Book - Contributions to Embryology Carnegie Institution No.12

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Cunningham RS. On the development of the lymphatics of the lungs in the embryo pig. (1916) Contrib. Embryol., Carnegie Inst. Wash. 7:45-68.

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This 1916 paper by Cunningham in the Carnegie Institution of Washington - Contributions to Embryology series describes the early lymphatic development of the embryonic pig lung. The pig was often used as a model of human development.

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1902 The Nasal Cavities and Olfactory Structures | 1906 Lung | 1912 Upper Respiratory Tract | 1912 Respiratory | 1914 Phrenic Nerve | 1918 Respiratory images | 1921 Respiratory | 1922 Chick Pulmonary Vessels | 1934 Right Fetal Lung | 1936 Early Human Lung | 1937 Terminal Air Passages | 1938 Human Histology
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On the Development of the Lymphatics of the Lungs in the Embryo Pig

By R. S. Cunningham



From an analysis of the literature on the development of the lymphatic system, it is clear that there is a general agreement among recent workers that the mammalian lymph-sacs precede the lymph-vessels in the time of their appearance, and hence constitute what may be called a primary lymphatic system. This system consists, in mammals, of 8 sacs: 3 paired, the jugular, the subclavian, and the posterior iliac lymph-sacs; and 2 unpaired, the retroperitoneal sac and the cysterna chyli.

The further development of the lymphatic system — that is, the formation of the thoracic ducts and the peripheral vessels — has been discussed at length by numerous workers during the past decade. These workers have been grouped into two general schools: the one holding that the lymphatics grow by a centrifugal sprouting of pre-existing endothelium, the other believing that these vessels are formed by a coalescence of numerous isolated spaces developing in the mesenchyme.

According to the centrifugal theory, briefly stated, the sacs arise from the veins and are johied together by vessels that sprout out from their endothelial walls. Thus the thoracic duct arises from both the retroperitoneal sac and the left jugular sac, and the two elements unite somewhere between the two points of origin. Supporters of the centrifugal theory claim that the secondary lymphatic system (the capillary bed) arises by the sprouting of the endothelial walls of the sacs and of the right and left thoracic ducts. These sprouts invade the organs and, becoming progressively more complex, assume the adult form of the lymphatic system. The supporters of the multiple-anlagen theories (whether they believe in coalescing tissue-spaces, multiple venous origins, or degenerating veno-lympha tics) agree in claiming that lymphatics do not grow by the centrifugal sprouting of the pre-existing endothelial walls.

It is not my intention to review here all the various theories that have been advanced, but only to call attention to the two general views, in order to correlate my findings with them. A very thorough discussion of these two views, as well as a comprehensive review of the literature, may be found in the Ergebnisse der Anatomie und Entwickelungsgeschichte, 1913. (Dr. F. R. Sabin. Der Ursprung und die Entwickelung des Lymphgef assy stems.)

Though primarily concerned with the problems of origin and the method of growth of the lymphatic vessels, the supporters of both theories have aided in establishing the morphology of the primary system and have laid the foundation for the further study of the development of the system as a whole. If the centrifugal theory is correct, it is clear that it should be possible to follow the growth of lymphatics from the sacs into anj- organ or group of organs. It should also be possible to demonstrate in progressively older stages constantly increasing lymphatic zones and decreasing non-lymphatic zones. The development of the lymphatics of the skin, of the intestine, and of the lung has now been studied in this manner.

In 1904, Dr. F. R. Sabin demonstrated that the skin received its lymphatic supply from the two jugular sacs and the two iliac sacs. From each of these sacs a group of radiating vessels invade the skin and form there a close-meshed plexus. These four plexuses gradually increase in size and finally unite, so that the entire skin is supplied with lymphatics. The differentiation which takes place varies with the location and depends upon the adaptation which the vessels must make to the other structures. Continuing the work of Baetjer (1908) on the retroperitoneal sac, Heuer (1909) studied the development of the intestinal lymphatics by the injection of this sac. He observed and described progressive changes in the intestinal supply, finding more complex injections possible in each older stage. He interpreted these results to mean that the lymphatics had not extended beyond the point which his injections reached and that the region beyond this point constituted a non-lymphatic zone.

There is, therefore, a i)riniary and a secondary lymphatic system. The former consists of a series of sacs formed from the veins and connected by the right and left thoracic ducts. The secondary system consists of the peripheral vessels, which are held by some to be outgrowths from the sacs and by others to be formed in situ. With regard to the development of these perpiheral vessels, only those of the skin and the intestine had been studied. There was need, therefore, for the study of the other abdominal and the thoracic lymphatics. This work was begun to establish a. clearer conception of the development of the secondary system.

In presenting this study, I do not claim to have found any new evidence as to the mode of growth of lymphatics. This work supports the centrifugal theory in the same manner as does that of Heuer (1909) ; and it is certain that the theory is sufficiently well established to .serve as a basis for this work. It is the object of the present paper to follow the gross morphological changes in 1h(> development of the Iymphatic vessels of the lung from the primary' stage to the adult form. It is desired to indicate the general lines of growth and the various stages which the system passes through in the course of its development. No attempt has been made to study the finer structure of the vessels or the mode of growth.

It is important to note that complete injections are very difficult to make, and that it is also difficult to be certain whether the injection in a i)articular specimen is complete or not. Therefore it is not claimed that any of the injections are complete; and the limits of the lymphatic and the non-lymphatic zones ai any stage are defined in a general uiaiincr, depending on the comparison of a number of specimens.

The lymphatic supply of the lungs develops from three sources: the thoracic duct, the right thoracic duct, and the cephalad portion of the retroperitoneal sac. In 1904, Sabin remarked: "The right lymphatic duct curves ventralward and grows to the heart and lungs." This is llic only statement which I \va\v Ix'cn iibic to find in the literature regarding the development of the cardiac and pulmonary lymphatics from the right duct, or the morphological fate of the right duct in mammals. In the same report attention ^vas called to the fact that the lung- vessels can be injected from the retroperitoneal sac, but this was not studied further at that time. The right duct grows primarily to the heart, just as the left grows to the aorta, this asymmetry depending upon that of the cardio-vascular system, according to the general rule that the principal lymphatic trunks follow the large blood-vessels, and grow with the greatest rapidity where the blood-supply is most abundant.

In the beginning I wish to lay emphasis upon the fact that the lung lymphatics develop partly from the retroperitoneal sac. and to call attention to the fact that these vessels persist in the adult as part of the permanent drainage of the lung, and hence may be of importance in pathology. On account of the complexity of the development of the lung lymphatics, it has seemed best to present this work, not by describing and figuring a series of progressively more complex specimens, but by describing the development as a consecutive growth and illustrating with those preparations that may seem best to clarify the text. However, as a matter of reference, the following table of periods has been arranged, in order to offer a brief outline of the complexity at varying stages. These stages are selected with regard to the more important principles of growth and are as follows:

  1. The (lowngrowth of the two ducts, completion of the primitive system, and the first vessels to the trachea and lungs. Embryos 2.3 to 3.5 cm.
  2. The migration of the heart ; the coalescence of the cardiac drainage with that of the lungs, by the formation of the tracheal plexus and the plexus on the arch of the aorta; the growth of the vessels in the lung from the earliest sprouts along the bronchi to the primitive pleural plexus, and the early marking-off of the connective-tissue septa; and the growth up from the retroperitoneal sac through the liganientum latum and the anastomosis in the primitive septa into which the vessels grow. Embryos 3. .5 to 4.5 cm.
  3. The completion of the primary lymphatic system; that is, when the entire organ is supplied, and the further development is in an increasing complexity of the plexuses already present, incident to the increase in the .size of the organ and its assumption of mature activities. During this period the formation of the valves and nodes begins. Embryos 4.5 to 7 cm.
  4. The remainder of the development is considered a period, as it is, in reality, an adaptation of the system already present to the increasing needs of the organ. This includes the differentiation of the drainage-lines and the final development of the nodes.

