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[[Paper - The anatomy and development of the systemic lymphatic vessels in the domestic cat|'''Huntington 1911''']]: [[Huntington1911 - 1|Part I. The development of the systemic lymphatic vessels in their relation to the blood-vascular system]] | [[Huntington1911 - 2|Part II. The development of the preazygos and azygos segments of the thoracic ducts]] | [[Huntington1911 - Bibliography|Bibliography]]
=Part I The Development Of The Systemic Lymphatic Vessels, In Their Relation To The Blood vascular System=
==Historical review of theories of lymphatic development==
The question as to the origin of the lymphatic vessels has, especially since 1902, occupied the attention of a number of American observers. These investigations have followed the older work on the same subject of Langer ('68), Budge ('80-'87), Gulland C94), Ranvier C95-'97) and Sala (1900), and the results have been published chiefly in the American Journal of Anatomy^ and in the Anatomical Record.*
During the progress of these researches a niunber of facts of primary importance bearing on the problem of lymphatic development and organization have been discovered. Some of these facts have been worked out in detail and are based on sufficiently extensive material and accurate observation to carry conviction by their constancy and consistency and to warrant their acceptance as definitely established ontogenetic conditions in the mammalian embryo. Other observations still lack complete confirmation, and in some others the methods employed in their determination create a doubt as to their validity, and tend to confuse the subject. Finally there are other conditions concerning which there still exists ah honest difference of opinion, and which hence require further study and definite determination. On the whole, however, the American work of the last six or seven years has led to considerable and permanent advance in our knowledge of the genesis of the mammalian lymphatic system.
» Vol. i, 1902; vol. iii, 1904; vol. iv, 1904; vol. v, 1905; vol. vi. 1907; vol. ix. 1909; vol. X, 1910
Vol. ii. 1908: vol, iv. 1910.
The results so far obtained, and the views based thereon, may, with inclusion of the older work on the subject of vertebrate lymphatic development in general, be briefly summed up as follows in the form of short theoretic statements:
I. The lymphatic system is developed independently of the blood- vascular system. It is formed by the confluence of independently developed mesenchymal spaces, and, in case of the avian thoracic duct, by canalization of preformed solid strands of differentiated mesenchyme.*'®'^
The works of Brachet and the combined researches of Brachet and Swaen,*in their relation to the interpretation of lymphatic development, also support the independent origin of the lymphatic system from the mesenchyme.
The interesting observations of Marcus on the development and organization of the lymphatic system in Hypogeophis* place the conclusions of this investigator in regard to the genesis of lymphatic structures in this general division, with the addition of the conception of the coelomata as primary lymphatic spaces (vide infra, pp. 25 and 26), and the phylogenetic derivation of the peripheral lymphatic system from the same.
•Budge: "Ueber ein Canalsystem im Mesoderm von Huhnerembryonen." Arch, fur Anal, und Phys., Anat. Abth., 1880, .s. 320. "Untereuchungen uber die Entwicklung des Lymphsystems beim Htihnerembrj'o." Arch. f. Anat. u. Phytt., Anat. Abth., 1887, s. 59.
• L. Sala: "Sullo sviluppo dei cuori linfatiei e dei dotti toracici nelT onibryone di polio." Ricerche fatta nel Laboratorio di Anatomia Normale della R. Univ. di Roma, vol. vii, p. 263-269, April, 1900.
'^G. Lovoll GuUand: "Tlic Dovelopment of Lyniphutic Glands", Jour. Path, and Bad., vol. ii, 1894, pp. 447-485.
A. Brachet, "Recherches sur le d^velopp. du coeur, des premiers vaisseaux
ct du sang chez les amphibiens urod^les," Arch, d^anat. microscopique, ii, 1898. Recherches sur I'origine de I'appareil vasculaire sanguin rhez les amphibiens," Arch, de Biologic, xix, 1903.
A. Swaon et A. Brachet, ftlude sur les premiers phases du d^velopp. clcs organs derives du m^^soblast chez les poissons t^^leostiens," Arch, de Biologic, xvi, 1899-1900.
• H. Marcus, "Bcitriige zur Kcnntnis der Gymnopliionen; II. I'eber intersegmentale Lymphherzen, nebst Bemerkungen iiber das Lymphsystem. Morphol. Jahrhuch. Bd. xxxviii. Heft 4, 1908.
II. The lymphatic vessels are du-ectly derived from the venous system, certain embryonic venous channels being transferred in toto to the lymphatic system.*®' "'^2, is
III. All systemic lymphatics are formed by union of multiple direct derivatives from the embryonic veins," or only the thoracic ducts are so developed, while the other sj'^stemic lymphatic vessels arise independently.*^
IV. The mammalian lymphatic system as a whole is developed by blind ducts which bud off from the embryonic veins of the cervical, and later from those of the inguinal region, widen out to form sacs, from which lymphatics grow to the skin and cover its surface, while at the same time a growth of ducts occurs along the dorsal line following the aorta to make a thoracic duct from which lymphatics grow to the various organs. The theory underlying this conception of lymphatic development assumes the primary formation of a number of sacs, derived from the veins, and lined by embryonic venous endothelium, from which, as the starting points, the lymph channels of the entire body devolop by a process of continuous and uninterrupted centrifugal "sprouting" toward the periphery.
'" C. Langer: Ueberdas LjrmphgefiisssystemsdesFrosches." Sitzb. d. Akad. d. Wissenschj Bd. Iviii.. I. Abth., 1868.
" L. Ranvier: Comptes Rendues, 1895, 1896. "Morphologie et developpement des vaissaux lymphatiques rhcz les mammifdrcs." Archives d^Anatomie Microscopique, Tome I, 1897.
Giuseppe Favaro, Richerche intorno alia morfologia ed alio sviluppo dei vasi, seni e cuori caudal i nei Ciclostoini e nei Pesci," Atti del Realilnslituto Veneto di Scienze, latere et Arti., anno accad. 1905-1906, Toino Ixv, Parte seconda. Appendice alia Dispensa X. Note fisiologiche intorno al cuore caudale dei Murenoidi (Tipo Anguilla vulgaris, Turt.)," Archiv. di Fisiologia, vol. ii, Fasc. V, Luglio, 1905. ** II cuori ed i seni caudali dei Teleostei," Anat. Am., xxvii. Band, no. 14 und 15, 1905.
" W. F. Allen, "The Distribution of the Lymphatics in the Head and in the Dorsal, Pectoral and Ventral Fins of Scorpaenichthys mamoratus," Proc. Washington Acad, of Sciences f vol. viii, pp. 41-90, May 18 1906. "The Distribution of the Subcutaneus Vessels in the Head region of the Ganoids, Polyodon and Lepidosteus,*' ibid.f vol. ix, pp. 79-158. July 1907. "The blood-vascular system of the Loricati, the mail-checked fishes," ibid., vol. vii, 1905.
"Distribution of the subcutaneous vessels in the tail region of l^episosteus," .4m. Jour. Anat. vol. viii, 190S.
^* V. T. I^wis: "The Development of the Lymphatic System in Rabbits.'* Am. Journ. of Anat., vol. v, 1905, pp. 95-111.
»• C. F. W. McClure: "The Development of the Thoracic and Right Lymphatic Ducts in the Domestic Cat." .47ia/. Anz., xxxii. Band, No. 21 and 22, 1908, p. 534.
V. The systemic lymphatics are formed by confluence of perivenous mesodermal spaces, developed, as separate anlages, outside the intima of the early venous channels, but not communicating with the same except at definite points of lymphaticovenous connection which are secondarily formed.*^
This view pronounces for the ontogenesis of endothelial cells, lining the separate mesodermal spaces, independently of the haemal vascular endothelium. The spaces ' forming the first anlages of the systemic Ijntnphatic vessels are in no sense derived from the embryonic veins, although closely associated with them topographicaUy.
At the time of the publication of the paper embodying these views, McClure and I were not aware of the important r61e played by the jugular lymph sacs, as affording the portals of entry of the entire systemic lymphatic circulation into the venous system. This relation was only subsequently ascertained
" F. R. Sabin: "On the Origin of the Lymphatic System from the Veins, and the Development of the Lymph Hearts and Thoracic Duct in the Pig/' Am. Jour. AnaL, vol. i, 1902, pp. 367-389. "On the Development of the Superficial Lymphatics in the Skin of the Pig/' Am. Jour, AnaL, vol. iii, 1904, pp. 183-195. "The Development of the Lymphatic Nodes in the Pig and the Relation to the Lymph Hearts," Am. Jour. Anat., vol. iv, 1905, p. 355-389. "Further Evidence on the Origin of the Lymphatic Endothelium from the Endothelium of the Blood Vascular System," Aruit. Record., vol. ii, 1908, pp. 4&-54. "The Lymphatic System in Human Embryos, with a Consideration of the Morphology of the System," Am. Jour. Anat., vol. ix, 1909, pp. 43-90.
" W. J. MacCallum: "Die Beziehung der Lymphgefasse zum Bindegewebe." Arch. f. Anat. und Phys., Anat. Abth., 1902.
" G. Heuer: "The Development of the Lymphatics in the Small Intestine of the Pig." Am. Jour. Anat., vol. ix, no. 1, 1909.
" W. A. Baetjer : ' The Origin of the Mesenteric Lymph Sac in the Pig." A nat. Record, vol. ii, 1908.
® H. Hoyer, Untersuchungen uber das Lymphgefasssystem der Froschlarven.
I. Theil." Extrait du Bulletin de V Academic des Sciences de Cracovie, CI iss2 des Sciences mathemaliques et naturelles. Juillet, 1905. II. Theil, ibid., Mai, IQOvH.
" G. S. Huntington and C. F. W. McClure: "The Development of the Main Lymph Channels of the Cat in their Relation to the Venous System." Am. J our. Anat., vol. vi, 1907. Abstr. Anat. Rec., vol. i, pp. 36-41.
in the course of a detailed joint investigation of the development of these organs. We consequently failed to correctly recognize the origin of the adult lymphatico-venous junctions, and regarded them as direct secondary connections of the systemic lymphatics with the veins. The paper quoted, however, describes the genesis of the lymphatic vessels in their relation to the venous system correctly.
VI. In 1907 I published, based on McClure's and my own joint investigations, a genetic interpretation of the development of the mammalian Ijntnphatic system as a whole, in which I defined the same as the product of the union of two genetically different and very unequal portions:
1. The entire extensive system of the lymphatic vessels proper of the adult animal, including the thoracic and right lymphatic ducts and their tributaries, is formed by the confluence of extra-venous intercellular mesodermal spaces, in the sense above defined (V).
These spaces are lined by a lymphatic vascular endothelium which is not derived from the haemal vascular endothelium, but develops independently of the same. The lymphatic channels, which result from the confluence of these spaces, follow in large part the embryonic veins closely, but they are neither derived from them, nor do they communicate with them, except at definite points, at which the rudimentary mammalian type of lymphatico-venous heart is developed.
2. A definite structure, the Jugular Lymph Sac, develops in the prevalent and typical mammalian lymphatic organization, directly from a perivenous capillary reticulum of the early preand postcardinal veins, adjacent to and including their point of confluence to form the duct of Cuvier. This jugular lymph sac, or rudimentary homologue of one of the lymph hearts of lower vertebratcKS, arising directly from the veins, subsequently separates for a short period entirely from the same, and finally makes two sets of permanent connections:
* G. S. Huntington: The Genetic Interpretation of the Development of the Mammalian Lymphatic System. Anat. Record, vol. ii, 1908, pp. 19-45.
(a) With the above defined independently formed systemic lymphatic channels of the entire body.
(6) Secondary connections with the venous system, re-entering the same at one or more typical and constant points, and thus forming the link which finally unites the venous and the lymphatic systems, developed independently of each other.
The above are, briefly summarized, the views of lymphatic development based on recent observations.
It will be seen, as previously stated, that opinions still differ as to the origin of the first lymphatic anlages and their subsequent method of growth, and as to the genetic derivation of the lymphatic vascular endothelium.
The following two main questions are therefore still to be definitely answered:
(1) Is the adult mammalian lymphatic system the result of continuous and uninterrupted growth from one or more central points toward the periphery, or is it genetically a channel system, developed on the same lines as the primary blood vascular system, by the confluence of a number of originally separate and independent anlages?
(2) Is the lymphatic vascular endothelium of the mammal derived from pre-existing haemal vascular endothelium, or is it the result of independent modification of mesodermal cells?
It now remains to answer definitely these questions, and, on the evidence of sufficiently extensive material and careful observations, to clear the field of theoretical considerations, and to establish, as far as possible, by sound methods and on a broad basis, the genesis of the mammalian lymphatic system as a whole. It is evident that an interpretation, which assumes to fulfill these conditions, must be capable of accurately standing the test of both ontogenetic and phylogenetic consistency.
Believing, as I do, and have, since my first expression of opinion on the subject, that the principles embodied in the genetic interpretation of mammalian lymphatic development above outlined (VI) are correct, I have undertaken to establish their truth by a detailed critical study of the lymphatic system, both in the adult and in the embryo, in one mammalian form, the Domestic Cat, which animal, by reason of its clear-cut type of venous development,*' and the great range of its adult venous variation,"* *^ seemed to me to offer the best opportunity of viewing the problem of mammalian lymphatic development both from the standpoint of its normal course in a representative form, and with reference to the variant conditions imposed upon it by correlated variants in the organization of the main systemic veins.
I have been further influenced in my selection of the cat for special and detailed study by the fact that in my experience the embryos of this carnivore offer uniformly histological pictures of lymphatic ontogenesis which are far more definite, clean-cut and conclusive than those obtained in ungulate, rodent or marsupial embryos. I believe that the cat is the only known available mammal in which the facts of systemic lymphatic development, as set forth in the following pages, could have been definitely ascertained. Guided by the clue thus furnished, it is not difficult to determine, by comparison, the existence of absolutely corresponding developmental conditions in the embryos of the pig, rat, rabbit, and opposum. But in none of these forms are the typical genetic stages as clearly marked and the tissues as definitely differentiated as in the cat.
The investigation of mammalian lymphatic development divides itself naturally, in accordance with the postulates of the genetic theory above advanced (VI), into three separate and distinct main parts:
(1) The development and adult anatomy of the jugular lymph sacs.
(2) The development and adult anatomy of the general systemic lymphatic vessels.
" Ct. S. Huntington and V. V. \V. McClure: "The Development of the Posteuva and Tributaries in the Domestic Cat." Am. Jour. Annt., vol. vi, 1907, Abstr. Anat. Record, vol. i.
•* Wm. Darrach: "Variations of the Postcava and its Tributaries in 605 Examples of the Domestic Cat." Am. Jour. Aunt., vol. vi, no. 3, 1907, Abstr. Anat. Record, vol. i, p. 30.
»G. S. Huntington and C. F. \V. McClure "The Interpretation of Variations of the Postcava and Tributaries in the Domestic C/at, bjised on their Development." -4m. Jour. Annt., vol. vi. 1907. Abstr. Anat. Record, vol. i, p. .33.
(3) The mode of union with each other of the two components just enumerated, and the resulting establishment of a continuous centripetal lymphatic vascular system, with definite and constant terminals in the venous trunks. The first part of this work has been completed in conjunction with Prof. C. F. W. McClure of Princeton University. The results of our joint investigation on the development and structure of the jugular lymph sacs of the Cat have been published in a preliminary account.*® The details, with critical analysis of a large series of embryos, and illustrations of the reconstructions of all the important stages, are given in an extensive paper recently published."
In these publications McClure and I have definitely demonstrated the fact that in the embryo of the cat the jugular lymph sacs develop as a small, but vitally important, part of the entire lymphatic system, directly from the pre- and postcardmal veins and their tributary plexuses, near to and including their Cuvierian junction.
The genesis of the jugular lymph sacs and their share in the adult organization having been thus definitely established in detail, I intend to follow independently the second postulate of the theory of the composite character of the adult mammalian lymphatic system above outlined (VI), and to show that the jugular lymph sacs, of direct venous origin, constitute the links uniting the hsemal vascular system and the general systeri of the lymphatic vessels, the latter developed independently of the veins, by the confluence of intercellular mesenchjntnal spaces surrounding, for the most part, the embryonic venous channels, but in no sense derived from the same.
==Material used in present investigation==
For the reasons stated above I have chiefly used the embryos of the domestic cat. Of these I have examined the following 107 individual embryos in complete serial sections:
G. S. Huntington and C. F. W. McClure: The Anatomy and Development
of the Jugular Lymph Sacs in the Domestic Cat." Anal. Recordy vol. ii, 1908, pp. 1-18.
" American Jour. ofAnat., vol. x, no. 2, April, 1910, pp. 177 to 311 with 67 figures.
RELATION OP LYMPHATIC TO BLOOD-VASCULAR SYSTEM
17
tBRIKS NO.
188 11 Somites
86 13 Somites
CKOWN RUMP MEASURE
(TAKEN ArTEK
fixation) mm,
82 4.5
93 4.5
226 5.18
110 5.6
138 5.6
103 5.7
84 6
85 6
115 6
116 6
117.. 6
128 6
187 6
109 6.2
129 6.5
130 6.5
131 6.5
186 6.5
105 6.8
135 7
137 7
108 7.2
119 7.2
121 7.2
S9 8
102 8
75A 8.5
106 9
136 9.2
132 9.5
133 9.5
230 9.5
79 10
101 10
111 10
112 10
113 10
114 10
. 140 10
237 10
81 10.3
CROWN RUMP MEASURE
(taken
AFTER FIXATION)
SERIES NO. mm.
• 118 10.5
120 10.5
77 11
98 11
213 11
256 11.5
78 12
97 12
100 12
217 12
92 13
107 13
76 13.5
189 13.5
223 13.5
127 14
210 14
211 14
212 14
214 14
75 15
91 15
216 15
218 15
219 15
243 15
244 15
245 15
246 15
141 15.6
143 15.5
215 15.5
247 15.5
95 16
96 16
222 16
224 16
230 16
248 16
240 16.5
94 17
142 17
198 17
258 17
18
DEVELOPMENT OF THE SYSTEMIC LYMPHATIC VESSELS
CROWK RUMP MBA8URR
(takbn
AFTER
fixation) BBRIB8 NO. mm.
87 18 •
88 18
199 18.6
249 18.5
250 18.5
254 18.5
80 19
197 19
252 19
253 19
CBOWNBCMP MEASURE
(taken
AFTER
fixation) SBRIE8 NO. mm.
83 20
255 20
241 20
242 21
147 25
168 34
144 31.5
90 35
104 51
These embryos are contained in the Embryological Collection of Columbia University. The majority of the preparations were fixed in Zenker's fluid and stained differentially on the slide with Haemotoxylon (Delafield) and Orange-G.
I have also had, through the courtesy of Professor McClure, the opportunity of carefully examining three very interesting cat embryos of the Princeton Collection, series 34 and 37, each of 14 mm. crown-rump measure, and series 53, a 15 mm. embryo.
A series of 180 adult animals with successful injection of the main systemic lymphatics served as control for the embryological determinations, and for the comparison of normal and variant adult conditions of the venous and lymphatic systems with the corresponding ontogenetic stages.
==Comparison of haemal and lymphatic vascular development==
The results of my observations on the development of the mammalian systemic lymphatic vessels, as distinguished from the jugular lymph sacs, studied jointly with McClure, may be briefly summed up as follows:
The systemic lymphatic vessels of the entire body are formed through confluence of numerous originally separate intercellular mesodermal spaces, which develop bx great part in close apposition to the walls of the embryonic venous channels, and in exactly the same way as the primary anlages of the hsemal vascular system, but independent of the latter. The endothelium lining these first anlages of the lymphatic vascular channels is from the beginning independent of the hsemal endothelium, and develops with the first appearance of the lymphatic spaces, from the indifferent mesodermal cells lining these spaces. In my opinion the lymphatic and haemal vascular endothelium have the same genetic derivation from the modified mesodermal cell lining the tissue spaces. The primary stage of endothelial differentiation is the same, whether the resulting channel system is to be assigned to the hsemal or the lymphatic division of the vascular system. We have therefore two generations of the embryonic vascular endothelial cell, a hsemal and a lymphatic. Both develop in the same way and as the result of identical genetic factors from the indifferent mesodermal cell. Both are from the very beginning of the process independent of each other in the mammalian embryo.
I desire again to emphatically aver my conviction that all the systemic lymphatic vessels of the mammalian embryo, including the thoracic ducts and their tributaries, are neither in their genesis continuous outgrowths or buds from sacs of venous origin, wherever situated, nor derived from multiple outgrowths from the embryonic veins, such outgrowths subsequently separating from the veins and fusing into continuous lymphatic channels. They are, in my opinion, on the contrary, from their very first inception, independent of the haemal vascular system, and their endothelial lining is not derived from the blood vascular endothelium. They develop as independent intercellular mesodermal spaces, which become confluent with each other to form larger and larger communicating channels. These finally attain their entrance into the venous system through the intervention of the jugular lymph sacs, in the manner outlined in the publications above quo ted. 22 '26, 27
Before taking up the details of the development of the first lymphatic anlages in the mammalian embryo, it seems advisable to refer briefly to a r^sum^ of known facts in regard to the earliest formative stages of the blood vascular system, in order to facilitate the comparison between haemal and lymphatic development.
Phylogenetically, the earliest form of a closed circulatory system in multicellular organisms consists of intercellular canals conveying a clear plasmatic fluid without cellular contents. The same picture is presented in the earliest stages of hsemal development in vertebrates. Thoma's^® investigations of the histogenesis of the blood vascular system in chick embryos have furnished us with a very clear picture of the process.
