pneumonias. There is necrosis of the epithelium of distal airways with infiltration of the bronchial walls by neutrophils and mononuclear cells. The interstitial infiltrate also extends into the adjacent alveolar walls.
· Staphylococcal pneumonia usually occurs either in the presence of a source of bacteremia or after viral infection.
· Hematogenous pneumonia is seen in those with soft-tissue infections, in patients undergoing long-term dialysis. The lesions may appear as septic infarcts that are yellow and purulent but preserve to some degree the wedge-shaped configuration of infarcts and are associated with thrombosed vessels, or they may be rounded patches of necrotizing pneumonia that break down, giving rise to abscesses.
· Staphylococcal pneumonia also results from spread of organisms from the colonized nasopharynx. The lesions are those of bronchopneumonia accompanied by a hemorrhagic and necrotizing bronchitis. Purulent exudate fills the bronchioles and spreads into the adjacent acini.
· Staphylococcal bronchopneumonia is not rare in children less than 6 months of age. A notable feature of staphylococcal pneumonia in small children is development of abscesss.
· Local complications of staphylococcal pneumonia include empyema and bronchopleural fistula.
Aspiration pneumonia results from inhaling different agents into the lungs. These substances include food, gastric contents, infected material from oral cavity, amniotic fluid or meconium in infants, etc.
Hypostatic pneumonia is the term used for the collection of edema fluid and secretions in the dependent parts of the lungs in bed-patients.
Infections by viruses, mycoplasma pneumonia, pneumocystis carinii, etc. result in varied clinical and pathologic patterns, ranging from relatively mild upper respiratory tract involvements to severe lower respiratory tract disease.
· Patchy or lobar areas of congestion without the consolidation of bacterial pneumonias.
· A predominance of interstitial pneumonitis with widened, edematous alveolar walls containing a mononuclear inflammatory cell infiltrates.
· The formation of hyaline membranes, reflecting diffuse alveolar damage.
· Pneumocystic pneumonia is characterized by desquamation of alveolar epithelium. Alveoli filled by foamy fluid and pneumocysts, and also hyperemia and inflammatory infiltration of the alveolar septs. It may pattern in AIDS.
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
The term Chronic Obstructive Pulmonary disease (COPD) refers to a group of conditions that share a major symptom – dyspnea - and are accompanied by chronic or recurrent obstruction to air flow within the lung.
· Obstructive diseases are characterized by increased resistance to airflow because of chronic or recurring expiratory obstruction.
· In their prototypical forms, these individual disorders – chronic bronchitis, bronchiectasis, asthma, emphysema – have distinct anatomic and clinical characteristic.
· Hypertension of pulmonary circulation and “cor pulmonale” develops in all Chronic Obstructive Pulmonary diseases.
· Amyloidosis of kidneys and chronic renal insufficiency may develop often.
· Death of the most patients with COPD is due to
1) Respiratory acidosis and coma,
2) Right-sided failure,
3) Massive collapse of the lung secondary to pneumothorax.
The widely accepted definition of chronic bronchitis is a clinical one – chronic bronchitis (CB) is present in any patient who has persistent cough with sputum production for at least 3 months in at least 2 consecutive years.
· This disorder, so common among habitual smokers and inhabitants of smog-laden cities, is not nearly so trivial as was once thought.
· The role of infection appears to be secondary. It is not responsible for the initiation of CB but is probably significant in maintaining it and may be criterial in producing acute exacerbations.
· Pathogenesis. Two sets of factors are important in the genesis of chronic bronchitis:
1. Chronic irritation by inhaled substances.
2. Microbiologic infections.
· The hallmark and earliest failure of CB is hypersecretion of mucus in the large airways, and is associated with hypertrophy of the submucosal glands in the trachea and bronchi.
· As CB persists, there is also a marked increase in goblet cells of small airways – small bronchi and bronchioles – leading to excessive mucus production that contributes to airway obstruction.
· Although mucus hypersecretion in large airways is the cause of sputum overproduction, it is now thought that accompanying alterations in the small airways of the lung can result in physiologically important and early manifestations of the chronic airway obstruction.
