Interstitial Suppurative Pneumonia
A second type of suppurative pneumonia is characterized by acute inflammation of interstitial tissue between the secondary lobules of the lung and by acute lymphangitis; suppuration involves the interstitial septa and the walls of the lymphatics. The lesion is designated by Kaufmann,[[82]] Beitzke[[83]] and others acute interstitial pneumonia. Pneumonia dissecans in which solution of interstitial tissue isolates sections of lung tissue is said to be a consequence of the lesion. Many text books of pathology, overlooking the occurrence of this lesion, limit the consideration of interstitial pneumonia to chronic processes in which the interlobular and interalveolar fibrous tissue is increased.
Acute inflammation and edema of the interlobular septa of the lung with no suppuration is often found with both lobar and bronchopneumonia and is occasionally so far advanced that it can be recognized on gross examination of the lungs. In a small area interlobular septa are conspicuous as yellowish lines of edematous appearance which may be 1 to 1.5 mm. in thickness and sometimes form a network with rectangular or polygonal meshes. The gelatinous appearance of the edematous fibrous tissue does not suggest suppuration. Microscopic examination shows that the tissue is distended by edema and contains fibrin and polynuclear leucocytes; the lymphatics are distended and contain a network of fibrin within which leucocytes are numerous. Inflammatory edema of the interstitial tissue has been recognized at autopsy four times in association with bronchopneumonia (Autopsy 253 with Pneumococcus II; Autopsy 335, with Pneumococcus IV and S. viridans; Autopsy 477 with S. hemolyticus and Autopsy 498 with S. viridans); twice with lobar pneumonia (Autopsy 343 with Pneumococcus IV and Autopsy 353 with atypical Pneumococcus II); twice with combined lobar and broncopneumonia (Autopsy 273 with S. hemolyticus and Pneumococcus IV and Autopsy 357 with Pneumococcus IV). Edema of interstitial septa was recognized at autopsy in the immediate neighborhood of an abscess three times (Autopsies 277 and 278 with hemolytic streptococci and Autopsy 282 with hemolytic streptococci and Pneumococcus II). In these instances of inflammation and edema the lymphatics are found distended by fibrinous thrombi, and it is probable that occlusion of lymphatics determines the occurrence of inflammatory edema within the surrounding tissue. Inflammation has not proceeded to suppuration.
With interstitial suppurative pneumonia, interlobular connective tissue is marked by conspicuous yellow lines, 1 to 3 or even 5 mm. in thickness, forming a network with polygonal meshes which represent secondary lobules (Figs. 10 and 11). The distended septa not infrequently have bead-like enlargements at intervals and from the cut surface it is often possible to scrape away creamy yellow pus. These lines of suppuration invariably extend up to the pleura and are often broadest immediately below it. Adjacent septa which have not undergone suppuration are much thickened and have the yellowish gray appearance produced by edema.
Fig. 10.—Interstitial suppurative pneumonia; interstitial septa are the site of suppuration and lymphatics are distended with purulent fluid; empyema. Autopsy 474, left lung. (See right lung) Fig. 9.
Fig 11.—Suppurative interstitial pneumonia; the left lower lobe is the site of almost uniform consolidation and here interstitial septa and their lymphatics are distended with pus. There is more extensive interstitial suppuration in the upper lobe where consolidation is absent. The cloudy appearance of the consolidated lung is well shown. Autopsy 452.
Suppurative interstitial pneumonia frequently occurs in association with bronchopneumonic consolidation which may be peribronchiolar, hemorrhagic or lobular, but there is in addition consolidation of the pulmonary tissue between the inflamed septa which may affect part of a lobe, an entire lobe, or parts of several lobes; it does not exhibit the characters of confluent lobular pneumonia.
