PART THIRD.

Original Communications.

ART. I.

On the Mode of Development of Tubercle in the Lungs in Chronic Phthisis: its connexion with Fatty Degeneration of the Epithelium of the Air- Vesicles, and its Early Manifestations by Fatty Epithelial Cells in the Sputa. By C. RADCLIFFE HALL, M. D., F. R. C. P. E., Physician to the Hospital for Consumption, and to the Institution for Ladies with Diseases of the Chest, Torquay.

To ascertain with precision the earliest deviation from the healthy state in the part invaded by tubercle, is obviously a point of the highest interest and importance; and the difficulty of obtaining the information, at first sight, appears to be commensurate; for, when tubercle is already present, the condition of tissue which immediately preceded its deposition may have passed away, and when no tubercle yet exists, we cannot be quite sure that any would ever have ensued. This difficulty, however, diminishes when we consider that tubercle is deposited not all at once, but progressively; that it increases by accretion at its circumference; and, consequently, that the peripheric portion of a slow tubercle must be more recent than its centre. Certain differences in colour and density are visible to the naked eye; and with the microscope we can readily discern that every tubercle of tolerable size presents a series of different appearances, as it shades off in irregular zones, from complete tubercle to healthy lung. Knowing that any given tubercle, if progressive, would have continued to enlarge by the peripheric addition of tuberculous matter, we have a right to infer that the condition of that part of it which is nearest to healthy lung represents the earliest local morbid change the first step in that local process which ends in the formation of tubercle. At all events, we approach as nearly to the facts as the nature of the circumstances will permit. It may be objected, that any given morbid condition around a tubercle may be the mere conse quence of the morbid deposit already there, and so can indicate nothing respecting the phases of primary tubercular deposition. Even then we should learn the nature of the condition which favours increased deposit, after tuberculization has once commenced. But the objection can be disarmed of much of its force, for it is only valid provided the presence of inflammation, or that of any kind of heterologous formation indifferently, is adequate to produce a similar morbid condition: if not, then tubercle coincides with this condition, not because it is a mere morbid deposit in the lung, nor because of the inflammation which often accompanies it, but because it is tubercle. Now, we can show that mere inflammatory exudation, in a lung without tubercle, is not surrounded by a similar morbid zone intervening between the solidified and the healthy portion of lung; whilst tubercle which has not yet any inflammation around it, is. Then, again, we can show, that a morbid deposit which is neither inflammatory nor tuberculous-as, for example, the entozoic disease in the lungs of sheep-has no such morbid zone. On the other hand, in connexion with tubercle, we find the same morbid condition in some parts of a tuberculous lung, which are not yet the seat either of tubercle or of inflammation; in the portion which forms the immediate margin of the tubercle; and, in the form of relics, in the mature tubercle itself.

Thus, one given morbid condition is found where tubercle does not yet exist, but where it would probably have ensued; and around existing tubercle where we know that more tubercle would have been formed; and vestiges of the same are met with amongst

the elements of completed tubercle. All this suffices to prove, at least, an intimate connexion of some sort between the condition in question and tubercle.

Development of Tubercle-Taking for examination any tolerably large distinct tubercle, we see with the naked eye that there is no abrupt line of demarcation between the healthy lung and the margin of the tubercle. A simple lens discloses further, that the tubercle has not any distinct and even margin at all, but has a jagged, irregular outline, from processes of tubercle jutting out into the surrounding lung. By means of

Fig. 1. Preliminary stages of tubercle. From soft, grey, uninflamed lung, bordering a yellow unsoftened tubercle. +250.

a. Epithelium, scarcely altered.

c. Epithelium, more fatty and enlarged.

b. Epithelium, fatty.
d. Compound cells.

the microscope we perceive that the edge of one of these jutting processes of tubercle is not the limit of the morbid change; but that what, on cursory inspection, appears to be not unhealthy lung, immediately bounding the real tubercle, is in reality diseased, though not tuberculized.

Tracing onwards from lung which has no abnormal appearance to the centre of a large crude tubercle, we find as follows:

1. The pavement-epithelium of the air-vesicles is more nebulous.

2. Each epithelial cell becomes enlarged, more cloudy, more prominent when seen in profile, and is studded here and there with oil-dots.

3. The epithelial cells become still larger, and more fatty. In many of them no distinct nucleus can now be made out, but large dots of oil occupy its place. Some of the cells are detached, leaving the wall of the air-vesicle in one part bare, in another coated with compound tubercle cells. These are the preliminary stages of tubercle.

