Peribronchial Hemorrhage and Pneumonia
In a considerable number of instances, namely, in 19 autopsies, hemorrhage about the small bronchi has been recognizable upon gross examination of the lung. A conspicuous zone of hemorrhage 2 or 3 mm. in thickness surrounds small (with no cartilage) often dilated bronchi and on longitudinal section may be tracted for a considerable distance along the bronchus (Fig. 7). In many additional instances peribronchial hemorrhage has been found by microscopic examination. In some instances the peribronchial zone of hemorrhage is firmer than the tissue elsewhere and it is occasionally difficult to determine whether the lesion is hemorrhage or pneumonia. In 7 instances frank red consolidation of peribronchial tissue was recognized at autopsy; this lesion will be considered later under peribronchial pneumonia. Hemorrhage about bronchi, like other evidences of severe injury to bronchi following influenza, is more frequently found in the lowermost parts of the lungs than elsewhere. It is invariably associated with severe bronchitis; the bronchi have contained purulent fluid in 15 of 19 instances of peribronchial hemorrhage and in 10 instances the lesion has been associated with dilatation of the bronchi.
Microscopic examination furnishes further evidence of the severity of the bronchial changes which have brought about hemorrhage into the surrounding alveoli. The lumen of the bronchus contains blood and leucocytes; the epithelium is sometimes raised in places from the underlying basement membrane by blood; blood vessels of the bronchial wall are engorged, and there is hemorrhage into the tissue of the bronchus. More frequently the bronchial epithelium is completely lost and the denuded surface is often covered by a layer of fibrin intimately adherent to the inflamed mucosa. Transitions between simple hemorrhage and pneumonia are found, polynuclear leucocytes being mingled with red blood corpuscles. In several instances the alveoli in immediate contact with the bronchial wall have contained fibrin, whereas those in the surrounding zone have contained blood.
Bacteria found in the bronchi in 10 instances of peribronchial hemorrhage have been as follows:
| Staphylococci | 1 |
| B. influenzæ, pneumococci | 1 |
| B. influenzæ, S. hemolyticus | 2 |
| B. influenzæ, pneumococci, staphylococci | 1 |
| B. influenzæ, S. hemolyticus, staphylococci | 4 |
| No organism found | 1 |
The high incidence of B. influenzæ and the frequent association of B. influenzæ and hemolytic streptococci are noteworthy. The instance in which no organisms were found is probably due to a defect in media and should perhaps be excluded from the list.
The percentage incidence of pneumococci, hemolytic streptococci, staphylococci and B. influenzæ in the bronchus, lungs and blood of the heart is an index of the facility with which these microorganisms penetrate internal organs when the bronchi are the site of this hemorrhagic lesion.
| Table XLI | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| NO. OF CULTURES | PNEUMOCOCCI | HEMOLYTIC STREPTOCOCCI | STAPHYLOCOCCI | B. INFLUENZÆ | |||||
| NO. POSITIVE | PER CENT POSITIVE | NO. POSITIVE | PER CENT POSITIVE | NO. POSITIVE | PER CENT POSITIVE | NO. POSITIVE | PER CENT POSITIVE | ||
| Bronchus | 10 | 2 | 20.0 | 6 | 60.0 | 6 | 60.0 | 8 | 80.0 |
| Lung | 13 | 4 | 30.8 | 7 | 53.8 | 3 | 23.1 | 5 | 38.5 |
| Blood | 17 | 4 | 23.5 | 9 | 52.9 | ||||
When these figures are compared with those for all forms of bronchitis no very noteworthy differences are found; the incidence of pneumococci here is less and that of hemolytic streptococci greater. In association with the severe changes present in the bronchi, hemolytic streptococci which enter the lungs almost invariably find their way into the blood.