The first histogenetic inception of the vertebrate hsemal vascular system is marked by the condensation of the mesoderm into cellular strands. Between the cells of these praevascular strands multiple oval or round spaces develop, which enlarge, elongate and become confluent, forming a network of inter-communicating channels, the hcBmal capillary anlages. These channels contain a clear colourless fluid, with no, or only very scattered, cellular elements. This fluid, obtained by secretion from the free surfaces of the cells limiting the spaces, is evidently under a certain definite pressure, which exerts an influence on the form of the cells lining the channels. These limiting cells lose their earlier isodiametric, more or less regular cuboidal form, and appear flattened, and on optical section spindle-shaped. They have begun to assume the endothelial character. Hence from its earliest inception the endothelial lining of vascular channels appears as an enviroiunental adaptation of the mesodermal cell. One surface of a cuboidal cell is freed from contact with adjacent cells by the development of an intercellular cleft, and this free surface is subjected to the pressure of the fluid contained in the earliest capillary anlages, modified by the tension pressure of the organism as a whole. This mechanical adaptation to the altered cellular milieu results in the formation of endothelium, and the process is identical in all portions of the mesoderm, independent of the question as to whether the resulting endothelial lined space shall subsequently be incorporated in a haemal or a lymphatic system of vascular channels, or shall remain as a closed non-vascular mesodermal space.
It seems to me futile to try to speculate on an ontogenetic stage in which endothelium acquires a "specific character. It
^■R. Thoma: Untersuchungen uberdie Histogenese und Histomechanik des Blutgefasssystems/' Stuttgart, 1893.
RELATION OF LYMPHATIC TO BLOOD-VASCULAR SYSTEM 21
develops de novo in the adult under appropriate normal conditions.
Furthermore, this endothelial characterization of modified mesodermal cells is from the beginning a multiple process, starting independently at innumerable separate and discrete points of the vascular area, and becoming only subsequently continuous by confluence of the individual separate anlages. This fact is of importance in drawing general conclusions as to the later extension of vascular endothelium, whether haemal or lymphatic.
Up to this point the histogenetic and physical characters of all developing vascular structures are identical. The picture just described applies equally to the earliest definite anlages of the haemal capillary system, and, as I shall show, to the first appearance of the earliest lymphatic structures of the body. In the case of the definite blood-vascular channels of the vertebrate embryo, however, a further developmental change occurs, namely, the addition of free, specially modified, mesodermal cells, as the red blood cells, to the clear plasma circulating in the channel-system of the earliest capillary anlages in response to the first pulsations of the heart.
The first blood vessels of the area pellucida appear, at least in part, to develop independentlyof the so-called Blood islands. These latter, originally, form broad cellular strands composed of closely packed uncolored cells, which are only distinguished from the solid strands of the earliest vascular anlages of the area pellucida by greater size and massiveness. After the vascular cellstrands of the area pellucida have developed in their interior the intercellular closed oval or round spaces of the first capillary anlages, similar spaces also appear in the more massive cell strands of the peripheral portion of the area vasculosa. In the subsequent confluence of these discretely developed spaces to form the early capillary reticulum, the blood islands become more and more surrounded by the forming channels and are thus separated from the adjacent tissues. New endothelial-lined spaces continue to develop on the surface of the blood-islands, enlarge and join the system of connected channels. The cells forming the walls of these primitive capillaries become, as above stated, transformed into the typical flattened endothelial cells of the vascular intima. Excepted from this endothelial transformation are only those cells of the vascular walls which differentiate as young blood cells. Thus eventually the confluence of the originally individual and separate spaces produces a continuous and connected channel system, lined by endothelium, which nearly encircles the blood islands. The latter are therefore now in large part included within the lumen of the capillaries, with whose walls they are from place to place continuous. It only requires a further and complete solution of this continuity, and the accompanying freeing of the blood cells, to add the latter to the plasma circulating in the preformed channels. In the chick, according to Thoma's observations, the resolution of the blood islands into separate blood cells occurs between the 45th and 55th hour of incubation, while the acquisition of haemoglobin by the cells occurs between the 40th and 45th hour. With this occurrence the development of the primary blood-vascular channels has reached its definite accomplishment.
The general picture presented by the earliest development of the blood-vascular system may therefore be summarized as follows:
(1) Differentiation of certain mesodermal areas and lines by the multiplication of mesodermal cells to form cell-strands of varying density and size (vascular strands).
This appears to be a common antecedent condition not only of all vascular mesodermal structures, but also of other mesodermal derivatives eventually destined to obtain a lumen and enter into the formation of canals, as the Wolffian tubules and the cell-strands of the gonad.
It possibly explains the conditions described, for example, by Sala in the development of the avian thoracic duct, is seen in the developing aortae of early chick embryos, and is especially significant in the pictures furnished by Sabotta of the development of the aortae in fishes.
(2) Development in the interior of these cellular strands of intercellular spaces in large numbers.
(3) Bio-mechanical modification of cells lining these spaces to produce typical flattened vascular endothelium.
RSLATION OF LYMPHATIC TO BLOOD-VASCULAR SYSTEM 23
(4) Confluence of these endothelial-lined spaces to form larger and larger vascular areas of intercommunicating channels, containing a clear plasmatic fluid, which circulates in the channels in response to the establishment of cardiac pulsation.
(5) Addition to the plasmatic contents of these channels, coincident with their further growth and extension into a continuous circulatory system, of cellular elements, derived from the mesoderm and specially modified to acquire haemoglobin and function as red blood cells. These cells, by solution of tissue continuity, are liberated from the blood islands which are first surrounded by the confluent spaces of the capillary anlages.
(6) Subsequent differentiation of the adventitia, with specialization of districts by cardiac concentration, amalgamation of the plexus into larger arterial and venous channels, definition of permanent capillary areas, valve and septal formation, etc.
The striking features of this ontogenetic history of the blood vascular system are:
1. The relatively late addition to the preformed non-cellular circulation of free cell elements, which, as the red blood cells, stamp, from the period of their liberation and inclusion in the circulating plasma, the resulting vascular system as fujemal,
2. The common origin from mesoderm of both characteristic components of the haemal system, viz., the vascular endothelium and the red blood cell. Both the vascular intima and the free cell contents of the channels lined by this intima appear as highly modified derivatives of the same mesodermal cellular ancestors, which constitute the cell-strands of the earliest period of vascular development. In their first inception the systemic lymphatic vessels of the mammalian embryo, as distinguished from the jugular lymph sacs of venous origin, repeat in every detail the primary stages of the developing haemal capillaries, prior to the inclusion within the lumen of the latter, of the cellular contents of the blood islands. They can be identified as distinct structures as soon as the blood channels proper have differentiated. Before that period direct observation cannot determine, in case of individual mesenchymal spaces, whether they are eventually to become part of the lymphatic or of the blood vascular system.
It is therefore quite possible that in the mammalian embryo both sets of intercellular mesodermal spaces develop side by side and simultaneously, although prior to the setting free of the hsBmoglobin cells and their appearance within the lumen of the haemal capillaries, there is no absolute criterion which would serve to distinguish intercellular spaces as belonging definitely to either the haemal or the lymphatic division of the general vascular anlage.
It hence appears to me futile to base serious conclusions in regard to the genesis of vascular structure on observations made on the vessels seen in the transparent tails of living anure amphibia. Phylogenetically, from the urodele standpoint, such larvae are adult organisms. We all know that, once established, all divisions of the vascular organization are, under the stimulus of normal or abnormal growth, capable of further increase and extension. The observations above referred to may offer, if correctly interpreted, interesting side lights on the method of vascular growth, but they cannot, in any valid sense, bear on the problem of vascular genesis, either haemal or lymphatic.
But in mammalian embryos of the proper stages, and specifically in embryos of the Cat between 10 and 12 mm., the first systemic lymphatic anlages are clearly differentiated in the circumscribed areas of their first appearance, coincident with the definition of the early intra-embryonic blood channels.
Thus in the omphalo-mesenteric district, and cephalad and caudad of this point, on each side of the aorta, isolated intercellular mesenchymal spaces appear at this period, closely applied to the walls of the neighboring venous plexuses of the postcardinal and mesonephroic veins, but not connected with the same. These intercellular clefts enlarge rapidly to form numerous oval or round spaces, closely interwoven with the venous network and later with the sympathetic anlages. The cells limiting these early lymphatic anlages become, with the further extension of the spaces which they line, flattened and assume typical endothelial characters.
Fig. 1 shows a transverse section of a 10 mm. cat embryo (series 111, slide viii, section 4) magnified 175 diameters, cephalad
RELATION OP LYMPHATIC TO BLOOD-VASCULAR SYSTEM 26
of the mesonephros and the subcardinal cross anastomosis, and gives a topographical view of. the region in which the first mesodermal intercellular lymphatic tissue spaces {77) appear, in the interval between aorta {73) , postcardinal vein {68) and coelom {78) .
Fig. 2 is the same section of this embryo, magnified 300 diameters, and shows the area to the left of the aorta. Between this vessel {73) and the well defined left postcardinal vein {68) dorsad, and the coelom cavity {78) ventrad, appear a number of clear mesenchymal spaces {77) which do not communicate with the adjacent venous channels. Some of these spaces extend from the coelom angle dorsad along the lateral aspect of the postcardinal. They are the first distinctly recognizable anlages of the lymphatic system, and they develop, from their first inception, as independent mesenchymal spaces, closely related to the adjacent haemal channels, but genetically independent of the latter.
Fig. 3 shows the same field in a magnification of 600 diameters. The spaces are clearly ciit, separate and distinct, and the limiting cells are beginning to assume endothelial character.
The relation between the haemal channels and the developing adjacent lymphatic spaces can be clearly traced in successive sections of this same embryo proceeding caudad.
Figs. 4, 5, 6, and 7 show, respectively, sections 7, 8, 9 and 10 of slide viii of series 111, magnified 300 diameters.
In all of these sections the uniformity, and the distinct structural character of the primary lymphatic tissue-spaces is clearly visible in the same situation and in identical relation to surrounding structures.
For comparison with the preceding series the same region is shown in another 10 mm. embryo (series 120, slide ix, sections 25 and 26) in two successive sections, magnified 300 diameters, in figs. 8 and 9.
In these sections the same independent mesodermal spaces {77) are seen in their typical relation to aorta {73) , post-cardinal vein {68) and coelom cleft {78).
The interesting question of the relationship between these early mesenchymal spaces and the coelom cavity can only be
26 DEVELOPMENT OF THE SYSTEMIC LYMPHATIC VESSELS
considered superficially at this time. Yet, in some regions, very suggestive pictures are obtained. Thus in section 4 of slide viii of series 111 (figs. 1, 2 and 3) the distinct appearance of a communication between the coelom cavity proper {78) and the early mesenchymal spaces {77) above described is given by a clearly limited and well defined funnel-shaped stoma, occuping the dorsal extremity of the coelomic cleft {79 in fig. 2), and apparently opening directly into the spaces of the early lymphatic plexus. The remaining sections of this series figured (figs. 4 to 7) confirm this impression.
The conditions here described for early embryos of the cat strongly support the views expressed by Marcus' in his studies on the lymphatic development of Hypogeophis. The microphotographs here given should be compared with his description on pp. 599-601 of the paper quoted, with his text fig. 6, and with his figs. 5 and 6 of plate xvi.
The early mesodermal spaces here described and figured are lymphatic in character and form part of the extensive temporary network of lymphatic channels which appears for a time during mammalian ontogenesis and which bears a close resemblance to the corresponding lymphatic organization in amphibia and reptiles. The peri-aortic lymphatic sinuses and the exaggerated subcutaneous lymph channels of the earlier mammalian stages are portions of this evanescent and reminiscent system, which subsequently in large part retrogrades, and either disappears altogether or is extremely modified to meet the definite permanent conditions of mammalian lymphatic organization. Thus the early periaortic spaces become much reduced in course of further development. They then become associated, in a way presently to be described in detail, with elements of the axial venous plexuses of the mammalian embryo and form the anlages of the main segments of the thoracic ducts. This ontogenetic temporary recall of antecedent phylogenetic types of vascular development appears to be chiefly centered, in the mammalian embryo, in the region around the omphalo-mesenteric artery, where, in the adult, the definite and permanent lymphatic trunks closely resemble in their arrangement the peri-omphalo-mesenteric annular veins of certain reptilian embryos.
In the succeeding stages the mesodermal lymphatic anlages assume, in large part, the very definite relation to certain embryonic venous channels, which led McClure and myself to describe them in 1906 in our preliminary account above quoted,^^ as extraintimaP' or ^'perivenous structures.
This relationship is of two kinds:
A. Total replacement of temporary embryonic veins by extraintimal lymphatic channels.
In the earlier embryonic stages the areas of the future definite venous channels are largely occupied by an antecedent venous or capillary network, out of which, along definite hydrostatic lines, the subsequent veins develop by confluence of the plexus elements occupying these lines. ^^ Parts of the early capillary reticulum, not thus included in the path of the definitely organized venous trunks, remain, after the latter have become established, as a perivenous plexus. Some of the elements of this secondarily established plexus develop into permanent tributaries of the main veins. Others undergo a process of separation from the permanent functional channels and degenerate. In many cases their blood-cell contents break down and are eliminated, w^hile their endothelial lining appears to revert to the indifferent type of the embryonic mesodermal cell.
Thus in embryos between 13.5 and 16 nmi. many striking instances of this reversion are to be observed. The former vascular channel appears as a collection of clearly differentiated and very highly stained mesodermal cells.
Figs. 47, 50, 61, in Part II, show these mesodermal vascular derivatives very clearly. They form the dark masses seen in the field dorsal and dorsolateral to the oesophagus and in the peritracheal region.
In many regions of the mammalian embryo, however, these detached and retrograding venous elements do not attain this condition, but in an earlier stage, constitute lines around which the most active primarj'^ lymphatic organization of the mammalian
• H. V. W. Schulte and Fred. Tilney: "Note on the Organization of the Venoufi
Return, with Especial Reference to the niac Veins." Anal. Record^ vol. iii, no. 11, 1909.
embryo centers. The intercellular mesodermal clefts above described develop especially along and around these decadent venules and finally envelop them. As the result of this process the lymphatic anlages appear in certain mammalian ontogenetic stages, in large part, as distinct spaces enclosing the remnant of the embryonic vein. The latter may still, for a time, contain a few degenerating red blood cells, but these soon disappear, and then the entire anlage is formed by a collapsed and empty endothelial tube, the abandoned chaniLel of the earlier vein, surrounded by a second endothelial tube, formed by the confluence of the independently developed extraintimal or perivenous mesodermal spaces. As these spaces enlarge and join each other their lumen increases, and the limiting cells become flattened and assume typical endothelial characters. The height of this phase of lymphatic development is reached in embryos of the cat in the 14 mm. stage, and numerous demonstrations of the appearance of the structures on section are given in Part II of this paper. The remnant of the embryonic vein bears a relation to the replacing perivenous lymphatic channel which is exactly the same as that of a collapsed inner tube to the enveloping shoe of a pneumatic tire. The inner skin of the shoe and the rim of the wheel represent the lymphatic inlimal endothelium. The space between the shoe and the collapsed inner tube is the lumen of the future lymphatic channel. The empty inner tube itself is the decadent embryonic vein upon and around which the secondary lymphatic channel is built. In the course of further development the venous remnant disintegrates and disappears, leaving a clear lumen for the lymphatic vessel, which thus completely replaces the earlier vein and comes to occupy absolutely the topographical position of the latter.
Often the replacing lymphatic begins as an extraintimal channel partially surrounding the receding vein. This leads in course of further development to an expansion of the lymphatic channel not concentric with the axial line of the shrinking vein. The remnant of the vein then retires to a point on the intiiiial surface of the new lymphatic channel, and appears to project into the lumen of the latter. The resulting histological picture will depend on the plane of section in reference to the course of the lymphatic and its contained venous remnant. Thus, as shown in the following schema, many sections give the appearance indicated in 1. If the plane of section should, however, lie in the line A B,it will divide the shrinking vein (4) and the enveloping lymphatic (5) in such a way as to produce the picture shown under 2. In other cases the lymphatic spaces unite around the entire circumference of the abandoned venule, and the lumen is then contained for long distances entirely within the lumen of the replacing lymphatic channel.
==Ontogeny of mammalian systemic lymphatic vessels==
The process just described is remarkably constant and uniform in the critical stages of mammalian lymphatic development. As can be readily seen in following the individual sections in the microphotographs published in PSart II, the significance of the conditions here shown is unmistakable. This is not a haphazard process, observed only occasionally, in a limited number of embryos, and then only in single sections, or, at most, in a few successive sections. In any average embryo of the proper age the same structures appear regularly in the same situatioi^s and in identical relationship to the embryonic environment. It is often possible, as the microphotographs and the corresponding reconstructions herewith published clearly show, to trace the forming Ijrmphatic withits atrophied vein kernel for long stretches, and in different embryos of approximately the same crown-rump measure the consistent repetition of identical histological pictures is remarkable.
There are, of course, as in the ontogeny of other structures, individual cases of variation in which systemic lymphatic development is either more advanced or more retarded than is normal for the average of any given stage. But if a large nmnber of embrj^os of each typical period are examined and compared, the average standard of extraintimal lymphatic development attained by the majority of individuals in each stage is remarkably constant and uniform.
The earliest stage in which I have encountered this typical replacement of an early embryonic vein by a perivenous extraintimal lymphatic is presented by certain 12 mm. cat embryos along the caudal circumference of the azygos-precardinal confluence. In the concavity of the azygos arch on each side, as this vessel turns ventrad to join the precardinal vein, these earliest evidences of the extraintimal replacement of preceding embryonic veins by independent perivenous lymphatic spaces are encountered. Thus, fig. 10 shows a section of this region in a 12 mm. cat embryo (series 217, slide x, section 12). Here the typical picture of the central collapsed core of the earlier vein (4) , enveloped by the clear extraintimal lymphatic space (5), is plainly to be seen. Fig. 11 shows the same region in another 12 mm. embryo (series 211, slide X, section 15). Both the degenerating venule (4) and the enveloping lymphatic (5) are larger than in the preceding series, and occupy the same position between aorta (7) and left precardinal vein {6).
In a 14 mm. embryo (series 127, slide viii, section 12, fig. 12) the section passing just caudad to the junction of left azygos (6) with left precardinal vein {6) shows these early lymphatic spaces (5) and their relation to the contained venous remnant (4) fully developed. Only one of the areas is denoted by leaders in the figure, but two equivalent areas are seen further dorsad and nearer to the ventral aspect of the azygos arch. The lymphatic plexus, as development proceeds, from the 12 mm. stage on, approaches the large venous trunks more and more, until the spaces lie in direct apposition with the same, and unite to form the lymphatic trunk eventually destined to replace the left azygos arch and adjacent position of the left precardinal vein. This trunk then constitutes the cephalic end of the bronchomediastinal duct (37). Thus figs. 13 and 14 show two sections through the same region in a 15 mm. embryo (series 219, slide xiv, sections 19 and 16). Compared with the 14 mm. embryo the left azygos vein shows a marked reduction. The lymphatic spaces have enlarged and present a clear lumen on section, the remnant of the earlier vein, around which they developed, having disappeared. The spaces lie between aorta and left precaval vein, in close approximation to the dorso-medial circumference of the latter. The azygos segment of the thoracic duct (36) is seen dorsal to the interval between aorta and oesophagus, and ventral to the scant remnants of the earlier interazygos venous anastomosis {16).
The reconstruction of a 15 mm. embryo (series 218) shown in fig. 170 in Part II, gives a clear idea of the extent and relations of this lymphatic complex (37) in this stage.
B, Partial replacement of portions of the territory of an early embryonic venons pathway by an extraintimal lymphatic vessel, both venous and lymphatic channels either persisting side by side up to later developmental periods, or forming correlated components of the permanent adult vascular organization.