4. We now arrive at the completed tubercle, which consists of compound tubercle cells, small free neuclei in abundance, and granules; and occasionally, in addition, of a few fatty epithelial cells in various stages of disintegration; all being held together by a tough matrix.

It now

5. So far, the deposit has been confined to the interior of the air-vesicles. invades the intercellular tissue of the lungs. For the first time we find tubercle corpuscles amongst the fine fibres which form the frame-work of the walls and septa of the air-vesicles. These fibres are here and there seen to be broken into lengths, and the en

tire tissue of the affected lung has become the seat of tubercle. In the first stages, tubercle is only intra-vesicular; at last, it is both intra-vesicular and interstitial. But it is to be remarked, that distinctly cemented in amongst the pulmonic fibres, we never find any of the compound tubercle cells, but only the free nuclei and granules.

The steps of the local morbid process, then, appear to be these:-Fatty degeneration of previously normal epithelium; shedding of this; its replacement by fresh epithelium, degenerate from the first, and rapidly becoming fatty; shedding of this; its replacement by large cells containing several nuclei: shedding of these; their replacement by free nuclei and granules, embedded in a structureless matrix. Up to this stage the tubercle is intra-vesicular only. The pulmonic fibres are next enclosed and separated by the morbid exudation, and free nuclei and granules are formed between and amongst them. The tubercle is now complete.

Tuberculization of the lungs thus commences as a degeneration of a normal tissue, proceeds as a production of this tissue in a depraved form; next, as an exudation capable of following only the lowliest process of organization up to maturity. Its ulterior

1. Air-cell, with its epithelium healthy and adherent.

2. Ditto, with epithelium fatty and enlarged, still adherent.

3. Ditto, with fatty epithelium detached in places; compound tubercle cells upon wall of air-vesicle in places; wall bared in places.

4. Ditto, ditto, with exudation of tubercle-blastema into air-vesicle.

5. Complete tubercle, bounded by irregular line of black pigment: consists of air-vesicles and their septa filled and infiltrated with blastema, with compound tubercle cells and fatty epithelial cells, as well as free tabercle-nuclei and granules in the air-vesicles, but only the free nuclei, granules, and black pigmant interstitially amongst the pulmonary fibres.

changes from maturity, also, are those of the degeneration of a lowly-organized product; but concerning these I have dealt elsewhere.*

The structural representatives of these several stages, starting from normal epithelium, are the following, and may be considered in their natural order. They may not all be detectible at once in every mature tubercle, particularly if softening be commencing; but they are to be found in various proportions in the great majority of tuberbles, provided we include along with the tubercle a certain portion of the pulmonary tissue around it.

Constant constituents of mature pulmonary tubercle at some period of its course:

1. Normal epithelial cells becoming fatty.

2. Fatty epithelial cells.

3. Many nucleated cells.

4. Free nuclei.

5. Granules.

6. Matrix.

Frequent constituents:

7. Small blood vessels in a state of fatty degeneration. 8. Red blood-corpuscles, and orange-brown pigment. 9. Black pigment.

10. Granule cells, and glomeruli.

11. Induration-matter.

1. Normal Epithelium becoming Fatty.-The existence of an epithelium at all in the air-vesicles has been questioned by physiologists of high repute, but is now very generally admitted. Blood-corpuscles seen through the walls of the capillaries were indicated by Mr. Rainey as having possibly been mistaken for epithelial cells. Such an error cannot arise when the lung of a bird, or of an amphibian, is examined. The even oval outline of the large and clearly-defined blood-corpuscle is too distinctive. In the frog, the epithelial cells are coarser, dimmer, and more separated from each other than in the bird or mammal; having reference, perhaps, to the greater expansibility of the lung-sac. In the bird, the cells run one into another, at their margins, showing only a faint outlining as their mark of division. In man also, the outlines are less sharply defined than in most other varieties of pavement-epithelium; but the flat cells are bounded by a dim line of limitation. In appearance they are thin, almost transparent, and have a slightly nebulous, somewhat ill-defined nucleus, very different from the bright sharply-cut nucleus of the pavement-epithelium of the mouth, for instance. A nucleolus is not distinctly to be made out. In size and shape the cells vary greatly; smaller and rounder when young, they become rather longer, flatter, and more angular with age. Pentagonal, hexagonal, or polygonal, with angles more or less acute or round, according to their mutual fitting into each other; their general character is, that they constitute a fine, but dimly-defined pavement-epithelium of a single layer. Whether this internal cuticle undergoes any regular process of desquamation and reproduction in health, is unknown. In all probability, it behaves very much like the pavement-epithelium of serous membranes, in being for the most part persistent, and only cast off and renewed when accidentally incapacitated. Like serous epithelium, too, it permits the transudation of a thin watery halitus (with the especial addition, in its own case, of the of respiration), whilst it prevents the gases passage complete blood-plasma, acting in this respect as a natural defensive coat of elastic cement. When becoming fatty, the flat epithelial cells first appear better defined at their edge, and more nebulous at their centre. Next, they are larger, plumper, and more distinctly separate one from another, though still adherent. Oil-drops, of different sizes, spot the whole of the nucleus, which either stands out in relief as full of oil-dots, whilst the surrounding portion of cell is only nebulous; or it is apparently converted into one large