In describing the development of the lymphatics of the lung, the growth of the left duct down to the aorta, of the right duct to the heart, and the formation of the primitive tracheal plexus and the early vessels to the lungs from both ducts will be considered first; the further development of the tracheal plexus, together with the changes incident to the descent of the heart, will follow; then the origin of the vessels from the retroperitoneal sac and their growth up through the ligamentum pulmonale into the lungs will be considered. After the anastomoses of the two sets of lymphatics, the lung will be considered as a whole, inasmuch as the further development is symmetrical for the entire organ, with the exception of the final lines of drainage and the development of the nodes.

I wish to express here my indebtedness to Professor F. R. Sabin for her constant advice and assistance throughout this work. Also I wish to thank ^Ir. James F. Didusch and Miss Flora SchaefTer for the illustrations.


The injection method has been principally used, but it has been supplemented and supported by evidence from both single and serial sections. The collection of pig embryo of the Anatomical Laboratory has been at my disposal, and I have also studied a number of especially prepared series. Many of the series have been of embryos in which the blood-vessels have been injected, and this has materially aided in their interpretation; in fact, in all the especially prepared series the blood-vessels were injected. All these embryos were fixed in Carnoy's fixing fluid, consisting of 6 parts of absolute alcohol, 3 parts of chloroform, and 1 part of glacial acetic acid.

The method of fixation is as follows: Place the embryo immediately in the fluid and allow it to remain there 6 to 8 hours; then transfer directly to 70 per cent alcohol; dehydrate by ascending grades of alcohol with 2 per cent difference until 95 per cent is reached; then change to absolute. This gives excellent fixation with very little shrinkage. The stains used were Ehrlich's hematoxylin and a mixture of eosin, aurantia, and orange (1.

The injection masses used were india ink, a saturated solution of prussian blue, a 5 per cent aqueous solution of silver nitrate, and an aqueous suspension of lamp-black. The india ink and prussian blue give about the same results, except that the specimens injected with prussian blue are more easily studied after clearing, as the ink renders them more opaque. The india ink, however, flows more easily and hence the injections are more nearly complete. The silver-nitrate injections are easiest to analyze and give beautiful preparations, but its caustic action prevents the finer vessels from filling, so that only the larger trunks are injected; however, it furnishes an extremely valuable method of following the principal drainage-lines at different stages. The lampblack is the mass which gives the most nearly complete injections, but unfortunately it precipitates in fine flakes and gives a feathery appearance to the specimen, thus rendering it difficult to use for illustrating.

It will be necessary to review the methods used in injecting the various stages, as they differ considerably and are of especial importance in interpreting the results. The earliest injections were made by filling the jugular sacs from the superficial plexuses and then gently moving the embryo. I have succeeded in injecting the early vessels to the trachea and the lungs in only a few pigs less than 3 cm. long, because the injection mass usually follows the path of least resistance, which is into the jugular vein.

In injecting embryos between 3 and (> cm. in length, three general nietluKls have been employed:

  1. The best and by far the easiest method of obtaining good preparations of the left part of the tracheal plexus is to inject through the retroperitoneal sac in the manner described by Heuer (1909); but this seldom gives good preparations of any of the vessels of the lung except those of the lower lobe. However, this method has been of particular importance in following the lymphatics uj) from the retroperitoneal sac to the posterior poles of the lower lobes.
  2. One may inject the tracheal plexus, especially the left i)ai(, l)y plunging (In- needle deep behind the aorta and injecting cerebral wards; the right plexus is sometimes filled also, and often the vessels of the left lobe of the lung.
  3. Finally, the vessels of the lung are best injected by a puncture just ventral to the trachea (the tracheal plexus) and behind the arch of the aorta. Here the

tracheal plexus is always extravasated, but the lung-vessels fill up nicely.

The embryos older than these mentioned, that is, longer than 7 cm. (or after the valves are formed), are much more difficult to inject, and this difficulty increases with further development. The method employed has been to inject directly into the connective tissue septa of the lung and to continue the injection slowly until there is some extravasation at the point of puncture, when a part of the lung surrounding the area of extravasation is well injected. This method has been very satisfactory in all specimens that were obtained very soon after the removal of the uterus; most of the injections were made while the heart was still beating.

In order to study the relations l)etween the l)lood-vessels, bronchi, and lymphatics, multiple injections had to be made, various combinations were employed. In some, the lymphatics were injected together with veins and arteries; others with either veins or arteries alone. Again, the lymphatics and the bronchi were injected; and in still others the lymphatics were combined with either veins or arteries. In these multiple injections prussian blue, India ink, and carmine were used, the lymphatics being injected with either the blue or the ink.

The specimens in which three systems were injected were difficult to clear, unless only the large bronchi and blood-vessels were filled.

In order to trace the vessels more accurately, many of the injected lungs were embedded in paraffin and cut in thick serial sections (100 to 500 m); these were mounted in balsam but not stained. Other lungs were cut at 10 to 20 ai and stained similarly to the series already referred to.

All measurements of embryos refer to crown-rump diameter and were taken before fixation, as is customary in this laboratory. The illustrations are labeled "C. R. L "; this refers to the crown-rump measurement.

In 1900, Flint published his study on the development of the lungs in the pig, and his work has been taken as a basis of the general structure of the lungs, especially with reference to the development of the bronchi and blood-vessels. He reviewed all the important literature on the embryology of the mammalian lung, studied the lymphatics in sections, and briefly summarized their structure and distribution at various stages, but he did not attempt to inject them. I have been able to confirm most of his observations. However, he labored under the difficulty of having neither reconstructions nor injections. He gives a short summary of each stage, and of these summaries I quote the more important parts :

Stage 3 cm.: At the root of the lung a few dilated lymphatics may be noted near the bronchi and pulmonary vessels; however, they have not grown bej'ond this point into the substance of the lung wings.

Stage 5 cm.: From the root of the lung the lymphatics have gone some distance into its substance. They have thin walls composed of young fibrils Hncd with endothelium with occasional valves. They are confined, however, to the immediate neighborhood of the main bronchi and their chief subdivisions.

Stage 7 cm.: The most interesting change, however, hes in the further growth of the lymphatics, which in the earlier stages are found in the root of the lung in the neighborhood of the pulmonary vessels and the large bronchi. .As they grow in. they accompany these structures for a distance; thou approaching the end branches tlny leave them and run in a plexiform manner midway between the broneliial tubes until they reach the pleura. This gives the kiiiK now an indefinitely lobulatcd appearance in which the periphery of the simple lobule is indicated by the lymphatic vessels and the center by the bronchi. The lymphatics are lined with flattened endothelium; their walls are formed by the young connective-tissue fibrils, and here and there valves are beautifully shown which, in general, point away from the pleura.

Stage IS cm.: The lymphatics, forming a plexus around the bronchial veins and arteries at the root of the lung, accompany them towards the periphery, giving off branches to the interlobular spaces en route. * * * On reaching the periphery of the lung they leave these structures and pass out, as in the preceding stages, to the pleura. They have a plexiform arrangement and may be traced at times into the substance of the lobules. This course may be observed in the deeper lobules of the lung as well as in those on the surface under the pleura.

Stage 19 cm.: In general the relations of the lymphatic systein have not changed.

Stage 23 cm.: At 23 cm. the first evidence of the submucous lymphatic system is seen in the stem bronchi. It may, however, be found earlier, but the vessels are difficult to follow. It would seem thus that we have in the pig's lung, liesidcs the lymphatic plexuses accompanying the bronchi, arteries, and veins, an interlobular system which IMiller has been unable to find in the human lung. Injections pointing to such a relationship he has interpreted as artefacts. If Miller's conclusions prove correct, then the Iymphatics of the human lung must develop, so far as the interlobular system is concerned, in some other way.

I quote at length from Flint because he alone, of the many workers on lung lymphatics, has api)roached the subject from the embryological side. As I have said. Flint was seriously handicapped by having only sections from which to draw his conclusions. He was especially struck by the prominence of the vessels lying in the interlobular septa, and attempted to explain their apparent change of course (j. €., from the bronchi to the septa) by the theory that the density of the tissue was greater around the bronchi and vessels and that the lymphatics chose the path of least resistance. He did not call attention to the relation of the veins to this point in the development of the lymphatics, which will be discussed later, but emphasized the fact, so amply shown by injections, that these interlobular vessels grow much more rapidly than the vessels around the bronchi and arteries.