The developmental processes just described appear most clearly marked in the earlier stages, and in connection with temporary embryonic channels and plexuses which are destined to undergo rapid degeneration and ultimate complete elimination. In the case of the embryonic veins which are retained for a longer period, or carried over into the permanent adult organization, the histogenetic stages of lymphatic development are identical in kind, and differ only in degree from those just detailed. In place of complete replacement of the antecedent vein by the lymphatic channel, this replacement is only partial and leads to the typical
close parallel association of lymphatic and venous vessels so characteristic of the later embryonic stages and of the permanent adult pathways of both the lymphatic and the venous systems.
Figs. 15 and 16 show transverse sections of a 14 mm. embryo (series 222, slide vii, section 26, and sUde viii, section 4) in the region of the external jugular vein. The lymphatic spaces (;87') are in full development, and are applied chiefly to the medial aspect of the plexus of the external jugular vein (27). The lymphatic endothelium is clearly marked.
Fig. 17 shows a transverse section in the upper thoracic region of another 14 mm. embryo (series 37, slide xiii, section 12). A typical lymphatic anlage (53) is applied to the medial wall of the left precaval vein.
Fig. 18 shows a transverse section through the mid-thoracic region in a 17 mm. cat embryo (series 258, slide xviii, section 9, X 225).
The extraintimal anlagesof the thoracic ducts (S6), which usually in thisstage have advanced to the production of a continuous and uninterrupted channel system, are seen on each side closely applied to the ventral aspect of the left and right azygos veins. The latter are in the height of their development, forming large and symmetrical longitudinal venous trunks (S, 6) connected by the supra-aortic interazygos anastomosis. In course of further development the left azygos vein and the interazygos anastomosis are destined to undergo progressive reduction until they are eventually entirely lost. Their topographical position is then occupied by the replacing left segment of the thoracic duct complex (36). The right azygos vein, which is carried as a permanent vessel into the adult organization, also undergoes considerable relative reduction, correlated to the corresponding increase in the caliber of the main (right) segment of this portion of the thoracic duct complex.
The beginning of this process is seen well in fig. 19, which shows a transection of the same region in a 19 mm. cat embryo (series 253, slide xxiv, section 9, X 225). The change from the preceding stage (fig. 18) is marked both in the venous and the lymphatic channels. The former are relatively much reduced, while the latter have correspondingly increased in extent. The azygos is mainly represented by the right channel (S). The left channel (6) has become small, but is still connected by the transverse interazygos anastomosis (15) with the larger and permanent right trunk. The right thoracic duct (36) is likewise large. A dorsomedial extension of the same, which carries into the interval between aorta and interazygos plexus, will, in later stages, replace the latter secondarily, after the complete recession of the left azygos vein. The left thoracic duct {S6) is also of large size and fills a considerable part of the area formerly (fig. 18) occupied by the left azygos trunk. Some decadent remnants of the ventromedial azygos plexus (4) are still seen associated with the left duct, and are in process of replacement by a lymphatic space (5) * destined to make connection between the left thoracic duct anlage and the mesenteric lymphatic plexuses (cf. p. 148, figs. 266 to 270, 51).
Figs. 20 to 24 show transverse sections in the region of the developing mesenteric lymphatics and of the ascending lumbar lymphatic trunks in a 17 mm. embryo (series 258, slide xxiii, sections 34, 33, 32 and 31.) The embryonic veins (74) occupying the root of the mesentery caudal to the subcardinal cross-anastomosis are in the process of being replaced by extraintimal lymphatic spaces . {61) which are destined to become confluent and form the anlage of the future mesenteric lymphatic sac.
The region in question is not only interesting in reference to the ontogenesis of the abdominal lymphatic sacs and channels, but the arrangement of the periaortic axial venous trunks and their relation to the developing lymphatics is, in combination with the next following stage (20 mm., figs. 25 and 26), of the highest importance in interpreting the phylogenetic relations of the main abdominal veins in mammalia. For these reasons a somewhat more detailed consideration of the sections may properly be introduced here.
Fig. 20 shows section 34 of slide xxiii of series 258 in a magnification of 75 diameters and affords a comprehensive picture of the entire
topographical field involved. The strands of the sympathetic (l) are supra-aortic. On each side of the aorta (7) are the large and symmetrically developed right and left postcardinal veins (67 and 68) , with the ascending tninks of the ilio-lumbar arteries (A.ilid-lumb. transv. ant.) (not labelled in the figure) applied to their ventrolateral circumference. The subaortic area shows the cross-sections of four symmetrical vascular channels, two venous and two lymphatic. Immediately venti alto the aorta, and closely applied to its ventral wall and to each other, are two longitudinal parallel axial veins which are connected at intervals by a few short transverse anastomoses. These vessels are the temporary and very evanescent homologues in the placental embryo of the channels which McClure'® has described as the "cardinal collateral trunks'* in the embryo of Didelphis marswpialis, and from which he has traced the development of the preaortic postcava characteristic of the Marsupalia. These vessels are derivatives from the earlier preaortic cardinal-subcardinal venous plexus below the crossanastomosis, but differentiate in Marsupials along separate and distinct axial lines. They are destined, as are the corresponding portions of the subcardinals proper, to be entirely replaced in the typical placental development by the chain of preaortic lymph channels and nodes, but are capable, in aberrant types among the placentalia, of yielding, by further and continuous development, a type of preaortic postcava which in every respect corresponds to that encountered in Marsupials. McClure^* has described this condition in Tragulus, and his observation has been confirmed in a number of dissections by Beddard and others. The fortunate acquisition recently of a series of Tragulus embryos, through the kindness of the officials of the Smithsonian Institution, has enabled my associate Tilney to trace, in a publication now in preparation for the press, the development of the venous and lymphatic systems in this aberrant ungulate in their mutual interdependence, and to show the correspondence of the venous genetic processes
•• C. F. W. McClure: "The Anatomy and Development of the Postcava in Didelphis marsupialis/' Am, Jour. Anat,, vol. v, 1906.
" C. F. W. McClure: "The Postcava of an Adult Indian Chevrotain {Tragulus meminnaj Erxleben). Anal, Anz., Band, xxix no. 13 and 14, 1906, pp. 375-377.
persistence and further development of the cardinal collateral veins. In other words, not a single individual in the entire seiies possessed a marsupial postcava, although every shade in the possible range of variation in the district of the post- and supracardinal lines was represented by numerous examples. Thus with an abdominal venous organization of very unstable equilibrium, as shown by the large percentage of cardinal variants,^^ the cat yet keeps entirely within the district of the common genetic ground plan assigned to the placentalia. This phylogenetic consistency is maintained in spite of the fact that, as just demonstrated in series 258, the embryo develops the raw materials, as cardinal collateral channels, out of which a preaortic postcava of the marsupial type could be evolved. In my own estimation cats possessing this form of postcava may exist and may eventually be found. But the failure to encounter them in the relatively large series of adults already examined speaks volumes for the value of vascular organization in interpreting phylogenetic relations.
In this light the postcaval development and adult structure of Tra^ulus, for example, are of the utmost importance and significance. The unprejudiced observer is often forced to wonder why'some exponents of palaeontological research are content to draw far-reaching phylogenetic conclusions from the remnants of the incomplete locomotory apparatus at their disposal, without utilizing the results of modern comparative anatomical and embrj'ological investigation in determining at least the mutual relations of the extant forms, massed by an ironclad taxonomy into more or less questionable groups, whose ancestry and derivation form one of the primary problems of the palaeontologist. The case of Tropins just alluded to, the parotid complex and alimentary canal of Hyrax, the amniote homologies of the derivatives of the Sulcus buccalis determined by Schulte, the sharp line of lymphatic demarcation recently shown by Silvester to structurally separate absolutely the platyrrhine and catarrhine divisions of the lower primates, these and other facts are only instances in which the inadequacy of a superficial convergence of dental and skeletal characters, for the purpose of establishing valid phylogenetic relations, is revealed by cardinal divergence in the far more stable and important organization of vascular and visceral structure
The prevalent lack of coordinate deduction between vertebrate morphology and palaeontology is accentuated by contrast with such publications as Weber's Saugethiere and, more recently, W. K. Gregory's The Orders of Mammals", based largely on the author's joint work with Osborn, and on the latter's previous classical researches, and published by the American Museum of Natural History (Bulletin, vol. 27, February, 1910).
Workers in the general field of vertebrate structure appreciate fully the immense practical value in their own special investigations of books of this type, in which, to quote Gregory's words, the data of sj^stematic mammologj', of comparative anatomy and embryology shall ultimately be integrated with the data of palaeontology, to the great advantage of these now more or less independent lines of study."
In embryo 258 (fig. 21) the space ventral to the cardinal collateral veins and the ascending lumbar lymphatic trijnks, is occupied by a plexus of mesenteric lymphatics (61) draining into the latter. On each side are seen sections of the ureter {68) y and further laterad of the iliac vessels (61), Ventral of the intestine {6S) are the Wolffian ducts (64) and the cloaca (63) j with the hypogastric arteries (66) laterally.
Fig. 21 shows the important central vascular region of the same section in a magnification of 150 diameters. The relation of the cardinal collateral trunks (74.) to the ascending lumbar lymphatics (7S), and of the latter to the postcardinal veins (67 y 68) can be more clearly seen. The lumen of the mesenteric lymphatics (61) still contains in places remnants of the decadent venous plexus around and upon which they developed as replacing extraintimal spaces.
The three succeeding sections, tracing the structures caudocephalad, are shown in figs. 22, 23 and 24, all in a magnification of 150 diameters. The connections of the lymphatic channels developing along the iliac vessels with the ascending lumbar trunks are especiall}^ well seen on the left side of the three figures, also the anastomoses between the two cardinal collateral veins in figs. 23 and 24.
Figs. 25 and 26 show transverse sections of the hinder end of the bodv in a 20 mm. embrvo (series 241).
Fig. 25 (series 241, slide xxx, section 4) gives, in a magnification of 76 diameters, a topographical view of the entire field. This stage, compared with the preceding 17 mm. embryo, is marked by the full development of the supracardinal venous line, responsible for the production of the greater portion of the typical adult placental postcava below the renal level, and by the correlated development of the supra- or retro-aortic lymphatic sinuses associated with the same.
The periaortic area in fig. 25 gives a ijlear view of the vascular relations and of the postcardinal and supracardinal axial venous trunks.
The former {67 , 68,) are seen on each side, between aorta (7) and metanephros {65), receiving the veins from the mesonephroi in whose dorso^-medial border they are lodged.
The latter {59, 60) lie dorsal to the aorta (7) between this vessel and the sympathetic strands {1 ) .
The right supracardinal {60) has already gained the ascendency and is in process of establishing the channel of a normal right retro-aortic postcava, which is the typical vein for the cat. The correspondingly reduced left supracardinal {59) occupies the same situation on the left side. Associated with the supracardinal venous channels are the supracardinal lymphatic trunks {76), which form the anlages of the main adult retro-aortic lymphatic plexus. These develop as extraintimal spaces replacing portions of the earlier supracardinal venous reticulum. In accordance with the normal type of development observed in this individual embryo, the large permanent supracardinal (postcaval) vein of the right side is accompanied by a relatively small lymphatic channel {76 right), while on the left side the much reduced left supracardinal {59) is already nearly replaced by the corresponding lymphatic vessel {76 left) . In course of further normal development this replacement will become complete and then the area formerly occupied by the left supracardinal vein will be entirely filled by the substituted large left retro-aortic lymphatic. The permanent functional venous channel of the right side {60) on the other hand, developing into the typical placental postcava, will be accompanied by a relatively small right lymphatic trunk following its dorso-lateral aspect. As will be shown later (Part v.), departures from the normal type of venous development in this region, and the substitution of other embryonic pathways for the right supracardinal in building up this section of the adult postcava, produce corresponding and correlated changes in the arrangement of the main retro-aortic lymphatic channels.
Fig. 26 shows the periaortic region of the same embryo, further caudad, in a magnification of 150 diameters (series 241, slide XXX, section 14.) The section is taken at the level of a pair of dorsal intersegmental arteries which pierce the supracardinal venous (5S, 60) and lymphatic {76) complex, and divide the vein of the right side into two components {60, 60) . Further ventrad the two postcardinal veins {67, 68) are seen, already considerably reduced, ventrolaterad to the ureters {58) and the accompanying ascending lumbar lymphatic trunks {75). The connection of the latter with the supracardinal lymphatic channel is especially clear on the right side of the embryo.
Taken together, the 17 mm. and 20 mm. embryos just figured and described afford a very clear and comprehensive picture of venous and lymphatic development in their mutual relationship in this region.
The schematic text figures A, B and C may help to explain this relationship.
Fig. A is based on the joint studies which McClure and I made on the development of the postcava in embryos of the domestic cat. The figure was demonstrated to the 21st Session of the Association of American Anatomists in 1906 at the time of presentation of the communications, although not reproduced in the brief abstracts of the papers subsequently published.**' ^^
The figure represents a composite schema of the main periaortic venous axial pathways of the abdominal region. These pathways developing along diefinite and constant axial hydrostatic lines out of the periaortic venous reticulum, have all been determined by us in embryos of the cat. They do not, of course, all coexist at the same time in any embryonic stage, but normally succeed each other in definite sequence. The entire range of extensive variations in the domain of the adult postcava of the cat can be clearly interpreted genetically^* on the basis of this common groundplan, through abnormal persistence of one or more of the embryonal pathways usually destined for complete obliteration, thus producing farreaching modifications in the structure and relations of the resulting atypical postrenal segment of the adult postcava.
This periaortic axial venous lattice with connecting transverse branches (Fig. A) contains four components on each side, which develop in the following order:
1 . The postcardinal veins (1 ) .
2. The subcardinal veins (£),
3. As secondary derivatives of these two veins, the preaortic cardinal collateral channels (S).
4. As secondary dorsal derivatives of the postcardinal trunks, the supracardinal veins (4) In the course of normal venous development along the line typical for the great majority of placental mammals the right supracardinal vein (4) obtains the preponderance and furnishes the postrenal segment of the adult postcava, thus freeing the ureter from its primitive retro-venous position.
A part of the early capillary periaortic reticulum, out of which this vessel develops, is secondarily replaced by extraintimal lymphatic spaces, which through their confluence form the relatively small retro-aortic lymph channel (40 > following in the adult the dorso-lateral circumference of the postcava (4). (Figs. B and
n.
The right and left postcardinal veins (1) are in part retained as the terminals of the sex veins, in part replaced by the accompanying lymphatic trunks (i')- (Figs. B and C).
The left supracardinal vein (4), and both subcardinal veins (j?) , below the cross-anastomosis, as well as both cardinal collateral veins (S), retrograde and are entirely replaced secondarily by lymphatic channels.
The lymphatic replacing the left supracardinal vein (40 forms normally in the adult the main retro-aortic lymphatic sinus. (4'i left, in figs. B and C).
The lymphatic channels replacing the subcardinal and cardinal collateral venous trunks fonn the extensive system of the adult ascending lumbar and preaortic lymphatic vessels and nodes (2' and S' in figs. B and C).
Of course it is quite apparent that the adult placental differentiation occurs in the district of the post- and supracardinal lines, with a strong predilection for the right supracardinal as the main path of the postrenal segment of the adtdt postcava. It is equally apparent that in correctly valuing the significance of the departures from the normal type of placental postcava all four of the available components, viz., right and left postcardinal and right and left supracardinal lines, must be taken into account as potential factors in the development of the atypical placental postcava. The relation of the veins to the ureter will then decide the question of the genetic derivation, as being either the persistent postcardinal or supracardinal channel of either the right or left sides, in the case of single trunks, or of both sides in instances of double bilateral adult channels.
Thus all the recorded cases of variant postcaval veins of the cat, and of man, can be clearly interpreted on this basis, as has been done by McClure, Darrach and myself in previous publications.2»'24,26
Furthermore, the placental types in which a normally so-called double postcaval vein occurs, as, e.g. in some of the aquatic carnivores, some insectivores and edentates, are readily led back to persistence of both right and left axial channels with absence or reduction of the iliac anastomosis. Again the position of the ureter in reference to the bilateral trunks will characterize each of them as being either post- or supracardinal in derivation.
In the marsupials McClure's researches already quoted,'^ show clearly that the members of this subclass depend upon the continued development of the ventral preaortic venous pathways (^, S) of the common vertebrate groundplan (fig. A) for the evolution of their typical ventral preaortic postrenal segment of the postcava, with consequent reduction of the postcardinal line (1) to the r61e of a sex vein terminal, and the complete suppression of the typical placental supracardinal lines (4) in most with the same. Nowhere is there any suggestion of a bud or an outgrowth from the vein as forming the origin of these lymphatic spaces. It now remains to clearly prove the genesis of these spaces, and to trace their growth from their inception up to the stages just pictured in which fully organized Isonphatic and venous channels lie side by side in the mutual relation above figured and described. The proof of their origin is furnished by the series of microphotographs of successive sections of the earlier stages given in Part II of this communication, in connection with the individual series described and figured in tracing the development of the preazygos and azygos portions of the thoracic ducts. The microphotographs, and especially the reduced reproductions figured, are not so clear as the actual preparations, because focal adjustment is required to follow the endothelial lining of the spaces in their entire circumference, and because they lack the differential stain of the sections. Still they are sufficiently distinct to establish definite conclusions. Merely referring, therefore, at this time to the following detailed illustrations, the general topic of extraintimal replacement of embryonic veins by lymphatic spaces and the character of the latter deserve some further consideration.
The lymphatic anlages, as above stated, if studied under sufficiently high power and with some care, are seen to begin as intercellular clefts in the periaortic mesoderm, adjacent to the postcardinal venous plexus, and chiefly on its ental aspect, between it and the aorta.
The individual lymphatic spaces, at first small and separated from each other, enlarge, elongate and become confluent, to form larger continuous channel segments, while innumerable newly formed spaces of the same character appear in the surrounding tissue, join with each other, and with the earlier preformed lymphatic channels, in exactly the same manner, and with the same appearance of lymph endothelial '* budding or *' sprouting" as is observed in haemal vascularization of new areas by the junction of the earlier blood capillary anlages with secondary haemal plexuses. In these later ^ages the veins are surrounded by a close lymphatic plexus, which, however, does not as yet form a connected channel system, but is composed of longer and shorter segments still independent of each other.
These finally become confluent, to form the main systemic lymphatic collecting trunks, and then onlj do these establish their final junction with the jugular lymph sacs, through whose interposition, as above stated, they gain in the typical mammal their permanent entry into the venous system.
In this ontogenesis of the systemic lymphatic vessels certain relations between them and the venous system deserve further notice.
In the early stages the lymphatic mesenchymal spaces form a wide meshed network (cf. series 111, figs. 1 to 7, series 120, figs. 8 and 9). There is thus a marked similarity in the earliest stages of both the haemal and the lymphatic vessels, for the peripheral venous embryonic pathways are in their corresponding stages likewise still largely in the condition of a capillary reticulum. As the main lines of venous drainage crystallize out of the antecedent plexiform arrangement, the adjacent enlarging lymphatic channels crowd in on the condensing venous line and continue the close relationship which the earliest lymphatic anlages maintain to the adjacent veins. Thus the main embryonic venous channels develop along certain definite hydrostatic lines by enlargement and confluence of the individual plexiform elements of the indefinite antecedent network occupying these lines. The capillaries outside of these lines retrograde, so that the area of crosssection of the defined venous channel is less than the cross-cut area of the plexiform network which it replaces.- '^