of

* In the Annual Address in Medicine for 1853, delivered before the members of the Provincial Medical and Surgical Association.

oil-dot; or, it is obscured or lost by general oil-dotting of the entire centre of the cell, the marginal portion only remaining clear.

2. Fatty Epithelium degenerate from the first.-Nearer to the tubercle than those air-vesicles which are lined with normal epithelium, which is becoming fatty, we find other air-vesicles, containing a quantity of detached epithelium, yet still having an epithelial coat on their walls, presenting cells in various stages of fatty degeneration. Fig. 3. Flakes of fatty epithelium from lung adjoining tubercle, Some of these are small and round, showing the various sizes of epithelium cell when becoming fatty.

evidently young, yet fatty. In many, the nucleus is not fatty, whilst the cell is. In others, the whole is fatty, both cell and nucleus; the situation of the latter being still traceable by the clustering of oil-dots there. Lastly, the fatty spotting is so universal, that nothing remains to indicate where the nucleus had originally been. Although we have no right to infer that all these forms may not be presented by the original epithelium in different stages of fatty degeneration, it is certain that there are successive generations of epithelial cells which, almost from the period of their formation, begin to fattily degenerate, indicating a proneness from the first to fall into this kind of atrophy. In the fist instance, the normal epithelium has existed indefinitely before it becomes fatty and is shed. In the last, the newly-formed epithelium is unable to maintain a normal life for more than a brief period of uncertain duration; it early becomes fatty, even whilst its growth is yet incomplete, and doubtless is rapidly shed, to make way for a fresh tribe of increasingly degenerate epithelial cells. I suspect that those cells in which we find the nucleus alone fatty, are the degenerated original normal cells; and that those in which we see the surrounding cells largely fatty, whilst the nucleus is less or not at all so, as well as those in which all is alike affected with fatty degeneration, represent the subsequent tribes of degenerate epithelial cells. As countenancing such an opinion, I may state that I have found the earliest evidence of morbus Brightii in renal epithelial cells discharged in the urine, in which the nuclei alone were fattily degenerated.

Passing by this supposed distinction, the fatty epithelial cells, taken indiscriminately, present considerable variety in appearance and size. The following may be given as examples (fig. 4):

a. A middle-sized, sub-angular, well-defined plate, having a large oil-globule in place of nucleus; the rest being merely nebulous near this oil-globule, and clear near the cir

cumference.

6. A rounder cell, either small or middle-sized, having a large oil-globule in place of nucleus and remainder of cell dotted with oil-dots of different sizes.

c. A flat cell, not generally fatty, containing two or three oil-globules in its centre. d. Flat-cells of very irregular outline, having a large nucleus with central oil-dots; rest of nucleus clear; cell around nucleus full of oil-dots of varying size.

e. The same as the last, but whole of nucleus fatty, though still discernible.

f. An irregular cell, not at all fatty, but having very large nucleus dotted all over with fat dots.

g. Flat cells of various but irregular outline, wholly fatty; nothing in place of nucleus detectible. Oil-dots very variable in size.

h. The same as the last, but with a margin of cell all round, not fatty, but dimly

clear.

i. Flakes of detached epithelium, showing the cells altogether fatty, having a subangular outline, still adherent at their edges; very varied in size and shape, but fitted one into another without any interval of separation.

j. Similar detached flakes, but the fatty epithelial cells more swollen, and, though still