· Histological features of the small airways:
1. Goblet cell metaplasia with mucus plugging of the lumen.
2. Clustering of pigmented alveolar macrophages.
3. Inflammatory infiltration.
4. Fibrosis of bronchiolar wall.
Outcomes and complications
· Lead to “cor pulmonale” and heart failure.
· Cause atypical metaplasia and dysplasia of the respiratory epithelium, providing a possible soil for cancerous transformation.
· Amyloidosis of kidneys.
· Lead to bronchiectasis.
BE is chronic necrotizing infection of the bronchi and bronchioles leading to or associated with abnormal dilation of these airways.
BE has many origins and usually develops in association with following conditions:
- Bronchial obstruction, due to tumor, foreign bodies, and occasionally mucous impaction, in which the BE are localized to the obstructed lung segment; or due to diffuse obstructive airway disease, most commonly atopic asthma and chronic bronchitis, measles.
2. Congenital or hereditary conditions, including congenital BE, cystic fibrosis, intralobar sequestration of the lung states, and immune cilia and Kartagener’s syndromes.
- Necrotizing pneumonia, most often caused by tubercle bacillus or staphylococci or mixed infections.
· BE usually affects the lower lobes bilaterally, particularly those air passages that is most vertical, and is most severe in the more distal bronchi and bronchioles.
· When tumors or aspiration of foreign bodies leads to BE, the involvement may be sharply localized to a single segment of the lungs.
· The pleura is usually fibrotic and thickened with adhesions to the chest wall. Cut surface has honey-combed appearance. The walls of bronchi are thickened and the lumen arc filled with mucus.
· The airways are dilated; sometime up to four times normal size. These dilations may produce:
1. Long, tube-like enlargements (cylindroid BE) in 1 to 4 type of bronchus.
2. May cause fusiform or even sharply saccular distention (saccular BE) in 6-10 types of bronchus.
· The histologic findings vary with the activity and chronicity of the disease:
1. In the full-down active case, there in an intense acute and chronic inflammatory exudation within the walls of bronchi and bronchioles, associated with desquamation of the lining epithelium and extensive areas of necrotizing ulceration. There may be squamous metaplasia of the remaining epithelium.
2. In some instances, the necrosis completely destroys the bronchial or bronchiolar walls and forms a lung abscess.
3. Fibrosis of the bronchial and bronchiolar walls and peribronchial fibrosis develop in the more chronic cases.
Outcomes and complications
1. Obstructive ventilatory insufficiency can lead to marked dyspnea and cyanosis.
2. Pulmonary hemorrhage.
3. Pulmonary abscess.
4. Empyema of the pleura.
5. Metastatic brain abscess.
6. “Cor pulmonale” and chronic cardiac-pulmonary insufficiency.
7. Amyloidosis are less frequent complications of BE.
Emphysema is a condition of the lung characterized by abnormal permanent enlargement of the airspace distal to the terminal bronchiole, accompanied by destruction of their walls, and without obvious fibrosis. In contrast, the enlargement of airspaces unaccompanied by destruction is termed overinflation, for example, the distention of airspaces in the opposite lung following unilateral pneumonectomy.
While details of the genesis of the two common forms of emphysema – centiacinar and panacinar – remain unsettled, the most plausible hypothesis to account for the destruction of alveolar walls is the protease-antiprotease mechanism. Thus, emphysema is seen to result from the destructive effect of the high protease activity in subjects with low antiprotease activity.
The protease-antiprotease hypothesis also explains the deleterious effect of cigarette smoking.
- Smokers have greater numbers of neutrophils and macrophages in their alveoli. The increased recruitment of neutrophils into the lung is likely to result, in part, from the release by activated alveolar macrophages of neutrophil chemotactic factors, this release being stimulated by smoking. In addition, nicotine is chemotactic for neutrophils, and cigarette smoke activates the alternative compliment pathway.
- Smoking stimulates release of elastase from neutrophils.
- Smoking enhances elastolytic proteases activity in macrophages; macrophage elastase is not inhibited by alpha-1 –AT and, indeed, can proteolytically digest this enzyme.
- Oxidants in cigarette smoke and oxygen free radicals secreted by neutrophils inhibit alpha-1-AT and thus decrease net antielastase activity in smokers.