In approximately half of the cases consolidation, associated with interstitial suppuration, has been lobar in distribution (Fig. 11). The tissue is laxly consolidated, finely granular, and has a cloudy red or gray appearance. The coarsely granular surface of lobar pneumonia is absent. The affected lung may weigh 1,500 or 1,650 grams. Occasionally, interstitial septa of air containing lung tissue is the site of suppurative inflammation or edema. In Autopsy 452 the lower lobe, save a small part at the base, is laxly consolidated; interstitial septa in the consolidated area are yellow, 1.5 to 2 mm. in thickness, beaded and exude purulent fluid on pressure. In the adjacent part of the upper lobe there is a patch of consolidation, and a network of yellow thickened septa extends from it far into the surrounding air containing tissue. The weight of the right lung is 635 grams; of the left, 1,650 grams.
The distribution of interstitial suppuration in 21 instances, including 4 in which the lesion has occurred in the same lungs with abscess formation, has been as follows: right upper lobe, 9 instances; middle lobe, 4; lower lobe, 5; left upper lobe, 7; left lower lobe, 6. In 6 of these autopsies more than one lobe of the same lung has been affected by the lesion; in 2 autopsies parts of both lungs have been affected. Localized abscess of the lung is more common in the lower than in the upper lobes, but suppuration of the interstitial tissue is more often found in the upper lobes.
The duration of illness with interstitial suppurative pneumonia has varied from six days to five weeks. In over half of the cases death has occurred during the second week of illness.
The bacteriology of these cases is shown in Table XLVIII.
| Table XLVIII | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| 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 | 9 | 90.0 | 5 | 50.0 | 10 | 100.0 | ||
| Lung | 20 | 1 | 5.0 | 17 | 85.0 | 5 | 25.0 | 7 | 35.0 |
| Blood | 21 | 2 | 9.5 | 17 | 81.0 | ||||
S. hemolyticus has been almost invariably present in lungs, heart’s blood and bronchi. In 16 of 21 autopsies hemolytic streptococci have been obtained from the blood in pure cultures, in one instance associated with pneumococcus. With associated empyema, pericarditis or peritonitis, the same microorganism has been found in the pleural cavities, pericardium or peritoneum. Furthermore, microscopic examination has demonstrated the presence of chains of streptococci in the affected interlobular tissue and in much greater abundance in the distended lymphatics.
Nevertheless in 2 instances no streptococci have been found. These cases are as follows:
Autopsy 330.—Illness began with symptoms of influenza ten days before death; signs of pneumonia were recognized three days before death. There is firm, gray red consolidation of the entire left upper lobe; the interlobular septa are here indicated by yellow lines of obvious suppuration and thick puslike fluid exudes from the cut surface of the consolidated tissue. The upper half of the left lower lobe has undergone gray hepatization, but here there is no distention of the interlobular septa. There is fibrinopurulent pleurisy on the left side with accumulation of 400 c.c. of fluid. Pneumococcus IV is obtained from the blood of the heart and from the lung. In the suppurating tissue diplococci which stain by Gram’s method are present in large number; there are a few short chains.
Autopsy 379.—Illness began seven days before death with influenza; signs of pneumonia were first recognized the day before death. The middle lobe of the right lung is firmly consolidated; on section there is mottling of deep red and pinkish red and the cut surface is coarsely granular. The interstitial septa are distended by fluid and are grayish yellow. There is fibrinopurulent pleurisy on the right side with accumulation of 600 c.c. of fluid. Pneumococcus atypical II is obtained from the blood of the heart. A large bacillus unstained by Gram’s method is obtained from the right lung and from the right main bronchus. In the bronchus are a few influenza bacilli. In the suppurating and necrotic tissue of the interstitial septa are found diplococci and chains of 4 to 6 cocci in great number; a few large Gram-negative bacilli are found.
In both these autopsies consolidation had the characters of lobar pneumonia, and pneumococci were obtained from the blood of the heart. It is possible that streptococci failed to grow or while present elsewhere were absent at the spot where cultures were made.
It is noteworthy that B. influenzæ was found in the bronchi in every instance (10) in which cultures were made, but was obtained much less frequently from the lung. In one instance (Autopsy 474) this microorganism was found in the blood in association with hemolytic streptococci. There was suppurative interstitial pneumonia in the left lung and abscess in the right lower lobe with rupture into the cavity and empyema. Hemolytic streptococci and B. influenzæ were found in the bronchus, right pleural cavity and blood of the heart.
