Degenerative change is characteristic of tubercle deposit and sometimes takes place early in the evolution of the lesion. Owing to the absence of newly formed blood-vessels, no nutriment is conveyed to the tissues within the tubercle. The avascular condition is an important cause of the degenerative change. Other factors responsible for its production are the specific effect of the living tubercle bacillus and the toxins. The degenerative processes consist of hyaline change, coagulation necrosis, a degree of fatty degeneration, varying degrees of caseation, and calcification. The degenerative changes usually take place early in the central cells of the tubercle, sometimes affecting the giant-cells before all others. Usually the lymphoid cells are transformed somewhat before the degenerative process attacks those of the epithelioid variety, which apparently are more resistant than other cells. Owing to the excess of lymphoid cells the epithelioid type is often not recognized until the former have degenerated and disappeared. Definite caseation is preceded by a slight granular change in the protoplasm of the cells. With later degeneration the nuclei are found more or less broken down and fragmentary, with lessened inclination to take ordinary stains. Some authors, however, have noted a bright staining reaction of the nuclei even in the midst of necrotic change. The contour of the cells becomes defined less sharply until the outlines are lost altogether, the affected portion of the tubercle consisting of a homogeneous necrotic area. In this manner, as a result of coagulation necrosis, the central portion of the tubercle is transformed into a broken-down mass, containing, in addition to the disintegrated cells, living and destroyed bacilli. Outside of the caseous center there are present epithelioid cells with an occasional giant-cell undergoing beginning degeneration, and at the periphery epithelioid and lymphoid cells representing the newer evolution as a result of cellular proliferation. In giant-cells the degenerative change also takes place in the center of the cell, particularly when the nuclei are disposed circularly at the periphery. Stengel and others have called attention to the fact that when the nuclei occur chiefly at one pole of an elongated giant-cell the coagulation necrosis usually takes place at the opposite pole. It has been previously stated that the tubercle bacilli, when found in giant-cells, occur at the center in case of peripheral nuclear distribution and at the pole opposite to the gathering of nuclei. It would thus seem to be a reasonable conclusion that the regional degenerative change in giant-cells corresponds closely to that portion of the cell in which the bacilli are grouped.

As the degenerative processes further advance the entire tubercle undergoes coagulation necrosis and the process of caseation becomes complete. Leukocytes are usually attracted in considerable numbers to the areas of degeneration, where they suffer the same fate as the fixed cells. The exudative processes and the resulting caseation are not confined to the tissue within the tubercle. This phase of the subject will be considered more fully in connection with diffuse tuberculous infiltration and the secondary inflammatory lesions. Of all the tissues involved in the structure of tubercle, the fibrous reticulum is the most resistant to degeneration. Connective-tissue proliferation may remain active in the periphery of the tubercle, and eventually produce a surrounding fibrous barrier delimiting the tuberculous process and entirely encapsulating the tubercle itself.

It will be seen, however, that the reactive connective-tissue hyper

plasia is not always sufficient to effect a complete encapsulation, opportunity being afforded in many instances through the lymph-channels, and as a result of wandering phagocytes, for the deposit of bacilli in fresh tissue areas. Occasionally it does happen that the proliferation of connective tissue is sufficient to wall off entirely the tuberculous area and to produce decided contraction change. The fibrosis eventually may involve the central portion of the tubercle as well as the surrounding parts. As a result of such reorganization small foci of infection may be converted into dense cicatricial tissue comparatively devoid of bloodvessels, and producing an eventual healing of the involved area. These constructive efforts on the part of the tissues constitute the only means of securing a permanent arrest of the disease, if not obliteration of the tuberculous lesion. It is generally thought that even the formation of tubercle is a natural conservative process, although for the time being admittedly destructive in nature. To the extent that the bacilli are inclosed or imprisoned effectually within an encircling defensive wall the process of tubercle formation with associated sclerotic change may assuredly be regarded as an effort on the part of the organism toward self-protection. Although this mechanism of defense is often somewhat. imperfect, it is true that the channels of escape for the bacillus are susceptible of complete occlusion by active cellular proliferation with dense connective-tissue encapsulation. This reactive protective effort of the invaded tissues is usually accepted as representing an inherent defensive action on the part of the animal organism. Theobald Smith, however, believes that there is a reciprocal protective action between the bacilli and the normal tissues, and ascribes the process of tubercle formation, with resulting connective-tissue proliferation, to an effort on the part of the parasite to obtain an abode where it may sojourn unmolested for indefinite periods.