It will be necessary hereafter to discuss the work of Miller on the adult lymphatic system, in connection with the later stages; therefore it will suffice to refer here to the statement which Flint discussed in the quotation given above. Miller has called attention to the fact that the terminal vein lies in the periphery of the lobule and that the lymphatics accompanying the vehi communicate with those of the pleura. He cites Councilman's (1900) description of the interlobular vessels, but does not claim to have found the same vessels. I think that these different views will be reconcilable when w^e have followed the development of the lymphatics through the various stages that lead to the adult form. The literature on the lymphatics of the adult mammalian lung is very large, and for a comprehensive review of it the reader is referred to the papers of :Miller (1893, 189(), 1900, 1902, 1911). It seems needless to discuss it more at length here.

The Vessels Arising from the Left Duct

As has been said, the lymphatics of the lungs arise partly from the two thoracic ducts by sprouts. These vessels grow to the mesenchymal wall of the trachea and form there a jjlexus which sends vessels down into the lungs. Other vessels grow directly into the lungs.

The thoracic duct, as has been shown by Sabin (1913), Baetjer (1908), and Kampmeier (1912), is complete — that is, it connects the jugular sac with the retroperitoneal sac — in a pig; embryo 2.5 cm. long. Very soon after this the first evidence of the pulmonary supply may be found. I have obtained partial injections at 2.8 cm., and have found some small vessels in serial sections at 2.6 cm.; so it is evident that these sprouts are either formed from the thoracic duct as it grows down or very soon after the primary system is completed.

About midway between the jugular anastomosis and the arch of the aorta the thoracic duct leaves its position lateral to the trachea and bends dorsalward to lie near the dorso-lateral border of the esophagus. In this position it comes down behind the arch of the aorta. This transition is shown by Sabin (1913, figures 12 and 13). Just at the point where the duct begins to bend dorsally the earliest sprout to the lung is formed. At this point a single large vessel buds off from the thoracic duct and passes down over the arch of the aorta to reach the hilum of the lung. This vessel unites with the vessels that grow up from the thoracic duct just caudal to the arch of the aorta and forms the lower part of the tracheal plexus. This vessel usually persists in the adult as one of the drainage trunks from the iliac nodes to the thoracic duct. It is shown m figure 5, plate 1, and figure 2, plate 4, marked with an asterisk. From the region of the thoracic duct, where this vessel buds off to a point about the level of the aortic arch, a number of other vessels are formed very soon afterwards. These vessels arise very close together and grow across to the lateral wall of the trachea, where they anastomose and form the primitive left tracheal plexus; thej' lie in the undifferentiated mesenchymal tissue that surrounds the tracheal lumen. These lymphatics have formed a plexus by the time the embryo has reached a length of 3 cm. From this plexus vessels grow across the trachea to anastomose with other vessels from the similar plexus on the opposite side; other lymphatics grow up the trachea and form a coarse-meshed plexus around it. This is the anlage of the adult supply of that structure. But the most important of the branches of this plexus, as far as the present work is concerned, are those from the lower part. These pass down the trachea and, being joined by other vessels that leave the duct near the arch, pass up over the bifurcation and into the lung. The left tracheal plexus is shown in figure 5, plate 1, and figiures 1 and 3, plate 2. Here must be noted the fact that the plexus of the left side supplies the greater portion of the ventral surface of the trachea and forms the largest part of the great sheet of lymphatics around the primary bronchi. Later these vessels anastomose freely with those from the right side. It is important to call especial attention to the difference in the richness of the supply of the dorsal and the ventral surfaces of the trachea. There are vessels that grow to each from the left plexus, but a much greater number pass to the ventral surface than to the dorsal. Thus the plexus formed from the two lateral groups is much more closely meshed on the ventral surface, and from it is derived the greater part of the lung supply. Over the bifurcation there is a very complex group of vessels, and these form tubes around the principal bronchi as they grow on into the lung.

Below the level of the hilum several vessels, three or four in number, grow up from the thoracic duct and its plexus surrounding the aorta, to join with the large vessel which has Ikhmi tlescribod as the first tu the king and wliicli comes over the arch to reach the hihnii. These vessels from the duct below the hilum form a plexus with the vessel from above, as has been described. It is well known that the thoracic duct is double below the level of the arch of the aorta and that the two divisions are connected by numerous anastomostic vessels (figure 1 , plate 2 ) . This system is the anlage of the vessels that surround the aorta in the adult. This relation has been figured by Heuer (1909). One of the lymphatics that pass up from below to join the first vessel from the thoracic duct above leaves the duct near the diaphragm and is consequently very conspicuous in injections of this region. Heuer has figured this lymphatic as one that goes to the heart, a conclusion entirely justifiable from the general appearance of the injected specimen. Figure 1, plate 2, is from a dissected embryo 4 cm. long, in which the lymphatics were injected from the retroperitoneal sac. The thoracic duct and \n\rt of the left tracheal plexus are injected, and the extension of the plexus down on the bronchus is also shown. Below the arch may be seen some of the vessels that grow up to meet the branch from above. These vessels have been cut off, with the arch, to expose the tracheal plexus. The double duct is also shown, the more ventral olemont being the one figured by Heuer.

The pulmonary vessels reach the hilum when the embryo is al^out 2.S cm. long, and can be seen in .sections at 3 cm. (see figure 1, plate 1). The lung-tissue is at this time very slightly differentiated mesenchyme, containing the early bronchi and blood-vessels. For a further description of the structure of the lung at this stage see Flint (1906). These early lymphatics are grouped in an irregular manner in the hilum of the lung and may be found at 2.9 and 3 cm. in sections. But I have not been able to inject them earlier than 3.3 and 3.5 cm. Figure 1, plate 1, is of a .section from an embryo 3 cm. long, in which the blood-vessels were injected while the embryo was still li\ing. The lymphatics are shown as a few dilated spaces (blue) in the hilum. These vessels are beginning their invasion of the lung-tissue while the tracheal plexus is forming. It is necessary, however, to complete the description of this plexus before considering the portion of this study which relates to the lung proper. The development of the vessels within the lung-substance will be considered after the formation of the right lymphatic plexus has been described. It is important, however, to note here that all the vessels to thi' left lung come from the closely united grouj) of vessels on the trachea and around the aortic arch, as has been described. This will be studied in relation to the first vessels to the lung on the right side, which will next be considered.

On the right .side the development is, in general, similar to that on the left, but differs in a few particulars, chiefly relating to and in consequence of the asymmetry of the vascular system. The right duct is primarily to the heart. or perhaps to the vena cava, since it follows that ve.s,sc"l to r(>ach the cardiac base. Hut while the heart supply is at first only from the right s'nU\ the vessels to the lung and the trachea develop at about the same time. The right duct grows caudalwaid i)arallel to the thoracic duct to the iwint where the vena cava arches ventralward to reach the heart. There it divides, and one branch follows the posterior wall of the vena cava to reach the cardiac, while the (.Hut p;is.scs into the hiluiii of the lung. The cardiac division, after reaching the base of the heart, along the posterior wall of the vena cava, passes around the bulbous arteriosus to reach the anterior surface of the heart, where it divides to form the primitive pericardial plexus. By introducing a canula dorsal to the vena cava and injecting towards the heart, I was able to fill this plexus in a p'\g 3 cm. long. At this stage it extends about one-fourth of the distance from the base to the apex of the heart. Figure 13 in Volume \ of the Johns Hopkins Hospital Reports, Monograph Series (Sabin on "The Origin and Development of the Lymphatic System"), shows the right duct near the heart in an embryo pig 2.5 cm. long. In that paper attention was called to the fact that the duct grows towards the heart and that it probably represents the cardiac supply.