The distinct impression is given that the space thus vacated by the condensation of the plexiform venous network of the earlier stages affords to the replacing lymphatic plexus the opportunity for greater growth and expansion, and that subsequently, in repetition of the process previously active in the venous reticulum, the lymphatic network condenses in a similar manner into more defined channels along similar hydrostatic drainage lines, so that the newly established main lymphatic vessel now closely follows the main venous channel. It is to be noted, however, that this organization of main vascular channels is usually less complete in case of the lymphatic vessels, as compared with the corresponding vein. The lymphatic system retains, much more perfectly than the venous, in many situations the original embryonic plexiform type.
At first the cells limiting the earliest lymphatic spaces are of the usual irregular cuboidal form. As the spaces enlarge, open out and thus become better defined, the limiting mesodermal cells become flattened, and finally assume a typical endothelial character and form. Thus, for example, the endothelial lining of the primitive mesodermal lymphatic spaces {77) is more clearly developed in the 10 mm. embryo, series 120, shown in figs. 8 and 9, than in the corresponding sections of embryo 111, of the same crown-rump measure (figs. 1 to 7). The former embryo is slightly in advance of the latter as regards the development of the parietal endothelial lining of the primitive mesodermal intercellular lymphatic spaces. In some instances a few modified mesodermal cells intervene between the cells limiting the lymphatic spaces and the endothelium of the adjacent venous radicle. In others no such intervening cell-layer exists, and the lymphatic space is separated from the venous lumen only by the latter's endothelial wall. In other words, in the extent of the lymphatic anlage, a single-celled membrane furnishes a part of the venous intima and at the same time contributes to the endothelial definition of the lymphatic space. This relation of vein and lymphatic anlage is shown very clearly in fig. 17. The lymphatic space (5S), which is closely applied to the medial wall of the left precardinal vein, is only separated from the lumen of the latter by the endothelial membrane which serves to line both spaces for the area of their mutual contact in this stage. Subsequently, with the regression of the left precardinal vein, this lymphatic anlage will correspondingly enlarge to form an extensive lymphatic plexus, which will eventually topographically replace the vein along which it arose. In order to briefly characterize this relation between vein and lymphatic, McClure and I defined in an earUer publication*^ these spaces as the Extra-intimal" anlages of the systemic lymphatic vessels, with due regard to the relation existing between them and the intimal endothelial lining of the embryonic veins. The mechanical concept involved in this term seems, to judge from a recent publication, to have been difficult to acquire. I am glad to be able to make myself clear by reference to fig. 17, where the mutual relation of the two vascular lumina is evident without further description, and to the numerous detailed illustrations on a larger scale of magnification which accompany the account of the development of the thoracic ducts in Part II of this communication.
By far the larger number of the early lymphatic channels are the product of fusion of these extra-intimar' spaces, and hence closely follow the veins of their respective regions. Subsequently, with the development of a venous adventitia, this relationship is somewhat altered in case of those veins which are included in the permanent venous organization. The close relation existing, however, throughout Ufe between these veins and the accompanying lymphatics is based on this intimate primitive association of their respective anlages.
On the other hand, the extra-intimal position of the earliest lymphatic spaces furnishes the explanation of another relation manifested between the developing systemic lymphatic channels and those embryonic veins which in course of normal venous development are destined to undergo reduction and finally complete suppression, when the primitive bilateral and symmetrical venous system of the earlier embryonic stages shifts to the dextral assymmetrical type of the main adult axial channels. In these circimfistances the systemic lymphatic vessel associated with the temporary embryonic vein experiences, apparently through the shrinkage of the latter, an impetus to its own more extensive development, so that it comes to occupy in general topographically the space filled by the vein in the earUer stages.
Thus the embryonic period which marks the normal ontogenetic swing of the main venous line to the right through the secondary sinistro-dextral iliac, hemiazygos and brachiocephalic cross anastomoses, sees the simultaneous increase in the corresponding lymphatic channels of the left side, which topographically replace the abandoned left embryonic venous pathways of the earlier and sym » Sabin: Anal. Rec, vol. ii, 1908, p. 50.
metrical stage. This occurrence leads to the well-known relative location of the main axial veins and lymphatics in the normal adult, in which the lymphatic vessels are chiefly situated on the left side and form, so to speak, a mirror-picture of the right sided axial venous channels.
Fig. 27 shows the reconstruction of the anterior venous and lymphatic complex in a cat embryo of 18 mm. (series 88) in the ventral view, and fig. 28 of the same preparation in the lateral aspect from the left side. The brachiocephaUc cross anastomosis is already well under way, resulting in a marked diminution of the left anterior caval vessel and a corresponding increase in the permanent right anterior cava or right duct of Cuvier. Conversely, the lymphatic vessel accompanying the diminishing left precaval vein is of large size, while that applied to the massive right precaval is comparatively small.
This principle of lymphatico-venous replacement, indicated clearly in the later embryonic stages, is strikingly illustrated in the adult. Thus, for example, the adult cat presents normally the arrangement of the great veins of the head and neck which is so frequently encountered in mammals below Primates, in which the large embryonic internal jugular vein is much reduced or even entirely obliterated, while secondarily the external jugular vein has assimied the function of the main vessel. Under these normal circumstances the lymphatic trunk accompanying the minute internal jugular vein or, in case of its entire default, occupying its position, is well developed and the largest element of the entire cervical lymphatic complex, while the external jugular vein is, on the other hand, accompanied usually by two very slender lymphatic vessels.
In instances, however, in which the embryonic proportion between the two jugular veins is retained in the adult, so that the internal jugular appears as a large and functionally important vessel, while the external is correspondingly diminished, the internal jugular lymphatic trunk is reduced, while the double lymphatic vessel along the external jugular is enlarged, and evidently acts in compensation in the cervical lymphatic return.
Again, in the same way, in adult animals with normally placed right postcava, the main supracardinal lymphatic trunk, draining the abdomen and the posterior extremities, follows the left side of the large artery.
In the not infrequent instances, however, of left sided postcava or postcardinal vein in the adult the reverse obtains, and the periaortic lymphatic channels predominate on the right side and occupy the place usually filled by the large vein in normal venous development.
I have encountered in the adult series so far examined no instance of persistent left precava replacing functionally the normal right superior cava, but have no doubt that this venous variation would involve a transposition of the proximal end of the thoracic duct to the right side, or at least a marked increase in the size and functional importance of the usually insignificant preazygos segment of the adult right lymphatic duct.
The developmental outline just given describes the mutual ontogenetic relations of the venous and lymphatic systems throughout the greater part of the body.
Systemic lymphatic development in these regions is, however, by no menas confined to the immediate environment of degenerating embryonic veins. The same field, which shows the above described histogenetic processes in the development of extraintimal lymphatic spaces surrounding and replacing a decadent venule, will at the same time contain numerous equivalent lymphatic mesenchymal clefts and spaces which continue to develop independently of any association with retrograding veins. Naturally, these independently developed early lymphatic anlages are less striking than those above described as developing in association with a receding vein. They are smaller, because they lack the bulk of the contained venous core, and they are more difficult to clearly differentiate against the surrounding mesenchyme. They are, however, always present and their eventual connection with the larger perivenous lymphatic spaces can be ascertained definitely by following their development through the proper stages.
In additioD, in certain areas, a small group of the earliest lymphatic anlages appear to develop in the mesenchyme along definite Unes, and in distinct patterns, but v^ithout any preceding venous reticulum. They impress me, for example, in the area surrounding the omphalomesenteric artery, as systemic lymphatic channels developing ia the placental embryo in regions which are no longer ontogenetically the seat of venous development, although occupied by vei 3S in other mammalian types. Thus the cardinal collateral line of the marsupials^'^ and the correlated venous area of the monotremes" no longer develops as a permanent veoous plexus in placentalia'* but only partially appears in certain fonns as a temporary and evanescent component of the abdominal venous complex, as described above for certain stages in the development of the cat (pp. 29 to 33 and figs. 20 to 24) . Its place, however, is partially occupied by an early lymphatic plexus de\ eloped in the preaortic mesoderm from the omphalomesenteric anlages caudad. Here we are apparently dealing with an instance in which general phylogenetic venous lines have been almost or entirely abandoned in favor of other pathways. Such lines appear, however, to be retained under these conditions in the lymphatic organization. Thus, the spaces just referred to, as will be shown subsequently, form the first inception of the extensive network of lymphatic vessels which in the adtdt cat surrounds the aorta and the origin of the superior mesenteric artery, closely interwoven wdth the semilunar sympathetic and the adrenal plexus, and connecting on the one hand with the portal and intestinal lymphatics, and on the other with the beginning of the thoracic duct. This adult mammalian lymphatic plexus forms a perfect lymphatic shadow-picture of the lacertilian ontogenetic peri-omphalomesenteric venous ring.
In conclusion, I wish to give briefly a simunary of my reasons for regarding the structures described in this communication as the anlages of the systemic lymphatic vessels.
Except, as recently determined, in Tragulus, in wnich Ungulate the adult
postcaval system is of the marsupial type, and in certain embryonic stages of the Cat (15.5-17 mm.) in which the channels appear as evanescent preaortic vessels, subsequently entirely replaced by lymphatics. (Cf. series 258; figs. 20 to 24.)
These early lymphatic anlages, whether formed independently in mesoderm, or on the site of phylogenetically abandoned venous Unes, or, as is generally the case throughout the body, in close correlation to the embryonic venous pathways, always appear in the same situations and, in the average embryo, at the same developmental period. Their constant character, and regular occurrence and relations, repeated within very narrow limits of individual variation in every embryo of the proper stage, imparts to them a definite morphological character. In every series of the proper age in my collection I find the same spaces in the same place and in identical relationship to the adjacent veins. In some individuals, as above stated, they develop earlier than usual, in others their appearance is retarded, but this applies only to the achievement of the full development typical for the average embryo of a given stage. In the retarded individuals the same structures are always present, only they are less strikingly developed and less niunerous when compared with the average normal type characteristic of the period under consideration. With sufficient magnification it is not difficult to distinguish sharply between the perihaemal lymphatic spaces and the blood-vascular channels proper.
With sufficient material every stage of their development can be followed up to the confluence of the entire system and its final entrance into the jugular lymph sacs.
These spaces are neither artefacts due to embryonic shrinkage, nor are they the unfilled portions of the blood-vascular capillary network. They are, on the other hand, the well-defined earliest anlages of the systemic lymphatic vessels. The more perfect, as a matter of fact, the embryonic fixation is, the more clearly can these structures be indentified under the microscope. Their history, as will be shown presently, can be traced with the utmost accuracy, and they can be followed step by step in their development up to their inclusion in the completed and connected lymphatic channel system.
But even in their earliest stages they possess an unmistakable and definite morphological character, quite as distinct as that of the adjacent blood channels. They can be followed closely in good serial sections of the proper thickness and fixation, and can be reconstructed in the same manner and with the same accuracy and certainty as the blood channels with which they are for the most part so closely associated, although their lumen connects at no point with that of the vascular channels.
These statements are based, not on isolated observations, but on the close and repeated examination of a very large number of embryos of the same form. It seems curious to me that the presence of the first lymphatic anlages, as above described, should be denied, or, as has been recently done, that the isolated appearance of these spaces should be ascribed to the sudden collapsing " of a lymph vessel. At the time at which they make their first appearance there are no lymph vessels to "collapse," no more than there are in the homologous haemal ontogenetic stages bloodvessels in the sense of continuous channels. On the contrary, when they reach their period of most striking development (cat, 13-14 mm.) these perivenous lymphatic spaces are, if anything, distended, not only by their fluid contents, but by the remnant of the embryonic atrophying vein which they are in the process of replacing. The only structure showing any sign of "collapse is the empty endothelial bag of the decadent venule. The spaces become relatively reduced in. size in the later stages, after the multiple separate early anlages have fused into a more continuous lymphatic channel system.
These spaces are always present in embryos of the proper stages in the typical position and in constant relation to the venous channels. By following carefully and with suflBcient material their further growth and development in succeeding stages, a clear and consecutive picture of systemic lymphatic genesis is given.
It is noteworthy, in view of the incorrect statements published to the contrary, that these primary anlages of the systemic lymphatic system develop constantly in embryos of the cat before the definite organization of the jugular Jymph sacs. These latter structures, in the 10 mm. cat embryo, are still largely in the condition of a perivenous capillary plexus, at a time when the first lymphatic anlages can be distinctly recognized in the axial mesoderm.
2 The lymphatic endothelium is an independent modification of the mesodermal cells lining the first anlages of the lymphatic spaces, and is not derived from the haemal vascular endothelium.
3 I am obliged to deny the assumption that the mammahan systemic lymphatic vessels arise by the confluence of numerous elements detached in course of development from the embryonic veins.
4 I am obliged to put myself emphatically on record against the assumption that the mammalian systemic lymphatic vessels arise by a progressive sprouting from center to periphery fron) the endothelium of veins, or from that lining the jugular lymph sacs, or equivalent structures in other regions of the body. The mammalian embryo offers no evidence of such occurrences.
PART I, PLATES
FIGURES 1 TO 28
The series here figured and de«oribed are in the embryological collection of Columbia University, with the exception of series 34, which belongs to the embryological collection of Princeton University. I am greatly indebted to Prof. C. F. W. McClure for the opportunity of studying this series and publishing the eight sections shown in figs. 245 to 251.
FIGURE 1
1 Transverse section of 10 mm. cat embryo (series HI, slide VIII, section 4), X 175*— Topographical picture of site of earliest lymphatic space development.
1 Sympathetic nervo.
8 Oesophagus.
S8 Left postcardinal vein.
69 Lungs.
72 Right dorsal aorta.
73 Left dorsal aorta.
77 Mesenchymal intorccllular lymphatic anlages.
78 Coelom.
FIGURE 2
2 Tranfiverre Mv-tion of 10 mm. cat embr>*o series 111. :«lide VIII. section 4) y 30O — left .siile of embrj'O.
GS I^eft iK>sicarrlinal vein.
73 I^ft dorsal aorta.
77 Mesench\-mal intercellular h-mphatic anlafces.
7S C'oelom.
79 Coelomic stoma.
FIGURE 3
3 Same. X 600.
FIGI'KES 4 AND 5
4 Transverse section of 10 mm. cat embryo (series 111. slide VIII. section 6), X 300.
5 Same, section 7,
FIGURES 6 AND 7
6 Same, section 8.
7 Same, section 9.
FKJl'RKS 8 AND {)
S Trafisvprsc sorti<»n of 10 inni. cat embryo (series 120, slide IX, section 25) X .WO. Saiiie, seel ion 2r>.
1 Syinpiithetic nerve.
(iS Left posteanlinal vein.
7.') Left dorsal aorta.
77 Mesenehynial int<'reelliilar lymphatic anlages.
78 Coeloni.
FIGURES 10 AND 11
10 Transverse section of anterior thoracic region of 12 mm. cat embryo (series 217. slide X, section 12). X 225 — showing early extraintimal lymphatic development.
11 Transverse section of anterior thoracic region in a 12 mm. cat embryo (series 211. slide X. section 15). X 225.
3 Prci-ardinal or precava. resp. azygos of right side.
4 Atrophying embryonal vein, forming kernel in interior of developing
and replacing lymphatic space.
5 E.Ytraintimal or perivenous lymphatic space surrounding degenerating
embryonal vein. Precardinal or precava, resp. azygos of left side.
7 Aorta.
8 Oesophagus.
9 Trachea.
10 Pulmonarv arterv. 22 Vagus.
FIGURE 12
12 Transverse section of anterior thoracic region in a 14 mm. embryo (series 127, slide VIII, section 12), X 225.
4 Atrophying embryonal vein, forming kernel in interior of develop ing and replacing lymphatic space.
5 Ex train timal or perivenous lymphatic space surrounding degen erating embryonal vein.
6 Precardinal or precava, reap, azygos of left side. 6' Left azygos vein, thoracic portion.
7 Aorta.
8 OosophagiLs.
FIGURES 6 AND 7
6 Same, section 8.
7 Same, section 9.
FIGURE 15
16 Transverse section through lower cervical region of a 14 mm. cat embryo (series 222, slide VII, section 26), X 150.
11 Jugular lymph sac.
25 Internal jugular vein.
27 External jugular vein.
27' External jugular lymphatics.
riGURE 10 . Ill Same, slide VIII, section 4.
11 Jugular lymph sac.
25 Internal jugular vein.
27 External jugular vein.
27' External jugular lymphatics.
I
FIGURE 17
17 Transverse section of upper thoracic region of 14 mm. embryo (series 37, slide XIII, section 12), X 150.
1 Sympathetic nerve.
3 Frecardinal or precava, resp. azygos of right side.
6 Frecardinal or precava, resp. azygos of left side.
7 Aorta.
8 Oesophagus.
9 Trachea. 22 Vagus.
53 Precaval lymphatics.
FIGURES 18 AXD 19
18 Transverse section of middle thoracic region in a 17 mm. cat embryo (series 258, slide XVIII, section 9), X 225.
19 Transverse section through mid-thoracic region of a 19 mm. cat embryo (series 253, slide XXIV, section 9), X 225.
1 Sympathetic nerve.
2 Intersegmental arteries.
3 Right azygos.
4 Atrophying embryonal vein.
5 Extraintimal or perivenous l>Tnphatic space.
6 Left azygos.
7 Aorta.
15 Interazygos venous ple.xus.
36 Azygos segment of thoracic duct.
FIGURE 20
20 Transverse section of upper abdominal region of a 17 mm. cat embryo, showing developing components of ascending Imnbar l3anphatic trunks and of mesenteric sac in relation to embryonic veins in the root of the dorsal mesentery and their relation to the cardinal collateral venous channels (series 258, slide XXIII, section
•M), X 75.
1 Sympathetic nerve.
7 Aorta.
51 Mesenteric lymphatics.
58 Ureters.
61 Iliac vessels.
62 End gut.
63 Ventral division of cloaca (urinary bladder).
64 Wolffian ducts.
66 Umbilical arteries.
67 Right postcardinal vein.
68 Left postcardinal vein.
74 Cardinal collateral veins.
75 Ascending lumbar hmphatic trunks.
FIGURE 21 21 Same section, X 150.
7 Aorta.
51 Mesenteric lymphatics.
58 Ureters.
67 Right postcardinal vein.
68 Left postcardinal vein.
74 Cardinal collateral veins.
75 Ascending lumbar lymphatic trunks.
FIGURE322 22 Same, section 33.
1 Sympathetic nerve.
7 Aorta.
51 Mesenteric lymphatics.
68 Ureters;
67 Right postcardinal vein.
68 Left postcardinal vein.
74 Cardinal collateral veins.
75 Ascending lumbar lymphatic trunks.
FRJURES 23 AND 24
23 Same, section 32.
24 Same, section 31.
7 Aorta.
61 Mesenteric lymphatics.
67 Right postcardinal vein.
68 Left postcardinal vein.
74 Cardinal collateral veins.
75 A.«<cending lumbar lymphatic trunks*
25 Transverse section of posterior end of a 2() mm. cat eml)ryo (series 241, sli(ie XXX, section 4), X 75 — showing extraintimal replacement of left supra cardinal vein (59) by ascending lumbar relroaortic lymphatic channel (76).
1 Sympathetic nerve.
7 Aorta.
58 Ureters.
59 Left supracardinal vein.
60 Right supracardinal vein.
62 End gut.
63 Ventral division of cloaca (urinary bladder).
64 Wolffian ducts.
65 Metanephros.
66 Umbilical arteries.
67 Right post cardinal vein. 6S Left postcardinal vein.
76 Hetroaortic supracardinal lyin])hatic trunks.
FKJUUE 26 26 Same, section 14, X 150.
1 Sympathetic nerve.
58 Ureters. .
59 Left supracardinal vein.
60 Right supracardinal vein.
67 Right postcardinal vein.
68 Left postcardinal vein.
75 Ascending lumbar lymphatic trunks.
76 Retroaortic supracardinal lymphatic trunks.
FIGURE 27
27 Reconstruction of anterior vascular complex in an IS mm. cat embrj^o (serie»< 88), X oO. Ventral view.
FIGUUK 28 28 Same, lateral view of left side.
it increasingly turns to the left and continues to develop cephalad along the ventral surface of the inter-azygos plexus, by extraintimal replacement of elements belonging to the latter. (Compare the series of six reconstructions shown in figs. 188, 189, 190, 191, 192, 193.)
[[Paper - The anatomy and development of the systemic lymphatic vessels in the domestic cat|Huntington1911]]: [[Huntington1911 - 1|Part I. The development of the systemic lymphatic vessels in their relation to the blood-vascular system]] | [[Huntington1911 - 2|Part II. The development of the preazygos and azygos segments of the thoracic ducts]] | [[Huntington1911 - Bibliography|Bibliography]]
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Huntington GS. The anatomy and development of the systemic lymphatic vessels in the domestic cat. (1911) Memoirs of the Wistar Institute of Anatomy and Biology No. 1.