While the bacillus undoubtedly affords the stimulus for the cellular proliferation, it would appear that the connective-tissue formation constitutes rather a mechanism of defense of the tissues against the invading parasite. It is apparent that the measure of the practical efficiency of the connective-tissue hyperplasia depends upon the rate of its formation. In the evolution of tubercle there are present two welldefined opposing forces, the eventual supremacy of one denoting tissue repair and recovery, the other, progressive degeneration and bacillary distribution to surrounding parts. Upon the one hand, there is a tendency for active cell-proliferation with fibrous tissue construction and encapsulation; upon the other, advancing caseation and extension of the infection to new areas beyond the limits of peripheral connective tissue. The situation resolves itself, therefore, into a race between the effort of construction and the tendency to destruction, the final issue being decided according to the relative rapidity of the contending processes. The same inclination to degeneration and to connective-tissue hyperplasia is observed in surrounding areas and even in diffuse tuberculous infiltration, large masses of involved tissue exhibiting varying degrees of necrotic and proliferative change.

An extension of the process from the initial tubercle takes place as a result of the penetration of the connective-tissue wall by the bacilli and the peripheral formation of miliary tubercles. In the same manner, from these secondary tubercles, new centers of growth are again formed. Not infrequently nodules are produced consisting of many miliary

tubercles which, as caseation advances in the center, become fused into large masses of broken-down tuberculous material, commonly called conglomerate tubercles, although by some the term "submiliary'' is employed. To such masses, which sometimes attain the size of a hen's egg, the appellation "crude tubercle' was applied by Laënnec. The same processes of degeneration and repair which take place in a single elementary tubercle also obtain in all the constituent tubercles comprising the entire mass. Caseation and softening with resulting excavation may develop as a result of the coalescence of the individual tubercles, or a firm network of fibrous tissue hyperplasia may supervene in others. The destructive tendency toward cavity formation not only involves structures of tuberculous formation, but often invades pneumonic areas resulting from secondary inflammatory changes. Factors of great importance in such cases are, first, the nature of the exudative process, which, though purulent, is not necessarily due to mixed infection, and, second, the invasion of these pneumonic areas with tubercle bacilli. Even in tubercle formation, without other associated inflammatory lesions, there is usually an abundant exudation which may consist either of polynuclear leukocytes or of serum. The exudation sometimes is fibrinous and may invade the caseous tissue or cover the surface of miliary tubercles. The exudate, of whatever character, though external to the tubercle itself, may be distributed extensively in the surrounding tissue, and considerably augment the size of nodules or conglomerate tubercles. Discrete tuberculous nodules are often absent altogether, and in their place there may exist a diffuse tuberculous infiltration containing numerous giant and epithelioid cells, with varying degrees of caseation and fibrosis. In addition to the necrotic and sclerotic changes possible of development in individual tubercles or in a conglomerate mass, the process of calcification occasionally ensues. This takes place, however, only after the formation of considerable connective-tissue proliferation. The bacilli are much more frequent in the broken-down débris of these diffuse processes after softening has become advanced than in the strictly caseous material. The content of the softened tuberculous mass is a thick, creamy, yellowish material, somewhat resembling pus, though differing from it histologically. There are present much granular débris, broken-down cells, and fat-drops.

In tuberculosis of the lungs, on account of the opening of tuberculous cavities into bronchi, the conditions are favorable for the entrance of numerous pyogenic bacteria. In pulmonary tissues the characteristic tubercle formation previously described is limited somewhat by the loose anatomic structure of the parts. The tissue is not sufficient in extent nor of such character as to permit the fullest elaboration of tubercle formation, although extensive hyperplasia occurs in surrounding areas. Exceptional opportunities are afforded, however, for dissemination of the tuberculous infection by the physiologic motion of the parts, the penetration of bronchi, and the luxuriant network of lymphatic channels and blood-vessels. While the movements of ordinary respiration must be regarded to some extent as inimical to rapid tissue repair, the deep inspiratory efforts attending violent attacks of coughing are assuredly instrumental in further distribution of the bacilli throughout the respiratory tract.

A most important feature of tuberculous infection of the pulmonary tissues is the frequent extensive development of secondary inflammatory