The second of the two terminal branches of the right duct passes down parallel to the dorsal wall of the trachea in about the same general jwsition as that occupied by the duct above the point of division. Thus it might seem proper to consider the lung division as the more fundamental of the two, as it appears to be the continuation of the undivided duct. However, the heart branch is probably the more fundamental and the earlier of the two, since it is a general principle in the growth of lymphatic trunks for the principal vessels to follow the larger blood vascular channels. Hence we consider the left duct as primarily aortic and the right as primariy cardiac in distribution.

This vessel enters the hilum of the lung and breaks up into a few- branches that are grouped around the bronchi and blood-vessels as on the left. The nature of the grouping and the further development are similar on the two sides, and hence both will be considered together. There is, however, an interesting difference between the two u])per lobes, which is dependent upon the relation of the aortic arch to the hilum on the left. On the right the lung is distinctly higher (i. e., nearer the neck) than on the left, because on the latter side the aortic arch lies in the groove made at the juncture of the upper lobe with the trachea. Thus the vein to the upper lobe on the left passes close to the bronchus under the aortic arch, while on the right it is well above the bronchus. This allows more freedom in the honphatic growth on the right, so that the vessels to the upper lobe come down directly into it instead of growing back from a single grouj), as they do on the left. It must be understood that the stage referred to is between 2.5 and 3 cm., when the heart is still higher than the bifurcation. Later the heart passes still farther down into the thoracic cavity, and these differences disappear as the cardiac and aortic relations to the lung begin to assume their adult form. There is, however, one verj^ important effect of this asynometry; the lymphatics of the right duct pass directh' into the lung, while of the left must course up over the arch of the aorta and the bifurcation of the trachea to reach the lung-tissue. This has been mentioned briefly before. It is clear that the principal supply of the bronchi, and therefore, ultimately, of the lungs, comes from the left duct. This is in large measm-e the result of the asymmetric relations of the heart and aorta.

The development of the first vessels to the trachea and lungs on the right side will next be described in detail. From the heart Umb of the right duct a few vessels arise and grow down over the vein to the upper lobe on the right side; after crossing the vein thev enter the lung near the hilum and divide into several branches, some of which anastomose with those mentioned above as growing down into the liiluni of the lung from the pulmonary limb of the right duct. Other vessels turn outwards along the bronchi and veins and grow into the lung-tissue of the upper lobe. This process will be described later.

Along the right duct, cephalad to the division into the two branches, other vessels are given off; some grow down to anastomose with ascending branches lying along the tracheal wall and coming from the vessels described above, while others grow to the tracheal wall at varying positions along the section lying between the jugular anastomosis and the bifurcation, corresponding somewhat to the vessels on the other side, with which their branches anastomose, forming the tracheal supply. The earliest injection of the lymphatics of the right side were at 2.8 and 2.9 cm.

Figure 2, plate 3, shows an embryo of 3 cm., where the injection was made into the right sac, which illustrates the relative position of the vessels to the upper right lobe and the limb that follows the vena cava to the heart. This drawling is diagram- matic and does not show the different vessels to the lobes on the right side, though some of them were injected. The left duct is shown without any branches.

In Figure 1, plate 2, the right tracheal plexus is represented. Though it is very incomplete it shows the general form of the plexus and its relation to the similar plexus on the other side. The right tracheal plexus, in its simplest form, consists of a few vessels which are beginning to anastomose along the lateral wall. These anastomoses become more and more complex and numerous until, along the right side of the trachea, a plexus somewhat similar to that of the other side is formed. They differ, however, in that on the right there is no aortic arch to complicate the form. Therefore the plexus is a simple sheet-like group of vessels which lie along the lateral wall of the trachea, but do not extend up over the ventral surface of the bifurcation, except by a few anastomosing vessels. It anastomoses frcelj' with the larger plexus from the other side on the ventral surface of the trachea, and later the combined plexuses lose their individuality and appear continuous. In the meantime the two tracheal plexuses have begun to anastomose. This will next be described.

Between 3.3 and 4.5 cm. the two tracheal plexuses anastomose by means of numerous vessels which grow around the trachea, both dorsally and ventrally. AI)ove the level of the aortic arch these connecting vessels are far less numerous than below, where the two are merged into a sheet-like plexus that surrounds the trachea and passes down into the lungs as tubes of vessels surrounding the bronchi. Above the bifurcation the dorsal surface of the trachea has fewer vessels than the ventral, while the two original lateral plexuses are much more closely meshed, representing the anlagen of the two lateral groups of lymph nodes of the adult.

From the close-meshed plexus on the left side of the trachea just at the bifurcation a group of lymjihatics pass up over the left stem bronchus and sweeps across to the right bronchus, forming the upper group of vessels lying on the bronchial wall. These grow down on the side and with the vessels coming down from the plexus on the right side. Thus it will be se(>n that the left supply is a more important part of the general origin than the right, supplying, as it does, all of the left lung and part of the right.

It is of importance to note here that the heart is migrating downwards (i. e., caudalwards) during this period, and, by the time the embryo has reached 4.5 cm. in length it has come to lie almost directly over the hilum of the lung. Hence the vessels that formerly ran in a long course from their point of origin in the heart limb of the right thoracic duct to reach the upper lobe and the hilum of the lung have become a part of the common tracheal plexus, and the formerly distinct duct to the heart has also been absorbed by the plexus over the bifurcation.

The cardiac vessels then (at 4.5 cm.) drain directly into the plexus over the hilum of the lung (figures 1 and 3, plate 2). This relation remains in the adult in the drainage of the cardiac vessels into the mediastinal nodes and the union of the efferent trunks of these nodes with those from the hilum of the lungs.

Here must be mentioned, though not bearing ixirticularly on the lymphatics of the lungs, the connection between the right and the left ducts. In specimens of about 3.5 to 4 cm. in length, I have regularlj^ found a vessel arising from the dorsal part of the right tracheal plexus and joining the thoracic duct behind the aorta. As has been said, it seems best to consider the vessel to the heart as the continuation of the right thoracic duct; hence this vessel must be considered, as was the one to the lung, as a part of the collateral supply.

The lung, as has been stated also derives lymphatics from another source — the cephalad portion of the retroperitoneal sac. These vessels are growing into the lung during the period when those already described arc differentiating, but it seems best to postpone the discussion of this portion of the pulmonic supply until we have studied the early changes that take i)lace in the lung itself, following the invasion by the vessels already described. The desirability of this is evident when it is remembered that the vessels from below must follow a similar course in the lung, with the exception that this course is reversed, due to the fact that these vessels invade the lung through the pleura instead of the hilum, and must reach the other supply through the interlobular septa, to be described later.

At 3 cm. there are two primary bronchi and two veins on either side, one of each to each upper lobe and one to each lower lobe. From these the secondary branches are beginning to form. From 3 cm. to o cm., these secondary branches are developing rapidly and are very large in comparison to the size of the lung. The arteries are very much smaller, and the veins are somewhat larger than the arteries, but much smaller than the bronchi. It is of great importance to note the relations of these structures to each other during this period. Flint has studied their develop- ment very thoroughly, but he does not call attention to the fact, so im])ortant with reference to the lymphatics, that the developing vein is separated as widely as possible from the bronchus with which it is morphologically associated. The artery, on the other hand, follows the bronchus very closely and is distributed with it to the center of the developing lobule. The two primary branches of the pulmonarj' vein lie close to the corresponding bronchi. This is, indeed, as far separate as is possible, since there is almc?*^ no lung-tissue at this period, while the secondary vessels which may be considered the terminal branches lie about equidistant from the two adjacent bronchi. The arteries follow the bronchi more closely. This fact is of the greatest importance in the development of the lymphatics and also m the relation of the veins to the periphery of the lobule in the adult, as has been shown by Miller (1900).

As till' lung iiKToascs in size and (Ik' \t'in.s and Ijionclii wliicii \vc have termed secondary give off other branches, these in turn become the terminal ones and assume the relations that have been described. The others are, bj' the increasing amount of lung-tissue, forced closer together. Thus it is seen that it is only the terminal veins that occupy the position described; that is, pass along the periphery of the k)l)ule. In the i^ig there is considerable connective tissue forming definite lobules in the adult lung; and these .septa, bounding as they do the area supplied by terminal bronchi, divide the lung into a large number of irregular cones or pyramids, which have the bronchus and artery in the center and the veins passing along the periphery until close to the apex, where thej^ enter veins of the next larger size. For further discussion of this arrangement see Miller's article (1900).