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Huntington 1911: Part I. The development of the systemic lymphatic vessels in their relation to the blood-vascular system | Part II. The development of the preazygos and azygos segments of the thoracic ducts | Bibliography

Part I The Development Of The Systemic Lymphatic Vessels, In Their Relation To The Blood vascular System

Historical review of theories of lymphatic development

The question as to the origin of the lymphatic vessels has, especially since 1902, occupied the attention of a number of American observers. These investigations have followed the older work on the same subject of Langer ('68), Budge ('80-'87), Gulland C94), Ranvier C95-'97) and Sala (1900), and the results have been published chiefly in the American Journal of Anatomy^ and in the Anatomical Record.*


During the progress of these researches a niunber of facts of primary importance bearing on the problem of lymphatic development and organization have been discovered. Some of these facts have been worked out in detail and are based on sufficiently extensive material and accurate observation to carry conviction by their constancy and consistency and to warrant their acceptance as definitely established ontogenetic conditions in the mammalian embryo. Other observations still lack complete confirmation, and in some others the methods employed in their determination create a doubt as to their validity, and tend to confuse the subject. Finally there are other conditions concerning which there still exists ah honest difference of opinion, and which hence require further study and definite determination. On the whole, however, the American work of the last six or seven years has led to considerable and permanent advance in our knowledge of the genesis of the mammalian lymphatic system.

» Vol. i, 1902; vol. iii, 1904; vol. iv, 1904; vol. v, 1905; vol. vi. 1907; vol. ix. 1909; vol. X, 1910

Vol. ii. 1908: vol, iv. 1910.


The results so far obtained, and the views based thereon, may, with inclusion of the older work on the subject of vertebrate lymphatic development in general, be briefly summed up as follows in the form of short theoretic statements:

I. The lymphatic system is developed independently of the blood- vascular system. It is formed by the confluence of independently developed mesenchymal spaces, and, in case of the avian thoracic duct, by canalization of preformed solid strands of differentiated mesenchyme.*'®'^

The works of Brachet and the combined researches of Brachet and Swaen,*in their relation to the interpretation of lymphatic development, also support the independent origin of the lymphatic system from the mesenchyme.

The interesting observations of Marcus on the development and organization of the lymphatic system in Hypogeophis* place the conclusions of this investigator in regard to the genesis of lymphatic structures in this general division, with the addition of the conception of the coelomata as primary lymphatic spaces (vide infra, pp. 25 and 26), and the phylogenetic derivation of the peripheral lymphatic system from the same.

•Budge: "Ueber ein Canalsystem im Mesoderm von Huhnerembryonen." Arch, fur Anal, und Phys., Anat. Abth., 1880, .s. 320. "Untereuchungen uber die Entwicklung des Lymphsystems beim Htihnerembrj'o." Arch. f. Anat. u. Phytt., Anat. Abth., 1887, s. 59.

• L. Sala: "Sullo sviluppo dei cuori linfatiei e dei dotti toracici nelT onibryone di polio." Ricerche fatta nel Laboratorio di Anatomia Normale della R. Univ. di Roma, vol. vii, p. 263-269, April, 1900.

'^G. Lovoll GuUand: "Tlic Dovelopment of Lyniphutic Glands", Jour. Path, and Bad., vol. ii, 1894, pp. 447-485.

A. Brachet, "Recherches sur le d^velopp. du coeur, des premiers vaisseaux ct du sang chez les amphibiens urod^les," Arch, d^anat. microscopique, ii, 1898. Recherches sur I'origine de I'appareil vasculaire sanguin rhez les amphibiens," Arch, de Biologic, xix, 1903.

A. Swaon et A. Brachet, ftlude sur les premiers phases du d^velopp. clcs organs derives du m^^soblast chez les poissons t^^leostiens," Arch, de Biologic, xvi, 1899-1900.

• H. Marcus, "Bcitriige zur Kcnntnis der Gymnopliionen; II. I'eber intersegmentale Lymphherzen, nebst Bemerkungen iiber das Lymphsystem. Morphol. Jahrhuch. Bd. xxxviii. Heft 4, 1908.


II. The lymphatic vessels are du-ectly derived from the venous system, certain embryonic venous channels being transferred in toto to the lymphatic system.*®' "'^2, is

III. All systemic lymphatics are formed by union of multiple direct derivatives from the embryonic veins," or only the thoracic ducts are so developed, while the other sj'^stemic lymphatic vessels arise independently.*^

IV. The mammalian lymphatic system as a whole is developed by blind ducts which bud off from the embryonic veins of the cervical, and later from those of the inguinal region, widen out to form sacs, from which lymphatics grow to the skin and cover its surface, while at the same time a growth of ducts occurs along the dorsal line following the aorta to make a thoracic duct from which lymphatics grow to the various organs. The theory underlying this conception of lymphatic development assumes the primary formation of a number of sacs, derived from the veins, and lined by embryonic venous endothelium, from which, as the starting points, the lymph channels of the entire body devolop by a process of continuous and uninterrupted centrifugal "sprouting" toward the periphery.




'" C. Langer: Ueberdas LjrmphgefiisssystemsdesFrosches." Sitzb. d. Akad. d. Wissenschj Bd. Iviii.. I. Abth., 1868.

" L. Ranvier: Comptes Rendues, 1895, 1896. "Morphologie et developpement des vaissaux lymphatiques rhcz les mammifdrcs." Archives d^Anatomie Microscopique, Tome I, 1897.

Giuseppe Favaro, Richerche intorno alia morfologia ed alio sviluppo dei vasi, seni e cuori caudal i nei Ciclostoini e nei Pesci," Atti del Realilnslituto Veneto di Scienze, latere et Arti., anno accad. 1905-1906, Toino Ixv, Parte seconda. Appendice alia Dispensa X. Note fisiologiche intorno al cuore caudale dei Murenoidi (Tipo Anguilla vulgaris, Turt.)," Archiv. di Fisiologia, vol. ii, Fasc. V, Luglio, 1905. ** II cuori ed i seni caudali dei Teleostei," Anat. Am., xxvii. Band, no. 14 und 15, 1905.

" W. F. Allen, "The Distribution of the Lymphatics in the Head and in the Dorsal, Pectoral and Ventral Fins of Scorpaenichthys mamoratus," Proc. Washington Acad, of Sciences f vol. viii, pp. 41-90, May 18 1906. "The Distribution of the Subcutaneus Vessels in the Head region of the Ganoids, Polyodon and Lepidosteus,*' ibid.f vol. ix, pp. 79-158. July 1907. "The blood-vascular system of the Loricati, the mail-checked fishes," ibid., vol. vii, 1905.

"Distribution of the subcutaneous vessels in the tail region of l^episosteus," .4m. Jour. Anat. vol. viii, 190S.

^* V. T. I^wis: "The Development of the Lymphatic System in Rabbits.'* Am. Journ. of Anat., vol. v, 1905, pp. 95-111.

»• C. F. W. McClure: "The Development of the Thoracic and Right Lymphatic Ducts in the Domestic Cat." .47ia/. Anz., xxxii. Band, No. 21 and 22, 1908, p. 534.


V. The systemic lymphatics are formed by confluence of perivenous mesodermal spaces, developed, as separate anlages, outside the intima of the early venous channels, but not communicating with the same except at definite points of lymphaticovenous connection which are secondarily formed.*^

This view pronounces for the ontogenesis of endothelial cells, lining the separate mesodermal spaces, independently of the haemal vascular endothelium. The spaces ' forming the first anlages of the systemic Ijntnphatic vessels are in no sense derived from the embryonic veins, although closely associated with them topographicaUy.

At the time of the publication of the paper embodying these views, McClure and I were not aware of the important r61e played by the jugular lymph sacs, as affording the portals of entry of the entire systemic lymphatic circulation into the venous system. This relation was only subsequently ascertained

" F. R. Sabin: "On the Origin of the Lymphatic System from the Veins, and the Development of the Lymph Hearts and Thoracic Duct in the Pig/' Am. Jour. AnaL, vol. i, 1902, pp. 367-389. "On the Development of the Superficial Lymphatics in the Skin of the Pig/' Am. Jour, AnaL, vol. iii, 1904, pp. 183-195. "The Development of the Lymphatic Nodes in the Pig and the Relation to the Lymph Hearts," Am. Jour. Anat., vol. iv, 1905, p. 355-389. "Further Evidence on the Origin of the Lymphatic Endothelium from the Endothelium of the Blood Vascular System," Aruit. Record., vol. ii, 1908, pp. 4&-54. "The Lymphatic System in Human Embryos, with a Consideration of the Morphology of the System," Am. Jour. Anat., vol. ix, 1909, pp. 43-90.

" W. J. MacCallum: "Die Beziehung der Lymphgefasse zum Bindegewebe." Arch. f. Anat. und Phys., Anat. Abth., 1902.

" G. Heuer: "The Development of the Lymphatics in the Small Intestine of the Pig." Am. Jour. Anat., vol. ix, no. 1, 1909.

" W. A. Baetjer : ' The Origin of the Mesenteric Lymph Sac in the Pig." A nat. Record, vol. ii, 1908.

® H. Hoyer, Untersuchungen uber das Lymphgefasssystem der Froschlarven. I. Theil." Extrait du Bulletin de V Academic des Sciences de Cracovie, CI iss2 des Sciences mathemaliques et naturelles. Juillet, 1905. II. Theil, ibid., Mai, IQOvH.

" G. S. Huntington and C. F. W. McClure: "The Development of the Main Lymph Channels of the Cat in their Relation to the Venous System." Am. J our. Anat., vol. vi, 1907. Abstr. Anat. Rec., vol. i, pp. 36-41.


in the course of a detailed joint investigation of the development of these organs. We consequently failed to correctly recognize the origin of the adult lymphatico-venous junctions, and regarded them as direct secondary connections of the systemic lymphatics with the veins. The paper quoted, however, describes the genesis of the lymphatic vessels in their relation to the venous system correctly.

VI. In 1907 I published, based on McClure's and my own joint investigations, a genetic interpretation of the development of the mammalian Ijntnphatic system as a whole, in which I defined the same as the product of the union of two genetically different and very unequal portions:

1. The entire extensive system of the lymphatic vessels proper of the adult animal, including the thoracic and right lymphatic ducts and their tributaries, is formed by the confluence of extra-venous intercellular mesodermal spaces, in the sense above defined (V).

These spaces are lined by a lymphatic vascular endothelium which is not derived from the haemal vascular endothelium, but develops independently of the same. The lymphatic channels, which result from the confluence of these spaces, follow in large part the embryonic veins closely, but they are neither derived from them, nor do they communicate with them, except at definite points, at which the rudimentary mammalian type of lymphatico-venous heart is developed.