In 4 instances (Autopsies 251, 259, 295 and 474) interstitial suppurative pneumonia has been associated with abscess formation. In one instance (Autopsy 251) the right middle lobe has been the site of interstitial suppuration and abscess formation; in another (Autopsy 295) the left lower lobe has been the site of both lesions, but in the other 2 instances suppurative interstitial pneumonia and abscess formation have occurred in opposite lungs. In all 4 autopsies hemolytic streptococci have been found in the blood of the heart and in lungs or bronchi.
Empyema has been present in all but 3 of 21 instances of interstitial suppurative pneumonia.
Fig. 12.—Suppurative interstitial pneumonia, showing an immensely dilated lymphatic containing purulent exudate, a short distance below the pleura. Autopsy 474.
Histologic examination of lungs with interstitial suppuration shows that the interlobular septa are distended by serum and contain a conspicuous network of fibrin. Polynuclear leucocytes are present in varying number, and at times densely infiltrate the distended tissue; it is not uncommon to find a zone of densely crowded polynuclear leucocytes along each edge of the septum, whereas the central part contains comparatively few. Occasionally, there is hemorrhage into the distended connective tissue.
Within the distended septa occur greatly dilated lymphatics filled with polynuclear leucocytes (Figs. 12 and 13). Thrombosis of the distended lymphatics has usually occurred, and a conspicuous network of fibrin in which are polynuclear leucocytes plugs the lumen. Streptococci in chains of variable length are found in the inflamed interstitial tissue, but are present in far greater number within the distended lymphatics.
Fig. 13.—Suppurative interstitial pneumonia showing a dilated lymphatic. Autopsy 428.
Necrosis of the cells which fill the lymphatics occurs in spots, usually in the center of the thrombus, and occasionally affects the entire contents of the lymphatic; polynuclear leucocytes have lost their nuclei or in some the nucleus has undergone fragmentation. In these spots the network of fibrin has disappeared. Not infrequently the wall of the lymphatic in a small sector or throughout the circumference has undergone necrosis, and spots of necrosis may occur in the interlobular septa distended by inflammatory exudate. Wherever necrosis has occurred, chains of streptococci are present in immense number.
Accumulation of polynuclear leucocytes, necrosis of these cells, solution of fibrin at first in the centers of the lymphatic thrombus and later throughout, occasionally with necrosis of the wall of the vessel, result in the formation of an abscess at the site of the distended lymphatic. These lymphatics, dilated by purulent fluid, may have a diameter from 2 to 3 mm. and may cause considerable compression and collapse of immediately adjacent alveoli. Lymphangitis, distention of lymphatics, thrombosis and finally suppuration may occur in the lymphatic vessels encircling the blood vessels and in those situated in the adventitia of the bronchi of medium size.
The alveoli adjacent to the distended septa are filled by inflammatory products; edema is almost invariably present and the alveoli may contain serum and desquamated epithelial cells; fibrin is often present, but more frequently polynuclear leucocytes are predominant. Not infrequently, abscess formation, recognized microscopically, has occurred in contact with septa most often immediately below the pleura. Polynuclear leucocytes are present in immense number and alveolar septa have disappeared; occasionally, with abscess formation there is more or less widespread necrosis of tissue, cells both of the exudate and of the alveolar walls having lost their nuclei.
Lymphatics in many places are distended and plugged by fibrinous thrombi, whereas elsewhere softening of the thrombus has been brought about by suppuration. Suppuration, both within the lymphatic and in adjacent alveoli, appears to be secondary to lymphatic obstruction. In some instances the lymphatic appears to have undergone distention after the thrombus has formed, for between the thrombus and the wall of the lymphatic a channel is occasionally found containing uncoagulated lymph.
Fig. 14.—Endophlebitis occurring in association with suppurative pneumonia; the intima contains lymphoid cells in great number; at one spot there is a small thrombus adherent to the intima. Autopsy 325.