As we have seen, a few dilated lymphatics are found in the hilum of the lung at 2.9 and 3 cm. These are the first branches from the vessels that are forming the plexus on the trachei and bronchi already described. The bronchi, as has been said, are surrounded by lymphatics which follow them into the lung-tissue; and, as secondary bronchi are formed, lymphatics from these plexuses branch off to follow them.

The primary veins lie very close to the corresponding bronchi at this stage, and are accompanied by a few lymphatic trunks which arise from the same general plexus that covers the bifurcation. These vessels anastomose very richly with those of the bronchi, and, close to the point where the trachea divides, they merge together. We have seen that the secondary veins lie midway between the adjacent bronchi, and represent the outer border of the primitive lobule of the developing lung. Along these veins the lymphatics grow towards the pleura; thej^ are derived both from the plexus that follows the primary vein and from the vessels that sur- round the primary bronchi. The lymphatics from the bronchial supply join those from the vein, and the combined grou)) passes along the vein, spreading out on either side to form a sheet, until the vessels reach the pleura. Flint observed these sheets of lymphatics, but thought that there must be some difference in the density of the tissues to account for their leaving the bronchi to run midway between. He did not recognize the relation between the veins and the lymphatics. It will be clear, when it is remembered that the smaller branches of one vein spread out fan-like to meet of the other vein, that the sheets of lymphatics lying between the bronchi are directed by the veins as well as the separate lymph vessels directly associated with them.

In this manner the true primitive lobules are formed by the interpolation of a sheet of rapidly growing lymphatics between the bronchial tubes. It is along the distal margin of plexuses that the pleural marking begins. When these vessels reach the pleura there is a marking-out of the characteristic coarsely-meshed plexus, each interspace corresponding to the sheet beneath (figure 3, plate 1). It must be remembered that these vessels, growing as they do very rapidly, reach the pleura very early, and hence the pleural plexus is developing while the above-mentioned interlobular plexuses are forming. We have so far described only the formation of the largely parallel plexuses shown in figure 1, i)late 4, figure 2, plate 5, and figure 1, plate 3. I*)iit ihe formation of \-eiiis in oilier ])lanes directs the growth of the lymphatics, so that with each bronchus there are several veins and several sheets of lymphatics developing. Thus the series of cone-shaped or pyramid-shaped lobules are surrounded by plexuses of lymphatics. Along these plexuses the differentiation of the connective-tissue layers takes place, for, when the lymphatics invade these areas, there is only an undifferentiated tissue, which is characteristic of the lung. Flint suggested that the lymphatics followed the bronchi for a certain distance and then turned away midway between them, because of some relative difference in the density of the tissues. It is quite impossible to observe the relation to the veins in uninfected sections, and consequently this point was not discussed in relation to the problem of the question of tissue density. Notwithstanding this phase of the development which Flint was unable to follow, there still remains considerable probability in his suggestion. The fundamental reason for the direction of growth is as yet entirely a mystery, but there .seems to be little doubt that the principal lines of lymphatic development are along the larger blood-channels; and, in general, the veins are chosen, though the left duct may be considered as following the aorta.

The much slower-growing lymph-vessels on the bronchi follow each branch out towards the periphery. The primary bronchus is surrounded by a very close-meshed plexus, which consists of a large number of vessels; in cross-section one can count from 50 to 75. However, this number is very greatly reduced on the secondary bronchi, each of which has four or five trunks following it. These are closely bound together by anastomosing collaterals.

With reference to the .secondary bronchi, almost the same series of events occur as given above for the primary ones. These secondary bronchi are likewise marked off by interlobular septa in which the lymphatics develop more rapidly than along the bronchus whose lobule they mark off. The lymphatics around the bronchus give off small vessels near each branch of the bronchus, and these pass across to join the plexuses that surround the area of the lobule (figure 1, plate 3). As the new-formed bronchi grow larger they are, in turn, followed by two or three lymphat- ics, which end, as did those around the secondary' bronchi, by passing over to join the septa or, if close to the pleura, the vessels there. These lymphatics that pass from the bronchial system to join those in the septa follow the branches of the veins which bend in from the septa to reach the capillary bed of the arterial tree. These persist in the adult as the vessels that pass from the bronchus to the vein and thence to the pleura (figure 2, plate 1).

We will consider now the lymphatics that grow up from the retroperitoneal sac into the caudal pole of the lower lobe.

In 1906 F. T. Lewis described, in rabbit embryos, a lymphatic sac just median to the mesonephritic vein. Baetjer (1908) showed that it arises from the ventral surface of the large vein which connects the two Wolffian bodies (embryos 17 to 23 mm.); Heuer, following Baetjer, found that numerous lymphatic sprouts arise from this sac and invade the intestine through the mesentery. This sac supphes lymph-vessels to the stomach, the liver capsule, the AVolffian bodies, and the repro- ductive glands.

The lower pole of the lower lobe of the lung is contmuous with the mesentery in the earlystages. As the embryo develops, this comiection becomes a thin band of tissue that passes down Ix'liiiid the (Uaphragni to end in the tissue around the aorta; it corresponds to the hgamentuni puhnonale in the human. It is through this prolongation of the lower lobe that the lymphatics from the retroperitoneal sac grow uji to reach the lung. These vessels arise from the cephalad portion of the sac and iias.s u]) l>ehind the dorsal w'all of the stomach to enter this long jiosterior or lower pole of the lung (figure 2, ])late 4). There are three or four vessels that grow out from the sac and up into the lung; these are closely associated with those that pass to the diaphragm and, in adult life, join with them just before reaching the nodes into which they drain. They pass upward and divide, on reaching the lung, into two groups, one of which passes up over the diaphragmatic surface and the other over the outer or lateral surface of the lower lobe.

The anlage of the ligamentum pulmonale is connected not only with the lower l)ole of the lung, but also with the median border of the lower lobe. Thus the lymphatics grow directly up about one-third of the way to the hilum in this medial extension of the ligament, and from there sweep out in a fork-like division which produces the two plexuses on the two borders of the lung (figure 3, plate 5) . I have injected these vessels at 3.4 cm.; but I think that they reach the lung border a little earlier.

From the two plexuses described above vessels grow into the lung in exactly the reverse order to that followed by those develojjing from the hilum. They grow in just where thej' wtU meet the veins, and along these form the septal plexuses, exactlj' similar to those described above. These rapidl} anastomose with the other lymi)hatics. and, by the time the embryo has reached 4 cm. in length, the entire lung is uniformly supplied.

It is very pertinent to infjuire why the lymphatics that reach the lung from below select these points for the; im'asion of the deeper tissue of the lung. However, when it is recalled that the lymphatic vessels which lie in the mesenchymal tissue (the pleural anlaga) are very large in proportion to the other structures and that the budding vessel would be in direct relation to the outgoing veins, it is easily understood that exactly the same causes must be acting here as those which direct the growth from above. So here, as above, the position of the veins controls the direction of growth. Of course, the plexuses on the two surfaces become more complex as the lung is invaded and follow the same steps as the pleural supply in general. As has been said, there are branches along the pleura, and these anastomose with the other pleural vessels, so that the supply becomes general. The drainage in the early stages — that is, before the formation of the valves— is probably divided; the flow of lymph might be to the retroperitoneal sac via the vessels that grow up from that structure, or to the thoracic ducts through the tracheal plexuses and the vessels accompanying the veins and the bronchi.

We have seen how the lymphatics grow into the lung-tissue and there form two distinct groups, and how one of these rapidly reaches the pleura and there forms the characteristic plexus-pattern marking off the boundaries of the lobules; also how the vessels grow into the posterior i)oles of the lower lobes and anastomose with the system from above, which follows the veins in the connective-tissue septa.