2. A definite structure, the Jugular Lymph Sac, develops in the prevalent and typical mammalian lymphatic organization, directly from a perivenous capillary reticulum of the early preand postcardinal veins, adjacent to and including their point of confluence to form the duct of Cuvier. This jugular lymph sac, or rudimentary homologue of one of the lymph hearts of lower vertebratcKS, arising directly from the veins, subsequently separates for a short period entirely from the same, and finally makes two sets of permanent connections:

  • G. S. Huntington: The Genetic Interpretation of the Development of the Mammalian Lymphatic System. Anat. Record, vol. ii, 1908, pp. 19-45.


(a) With the above defined independently formed systemic lymphatic channels of the entire body.

(6) Secondary connections with the venous system, re-entering the same at one or more typical and constant points, and thus forming the link which finally unites the venous and the lymphatic systems, developed independently of each other.

The above are, briefly summarized, the views of lymphatic development based on recent observations.

It will be seen, as previously stated, that opinions still differ as to the origin of the first lymphatic anlages and their subsequent method of growth, and as to the genetic derivation of the lymphatic vascular endothelium.

The following two main questions are therefore still to be definitely answered:

(1) Is the adult mammalian lymphatic system the result of continuous and uninterrupted growth from one or more central points toward the periphery, or is it genetically a channel system, developed on the same lines as the primary blood vascular system, by the confluence of a number of originally separate and independent anlages?

(2) Is the lymphatic vascular endothelium of the mammal derived from pre-existing haemal vascular endothelium, or is it the result of independent modification of mesodermal cells?

It now remains to answer definitely these questions, and, on the evidence of sufficiently extensive material and careful observations, to clear the field of theoretical considerations, and to establish, as far as possible, by sound methods and on a broad basis, the genesis of the mammalian lymphatic system as a whole. It is evident that an interpretation, which assumes to fulfill these conditions, must be capable of accurately standing the test of both ontogenetic and phylogenetic consistency.

Believing, as I do, and have, since my first expression of opinion on the subject, that the principles embodied in the genetic interpretation of mammalian lymphatic development above outlined (VI) are correct, I have undertaken to establish their truth by a detailed critical study of the lymphatic system, both in the adult and in the embryo, in one mammalian form, the Domestic Cat, which animal, by reason of its clear-cut type of venous development,*' and the great range of its adult venous variation,"* *^ seemed to me to offer the best opportunity of viewing the problem of mammalian lymphatic development both from the standpoint of its normal course in a representative form, and with reference to the variant conditions imposed upon it by correlated variants in the organization of the main systemic veins.

I have been further influenced in my selection of the cat for special and detailed study by the fact that in my experience the embryos of this carnivore offer uniformly histological pictures of lymphatic ontogenesis which are far more definite, clean-cut and conclusive than those obtained in ungulate, rodent or marsupial embryos. I believe that the cat is the only known available mammal in which the facts of systemic lymphatic development, as set forth in the following pages, could have been definitely ascertained. Guided by the clue thus furnished, it is not difficult to determine, by comparison, the existence of absolutely corresponding developmental conditions in the embryos of the pig, rat, rabbit, and opposum. But in none of these forms are the typical genetic stages as clearly marked and the tissues as definitely differentiated as in the cat.

The investigation of mammalian lymphatic development divides itself naturally, in accordance with the postulates of the genetic theory above advanced (VI), into three separate and distinct main parts:

(1) The development and adult anatomy of the jugular lymph sacs.

(2) The development and adult anatomy of the general systemic lymphatic vessels.

" Ct. S. Huntington and V. V. \V. McClure: "The Development of the Posteuva and Tributaries in the Domestic Cat." Am. Jour. Annt., vol. vi, 1907, Abstr. Anat. Record, vol. i.

•* Wm. Darrach: "Variations of the Postcava and its Tributaries in 605 Examples of the Domestic Cat." Am. Jour. Aunt., vol. vi, no. 3, 1907, Abstr. Anat. Record, vol. i, p. 30.

»G. S. Huntington and C. F. \V. McClure "The Interpretation of Variations of the Postcava and Tributaries in the Domestic C/at, bjised on their Development." -4m. Jour. Annt., vol. vi. 1907. Abstr. Anat. Record, vol. i, p. .33.


(3) The mode of union with each other of the two components just enumerated, and the resulting establishment of a continuous centripetal lymphatic vascular system, with definite and constant terminals in the venous trunks. The first part of this work has been completed in conjunction with Prof. C. F. W. McClure of Princeton University. The results of our joint investigation on the development and structure of the jugular lymph sacs of the Cat have been published in a preliminary account.*® The details, with critical analysis of a large series of embryos, and illustrations of the reconstructions of all the important stages, are given in an extensive paper recently published."

In these publications McClure and I have definitely demonstrated the fact that in the embryo of the cat the jugular lymph sacs develop as a small, but vitally important, part of the entire lymphatic system, directly from the pre- and postcardmal veins and their tributary plexuses, near to and including their Cuvierian junction.

The genesis of the jugular lymph sacs and their share in the adult organization having been thus definitely established in detail, I intend to follow independently the second postulate of the theory of the composite character of the adult mammalian lymphatic system above outlined (VI), and to show that the jugular lymph sacs, of direct venous origin, constitute the links uniting the hsemal vascular system and the general systeri of the lymphatic vessels, the latter developed independently of the veins, by the confluence of intercellular mesenchjntnal spaces surrounding, for the most part, the embryonic venous channels, but in no sense derived from the same.

Material used in present investigation

For the reasons stated above I have chiefly used the embryos of the domestic cat. Of these I have examined the following 107 individual embryos in complete serial sections:

G. S. Huntington and C. F. W. McClure: The Anatomy and Development of the Jugular Lymph Sacs in the Domestic Cat." Anal. Recordy vol. ii, 1908, pp. 1-18.

" American Jour. ofAnat., vol. x, no. 2, April, 1910, pp. 177 to 311 with 67 figures.


RELATION OP LYMPHATIC TO BLOOD-VASCULAR SYSTEM


17


tBRIKS NO.

188 11 Somites

86 13 Somites

CKOWN RUMP MEASURE

(TAKEN ArTEK

fixation) mm,

82 4.5

93 4.5

226 5.18

110 5.6

138 5.6

103 5.7

84 6

85 6

115 6

116 6

117.. 6

128 6

187 6

109 6.2

129 6.5

130 6.5

131 6.5

186 6.5

105 6.8

135 7

137 7

108 7.2

119 7.2

121 7.2

S9 8

102 8

75A 8.5

106 9

136 9.2

132 9.5

133 9.5

230 9.5

79 10

101 10

111 10

112 10

113 10

114 10

. 140 10

237 10

81 10.3


CROWN RUMP MEASURE

(taken

AFTER FIXATION)

SERIES NO. mm.

• 118 10.5

120 10.5

77 11

98 11

213 11

256 11.5

78 12

97 12

100 12

217 12

92 13

107 13

76 13.5

189 13.5

223 13.5

127 14

210 14

211 14

212 14

214 14

75 15

91 15

216 15

218 15

219 15

243 15

244 15

245 15

246 15

141 15.6

143 15.5

215 15.5

247 15.5

95 16

96 16

222 16

224 16

230 16

248 16

240 16.5

94 17

142 17

198 17

258 17


18


DEVELOPMENT OF THE SYSTEMIC LYMPHATIC VESSELS


CROWK RUMP MBA8URR

(takbn

AFTER

fixation) BBRIB8 NO. mm.

87 18 •

88 18

199 18.6

249 18.5

250 18.5

254 18.5

80 19

197 19

252 19

253 19


CBOWNBCMP MEASURE

(taken

AFTER

fixation) SBRIE8 NO. mm.

83 20

255 20

241 20

242 21

147 25

168 34

144 31.5

90 35

104 51


These embryos are contained in the Embryological Collection of Columbia University. The majority of the preparations were fixed in Zenker's fluid and stained differentially on the slide with Haemotoxylon (Delafield) and Orange-G.

I have also had, through the courtesy of Professor McClure, the opportunity of carefully examining three very interesting cat embryos of the Princeton Collection, series 34 and 37, each of 14 mm. crown-rump measure, and series 53, a 15 mm. embryo.

A series of 180 adult animals with successful injection of the main systemic lymphatics served as control for the embryological determinations, and for the comparison of normal and variant adult conditions of the venous and lymphatic systems with the corresponding ontogenetic stages.


Comparison of haemal and lymphatic vascular development

The results of my observations on the development of the mammalian systemic lymphatic vessels, as distinguished from the jugular lymph sacs, studied jointly with McClure, may be briefly summed up as follows:


The systemic lymphatic vessels of the entire body are formed through confluence of numerous originally separate intercellular mesodermal spaces, which develop bx great part in close apposition to the walls of the embryonic venous channels, and in exactly the same way as the primary anlages of the hsemal vascular system, but independent of the latter. The endothelium lining these first anlages of the lymphatic vascular channels is from the beginning independent of the hsemal endothelium, and develops with the first appearance of the lymphatic spaces, from the indifferent mesodermal cells lining these spaces. In my opinion the lymphatic and haemal vascular endothelium have the same genetic derivation from the modified mesodermal cell lining the tissue spaces. The primary stage of endothelial differentiation is the same, whether the resulting channel system is to be assigned to the hsemal or the lymphatic division of the vascular system. We have therefore two generations of the embryonic vascular endothelial cell, a hsemal and a lymphatic. Both develop in the same way and as the result of identical genetic factors from the indifferent mesodermal cell. Both are from the very beginning of the process independent of each other in the mammalian embryo.


I desire again to emphatically aver my conviction that all the systemic lymphatic vessels of the mammalian embryo, including the thoracic ducts and their tributaries, are neither in their genesis continuous outgrowths or buds from sacs of venous origin, wherever situated, nor derived from multiple outgrowths from the embryonic veins, such outgrowths subsequently separating from the veins and fusing into continuous lymphatic channels. They are, in my opinion, on the contrary, from their very first inception, independent of the haemal vascular system, and their endothelial lining is not derived from the blood vascular endothelium. They develop as independent intercellular mesodermal spaces, which become confluent with each other to form larger and larger communicating channels. These finally attain their entrance into the venous system through the intervention of the jugular lymph sacs, in the manner outlined in the publications above quo ted. 22 '26, 27


Before taking up the details of the development of the first lymphatic anlages in the mammalian embryo, it seems advisable to refer briefly to a r^sum^ of known facts in regard to the earliest formative stages of the blood vascular system, in order to facilitate the comparison between haemal and lymphatic development.


Phylogenetically, the earliest form of a closed circulatory system in multicellular organisms consists of intercellular canals conveying a clear plasmatic fluid without cellular contents. The same picture is presented in the earliest stages of hsemal development in vertebrates. Thoma's^® investigations of the histogenesis of the blood vascular system in chick embryos have furnished us with a very clear picture of the process.


The first histogenetic inception of the vertebrate hsemal vascular system is marked by the condensation of the mesoderm into cellular strands. Between the cells of these praevascular strands multiple oval or round spaces develop, which enlarge, elongate and become confluent, forming a network of inter-communicating channels, the hcBmal capillary anlages. These channels contain a clear colourless fluid, with no, or only very scattered, cellular elements. This fluid, obtained by secretion from the free surfaces of the cells limiting the spaces, is evidently under a certain definite pressure, which exerts an influence on the form of the cells lining the channels. These limiting cells lose their earlier isodiametric, more or less regular cuboidal form, and appear flattened, and on optical section spindle-shaped. They have begun to assume the endothelial character. Hence from its earliest inception the endothelial lining of vascular channels appears as an enviroiunental adaptation of the mesodermal cell. One surface of a cuboidal cell is freed from contact with adjacent cells by the development of an intercellular cleft, and this free surface is subjected to the pressure of the fluid contained in the earliest capillary anlages, modified by the tension pressure of the organism as a whole. This mechanical adaptation to the altered cellular milieu results in the formation of endothelium, and the process is identical in all portions of the mesoderm, independent of the question as to whether the resulting endothelial lined space shall subsequently be incorporated in a haemal or a lymphatic system of vascular channels, or shall remain as a closed non-vascular mesodermal space.

It seems to me futile to try to speculate on an ontogenetic stage in which endothelium acquires a "specific character. It

^■R. Thoma: Untersuchungen uberdie Histogenese und Histomechanik des Blutgefasssystems/' Stuttgart, 1893.


RELATION OF LYMPHATIC TO BLOOD-VASCULAR SYSTEM 21

develops de novo in the adult under appropriate normal conditions.

Furthermore, this endothelial characterization of modified mesodermal cells is from the beginning a multiple process, starting independently at innumerable separate and discrete points of the vascular area, and becoming only subsequently continuous by confluence of the individual separate anlages. This fact is of importance in drawing general conclusions as to the later extension of vascular endothelium, whether haemal or lymphatic.

Up to this point the histogenetic and physical characters of all developing vascular structures are identical. The picture just described applies equally to the earliest definite anlages of the haemal capillary system, and, as I shall show, to the first appearance of the earliest lymphatic structures of the body. In the case of the definite blood-vascular channels of the vertebrate embryo, however, a further developmental change occurs, namely, the addition of free, specially modified, mesodermal cells, as the red blood cells, to the clear plasma circulating in the channel-system of the earliest capillary anlages in response to the first pulsations of the heart.

The first blood vessels of the area pellucida appear, at least in part, to develop independentlyof the so-called Blood islands. These latter, originally, form broad cellular strands composed of closely packed uncolored cells, which are only distinguished from the solid strands of the earliest vascular anlages of the area pellucida by greater size and massiveness. After the vascular cellstrands of the area pellucida have developed in their interior the intercellular closed oval or round spaces of the first capillary anlages, similar spaces also appear in the more massive cell strands of the peripheral portion of the area vasculosa. In the subsequent confluence of these discretely developed spaces to form the early capillary reticulum, the blood islands become more and more surrounded by the forming channels and are thus separated from the adjacent tissues. New endothelial-lined spaces continue to develop on the surface of the blood-islands, enlarge and join the system of connected channels. The cells forming the walls of these primitive capillaries become, as above stated, transformed into the typical flattened endothelial cells of the vascular intima. Excepted from this endothelial transformation are only those cells of the vascular walls which differentiate as young blood cells. Thus eventually the confluence of the originally individual and separate spaces produces a continuous and connected channel system, lined by endothelium, which nearly encircles the blood islands. The latter are therefore now in large part included within the lumen of the capillaries, with whose walls they are from place to place continuous. It only requires a further and complete solution of this continuity, and the accompanying freeing of the blood cells, to add the latter to the plasma circulating in the preformed channels. In the chick, according to Thoma's observations, the resolution of the blood islands into separate blood cells occurs between the 45th and 55th hour of incubation, while the acquisition of haemoglobin by the cells occurs between the 40th and 45th hour. With this occurrence the development of the primary blood-vascular channels has reached its definite accomplishment.

The general picture presented by the earliest development of the blood-vascular system may therefore be summarized as follows:

(1) Differentiation of certain mesodermal areas and lines by the multiplication of mesodermal cells to form cell-strands of varying density and size (vascular strands).

This appears to be a common antecedent condition not only of all vascular mesodermal structures, but also of other mesodermal derivatives eventually destined to obtain a lumen and enter into the formation of canals, as the Wolffian tubules and the cell-strands of the gonad.

It possibly explains the conditions described, for example, by Sala in the development of the avian thoracic duct, is seen in the developing aortae of early chick embryos, and is especially significant in the pictures furnished by Sabotta of the development of the aortae in fishes.

(2) Development in the interior of these cellular strands of intercellular spaces in large numbers.

(3) Bio-mechanical modification of cells lining these spaces to produce typical flattened vascular endothelium.


RSLATION OF LYMPHATIC TO BLOOD-VASCULAR SYSTEM 23

(4) Confluence of these endothelial-lined spaces to form larger and larger vascular areas of intercommunicating channels, containing a clear plasmatic fluid, which circulates in the channels in response to the establishment of cardiac pulsation.

(5) Addition to the plasmatic contents of these channels, coincident with their further growth and extension into a continuous circulatory system, of cellular elements, derived from the mesoderm and specially modified to acquire haemoglobin and function as red blood cells. These cells, by solution of tissue continuity, are liberated from the blood islands which are first surrounded by the confluent spaces of the capillary anlages.

(6) Subsequent differentiation of the adventitia, with specialization of districts by cardiac concentration, amalgamation of the plexus into larger arterial and venous channels, definition of permanent capillary areas, valve and septal formation, etc.

The striking features of this ontogenetic history of the blood vascular system are:

1. The relatively late addition to the preformed non-cellular circulation of free cell elements, which, as the red blood cells, stamp, from the period of their liberation and inclusion in the circulating plasma, the resulting vascular system as fujemal,

2. The common origin from mesoderm of both characteristic components of the haemal system, viz., the vascular endothelium and the red blood cell. Both the vascular intima and the free cell contents of the channels lined by this intima appear as highly modified derivatives of the same mesodermal cellular ancestors, which constitute the cell-strands of the earliest period of vascular development. In their first inception the systemic lymphatic vessels of the mammalian embryo, as distinguished from the jugular lymph sacs of venous origin, repeat in every detail the primary stages of the developing haemal capillaries, prior to the inclusion within the lumen of the latter, of the cellular contents of the blood islands. They can be identified as distinct structures as soon as the blood channels proper have differentiated. Before that period direct observation cannot determine, in case of individual mesenchymal spaces, whether they are eventually to become part of the lymphatic or of the blood vascular system.


It is therefore quite possible that in the mammalian embryo both sets of intercellular mesodermal spaces develop side by side and simultaneously, although prior to the setting free of the hsBmoglobin cells and their appearance within the lumen of the haemal capillaries, there is no absolute criterion which would serve to distinguish intercellular spaces as belonging definitely to either the haemal or the lymphatic division of the general vascular anlage.

It hence appears to me futile to base serious conclusions in regard to the genesis of vascular structure on observations made on the vessels seen in the transparent tails of living anure amphibia. Phylogenetically, from the urodele standpoint, such larvae are adult organisms. We all know that, once established, all divisions of the vascular organization are, under the stimulus of normal or abnormal growth, capable of further increase and extension. The observations above referred to may offer, if correctly interpreted, interesting side lights on the method of vascular growth, but they cannot, in any valid sense, bear on the problem of vascular genesis, either haemal or lymphatic.