In 6 instances there has been frank pneumonic consolidation limited to a zone encircling small and medium-sized bronchi which have often been obviously dilated. On cross section these patches of pneumonia are circular, from 1 to 2 cm. in diameter and each contains a bronchus at its center. When the bronchus is cut longitudinally it is evident that pneumonic consolidation forms a cylindrical sheath about the tube. The consolidation varies in color from red to grayish red. In one instance (Autopsy 253) the consolidated tissue has formed a gray zone in contact with the bronchus and is red in a peripheral zone; microscopic examination shows that the alveoli about the bronchus contain fibrin, whereas those at a greater distance contain red blood corpuscles. In this instance, the associated pneumonia in another part of the lung has been somewhat anomalous and has had characters both of lobar and bronchopneumonia, for scattered in the left lung there have been patches of firm consolidation not more than 2 cm. across. The smaller of these patches are deep red, but the larger are coarsely granular and gray in the center. The patchy character of the lesion has suggested bronchopneumonia, but the coarse granulation on section and the presence of fibrinous plugs within the small bronchi have presented a close resemblance to lobar pneumonia. This autopsy is one of the few instances in which Pneumococcus II has been found, Pneumococcus II being present in blood and lungs, B. influenzæ, in lungs and bronchi. In 2 additional instances (Autopsies 374 and 392) peribronchial pneumonia, recognizable at autopsy, has been associated with consolidation having the characters of lobar pneumonia. In one instance, Autopsy 374, the right lung has contained two patches of firm, mottled red and pinkish red coarsely granular consolidation each about 6 cm. across, one situated in the upper lobe and the other in the lower lobe. Elsewhere in the lung, in definite relation to dilated bronchi, occur patches of firm, red, coarsely granular consolidation from 1 to 1.5 cm. in diameter when cut transversely. The bronchus in the center has contained purulent fluid. In the opposite lung similar consolidation has been limited to zones about dilated bronchi which contain purulent fluid. Pneumococcus IV has been obtained from the blood of the heart.
The peribronchial pneumonia which has been described occurs in association with evidence of profound injury to the bronchial wall. In 5 of 6 instances purulent bronchitis has been found at autopsy; in half of these instances bronchiectasis has been noted. The epithelium of the bronchus has been found separated from the underlying tissue by serous exudate, blood and leucocytes; epithelial cells undergo necrosis and disappear, the denuded surface being covered by fibrin. Necrosis extends a varying depth into the wall of the bronchus; blood vessels are engorged, and there is in some instances hemorrhage throughout the wall of the bronchus.
The character of the exudate in the alveoli surrounding the bronchus differs considerably in different instances. In some instances (Autopsies 374 and 392) red blood corpuscles are predominant in the alveoli in contact with the bronchial wall, whereas in a peripheral zone polynuclear leucocytes are more abundant. In other instances (Autopsies 253 and 402) alveoli next the bronchial wall contain abundant fibrin and these are surrounded by a zone in which the alveoli are filled with blood.
Peribronchial pneumonia is the result of the direct extension of the inflammatory process through the wall of the bronchus; it occurs when the epithelium of the bronchus is destroyed and the underlying tissues are injured, but may be present in a wide encircling zone even when the lesion has not penetrated the bronchial wall. The distribution of the pneumonia demonstrates very clearly that the inflammatory process does not reach the affected peribronchial alveoli by way of the bronchioles tributary to the bronchus.
The bacteriology of these instances of peribronchial pneumonia is noteworthy. (Table XLII.)
| Table XLII | |||
|---|---|---|---|
| AUTOPSY | BLOOD | LUNG | BRONCHUS |
| 253 | Pneum. II | Pneum. II, B. inf. | Staph., B. inf. |
| 374 | Pneum. IV | ||
| 387 | Pneum. II, S. hem. | Pneum. II, staph., B. inf. | Pneum. II, S. hem., staph., B. inf. |
| 392 | Pneum. II | ||
| 402 | Pneum. IV, S. hem. | ||
| 424 | ? | Pneum. IV | |
Pneumococcus has been found in every instance either in the lungs or blood. Pneumococcus II, which has been uncommon with the pneumonia following influenza at Camp Pike and has occurred only ten times in more than 200 autopsies, has been present in one-half of these cases. The constant association of the lesion with pneumococcus is particularly significant when a comparison is made between the incidence of pneumococcus with peribronchial hemorrhage, on the one hand, and peribronchial pneumonia on the other; pneumococcus has been present in less than a third of the instances of hemorrhage but in all instances of pneumonia.