Now, it will be well to review briefly the state of the development of the lung lymphatics at the time that the primary system is complete — that is, in 6 cm. embryos. At 6 cm. the lymphatics around the trachea form a dose-meshed ple.xus near the bifurcation, extending down into the lung around the bronchi. Above the bifurcation there are only a few connecting vessels on the ventral and dorsal surfaces of the trachea, but the two plexuses on the lateral surface are very close-meshed. From the left plexus the principal supply of both lungs is derived, but there are numerous vessels passing down into the right lung from the right plexus, and the two are closely bound together, especially near the bifurcation, where they have fused into one plexus. The vessels surrounding the bronchi follow them towards the periphery, giving off branches to the venous tree at eveiy division of the bronchial tree. Ear-h smaller lironchus derives its lymj^hatic supply from the jilexus that accompanies the i)arent bronchus. These vessels are very difficult to inject.

Accompanying the primary divisions of the pulmonarj- vein there is another group of vessels that is closely bound, by anastomoses, to the honphatics around the principal bronchi (figure 4, plate 1). Along each of the tributary veins vessels pass to the pleura and spread out in the region that has been described as the septa between the lobules. Each of these dividing sheets anastomose with other sheets and with the pleural vessels. Th*^ vessels derived from the retroperitoneal sac are continouus \\-ith those derived from the two ducts; there can be determined no line of differentiation either within the lung-tissue or on the pleural surface. The poste- rior pole is connected with the retroperitoneal sac by three or four vessels that pass down in the fold of tissue that precedes the ligamentum inilmonale (figure 3, plate 5). The pleural plexus has begun to form within the gross markings that we have described as corresponding to the connective-tissue septa. These vessels are very superficial and are not connected, at this time, with the deeper vessels.

The further development is chiefly due to the multiphcation of the lung units and the increase in volume of the intcrbronchial tissue. As new bronchi are formed, new groups of lymphatics bud off from the plexus that accompanied the parent bronchus and follow the new-formed structure towards the periphery. These lymphatics leave the bronchus and pass to the venous group when they reach the region where the air-sacs are developing.

As the lung-tissue differentiates further and further, the larger veins become more closely associated with the bronchi and only the terminal vessels are peripheral with reference to the lobule. This brings about the relations that are found in the adult, where the principal veins and bronchi are closel}- associated, while the terminal ones have the same relative positions that have been described for the developing structures.

The arteries in early stages lie very close to the bronchi and arc associated with the plexuses that follow that structure. As these blood-vessels increase in size the bronchial plexus differentiates into two parts, following the arteries and the bronchi. This is accompUshed by the growth of vessels around the arteries, and, as the artery increases in size, The two plexuses become entirely distinct, but are still connected bv numerous anastomotic vessels.

In the meantime, the vessels of the pleurii, which at from o to 6 cm. we have seen hefjinning to form the true pleiiral plexus, continue to proliferate, and thus form a tine-meshed plexus in the pleura between the bli)ckin<2;-off of the lobules.

The completion of the primary plexus is shown in figure 3, plate 1. This is the surface of the lung in a pig embryo of 6 cm. with the pleural vessels injected. Each of these uninjected areas represents a primary lobule, and the surrounding lymphatics mark out the connective-tissue plexuses. Figure 1, plate 5, illustrates one of the primary lobules, and the close-meshed plexus is the true pleural supply. It is still seen to be connected with the deep vessels of the septum.

Here and there one finds vessels passing from the terminal bronchi to thc^ sur- face, in the lobule proper, to join with the fine-meshed plexus of the pleura. These pass around the air-cells, but are never found on their walls, and, uniting with the terminal vessels of the end veins, pass to join in the pleura. These are the vessels described by Hint (1906) as seeming to di]) down into the lobules from the pleura; these, he said, he could follow only a little way into the lobule. This is easily understood from the information gained from injections, for the vessels around the bronchi can not be seen, in uninjected specimens, and consequently those which remain patent in sections seem to end abruptly in the midst of a lobule, whereas they in reality connect with those following the bronchi and terminal veins. The lymjihatics that follow the terminal bronchi leave them just before the atria are reached and cross over to join the lymphatics which follow the veins. The lymphatics which accompany the veins ])ass to the ])leura just where the veins bend to reach the center of the lobule.

Flint first observed the submucous plexus of the bronchi and trachea in embryos 23 cm. long. It was surprising that injections did not reveal this i)lexus very much earlier. I have not been able to demonstrate any lymphatics in the before the embryo reached a length of 19 cm. This plexus develops, as do all the secondary i)lexuses, by the outgrowth of vessels from the primary one and their coalescence to form the new group. This process has been carefully studied by Heuer in the formation of the mucosal plexus in the intestine. The submucosal jjlexus is complete just before birth and consists of numerous fine vessels that lie beneath the bronchial epithelium. From this plexus numerous vessels i)ass down between the cartilaginous rings and join the lymphatic trunks which follow the bronchi, as has been descrilx'd. In those bronchi having no cartilaginous rings there is only the one grouj) of lym])h-vessels to be found, and these have already been described.

The lymphatics of the adult lung were first described by Olaf Rudbeck in 16.51-1054 ((juoted from Miller, 1900). Since that time numerous workers have .studied these vessels. In 1900 W. S. Miller reviewed the literature very thoroughly, and it will, therefore, be unneces.sarv to repeat that here. Miller studied the lymiihatics in the lungs of adult cats and dogs by injecting them from one of tlu> pleural vessels. He divided the lymphatics into four groups, as follows:

The lymphatics of the bronchi. — Miller describes two sets of lymph-vessels asso- ciated with those bronchi which have cartilaginous rings and only one with those which have no rings. In the former the two sets are connected by vessels that pass between the rings and join the trunks situated on the outer side of these structures. These trunks drain the lymphatics that accompany the smaller bronchi and empty into the nodes which are situated at the hilum of the lung. While there are several Ij'^mphatics accompanying the larger bronchi, only three are to be found with those nearer the air-sacs. end by leaving the terminal bronchus just before it ends in the atria; one of them passes to the artery, while the other two join the lymphatics of the vein.

The lymphatics of the veins. — There is a .single group of vessels that extends from the terminal vein to the hilac nodes. Along the larger veins there are several vessels, but the terminal ones are accompanied by only one or two lymphatics. Anas- tomotic vessels pass from the bronchial lymphatics to join those of the vein at each branching of the bronchial tree. The lymphatics that accompany those veins which go to the pleura join the pleural lymphatics.

The lymphatics of the arteries. — The lymphatics which accomi)any the arteries are very similar to those of the veins, with th(> exce])tion that none of them pass to the pleura.

The lymphatics of the pleura. — There is only one plexus in the pleura, and this drains through several large trunks to the nodes at the hilum. There are anasto- moses with the lymphatics of the veins, as has been said, but the drainage probabh- does not pass through these. ]Miller put his canula into a large pleural vessel and injected towards the hihmi. After some time the deep h'mphatics, as well as those of the pleura, were filled. He thought that the injection mass backed up into the deep ves.sels from the nodes at the hiknn, since both the sets of vessels drain into the same nodes.

Miller does not confirm the findings of Sappey (,1874) and of Councilman (1900) with regard to the interlobular IjTnphatics. Sappy thought that it was wrong to divide the lung lymphatics into superficial and deep groups on account of the rich anastomosis of these vessels. He thought that the lobules were surrounded by lymphatics which formed networks between the adjacent lobules in much the same manner as the blood capillaries do around the air-sacs. Councilman divided the deep lymphatics of the lung into two sets, the bronchial and the interlobular; the latter he interpreted as veryimportant in infections.

While Miller does not agree with these observers in regard to the interlobular lymphatics, he does describe anastomoses between the hTuph-ve-ssels of the venous radicles and those of the pleura, and he emphasizes the peripheral location of the veins. It might well be that the vessels which Sappey and Councilman found in the interlobular septa were the hTnphatics of the veins, since they did not have verj' accurate methods for the differentiation of these structures. It becomes more difficult to reconcile Miller's findings with those of FUnt and the results of this study. Both Flint and I have found distmct groups of vessels in the interlobular connective tissue in embryo pigs. These groups of vessels are directed in their growth and location by the position of the veins, but are not limited in their distribution to (he venous trunks. The fact tliat so careful an observer as Miller does not find these lymphatics in the septa suggests the possibility that the assumption of mature activities in some way brings about the atrophy of all of the interlobular lymjihatics except those that accompany the veins. Again, this plexus may be peculiar to the pig. It seems necessary that this question must remain unsettled until studied by some method other than simple injection.