But in mammalian embryos of the proper stages, and specifically in embryos of the Cat between 10 and 12 mm., the first systemic lymphatic anlages are clearly differentiated in the circumscribed areas of their first appearance, coincident with the definition of the early intra-embryonic blood channels.

Thus in the omphalo-mesenteric district, and cephalad and caudad of this point, on each side of the aorta, isolated intercellular mesenchymal spaces appear at this period, closely applied to the walls of the neighboring venous plexuses of the postcardinal and mesonephroic veins, but not connected with the same. These intercellular clefts enlarge rapidly to form numerous oval or round spaces, closely interwoven with the venous network and later with the sympathetic anlages. The cells limiting these early lymphatic anlages become, with the further extension of the spaces which they line, flattened and assume typical endothelial characters.

Fig. 1 shows a transverse section of a 10 mm. cat embryo (series 111, slide viii, section 4) magnified 175 diameters, cephalad


RELATION OP LYMPHATIC TO BLOOD-VASCULAR SYSTEM 26

of the mesonephros and the subcardinal cross anastomosis, and gives a topographical view of. the region in which the first mesodermal intercellular lymphatic tissue spaces {77) appear, in the interval between aorta {73) , postcardinal vein {68) and coelom {78) .

Fig. 2 is the same section of this embryo, magnified 300 diameters, and shows the area to the left of the aorta. Between this vessel {73) and the well defined left postcardinal vein {68) dorsad, and the coelom cavity {78) ventrad, appear a number of clear mesenchymal spaces {77) which do not communicate with the adjacent venous channels. Some of these spaces extend from the coelom angle dorsad along the lateral aspect of the postcardinal. They are the first distinctly recognizable anlages of the lymphatic system, and they develop, from their first inception, as independent mesenchymal spaces, closely related to the adjacent haemal channels, but genetically independent of the latter.

Fig. 3 shows the same field in a magnification of 600 diameters. The spaces are clearly ciit, separate and distinct, and the limiting cells are beginning to assume endothelial character.

The relation between the haemal channels and the developing adjacent lymphatic spaces can be clearly traced in successive sections of this same embryo proceeding caudad.

Figs. 4, 5, 6, and 7 show, respectively, sections 7, 8, 9 and 10 of slide viii of series 111, magnified 300 diameters.

In all of these sections the uniformity, and the distinct structural character of the primary lymphatic tissue-spaces is clearly visible in the same situation and in identical relation to surrounding structures.

For comparison with the preceding series the same region is shown in another 10 mm. embryo (series 120, slide ix, sections 25 and 26) in two successive sections, magnified 300 diameters, in figs. 8 and 9.

In these sections the same independent mesodermal spaces {77) are seen in their typical relation to aorta {73) , post-cardinal vein {68) and coelom cleft {78).

The interesting question of the relationship between these early mesenchymal spaces and the coelom cavity can only be


26 DEVELOPMENT OF THE SYSTEMIC LYMPHATIC VESSELS

considered superficially at this time. Yet, in some regions, very suggestive pictures are obtained. Thus in section 4 of slide viii of series 111 (figs. 1, 2 and 3) the distinct appearance of a communication between the coelom cavity proper {78) and the early mesenchymal spaces {77) above described is given by a clearly limited and well defined funnel-shaped stoma, occuping the dorsal extremity of the coelomic cleft {79 in fig. 2), and apparently opening directly into the spaces of the early lymphatic plexus. The remaining sections of this series figured (figs. 4 to 7) confirm this impression.

The conditions here described for early embryos of the cat strongly support the views expressed by Marcus' in his studies on the lymphatic development of Hypogeophis. The microphotographs here given should be compared with his description on pp. 599-601 of the paper quoted, with his text fig. 6, and with his figs. 5 and 6 of plate xvi.

The early mesodermal spaces here described and figured are lymphatic in character and form part of the extensive temporary network of lymphatic channels which appears for a time during mammalian ontogenesis and which bears a close resemblance to the corresponding lymphatic organization in amphibia and reptiles. The peri-aortic lymphatic sinuses and the exaggerated subcutaneous lymph channels of the earlier mammalian stages are portions of this evanescent and reminiscent system, which subsequently in large part retrogrades, and either disappears altogether or is extremely modified to meet the definite permanent conditions of mammalian lymphatic organization. Thus the early periaortic spaces become much reduced in course of further development. They then become associated, in a way presently to be described in detail, with elements of the axial venous plexuses of the mammalian embryo and form the anlages of the main segments of the thoracic ducts. This ontogenetic temporary recall of antecedent phylogenetic types of vascular development appears to be chiefly centered, in the mammalian embryo, in the region around the omphalo-mesenteric artery, where, in the adult, the definite and permanent lymphatic trunks closely resemble in their arrangement the peri-omphalo-mesenteric annular veins of certain reptilian embryos.


In the succeeding stages the mesodermal lymphatic anlages assume, in large part, the very definite relation to certain embryonic venous channels, which led McClure and myself to describe them in 1906 in our preliminary account above quoted,^^ as extraintimaP' or ^'perivenous structures.

This relationship is of two kinds:

A. Total replacement of temporary embryonic veins by extraintimal lymphatic channels.

In the earlier embryonic stages the areas of the future definite venous channels are largely occupied by an antecedent venous or capillary network, out of which, along definite hydrostatic lines, the subsequent veins develop by confluence of the plexus elements occupying these lines. ^^ Parts of the early capillary reticulum, not thus included in the path of the definitely organized venous trunks, remain, after the latter have become established, as a perivenous plexus. Some of the elements of this secondarily established plexus develop into permanent tributaries of the main veins. Others undergo a process of separation from the permanent functional channels and degenerate. In many cases their blood-cell contents break down and are eliminated, w^hile their endothelial lining appears to revert to the indifferent type of the embryonic mesodermal cell.

Thus in embryos between 13.5 and 16 nmi. many striking instances of this reversion are to be observed. The former vascular channel appears as a collection of clearly differentiated and very highly stained mesodermal cells.

Figs. 47, 50, 61, in Part II, show these mesodermal vascular derivatives very clearly. They form the dark masses seen in the field dorsal and dorsolateral to the oesophagus and in the peritracheal region.

In many regions of the mammalian embryo, however, these detached and retrograding venous elements do not attain this condition, but in an earlier stage, constitute lines around which the most active primarj'^ lymphatic organization of the mammalian

• H. V. W. Schulte and Fred. Tilney: "Note on the Organization of the Venoufi Return, with Especial Reference to the niac Veins." Anal. Record^ vol. iii, no. 11, 1909.


embryo centers. The intercellular mesodermal clefts above described develop especially along and around these decadent venules and finally envelop them. As the result of this process the lymphatic anlages appear in certain mammalian ontogenetic stages, in large part, as distinct spaces enclosing the remnant of the embryonic vein. The latter may still, for a time, contain a few degenerating red blood cells, but these soon disappear, and then the entire anlage is formed by a collapsed and empty endothelial tube, the abandoned chaniLel of the earlier vein, surrounded by a second endothelial tube, formed by the confluence of the independently developed extraintimal or perivenous mesodermal spaces. As these spaces enlarge and join each other their lumen increases, and the limiting cells become flattened and assume typical endothelial characters. The height of this phase of lymphatic development is reached in embryos of the cat in the 14 mm. stage, and numerous demonstrations of the appearance of the structures on section are given in Part II of this paper. The remnant of the embryonic vein bears a relation to the replacing perivenous lymphatic channel which is exactly the same as that of a collapsed inner tube to the enveloping shoe of a pneumatic tire. The inner skin of the shoe and the rim of the wheel represent the lymphatic inlimal endothelium. The space between the shoe and the collapsed inner tube is the lumen of the future lymphatic channel. The empty inner tube itself is the decadent embryonic vein upon and around which the secondary lymphatic channel is built. In the course of further development the venous remnant disintegrates and disappears, leaving a clear lumen for the lymphatic vessel, which thus completely replaces the earlier vein and comes to occupy absolutely the topographical position of the latter.

Often the replacing lymphatic begins as an extraintimal channel partially surrounding the receding vein. This leads in course of further development to an expansion of the lymphatic channel not concentric with the axial line of the shrinking vein. The remnant of the vein then retires to a point on the intiiiial surface of the new lymphatic channel, and appears to project into the lumen of the latter. The resulting histological picture will depend on the plane of section in reference to the course of the lymphatic and its contained venous remnant. Thus, as shown in the following schema, many sections give the appearance indicated in 1. If the plane of section should, however, lie in the line A B,it will divide the shrinking vein (4) and the enveloping lymphatic (5) in such a way as to produce the picture shown under 2. In other cases the lymphatic spaces unite around the entire circumference of the abandoned venule, and the lumen is then contained for long distances entirely within the lumen of the replacing lymphatic channel.


Ontogeny of mammalian systemic lymphatic vessels

The process just described is remarkably constant and uniform in the critical stages of mammalian lymphatic development. As can be readily seen in following the individual sections in the microphotographs published in PSart II, the significance of the conditions here shown is unmistakable. This is not a haphazard process, observed only occasionally, in a limited number of embryos, and then only in single sections, or, at most, in a few successive sections. In any average embryo of the proper age the same structures appear regularly in the same situatioi^s and in identical relationship to the embryonic environment. It is often possible, as the microphotographs and the corresponding reconstructions herewith published clearly show, to trace the forming Ijrmphatic withits atrophied vein kernel for long stretches, and in different embryos of approximately the same crown-rump measure the consistent repetition of identical histological pictures is remarkable.

There are, of course, as in the ontogeny of other structures, individual cases of variation in which systemic lymphatic development is either more advanced or more retarded than is normal for the average of any given stage. But if a large nmnber of embrj^os of each typical period are examined and compared, the average standard of extraintimal lymphatic development attained by the majority of individuals in each stage is remarkably constant and uniform.

The earliest stage in which I have encountered this typical replacement of an early embryonic vein by a perivenous extraintimal lymphatic is presented by certain 12 mm. cat embryos along the caudal circumference of the azygos-precardinal confluence. In the concavity of the azygos arch on each side, as this vessel turns ventrad to join the precardinal vein, these earliest evidences of the extraintimal replacement of preceding embryonic veins by independent perivenous lymphatic spaces are encountered. Thus, fig. 10 shows a section of this region in a 12 mm. cat embryo (series 217, slide x, section 12). Here the typical picture of the central collapsed core of the earlier vein (4) , enveloped by the clear extraintimal lymphatic space (5), is plainly to be seen. Fig. 11 shows the same region in another 12 mm. embryo (series 211, slide X, section 15). Both the degenerating venule (4) and the enveloping lymphatic (5) are larger than in the preceding series, and occupy the same position between aorta (7) and left precardinal vein {6).

In a 14 mm. embryo (series 127, slide viii, section 12, fig. 12) the section passing just caudad to the junction of left azygos (6) with left precardinal vein {6) shows these early lymphatic spaces (5) and their relation to the contained venous remnant (4) fully developed. Only one of the areas is denoted by leaders in the figure, but two equivalent areas are seen further dorsad and nearer to the ventral aspect of the azygos arch. The lymphatic plexus, as development proceeds, from the 12 mm. stage on, approaches the large venous trunks more and more, until the spaces lie in direct apposition with the same, and unite to form the lymphatic trunk eventually destined to replace the left azygos arch and adjacent position of the left precardinal vein. This trunk then constitutes the cephalic end of the bronchomediastinal duct (37). Thus figs. 13 and 14 show two sections through the same region in a 15 mm. embryo (series 219, slide xiv, sections 19 and 16). Compared with the 14 mm. embryo the left azygos vein shows a marked reduction. The lymphatic spaces have enlarged and present a clear lumen on section, the remnant of the earlier vein, around which they developed, having disappeared. The spaces lie between aorta and left precaval vein, in close approximation to the dorso-medial circumference of the latter. The azygos segment of the thoracic duct (36) is seen dorsal to the interval between aorta and oesophagus, and ventral to the scant remnants of the earlier interazygos venous anastomosis {16).

The reconstruction of a 15 mm. embryo (series 218) shown in fig. 170 in Part II, gives a clear idea of the extent and relations of this lymphatic complex (37) in this stage.

B, Partial replacement of portions of the territory of an early embryonic venons pathway by an extraintimal lymphatic vessel, both venous and lymphatic channels either persisting side by side up to later developmental periods, or forming correlated components of the permanent adult vascular organization.

The developmental processes just described appear most clearly marked in the earlier stages, and in connection with temporary embryonic channels and plexuses which are destined to undergo rapid degeneration and ultimate complete elimination. In the case of the embryonic veins which are retained for a longer period, or carried over into the permanent adult organization, the histogenetic stages of lymphatic development are identical in kind, and differ only in degree from those just detailed. In place of complete replacement of the antecedent vein by the lymphatic channel, this replacement is only partial and leads to the typical

close parallel association of lymphatic and venous vessels so characteristic of the later embryonic stages and of the permanent adult pathways of both the lymphatic and the venous systems.

Figs. 15 and 16 show transverse sections of a 14 mm. embryo (series 222, slide vii, section 26, and sUde viii, section 4) in the region of the external jugular vein. The lymphatic spaces (;87') are in full development, and are applied chiefly to the medial aspect of the plexus of the external jugular vein (27). The lymphatic endothelium is clearly marked.

Fig. 17 shows a transverse section in the upper thoracic region of another 14 mm. embryo (series 37, slide xiii, section 12). A typical lymphatic anlage (53) is applied to the medial wall of the left precaval vein.

Fig. 18 shows a transverse section through the mid-thoracic region in a 17 mm. cat embryo (series 258, slide xviii, section 9, X 225).

The extraintimal anlagesof the thoracic ducts (S6), which usually in thisstage have advanced to the production of a continuous and uninterrupted channel system, are seen on each side closely applied to the ventral aspect of the left and right azygos veins. The latter are in the height of their development, forming large and symmetrical longitudinal venous trunks (S, 6) connected by the supra-aortic interazygos anastomosis. In course of further development the left azygos vein and the interazygos anastomosis are destined to undergo progressive reduction until they are eventually entirely lost. Their topographical position is then occupied by the replacing left segment of the thoracic duct complex (36). The right azygos vein, which is carried as a permanent vessel into the adult organization, also undergoes considerable relative reduction, correlated to the corresponding increase in the caliber of the main (right) segment of this portion of the thoracic duct complex.

The beginning of this process is seen well in fig. 19, which shows a transection of the same region in a 19 mm. cat embryo (series 253, slide xxiv, section 9, X 225). The change from the preceding stage (fig. 18) is marked both in the venous and the lymphatic channels. The former are relatively much reduced, while the latter have correspondingly increased in extent. The azygos is mainly represented by the right channel (S). The left channel (6) has become small, but is still connected by the transverse interazygos anastomosis (15) with the larger and permanent right trunk. The right thoracic duct (36) is likewise large. A dorsomedial extension of the same, which carries into the interval between aorta and interazygos plexus, will, in later stages, replace the latter secondarily, after the complete recession of the left azygos vein. The left thoracic duct {S6) is also of large size and fills a considerable part of the area formerly (fig. 18) occupied by the left azygos trunk. Some decadent remnants of the ventromedial azygos plexus (4) are still seen associated with the left duct, and are in process of replacement by a lymphatic space (5) * destined to make connection between the left thoracic duct anlage and the mesenteric lymphatic plexuses (cf. p. 148, figs. 266 to 270, 51).

Figs. 20 to 24 show transverse sections in the region of the developing mesenteric lymphatics and of the ascending lumbar lymphatic trunks in a 17 mm. embryo (series 258, slide xxiii, sections 34, 33, 32 and 31.) The embryonic veins (74) occupying the root of the mesentery caudal to the subcardinal cross-anastomosis are in the process of being replaced by extraintimal lymphatic spaces . {61) which are destined to become confluent and form the anlage of the future mesenteric lymphatic sac.

The region in question is not only interesting in reference to the ontogenesis of the abdominal lymphatic sacs and channels, but the arrangement of the periaortic axial venous trunks and their relation to the developing lymphatics is, in combination with the next following stage (20 mm., figs. 25 and 26), of the highest importance in interpreting the phylogenetic relations of the main abdominal veins in mammalia. For these reasons a somewhat more detailed consideration of the sections may properly be introduced here.

Fig. 20 shows section 34 of slide xxiii of series 258 in a magnification of 75 diameters and affords a comprehensive picture of the entire


topographical field involved. The strands of the sympathetic (l) are supra-aortic. On each side of the aorta (7) are the large and symmetrically developed right and left postcardinal veins (67 and 68) , with the ascending tninks of the ilio-lumbar arteries (A.ilid-lumb. transv. ant.) (not labelled in the figure) applied to their ventrolateral circumference. The subaortic area shows the cross-sections of four symmetrical vascular channels, two venous and two lymphatic. Immediately venti alto the aorta, and closely applied to its ventral wall and to each other, are two longitudinal parallel axial veins which are connected at intervals by a few short transverse anastomoses. These vessels are the temporary and very evanescent homologues in the placental embryo of the channels which McClure'® has described as the "cardinal collateral trunks'* in the embryo of Didelphis marswpialis, and from which he has traced the development of the preaortic postcava characteristic of the Marsupalia. These vessels are derivatives from the earlier preaortic cardinal-subcardinal venous plexus below the crossanastomosis, but differentiate in Marsupials along separate and distinct axial lines. They are destined, as are the corresponding portions of the subcardinals proper, to be entirely replaced in the typical placental development by the chain of preaortic lymph channels and nodes, but are capable, in aberrant types among the placentalia, of yielding, by further and continuous development, a type of preaortic postcava which in every respect corresponds to that encountered in Marsupials. McClure^* has described this condition in Tragulus, and his observation has been confirmed in a number of dissections by Beddard and others. The fortunate acquisition recently of a series of Tragulus embryos, through the kindness of the officials of the Smithsonian Institution, has enabled my associate Tilney to trace, in a publication now in preparation for the press, the development of the venous and lymphatic systems in this aberrant ungulate in their mutual interdependence, and to show the correspondence of the venous genetic processes

•• C. F. W. McClure: "The Anatomy and Development of the Postcava in Didelphis marsupialis/' Am, Jour. Anat,, vol. v, 1906.