It is thus postulated that impaction of smoke particles in the small bronchi and bronchioles, with the resultant influx of neutrophils and macrophages, and increased elastase and decreased alpha-1-AT activity causes to the centriacinar emphysema seen in smokers.
Although the term “emphysema” is sometimes loosely applied to diverse conditions, there are four types:
1. Centriacinar (cenrolobular) emphysema. The distinctive feature of this type is the pattern of involvement of the lobules; the central or proximal parts of the acini, formed by respiratory bronchioles, are affected, whereas distal alveoli are spared. The walls of the emphysematous spaces often contain large amount of black pigment. Inflammation around bronchi and bronchioles and in the septa is common. Moderate-to-severe degrees of emphysema occur predominantly in heavy smokers, often in association with chronic bronchitis. In addition, some lesions of so-called coal workers’ pneumoconiosis bear a striking resemblance to centriacinar emphysema.
2. Panacinar (panlobular) emphysema. In this type the acini are uniformly enlarged from the level at the respiratory bronchiole to the terminal blind alveoli. This type of emphysema is associated with alpha-1-antitrypsin deficiency.
3. Paraseptal (distal acinar) emphysema. In this type the proximal portion of the acinus is normal, but the distal part is dominantly involved. The emphysema is more striking adjacent to the pleura, along the lobular connective tissue septa, and at the margins of the lobules. This type of emphysema probably underlies many of the cases of spontaneous pneumothorax in young adults.
4. Irregular emphysema, so named because the acinus is the irregularly involved, is almost invariably associated with scarring. Thus, it may be the most common form of emphysema, as careful search of most lungs at autopsy shows one or more scars from a healed inflammatory process. In most instances, these foci of irregular emphysema are asymptomatic.
Types of emphysema according to cause
1. Compensatory E. This term is sometimes used to designate dilation of alveoli but not destruction of septal walls in response to loss of lung substance elsewhere. It is best exemplified by the hyperexpansion of the residual lung parenchyma that follows surgical removal of a diseased lung or lobe.
2. Obstructive overinflation refers to the condition in which the lung expands because air is trapped within it.
3. Senile E. refers to the overdistended, sometimes voluminous lungs found in the aged.
Bullous E. refers merely to at any form of E. that produces large subpleural blebs or bullae (spaces more than 1 cm in diameter in the distended state).
4. Interstitial E. The entrance of air into the connective tissue stroma of the lung, mediastinum, or subcutaneous tissue is designated interstitial emphysema.
· The diagnosis and classification of the emphysemas are based on naked eye (or hand lens) examination of lungs fixed in a state of inflation.
· Panacinar emphysema, when well developed, produces voluminous lungs, often overlapping the heart and hiding it when the anterior chest wall is removed.
· The macroscopic signs of centriacinar emphysema are less impressive. The lungs may not appear particularly pale or voluminous unless the disease is well advanced.
· Generally, the upper two-thirds of the lungs are more severely affected.
· Large apical blebs or bulla are more characteristic of irregular emphysema secondary to scarring.
· Microscopical examination is accessory to visualize the abnormal fenestrations in the walls of the alveoli, the complete destruction of septal walls, and the distribution of damage within the pulmonary lobule. With advance of the disease, adjacent alveoli fuse, producing even larger abnormal airspaces and possibly blebs or bulla. Often the respiratory bronchioles and vasculature of the lung are deformed and compressed by the emphysematous distortion of the airspaces, and, as mentioned, there may or may not be evidence of bronchitis or bronchiolitis.
Bronchial Asthma (BA)
Bronchial asthma is a disease characterized by hyper-reactive airways, leading to episodic, reversible bronchoconstriction, owing to increased responsiveness of the tracheobronchial tree to various stimuli. A severe and unremitting type of the disease termed status asthmaticus may prove fatal.
· Chronic airway inflammation involving many cell types and inflammatory mediators accompanies the bronchial hyper-responsiveness of asthma.
· Nevertheless, the relationship of the inflammatory cells and their mediators to airway hyper-reactivity is not fully understood.