Acute endophlebitis has been repeatedly observed in association with interstitial suppurative pneumonia (Fig. 14). The lesion usually occurs in veins situated within the septa which are the site of intensely acute inflammation associated with necrosis. The wall of the vein appears to be so injured by the surrounding changes that polynuclear leucocytes and small mononuclear cells accumulate below the endothelium. Throughout the circumference of the veins, often 0.5 to 1 mm. in diameter, the endothelium is separated from the underlying media by polynuclear leucocytes which form a conspicuous zone encircling the lumen. Some cells of lymphoid type are usually present among the polynuclear leucocytes. Polynuclear leucocytes are often adherent to the endothelial lining of the vessel and are not infrequently fixed in the process of passing through the endothelium. The lesion may be more severe (Autopsy 325), so that the endothelium has disappeared, and upon the exposed surface fibrin is deposited; within this fibrin polynuclear leucocytes are numerous and nuclear fragmentation has occurred. The middle coat of the vessel usually contains few cells; some polynuclear leucocytes within it may be stretched out as if in process of wandering through the wall.
In other instances the accumulation of cells below the endothelium is almost wholly mononuclear. Cells of the type of lymphocytes occur, but more abundant are slightly larger cells with more abundant cytoplasm. These cells may form a thick zone below the intima throughout the entire circumference of the lesion. It seems probable that these cells, like the polynuclear leucocytes, are derived from circulating blood within the lumen of the vessel, for small cells of the type of lymphocytes are not infrequently found adherent to the lumen and occasionally one is fixed in process of passing through the endothelium.
This endophlebitis appears to be the result of changes outside the vessel; there is usually necrosis of the adjacent tissue and the production of the lesion is favored by lymph stasis; as the result of injury to the vessel wall, polynuclear leucocytes in response to chemotaxis, or with milder irritation, mononuclear cells, wander through the endothelium and accumulate below it perhaps on account of the greater impermeability of the middle coat to the passage of cells.
The lesion described does not occur exclusively with interstitial suppurative pneumonia caused by hemolytic streptococci, but has been found in association with abscess formation (Autopsies 354 and 383) caused by hemolytic streptococci or (Autopsy 322) caused by staphylococci. In 1 instance it has been found with lobar pneumonia (Autopsy 320) caused by atypical Pneumococcus II and in 2 instances with combined lobar and bronchopneumonia (Autopsy 357 with Pneumococcus IV; Autopsy 392 with Pneumococcus II). In these 3 instances there has been interstitial inflammation, edema and lymphangitis without suppuration.
Interstitial suppurative pneumonia of long standing may occasionally be accompanied by chronic changes which bring about thickening of the interlobular tissue. In the following autopsy acute suppurative inflammation in the left lung has been associated with conspicuous thickening of interlobular septa in the right lung.
Autopsy 474.—I. H., white, aged twenty-one, was a native of Oklahoma and had been in military service one month. His illness began with influenza thirty-six days before death; he was admitted to the base hospital thirty-one days before his death with signs of pneumonic consolidation of the right lower lobe. Evidence of fluid in the right pleural cavity was obtained two weeks before death, and from 100 to 700 c.c. of thick purulent fluid were aspirated on five occasions. Hemolytic streptococci were found in the aspirated fluid.
Anatomic Diagnosis.—Interstitial suppurative pneumonia in left lung; abscess of right lower lobe with rupture into pleural cavity; thickening of interlobular septa of right lower lobe; double purulent pleurisy with thoracotomy on right side; serofibrinous pericarditis.
The right pleural cavity contains 85 c.c. of thick purulent fluid; the right lung (Fig. 9) is collapsed and pushed to the median line, being bound by firm adhesions to the pericardium. Over the external and basal surfaces is a localized cavity walled off by adhesions. An abscess cavity in the lower part of the lower lobe communicates through a perforation in the basal surface of the lung with the pleural cavity and is in free communication with a small bronchus. About the abscess the lung is red and laxly consolidated, but elsewhere air containing; throughout the lower half of the lower lobe, the interlobular septa are marked by conspicuous yellowish gray lines about 1 mm. in thickness. Between these thickened septa the lung tissue contains air. The lung weighs 600 grams. The left lung (Fig. 10) is voluminous and heavy, weighing 1,320 grams. The surface is everywhere covered by thickened pleura and fibrin, the pleural cavity containing 150 c.c. of thick purulent fluid. The lung is consolidated varying in color from a fleshy red to yellowish gray. The surface is very conspicuously marked by yellow lines 2 or 3 mm. thick, corresponding to the interlobular septa which have undergone suppuration. The septa have bead-like swellings along their course, and when pus escapes from the cut surface small cavities remain at the site of these swellings.