In addition to the instances in which gross peribronchial consolidation has been noted at autopsy, microscopic examination has demonstrated the presence of fibrinous pneumonia surrounding bronchi in a considerable number of autopsies. In a zone encircling small bronchi (with no cartilage) alveoli are filled by plugs of dense fibrin (Fig. 20) containing in variable number polynuclear leucocytes and mononuclear cells. The width of the zone is often equal or greater than the diameter of the bronchus. Alveoli outside the zone of fibrinous inflammation may contain red blood corpuscles or serum, and desquamated epithelial cells are often abundant.
Of 21 instances of peribronchial fibrinous pneumonia 20 were associated with purulent bronchitis. Further evidence of the relation of the lesion to profound injury to the bronchi is its association with bronchiectasis in 17 instances.
Peribronchial fibrinous pneumonia, like other lesions encircling the small bronchi, bears a direct relation to the severity of microscopic changes in the bronchus. The epithelium of the bronchus is either partially or completely lost. Occasionally epithelium is raised by hemorrhage or leucocytes from the underlying tissue but more frequently it is wholly lost and the surface is covered by a layer of fibrin. In the early stages of the lesion, polynuclear leucocytes may be numerous throughout the bronchial wall, indicating that the inflammatory irritant within the lumen is affecting the entire wall and extending its influence to the surrounding pulmonary tissue. Later lymphoid and plasma cells are more abundant than polynuclear leucocytes. Coagulative necrosis and disintegration of the bronchial wall, proceeding from the inner surface outward, may extend more or less deeply, and fibrinous inflammation of adjacent alveoli is often more extensive about that segment of the bronchus which shows the greatest change. In some instances segments of the bronchial wall or even the entire wall has disappeared, so that alveoli containing fibrin form part of the wall of the cavity thus formed. When bronchiectasis has occurred, there are often fissures from the lumen through the entire wall extending into the surrounding lung tissue: here fibrinous pneumonia is particularly conspicuous, occurring in a zone about the edges of the defect. This deposition of fibrin within the alveoli adjacent to the injury doubtless has a part in limiting the distribution of bacterial infection. Nevertheless breaks in the continuity of the bronchial wall are not essential to the production of the lesion and the irritant, which is responsible for the lesion, may penetrate through the bronchial wall to surrounding alveoli and from alveoli to other alveoli immediately adjacent.
With this peribronchial pneumonia the smallest bronchi are distended with pus and their walls are infiltrated with polynuclear leucocytes, lymphoid and plasma cells. In a broad zone encircling the bronchus the alveoli are filled with plugs of fibrin. Bronchioles are similarly distended with polynuclear leucocytes; the alveoli which occur upon the wall of the bronchiole are often limited to one side of the wall and are filled with fibrin. This fibrin occasionally projects into the lumen of the bronchiole and forms a continuous layer in contact with the wall on the same side. The alveolar duct and infundibulum are distended with polynuclear leucocytes. The alveoli upon the wall of the alveolar duct and upon the proximal part of the infundibulum are filled with fibrin. The bronchus, bronchiole, alveolar duct and part of the infundibulum are thus surrounded by a continuous zone of alveoli containing fibrin. The alveoli about the distal part of the infundibulum may be filled with polynuclear leucocytes. Lung tissue between adjacent zones of fibrinous pneumonia may contain serum and desquamated epithelial cells.