1. Extrinsic BA is initiated by a type 1 hypersensitivity reaction induced by exposure to an extrinsic antigen. Subtypes include atopic (allergic), BA, occupational BA (many forms), and allergic bronchopulmonary aspergillosis (bronchial colonization with aspergillus organisms followed by development of IgE antibodies).
2. In contrast, intrinsic BA is initiated by diverse, nonimmune mechanisms, including aspirin, pulmonary infections; especially those caused by viruses, cold, inhaled irrigants (pollutants such as sulfur dioxide), stress, and exercise.
The morphologic changes in asthma have been described principally in patients dying of status asthmaticus, but it appears that the pathology in nonfatal cases is similar.
· Grossly, the lungs are overdistended because of overinflation, and there may be small areas of atelectasis.
· The most striking macroscopic finding is occlusion of bronchi and bronchioles by thick, tenacious mucous plaques.
· Histologically, the mucous plaques whorls of shed epithelium, which give, rise to the well-known Curschmann’s spirals.
· Numerous eosinophils and Charcot-Leyden crystals are present.
· The other characteristic histologic findings of BA include:
- Thickening of the basement membrane of the bronchial epithelium.
- Edema and inflammatory infiltrate in the bronchial walls, with a prominence of eosinophils, which form 5 to50% of the cellular infiltrate.
- An increase in size of the submucosal glands.
- Hypertrophy of the bronchial wall muscle, a reflection of prolonged bronchoconstriction.
- Emphysematous changes sometimes occur, and if chronic bacterial infection has supervened, bronchitis may occur.
The classic asthmatic attack lasts up to several hours and is followed by prolonged coughing; the raising of copious mucous secretions provides considerable relief of the respiratory difficulty. In some patients, these symptoms persist at a low level all the time. In its most severe form, status asthmaticus, the severe acute paroxysm persists for days and even weeks, and, under these circumstances, ventilatory function may be so impaired as to cause severe cyanosis and even death.
Chronic Lung Abscess (LA)
The term “LA” describes a local suppurative process within the lung characterized by necrosis of lung tissue.
· Oropharyngeal surgical procedures, bronchial infections, dental sepsis, and bronchiectases play important roles in their development.
· The causative organisms are introduced by the following mechanisms:
- Aspiration of infective material.
- Antecedent primary bacterial infection.
- Septic embolism.
- Obstructive tumors.
- Direct traumatic punctures.
· When all these causes are excluded, there are still cases in which no reasonable basis for the LA formation can be identified. These are referred to as “primary cryptogenic” LA.
· Abscesses vary in diameter from lesions of a few millimeters to large cavities of 5 to 6 cm.
· They may affect any part of the lung and may be single or multiple.
· The cavity may or may not be filled with suppurative debris, depending on the presence or absence of a communication with one of the air passages.
· When such communications exist, the contained exudate may be partially drained to create an air-containing cavity.
· Superimposed saprophytic infections are prone to flourishing within the already necrotic debris of the abscess cavity.
· Continued infection leads to large, fetid, green-black, multilocular cavities with poor demarcation of their margins, designated gangrene of the lung.
· The cardinal histologic change in all abscesses is suppurative destruction of the lung parenchyma within the central area of cavitation.
· A reactive fibrous wall often surrounds chronic abscesses.
Complications include extension of the infection into the pleural cavity, hemorrhage, the development of brain abscesses or meningitis from septic emboli, and rarely reactive secondary amyloidosis.
Idiopathic Pulmonary Fibrosis
Diffuse interstitial fibrosis occurs as a result of different pulmonary diseases. It is so called “idiopathic pulmonary fibrosis” or “cryptogenic fibrosing alveolitis” or “chronic interstitial pneumonitis”
· Pathological changes are bilateral and widespread.
· Macroscopically the lungs are dense, reduced volume.
· Honey-combing (i.e. enlarged, thick-walled air spaces) develops in parts of lung. Microscopically, changes vary according to the stage of the disease with formation of hyaline membranes.
· There is edema and cellular infiltrate in the alveolar septa in early stage.
· There is organization of the alveolar exudate and replacement fibrosis in the alveoli and in the interstitial septal wall with variable amount of inflammation in advanced stage.