Bacteriologic examination has shown hemolytic streptococci in the blood, left lung, right and left pleural cavities, and right bronchus. B. influenzæ has been found in the bronchus, in the right pleura and in the heart’s blood. A few colonies of S. aureus have been found on the plate from the right pleural cavity (site of thoracotomy).
Microscopic examination of the right lower lobe shows that the interstitial septa are much thickened by young fibrous tissue infiltrated with lymphoid and a few plasma cells. Large mononuclear cells with granular cytoplasm are very numerous. A lymphatic is much distended and contains a few polynuclear leucocytes and many lymphoid and large mononuclear cells. There is no suppuration. Sections from the right lung show suppurative lymphangitis with suppurative inflammation of interstitial tissue.
The right lung is the site of a healing lesion of the interstitial tissue which has developed simultaneously with acute interstitial suppurative pneumonia in the left lung. Both lesions are doubtless caused by S. hemolyticus. This healing lesion exhibits little similarity to the interstitial bronchopneumonia described by several observers with both measles and influenza.
The following autopsy furnishes further evidence that interstitial suppurative pneumonia exhibits a tendency to heal. Proliferation of endothelial cells lining the inflamed lymphatics gives rise to phagocytic cells which aid in removing the accumulated leucocytes.
Autopsy 397.—N. P., white, aged twenty-one, farmer, a native of Oklahoma, had been in military service twenty-one days. Illness began twenty-two days before death, the patient being admitted on the day following onset with influenza, pharyngitis and bronchitis. A diagnosis of lobar pneumonia was made fourteen days before death. The left pleural cavity was aspirated twelve days later and 800 c.c. of thick yellow pus were withdrawn. Hemolytic streptococci were found in the sputum five days before death.
Anatomic Diagnosis.—Interstitial suppurative pneumonia in left upper lobe; acute bronchopneumonia with lobular consolidation in right upper lobe; localized purulent pleurisy on left side with compression and atelectasis of left lung; compensatory emphysema of right lung; purulent bronchitis; beginning serofibrinous pericarditis; chronic passive congestion of liver, spleen and kidneys.
The right lung is very voluminous, free from coal pigment and bright pink save over lobular patches of consolidation which have a bluish red color; the bronchi contain mucopurulent material. The anterior surface of the left lung is bound to the chest wall by firm adhesions, but over the external and posterior surfaces of the lung there is a localized cavity containing 1,100 c.c. of turbid fluid. The left lung is collapsed and airless with deep fleshy red color. In the upper lobe there are scattered patches of consolidation 1.5 to 2.5 cm. across where the tissue is grayish red and coarsely granular. In the adjacent tissue interstitial septa are thickened to 1 or 2 mm. and are conspicuous as gray bands. Along their course occur bead-like swellings from which purulent fluid can be scraped. These septa at one point reach the anterior surface of the lung where the pleural cavity is in large part obliterated by adhesions; here there is an encapsulated pocket 4 x 1.5 cm. containing thick creamy pus.
Bacteriologic examination of the blood shows the presence of hemolytic streptococci; cultures from the lungs contain hemolytic streptococci and B. influenzæ.
Microscopic examination shows that interlobular septa are thickened and infiltrated with plasma cells in large number. Leucocytes in the center of much dilated lymphatics have undergone necrosis and have lost their nuclear stain. About the periphery of the lumen and evidently derived from the swollen endothelial cells which surround it, are numerous large mononuclear cells. They act as phagocytes and ingest polynuclear leucocytes. Multinucleated giant cells, derived from these cells, occur. In several places thrombosed lymphatics in process of organization occur; the lumen is filled with compact fibrin which is invaded by fibroblasts and newly formed capillaries.