The question of the drainage of the lung lymphatics is of exc{'i)tioual interest and importance; and while we must deixMul, for the final settlement, upon physio- logical methods, there is much e\'idence available from morphological observations. In the larger vessels on the bronchi, the veins, and the arteries there are valves which point towards the hilum. This is assumed to be very good evidence that the flow is in that direction. No \alves have been described in the lymph-vessels which accompany the smaller bronchi, veins, and arteries. Hence it can not be stated whether the lymph flow, in the lymph-vessels of the veins, is towards the ])leura of the hilum; and, in like manner, the flow in the bronchial vessels might be either towards the hilum or towards the veins and arteries. With regard to the vessels on the pleura, all of the lymphatics above a certain regional level of the lower lobe drain either towards the mid-line and then course up in the pulmonary hgament to end in the nodes at the hilum, or joass by direct paths to these nodes. Those below this level drain to the nodes lying in the mesenterj- of the lesser curvature of the stomach. Home of these drain as do those above — towards the median and ])ass down in the ligamentum pulmonale — while others pass directly down from the posterior pole. This group of vessels which pass to the preaortic nodes drains about one-third of the lower lobe of the lung. This varies considerably; in some specimens as much as half of the lung has been found to drain in this direction.

This peculiar drainage of the lower lobes seems especially important from the bearing that it may have on the jiathology of the lungs. It has long been kiu)wn that the diaphragmatic vessels drain to these nodes, but there is no connection iK'tween these vessels and those of the lung jiroper. The lymphatics that pass through the pulmonary ligament apparently drain only the pleura; but, as has been shown, the deep lymphatics anastomose with those of the pleura, and therefore it seems possible for substances to pass from the lung-tissue to the preaortic nodes. What bearing this may have upon the pathology of the lungs or of the abdomen remains to be settled.


The lymphatics of the lungs are derived from three sources — the right and the left thoracic ducts and the retroperitoneal sac.

In embryos 2.6 to 3 cm. long, vessels bud ofT from the thoracic duct and grow across to the trachea, forming ther(> a plexus that gradually extends over the ventral surface of the trachea, and especially down over (lie hifurcnlion. I'roni this plcwis vessels pass into both lungs and into the ])leura.

The right thoracic duct divides, in embryos about 2.5 cm. long, uito two ves.sels. One to the heart, while the other breaks up to form a plexus on the right lateral wall of the trachea. Some vessels from this plexus pass down into the hilum of the right king;, while others anastomose with the plexus from the left side, which extends up over the trachea. The development of the lymphatics within the lung depends upon the division of the vessels into two groups — those associated with the veins and connective-tissue septa, and those associated with the arteries and the bronchi.

The former grow verj- rai)idly, and following each of the branches of the jjuhnonary vein, j^ass to the pleura. There are at first onlj' two or three h'mphatics with each vein. In the early stages the terminal veins He about midway between the adjacent bronchi, and in this plane a sheet of lymphatics develops from the vessels surrounding the veins and passes to the pleura, where they mark out the l)oundaries of the distribution of each bronchus. These vessels with those thot grow direct to the pleura from the i)lexus on the trachea.

The bronchial vessels develoj) more slowly and at first are to be found only around the larger bronchi. As these structures increase in size and number,, the lymphatics surrounding the main bronchi send vessels to the smaller ones and these form a plexus around each of the bronchi, so that the bronchial tree is sur- rounded by a continual series of branching tubes made up of lymphatic vessels. From every point of division of the l)ronchi. lymphatic vessels pass to the lymphatics of the veins; those around the terminal ])ronchus leave it near its ending in the atria, and pass to join the lymphatics of the veins or sei)ta, or, more rarely, those of the pleura.

Lymphatics also arise from the retroperitoneal sac and grow up posterior to the diaphragm to enter the lower pole of the lower lobe of the lung. These vessels form a plexus on the median surface of the lower lobe, and send branches both to the pleura of the other surfaces and into the lung along the veins. Plexuses develop here as with those that come from above and the two groups .soon anastomose.

The further development consists m the multijjlication of the plexuses on the bronchi and blood-vessels, following their continued differentiation. As the lung increases in size, the larger veins become approximated to the bronchi and only the terminal ones are separated from them; these lie in the periphery of the lobule. Connective tissue is formed along the sheets of lymphatic vessels, and these become the septa of the lung, containing a definite set of vessels which develop from the early vessels following the veins. The lymphatics accompanying the veins remain connected with those of the bronchi and septa.

The common plexus surrounding the artery and bronchus is separated into two mdividual plexuses, incident to the increase in size of the artery-; however, these continue to have anastomosing branches.

The vessels of the pleura mark out the early connective-tissue septa, but later there develops a fine-meshed plexus between these larger vessels, which is not connected with the vessels of the lung-tissue. The valves begin to form at about 6 cm. and. in general, point away from the pleiu-a. None, however, have been found in the smaller vessels which accompany the terminal bronchi.

In the adult there are lymphatic vessels accompanying the bronchi, the arteries and the veins; these anastomose freely. There are also vessels in the connective- tissue septa which drain chiefiy into those around the veins, and, to some extent into those of tlio bronchi and arteries, near the i)oint where the vein and the bronchus separate to take their rehUive positions with rehition to the lobule. There are numerous anastomoses between the deep vessels and those of the i)leura, but probably most of the flow is towards the hilum. All the deep vessels, together with the greater number of the pleural vessels, drain into the nodes at the hilum; but the vessels of the lower half of the pleura of the lower lobe drain through several vessels to the preaortic nodes. These vessels pass through the ligament of the lower lobe and behind the diaphragm.


BAETJER, Walter A. : On the origin of the mesenteric s.ic and thoracic duct in the embrj-o pig. Amer. Jour. Anat., Philadelphia. 190S, viii.

Clark, .V. H.: On the fate of the jugular lymph sacs, and the development of the lymph charmels in the neck of the pin. Amer. Jour. Anat., Philadelphia, 1912, ix.

Clark, E. R.: Observations on living growing lymphatics in the tail of the frog lar\-a. Anat. Record, Philadelphia, 1909, HI. An examination of the methods used in the study of the development of the lymphatic system.

.■Vnat. Record, Philadelphia, 1911, v. Further observations on living growing lymphatics: their relation to the mesenchyme cells. Amer.

Journ. Anat., Philadelphia, 1912, xiii. Councilman, W. T.; The lobule of the lung and its relations to the l.vmphatics. Journ. Boston Soc. Med. Science, Boston, 1900, iv.

Criikshank, W.: The anatomy of the absorbing vessels of the human body. London, 1790.

Delemere, G., p. Poirier, and B. Ci'neo: The lymphatics. 1904.

Flint, J. M.: The development of the lungs. Amer. Jour. Anat., Philadelphia, 1900, vi.

Hei'Er, G. J.: The development of the l.vmphatics in the small intestine of the pig. Amer. Jour. Anat., Philadelphia, 1909, ix.

Kampmeier, O. F.: The development of the thoracic duct in the pig. Amer. Jour. Anat., Philadelphia, 1912, XII.

Klein, E. : Anat. of the lymphatic system. London, 1875, ii.

Lewis, F. T.: The development of the lymphatic system in rabbits. Amer. Jour, of Anat., Philadelphia, 1906, V.

McClire, C. F. W. : The development of the thoracic duct and right l.vmphatic duct-s in the domestic cat. Anat. Anr... Jena, 1908, xxxii. Mabcaoni, Pai'l.: Vasorum lynijihaticoruin corporis humniii hiHloria ct ichnographia. Senis 1787.

Miller, W. S. : The structure of the lungs. Jour. Moiph., 1S9;{, viii. . The lymphatics of the lungs. Anat. .\nz., Jena, 1896, xii.