lesions. The most perfect example of typical tubercle formation in the lungs is found in miliary tuberculosis, although even in such cases exudation is not entirely absent. The tubercles are found in the walls of the alveoli, of the bronchi, and of the blood-vessels. Areas of tuberculous bronchopneumonia with extensive retroactive inflammatory change are sometimes accompanied by miliary tubercles. These inflammatory lesions, dependent largely upon exudative processes, may partake of the nature of catarrhal or fibrinous pneumonia, and in exceptional instances give rise to marked proliferation of connective tissue, inducing pronounced contraction change. The areas of pneumonic involvement may vary greatly in size, sometimes the process being confined to tiny areas, in other instances being distributed throughout a single lobe or an entire lung. Extensive areas may be affected simultaneously, or adjacent foci may subsequently become confluent. Caseation may supervene precisely as described in connection with the elementary tubercle. The degenerative change may involve wide areas of pulmonary tissue or appear in the form of discrete foci of necrosis. The inflammatory process sometimes involves the wall of the bronchi as well as pulmonary tissue. Caseation, either with or without the formation of genuine tubercle, may develop within the wall, resulting in its eventual penetration and communication with pulmonary cavities. The process of excavation may be astonishingly rapid in areas of pneumonic consolidation, the destruction of tissue sometimes extending into and through the walls of several bronchi. The rapidity of the softening, with added increase in the size of the pulmonary excavation, is dependent largely upon the character of the tissue comprising its encircling wall. If the wall of the cavity consists of an area of tuberculous pneumonia, further excavation is much more likely than if the adjacent tissue consists of elementary tubercle formation or chronic tuberculous infiltration, in which event the conditions are much more favorable for limiting cavity formation. Thus the remarkable diversity in the rapidity and extent of cavity formation is explained almost entirely by the character of the contiguous tissue. It is not to be understood that pulmonary excavation must necessarily be accompanied by rapid softening, copious expectoration, increase of bacilli in the sputum, temperature elevation, or general decline, although such clinical manifestations are common. Neither is it always true that cavity formation is associated with further dissemination of tubercle bacilli.

The development of pulmonary hemorrhage is not always occasioned by a destructive tuberculous change involving the wall of the bloodvessels, although some are probably attributable to its caseation and rupture. In the event of cavity formation with removal of the support of the arterial wall, aneurysmal dilatation not infrequently results. Rupture subsequently takes place by reason of purely mechanical causes, without definite tubercle deposit in the wall of the artery. The small hemorrhages so frequently observed in all stages of tuberculosis, sometimes even in advance of physical signs, would seem somewhat difficult of explanation, because in areas of tuberculous deposit with or without caseation and excavation the small blood-vessels are obliterated. It is known, however, that the surrounding blood-vessels which make up the collateral circulation are engorged to a considerable extent, and at times of temporary excitement or strain are incapable of withstanding the intra-arterial pressure.

CHAPTER XV

GROSS APPEARANCES

THE macroscopic appearance of tuberculous pulmonary lesions varies remarkably according to the course, duration, type, and complications of the disease. While degenerative change may be said to constitute the chief pathologic characteristic of pulmonary consumption, there are present in many cases features of essential importance aside from recognized areas of necrosis. These consist of miliary tubercles and of differing degrees and extent of pneumonic consolidation, catarrhal inflammation, caseation, cavity formation, calcification, fibrosis, compensatory emphysema, atelectasis, both from compression and from local occlusion of bronchioles, pleural inflammation with tubercle deposit, thickening, adhesions, perforation, and resulting pneumothorax. In addition to these conditions of pathologic interest incident to the invasion of the bacillus, there is exhibited a wide divergence in different cases in the amount of connective-tissue proliferation. This may be comparatively slight or absent altogether, particularly in cases of the acute pneumonic type the so-called tuberculous pneumonia. Upon the other hand, the connective-tissue hyperplasia is well marked in the more chronic cases of caseofibroid pulmonary tuberculosis, and not infrequently becomes a conspicuous anatomic feature, as in fibroid phthisis. In the same manner other pathologic conditions are subject to considerable variation in differing groups. The degenerative change may be rapid and extensive, with speedy formation of cavities, or slow and unaccompanied by recognized destruction of tissue, the process of repair being continually maintained in minute centers of infection. Generally speaking, the caseous degeneration is more marked in acute cases, in which it sometimes appears as an early pathologic manifestation. The necrotic changes leading to cavity formation, though present both in acute and in chronic cases, are not always exhibited in acute pneumonic phthisis on account of its very rapid development and brief duration. In this disease the early consolidation overshadows all other conditions and often imparts but the clinical aspect of either an ordinary catarrhal or fibrinous pneumonia, the victims sometimes succumbing before the development of extensive cavity formation. In miliary tuberculosis the degenerative process is present in disseminated tubercles, which are changed from almost invisible, gray, translucent specks into opaque, yellowish spots. In such cases gross areas of softening and excavation are seldom observed, on account of the rapid progress of the disease to a fatal termination. It is true that, exclusive of genuine miliary tuberculosis, fresh miliary tubercles may be present in association with large areas of pneumonic consolidation or with masses of caseous degeneration, but in such instances the tubercle does not form the essential or characterizing pathologic condition. Though tubercles are often found along the edges of consolidated, cheesy, or necrotic tissue, the macroscopic appearance of the involved lung, as a whole, is entirely different from that exhibited in miliary tuberculosis.

Again, pneumonic consolidation, although present in differing degrees in almost all cases of pulmonary tuberculosis, and even to some