Organization of peribronchial fibrin was found in 10 of the 22 autopsies in which peribronchial fibrinous pneumonia had been found. Fibroblasts have invaded the fibrin and newly formed capillaries have penetrated into it. In some instances the interalveolar septa are thickened and infiltrated with lymphoid and plasma cells, and in 7 instances there was chronic pneumonia with thickening and mononuclear infiltration of the interstitial tissue about the bronchi and blood vessels, and elsewhere. The duration of the fatal illness in 12 instances with no organization was usually from ten days to two weeks, though in 3 instances there was no organization although the respiratory disease had lasted from seventeen to nineteen days (average duration with no organization, 13.5 days). The duration of illness in 10 instances with organization of fibrin was slightly less than three weeks (average 18.9 days). These figures do not accurately represent the duration of pneumonia which usually develops after a period of several days following onset of influenza.
This group of instances of peribronchial fibrinous pneumonia has offered an opportunity to study the bacteriology of pneumonia with organization and to determine if it presents any unusual characters. The bacteriology of autopsies with peribronchial fibrinous pneumonia with no organization is shown in Table XLIII:
| Table XLIII | |||
|---|---|---|---|
| AUTOPSY | BLOOD | LUNG | BRONCHUS |
| 289 | Pneum. IV | Pneum. IV | Pneum. IV, B. inf., staph. |
| 372 | |||
| 376 | S. hem. | S. hem. | S. hem., B. inf., S. aur. |
| 409 | 0 | ||
| 410 | S. hem., B. inf. S. aur. | ||
| 412 | Pneum. II | Pneum. II, B. inf. | |
| 420 | S. hem. | S. hem., B. inf. S. aur. | |
| 423 | S. hem. | S. hem., B. inf. | |
| 440 | 0 | B. inf., S. aur. | B. inf., S. aur. |
| 448 | 0 | 0 | 0 |
| 482 | 0 | B. inf., Pneum. IV | B. inf., Pneum. IV, S. hem. |
| 489 | 0 | Pneum. IV, B. inf. | Pneum. IV, B. inf. |
The bacteriology of instances of peribronchial fibrinous pneumonia with organization of the intraalveolar fibrin is shown in Table XLIV:
| Table XLIV | |||
|---|---|---|---|
| AUTOPSY | BLOOD | LUNG | BRONCHUS |
| 283 | Pneum. IV | Staph., B. inf. | B. inf., Pneum. IV, staph. |
| 291 | 0 | 0 | B. inf., staph. |
| 398 | 0 | ||
| 419 | 0 | Pneum. II, B. inf. | Pneum. II, B. inf. |
| 421 | S. hem. | Pneum. IV, S. hem. | |
| 422 | 0 | Pneum. II atyp., B. inf. | |
| 425 | S. hem. | S. hem., B. inf., S. alb. | |
| 433 | 0 | S. hem., B. inf., S. aur. | |
| 460 | S. hem. | S. hem., B. inf. | S. hem., B. inf., staph. |
| 463 | 0 | B. inf., staph. | B. inf., staph., Pneum. IV |
B. influenzæ has been present in the bronchi in every instance save one in which cultures have been made, and it is probable that in this exceptional instance cultures have remained sterile because the media employed have been defective. The incidence of B. influenzæ in the lung has been unusually high both with and without organization (66.7 per cent with no organization; 77.8 per cent with organization). Streptococci and staphylococci have been found in a considerable proportion of all instances of peribronchial fibrinous pneumonia, but there has been no notable preponderance of these microorganisms when organization has occurred. Organization has been present in instances in which pneumonia is referable to pneumococcus associated with B. influenzæ and unaccompanied by either streptococci or staphylococci (Autopsies 419 and 422). Wadsworth[[81]] found no organization after inoculation of the lungs of dogs with pneumococcus or with staphylococcus alone, but produced organization when he inoculated animals with both microorganisms.
Injury to bronchi produced in part at least by B. influenzæ exposes the bronchi and lung tissue to repeated infection with a variety of microorganisms; absorption of fibrin and regeneration of alveolar epithelium are prevented, resolution fails to occur and organization of fibrin follows.