. Das Lungcnldppchen, seine, Bliit- und Lymphgefiisse. Archiv. filr Anat. und Physiologic, Leipzig, 1900.

. Anatomy of the lungs. Reference Handbook of the Med. Sciences, 1902. 575-586.

. Lymphoid tissue of the lung. Anat. Record, Philadelphia, 1911, V.

Pappenheim, — : Sur les Ijmphatiques des poumons et du diaphragmc. C'ompt. Rend., 1860, xxx.

Poirier and Ch.\rpey: Treatise of human anatomy.

Sabin, F. R.: On the development of the superficial lymphatics in the skin of the pig. Amer. Jour. Anat., Baltimore, 1904, iir.

. The lymphatic system in human embryo, with a consideration of the morphology of the system as a whole. .■Vmer. Jour. Anat., Philadelphia, 1909, ix.

. Der Ursprung und die Entwickclung des Lymphgefass.vstems. }>gcbnisse der Anatomic und Entwickelungsgeschichte, Wiesbaden, 1913, xxi.

. The origin and development of the lymphatic system. The Johns Hopkins Hospital Reports, Monographs, new scries, 1913, v.

S.VPPEY, P. C. : Anatomic, physiologic, pathologic des vaisscaux lymphatiqucs. Paris, 1874.

SiKORSKi, J.: Uebcr die L.vmphgefiisse der Lungcn. C'entralbl. f. Medicin. Wisscnsch., 1870.

Teichman, L. : Uebcr Lungcnlyn'phgcfiissc. Anz. d. Akad. d. Wissen.sch., in Krakau, 1896.

vox WiTTiCH, W.: LTebcr die Bczichungcn der Lungenalveolcn zum Lymphsystem. Mitth. Anx. d. Konigsbcrger Phys. Laborat., 1878.

Wywodzoff, — . : Die L.vmphgewege der Lunge. Wiener Medicin. Jahrbucher, 18G6, xi.

Explanation of Plates

Plate 1

Fig. 1 . DiaKram of transverse sect ion of left lung of an embrj'o pig 3 cm. long, in which the blood-vessels were injected through the umbilical artery with india ink. The lymphatics appear as dilated spaces (blue). The section is 20 microns thick and is stained with hematoxj'lin and eosin, aurantia, and orange G. X55. Ao, aorta; 7', trachea.

Fig. 2. Diagram of section through lobule of lung of an erabrj-o pig 7 cm. long, in wliich the lymphatics were injected with india ink through the left tracheal plexus. The veins were slightly injected by the rupture of a lymphatic vessel into a vein near the hilum. The section is lOO/i thick and is unstained. X47.5. A, artery; B, bronchus, ]', vein; PI, pleura.

Fig. 3. Surface of lung of an embrj-o pig cm. long, in which the lymphatics were injected with india ink through the left tracheal plexus. The section was taken from the ventro-lateral surface of the left lower lobe and is about 200 microns thick and is unstained. X29.4. /' L, primary lobule.

Fig. 4. Longitudinal section of lung of an embryo pig 6 cm. long, in which the lymphatics were injected with india ink through the left tracheal plexus. The veins contain some blood pigment. The section is 400 /i thick and is un.stained. X3.'?. V, vein; B, bronchus.

Fig. 5. Diagram of left tracheal plexus in an embryo pig 6 cm. long, in which the lymphatics were injected through the thoracic duct. Cleared by Spalteholz method. Note that part of the vessel marked with an asterisk (*) has been removed in di.ssecting the body-wall away. This vessel is the one described as the first to the lung. X15. *, first vessel to lung; T, trachea; Th D, thoracic duct; L T P.. left tracheal plexus; Ao, aorta.

Plate 2

F'iG. 1. Dissection of an embryo pig 4 cm. long, in which the lymphatics were injected with prussian blue through the retroperitoneal sac. The heart, aortic arch, left lung, and the body-wall have been removed. Cleared by the Spalteholz method. X19. Th D, thoracic duct; R Th D right thoracic duct; R T P, right tracheal plexus; L T P, left tracheal plexus; C L, cardiac lymphatics; Ao, aorta; B, bronchus; Oe, oesophagus.

Fig. 2. Section of a small area of the lung of an embryo pig 7 cm. long, in which the lymphatics were injected with Prussian blue through the retroperitoneal sac. Drawing to show the relation of the peri-bronchial lymphatics to the wall of the bronchus. Section is 20fi thick and is stained with hematoxj-lin and eosin, aurantia, and orange G. X93. B, bronchus.

Fig. 3. Dissection of an embryo pig 4 cm. long, in which the Ij-mphatics were injected with prussian blue through the retroperitoneal sac. The left lung, the arch of the aorta, the pulmonary artery, and the body-wall have been removed. Cleared by the Spalteholz method. The left tracheal plexus is shown as a solid blue mass because the meshes are so close that they could not be analyzed in the drawing. X 15. Th D, thoracic duct; R Th D, right thoracic duct; Ao, aorta; L T P, left tracheal plexus; B. bronchus.

Fig. 4. Longitudinal section of upper lobe of right lung of an embrj-o pig 6 em. long, in which the lymphatics were injected with prussian blue through the retroperitoneal sac, and the veins were injected with india ink through the pulmonary vein. The section is 400m thick and is unstained. Cleared by the Spalteholz method. X39.

Plate 3

Fig. 1. Small block of an embryo pig lA cm. long, in which the lymphatics were injected with prussian blue by puncture of an interlobular septum. The arteries were injected with india ink through the pulmonary artery. Cleared by the Spalteholz methotl and mounted in balsam. The specimen was mounted at a convenient angle to best show the interlobular septum; unfortunately, it was jarred out of position while being drawn and hence the group of lymphatics in the septum is shown bent to one side. X40. PI, pleura: .1, artery; / L S, interlobular septum.

Fig. 2. Diagram of a dissection of an embrjo pig 3 cm. long, in which both the right and left jugular sacs were injected and, from them, the right and the left thoracic ducts respectively. India ink was useil. The body-wall, heart, and left lung have been removed. Cleared by Spalteholz method. X30. T/i D, thoracic duct ; R Th D, rig' t thoracic duct; V C .S, vena cava superior; Ao. aorta; P A, pulmonary artery; C L, cardiac branch of the right thoracic duct.

Fig. 3. Diagram of a section of the right lung of an embryo pig 6 cm. long. This is the same specimen from which figure 4, plate 2, was made; the part of the section shown in that figure is indicated b>- an X. X20.

Plate 4

Fig. 1. Longitudinal spction of the left lung of an embryo pig 5 cm. long, in wliich the lymphatics were injected with Prussian blue througli the rctro|)eritoneal sac. The veins have some blood pigment in them. The section is 400/i thick and is unstained. X22. V, vein.

Fig. 2. Dissection of an embryo pig 4 cm. long, in which the lymphatics were injected with prussian blue from the retroperitoneal sac. The right lung, esophagus, and body-wall have been removed. The stomach was pulled to the left side of the embryo in order to expose the retroperitoneal sac. Cleared by the Spalteholz method. X20. Ao, aorta; L L, left lung; Th D, thoracic duct; D, diaphragm; li P S, retro- peritoneal sac; *, first vessel to the lung.

Plate 5

Fig. 1. Surface of lung of an embryo pig 23 cm. long, in which the lymphatics wore injected with prussian blue, by puncture of an interlobular septum. Cleared by Spaltcholz metliod. The interlobular septum is indicated by a very large lymphatic trunk. X2S. / L S, interlobular septum.

Fig. 2. Longitudinal section of the upper portion of the lower lobe of the left lung of an embryo pig 5 cm. long, in which the lymphatics were injected with prussian blue through the retroperitoneal sac, and the veins have retained a little blood pigment. The section is 400 ;u thick and is unstained. X57. V, vein; .4, art en,-; PI, pleura; B, bronchus.

Fig. 3. Lower portion of left lung of an embryo pig 5 cm. long, in which the lymphatics were injected with india ink through the retroperitoneal sac. Cleared by the Spalteholz method and mounted in balsam. X28.

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