The process just described is analogous to that which occurs whenever an unopened abscess heals; mononuclear cells accumulate and act as phagocytes ingesting polynuclear leucocytes.
The following instance of streptococcus empyema is noteworthy because no suppurative pneumonia has been found in association with it. Nevertheless the character of the changes present in the lung indicate that the organ has been the site of an interlobular inflammation which has healed.
Autopsy 499.—J. H. M., white, aged twenty-four, a farmer from Arkansas, had been in military service five months. Onset of illness began two weeks before his admission to the hospital on November 15 with cough, fever, headache and malaise; on admission there was acute bronchitis. Thirteen days after admission the patient developed parotitis (mumps?); five days later and five days before death pleurisy was recognized on the right side and pneumonia was suspected. Death occurred thirty-six days after onset. The temperature on admission was 103.2° F. and remained elevated during one week falling by lysis; from this time until the pleurisy was recognized it was normal and later it remained approximately 103° F.
Anatomic Diagnosis.—Fibrinopurulent pleurisy on right side; fibrinous pleurisy on left side; fibrinopurulent pericarditis; chronic interstitial (interlobular) pneumonia in process of healing; purulent bronchitis; acute splenic tumor; parenchymatous degeneration of kidneys.
The right pleural cavity contains 1,650 c.c. of grayish yellow fluid containing an abundant sediment of softened fibrin. Part of this fluid, more opaque than the remainder is confined in a localized pocket between the inner surface of the lung and the pericardium. The apex and anterior surface of the right upper lobe, over an area about 7 cm. across, is held by fibrinous adhesions to the chest wall; when this adhesion is broken a pocket is exposed 6.5 x 2.5 cm. containing fibrin and fluid. The pericardial cavity is distended by 350 c.c. of turbid yellow seropurulent fluid. The pericardial surfaces are covered by shaggy, tough gray fibrin.
The right lung is collapsed; the lower and posterior part of the upper lobe is deep red and atelectatic. Throughout the upper lobe the interlobular septa are thickened, often 1 mm. across and very conspicuous; in the lower and anterior tip of the lobe is an area where tissue is firm grayish red and heavier than water. The lower and posterior half of the right lower lobe is firm and airless, and the tissue is reddish gray or gray and in places finely granular on section; interlobular septa are conspicuous. Although the lung is cut into thin sections, no abscesses are found. Bronchi throughout the lung contain mucopurulent fluid.
The left lung over its lower half is covered by a thin layer of fibrin. The tissue is crepitant throughout and moderately edematous. Bronchi contain mucopurulent fluid.
Hemolytic streptococci in pure culture are obtained from the blood of the heart, right pleural cavity and pericardium. No growth is obtained on a plate inoculated with material from the right lower lobe. The right bronchus contains hemolytic streptococci and B. influenzæ.
The pleural surface of the right lung is covered by a thick layer of fibrin which has undergone advanced organization. Fibrous septa within the lung are much thickened by the presence of newly formed fibrous tissue; the interstices of the tissue are distended and contain fibrin into which fibroblasts and new blood vessels have penetrated. Some lymphatics are plugged with fibrin and contain polynuclear leucocytes, lymphoid and large mononuclear cells. In several places organization of these thrombi is beginning. About the blood vessels are thrombosed lymphatics in which polynuclear leucocytes and mononuclear cells are equally abundant. Alveoli immediately adjacent to blood vessels and to fibrous septa often contain fibrin, and alveoli elsewhere contain desquamated cells in abundance.
In association with hemolytic streptococci in the blood, pleura and pericardium, there has been inflammation of the interlobular septa of the lungs with acute lymphangitis; there has been no suppuration and the lesion is in process of healing with new formation of fibrous tissue. It is evident that this lesion, as well as pleurisy with advanced organization, preceded the exacerbation of the patient’s illness which occurred five days before death. The advanced chronic changes found at autopsy indicate that the pulmonary and pleural lesions had their origin during the illness which was present at the time of admission to the hospital. Interstitial pneumonia caused by hemolytic streptococci was of mild character and did not produce suppuration within the lung; nevertheless, hemolytic streptococci which reached the pleura caused empyema.