" C. F. W. McClure: "The Postcava of an Adult Indian Chevrotain {Tragulus meminnaj Erxleben). Anal, Anz., Band, xxix no. 13 and 14, 1906, pp. 375-377.


persistence and further development of the cardinal collateral veins. In other words, not a single individual in the entire seiies possessed a marsupial postcava, although every shade in the possible range of variation in the district of the post- and supracardinal lines was represented by numerous examples. Thus with an abdominal venous organization of very unstable equilibrium, as shown by the large percentage of cardinal variants,^^ the cat yet keeps entirely within the district of the common genetic ground plan assigned to the placentalia. This phylogenetic consistency is maintained in spite of the fact that, as just demonstrated in series 258, the embryo develops the raw materials, as cardinal collateral channels, out of which a preaortic postcava of the marsupial type could be evolved. In my own estimation cats possessing this form of postcava may exist and may eventually be found. But the failure to encounter them in the relatively large series of adults already examined speaks volumes for the value of vascular organization in interpreting phylogenetic relations.

In this light the postcaval development and adult structure of Tra^ulus, for example, are of the utmost importance and significance. The unprejudiced observer is often forced to wonder why'some exponents of palaeontological research are content to draw far-reaching phylogenetic conclusions from the remnants of the incomplete locomotory apparatus at their disposal, without utilizing the results of modern comparative anatomical and embrj'ological investigation in determining at least the mutual relations of the extant forms, massed by an ironclad taxonomy into more or less questionable groups, whose ancestry and derivation form one of the primary problems of the palaeontologist. The case of Tropins just alluded to, the parotid complex and alimentary canal of Hyrax, the amniote homologies of the derivatives of the Sulcus buccalis determined by Schulte, the sharp line of lymphatic demarcation recently shown by Silvester to structurally separate absolutely the platyrrhine and catarrhine divisions of the lower primates, these and other facts are only instances in which the inadequacy of a superficial convergence of dental and skeletal characters, for the purpose of establishing valid phylogenetic relations, is revealed by cardinal divergence in the far more stable and important organization of vascular and visceral structure


The prevalent lack of coordinate deduction between vertebrate morphology and palaeontology is accentuated by contrast with such publications as Weber's Saugethiere and, more recently, W. K. Gregory's The Orders of Mammals", based largely on the author's joint work with Osborn, and on the latter's previous classical researches, and published by the American Museum of Natural History (Bulletin, vol. 27, February, 1910).

Workers in the general field of vertebrate structure appreciate fully the immense practical value in their own special investigations of books of this type, in which, to quote Gregory's words, the data of sj^stematic mammologj', of comparative anatomy and embryology shall ultimately be integrated with the data of palaeontology, to the great advantage of these now more or less independent lines of study."

In embryo 258 (fig. 21) the space ventral to the cardinal collateral veins and the ascending lumbar lymphatic trijnks, is occupied by a plexus of mesenteric lymphatics (61) draining into the latter. On each side are seen sections of the ureter {68) y and further laterad of the iliac vessels (61), Ventral of the intestine {6S) are the Wolffian ducts (64) and the cloaca (63) j with the hypogastric arteries (66) laterally.

Fig. 21 shows the important central vascular region of the same section in a magnification of 150 diameters. The relation of the cardinal collateral trunks (74.) to the ascending lumbar lymphatics (7S), and of the latter to the postcardinal veins (67 y 68) can be more clearly seen. The lumen of the mesenteric lymphatics (61) still contains in places remnants of the decadent venous plexus around and upon which they developed as replacing extraintimal spaces.

The three succeeding sections, tracing the structures caudocephalad, are shown in figs. 22, 23 and 24, all in a magnification of 150 diameters. The connections of the lymphatic channels developing along the iliac vessels with the ascending lumbar trunks are especiall}^ well seen on the left side of the three figures, also the anastomoses between the two cardinal collateral veins in figs. 23 and 24.

Figs. 25 and 26 show transverse sections of the hinder end of the bodv in a 20 mm. embrvo (series 241).


Fig. 25 (series 241, slide xxx, section 4) gives, in a magnification of 76 diameters, a topographical view of the entire field. This stage, compared with the preceding 17 mm. embryo, is marked by the full development of the supracardinal venous line, responsible for the production of the greater portion of the typical adult placental postcava below the renal level, and by the correlated development of the supra- or retro-aortic lymphatic sinuses associated with the same.

The periaortic area in fig. 25 gives a ijlear view of the vascular relations and of the postcardinal and supracardinal axial venous trunks.

The former {67 , 68,) are seen on each side, between aorta (7) and metanephros {65), receiving the veins from the mesonephroi in whose dorso^-medial border they are lodged.

The latter {59, 60) lie dorsal to the aorta (7) between this vessel and the sympathetic strands {1 ) .

The right supracardinal {60) has already gained the ascendency and is in process of establishing the channel of a normal right retro-aortic postcava, which is the typical vein for the cat. The correspondingly reduced left supracardinal {59) occupies the same situation on the left side. Associated with the supracardinal venous channels are the supracardinal lymphatic trunks {76), which form the anlages of the main adult retro-aortic lymphatic plexus. These develop as extraintimal spaces replacing portions of the earlier supracardinal venous reticulum. In accordance with the normal type of development observed in this individual embryo, the large permanent supracardinal (postcaval) vein of the right side is accompanied by a relatively small lymphatic channel {76 right), while on the left side the much reduced left supracardinal {59) is already nearly replaced by the corresponding lymphatic vessel {76 left) . In course of further normal development this replacement will become complete and then the area formerly occupied by the left supracardinal vein will be entirely filled by the substituted large left retro-aortic lymphatic. The permanent functional venous channel of the right side {60) on the other hand, developing into the typical placental postcava, will be accompanied by a relatively small right lymphatic trunk following its dorso-lateral aspect. As will be shown later (Part v.), departures from the normal type of venous development in this region, and the substitution of other embryonic pathways for the right supracardinal in building up this section of the adult postcava, produce corresponding and correlated changes in the arrangement of the main retro-aortic lymphatic channels.

Fig. 26 shows the periaortic region of the same embryo, further caudad, in a magnification of 150 diameters (series 241, slide XXX, section 14.) The section is taken at the level of a pair of dorsal intersegmental arteries which pierce the supracardinal venous (5S, 60) and lymphatic {76) complex, and divide the vein of the right side into two components {60, 60) . Further ventrad the two postcardinal veins {67, 68) are seen, already considerably reduced, ventrolaterad to the ureters {58) and the accompanying ascending lumbar lymphatic trunks {75). The connection of the latter with the supracardinal lymphatic channel is especially clear on the right side of the embryo.

Taken together, the 17 mm. and 20 mm. embryos just figured and described afford a very clear and comprehensive picture of venous and lymphatic development in their mutual relationship in this region.

The schematic text figures A, B and C may help to explain this relationship.

Fig. A is based on the joint studies which McClure and I made on the development of the postcava in embryos of the domestic cat. The figure was demonstrated to the 21st Session of the Association of American Anatomists in 1906 at the time of presentation of the communications, although not reproduced in the brief abstracts of the papers subsequently published.**' ^^

The figure represents a composite schema of the main periaortic venous axial pathways of the abdominal region. These pathways developing along diefinite and constant axial hydrostatic lines out of the periaortic venous reticulum, have all been determined by us in embryos of the cat. They do not, of course, all coexist at the same time in any embryonic stage, but normally succeed each other in definite sequence. The entire range of extensive variations in the domain of the adult postcava of the cat can be clearly interpreted genetically^* on the basis of this common groundplan, through abnormal persistence of one or more of the embryonal pathways usually destined for complete obliteration, thus producing farreaching modifications in the structure and relations of the resulting atypical postrenal segment of the adult postcava.

This periaortic axial venous lattice with connecting transverse branches (Fig. A) contains four components on each side, which develop in the following order:

1 . The postcardinal veins (1 ) .

2. The subcardinal veins (£),

3. As secondary derivatives of these two veins, the preaortic cardinal collateral channels (S).

4. As secondary dorsal derivatives of the postcardinal trunks, the supracardinal veins (4) In the course of normal venous development along the line typical for the great majority of placental mammals the right supracardinal vein (4) obtains the preponderance and furnishes the postrenal segment of the adult postcava, thus freeing the ureter from its primitive retro-venous position.

A part of the early capillary periaortic reticulum, out of which this vessel develops, is secondarily replaced by extraintimal lymphatic spaces, which through their confluence form the relatively small retro-aortic lymph channel (40 > following in the adult the dorso-lateral circumference of the postcava (4). (Figs. B and

n.

The right and left postcardinal veins (1) are in part retained as the terminals of the sex veins, in part replaced by the accompanying lymphatic trunks (i')- (Figs. B and C).

The left supracardinal vein (4), and both subcardinal veins (j?) , below the cross-anastomosis, as well as both cardinal collateral veins (S), retrograde and are entirely replaced secondarily by lymphatic channels.

The lymphatic replacing the left supracardinal vein (40 forms normally in the adult the main retro-aortic lymphatic sinus. (4'i left, in figs. B and C).


The lymphatic channels replacing the subcardinal and cardinal collateral venous trunks fonn the extensive system of the adult ascending lumbar and preaortic lymphatic vessels and nodes (2' and S' in figs. B and C).

Of course it is quite apparent that the adult placental differentiation occurs in the district of the post- and supracardinal lines, with a strong predilection for the right supracardinal as the main path of the postrenal segment of the adtdt postcava. It is equally apparent that in correctly valuing the significance of the departures from the normal type of placental postcava all four of the available components, viz., right and left postcardinal and right and left supracardinal lines, must be taken into account as potential factors in the development of the atypical placental postcava. The relation of the veins to the ureter will then decide the question of the genetic derivation, as being either the persistent postcardinal or supracardinal channel of either the right or left sides, in the case of single trunks, or of both sides in instances of double bilateral adult channels.

Thus all the recorded cases of variant postcaval veins of the cat, and of man, can be clearly interpreted on this basis, as has been done by McClure, Darrach and myself in previous publications.2»'24,26

Furthermore, the placental types in which a normally so-called double postcaval vein occurs, as, e.g. in some of the aquatic carnivores, some insectivores and edentates, are readily led back to persistence of both right and left axial channels with absence or reduction of the iliac anastomosis. Again the position of the ureter in reference to the bilateral trunks will characterize each of them as being either post- or supracardinal in derivation.

In the marsupials McClure's researches already quoted,'^ show clearly that the members of this subclass depend upon the continued development of the ventral preaortic venous pathways (^, S) of the common vertebrate groundplan (fig. A) for the evolution of their typical ventral preaortic postrenal segment of the postcava, with consequent reduction of the postcardinal line (1) to the r61e of a sex vein terminal, and the complete suppression of the typical placental supracardinal lines (4) in most with the same. Nowhere is there any suggestion of a bud or an outgrowth from the vein as forming the origin of these lymphatic spaces. It now remains to clearly prove the genesis of these spaces, and to trace their growth from their inception up to the stages just pictured in which fully organized Isonphatic and venous channels lie side by side in the mutual relation above figured and described. The proof of their origin is furnished by the series of microphotographs of successive sections of the earlier stages given in Part II of this communication, in connection with the individual series described and figured in tracing the development of the preazygos and azygos portions of the thoracic ducts. The microphotographs, and especially the reduced reproductions figured, are not so clear as the actual preparations, because focal adjustment is required to follow the endothelial lining of the spaces in their entire circumference, and because they lack the differential stain of the sections. Still they are sufficiently distinct to establish definite conclusions. Merely referring, therefore, at this time to the following detailed illustrations, the general topic of extraintimal replacement of embryonic veins by lymphatic spaces and the character of the latter deserve some further consideration.

The lymphatic anlages, as above stated, if studied under sufficiently high power and with some care, are seen to begin as intercellular clefts in the periaortic mesoderm, adjacent to the postcardinal venous plexus, and chiefly on its ental aspect, between it and the aorta.

The individual lymphatic spaces, at first small and separated from each other, enlarge, elongate and become confluent, to form larger continuous channel segments, while innumerable newly formed spaces of the same character appear in the surrounding tissue, join with each other, and with the earlier preformed lymphatic channels, in exactly the same manner, and with the same appearance of lymph endothelial '* budding or *' sprouting" as is observed in haemal vascularization of new areas by the junction of the earlier blood capillary anlages with secondary haemal plexuses. In these later ^ages the veins are surrounded by a close lymphatic plexus, which, however, does not as yet form a connected channel system, but is composed of longer and shorter segments still independent of each other.

These finally become confluent, to form the main systemic lymphatic collecting trunks, and then onlj do these establish their final junction with the jugular lymph sacs, through whose interposition, as above stated, they gain in the typical mammal their permanent entry into the venous system.

In this ontogenesis of the systemic lymphatic vessels certain relations between them and the venous system deserve further notice.

In the early stages the lymphatic mesenchymal spaces form a wide meshed network (cf. series 111, figs. 1 to 7, series 120, figs. 8 and 9). There is thus a marked similarity in the earliest stages of both the haemal and the lymphatic vessels, for the peripheral venous embryonic pathways are in their corresponding stages likewise still largely in the condition of a capillary reticulum. As the main lines of venous drainage crystallize out of the antecedent plexiform arrangement, the adjacent enlarging lymphatic channels crowd in on the condensing venous line and continue the close relationship which the earliest lymphatic anlages maintain to the adjacent veins. Thus the main embryonic venous channels develop along certain definite hydrostatic lines by enlargement and confluence of the individual plexiform elements of the indefinite antecedent network occupying these lines. The capillaries outside of these lines retrograde, so that the area of crosssection of the defined venous channel is less than the cross-cut area of the plexiform network which it replaces.- '^

The distinct impression is given that the space thus vacated by the condensation of the plexiform venous network of the earlier stages affords to the replacing lymphatic plexus the opportunity for greater growth and expansion, and that subsequently, in repetition of the process previously active in the venous reticulum, the lymphatic network condenses in a similar manner into more defined channels along similar hydrostatic drainage lines, so that the newly established main lymphatic vessel now closely follows the main venous channel. It is to be noted, however, that this organization of main vascular channels is usually less complete in case of the lymphatic vessels, as compared with the corresponding vein. The lymphatic system retains, much more perfectly than the venous, in many situations the original embryonic plexiform type.

At first the cells limiting the earliest lymphatic spaces are of the usual irregular cuboidal form. As the spaces enlarge, open out and thus become better defined, the limiting mesodermal cells become flattened, and finally assume a typical endothelial character and form. Thus, for example, the endothelial lining of the primitive mesodermal lymphatic spaces {77) is more clearly developed in the 10 mm. embryo, series 120, shown in figs. 8 and 9, than in the corresponding sections of embryo 111, of the same crown-rump measure (figs. 1 to 7). The former embryo is slightly in advance of the latter as regards the development of the parietal endothelial lining of the primitive mesodermal intercellular lymphatic spaces. In some instances a few modified mesodermal cells intervene between the cells limiting the lymphatic spaces and the endothelium of the adjacent venous radicle. In others no such intervening cell-layer exists, and the lymphatic space is separated from the venous lumen only by the latter's endothelial wall. In other words, in the extent of the lymphatic anlage, a single-celled membrane furnishes a part of the venous intima and at the same time contributes to the endothelial definition of the lymphatic space. This relation of vein and lymphatic anlage is shown very clearly in fig. 17. The lymphatic space (5S), which is closely applied to the medial wall of the left precardinal vein, is only separated from the lumen of the latter by the endothelial membrane which serves to line both spaces for the area of their mutual contact in this stage. Subsequently, with the regression of the left precardinal vein, this lymphatic anlage will correspondingly enlarge to form an extensive lymphatic plexus, which will eventually topographically replace the vein along which it arose. In order to briefly characterize this relation between vein and lymphatic, McClure and I defined in an earUer publication*^ these spaces as the Extra-intimal" anlages of the systemic lymphatic vessels, with due regard to the relation existing between them and the intimal endothelial lining of the embryonic veins. The mechanical concept involved in this term seems, to judge from a recent publication, to have been difficult to acquire. I am glad to be able to make myself clear by reference to fig. 17, where the mutual relation of the two vascular lumina is evident without further description, and to the numerous detailed illustrations on a larger scale of magnification which accompany the account of the development of the thoracic ducts in Part II of this communication.

By far the larger number of the early lymphatic channels are the product of fusion of these extra-intimar' spaces, and hence closely follow the veins of their respective regions. Subsequently, with the development of a venous adventitia, this relationship is somewhat altered in case of those veins which are included in the permanent venous organization. The close relation existing, however, throughout Ufe between these veins and the accompanying lymphatics is based on this intimate primitive association of their respective anlages.

On the other hand, the extra-intimal position of the earliest lymphatic spaces furnishes the explanation of another relation manifested between the developing systemic lymphatic channels and those embryonic veins which in course of normal venous development are destined to undergo reduction and finally complete suppression, when the primitive bilateral and symmetrical venous system of the earlier embryonic stages shifts to the dextral assymmetrical type of the main adult axial channels. In these circimfistances the systemic lymphatic vessel associated with the temporary embryonic vein experiences, apparently through the shrinkage of the latter, an impetus to its own more extensive development, so that it comes to occupy in general topographically the space filled by the vein in the earUer stages.

Thus the embryonic period which marks the normal ontogenetic swing of the main venous line to the right through the secondary sinistro-dextral iliac, hemiazygos and brachiocephalic cross anastomoses, sees the simultaneous increase in the corresponding lymphatic channels of the left side, which topographically replace the abandoned left embryonic venous pathways of the earlier and sym » Sabin: Anal. Rec, vol. ii, 1908, p. 50.


metrical stage. This occurrence leads to the well-known relative location of the main axial veins and lymphatics in the normal adult, in which the lymphatic vessels are chiefly situated on the left side and form, so to speak, a mirror-picture of the right sided axial venous channels.

Fig. 27 shows the reconstruction of the anterior venous and lymphatic complex in a cat embryo of 18 mm. (series 88) in the ventral view, and fig. 28 of the same preparation in the lateral aspect from the left side. The brachiocephaUc cross anastomosis is already well under way, resulting in a marked diminution of the left anterior caval vessel and a corresponding increase in the permanent right anterior cava or right duct of Cuvier. Conversely, the lymphatic vessel accompanying the diminishing left precaval vein is of large size, while that applied to the massive right precaval is comparatively small.

This principle of lymphatico-venous replacement, indicated clearly in the later embryonic stages, is strikingly illustrated in the adult. Thus, for example, the adult cat presents normally the arrangement of the great veins of the head and neck which is so frequently encountered in mammals below Primates, in which the large embryonic internal jugular vein is much reduced or even entirely obliterated, while secondarily the external jugular vein has assimied the function of the main vessel. Under these normal circumstances the lymphatic trunk accompanying the minute internal jugular vein or, in case of its entire default, occupying its position, is well developed and the largest element of the entire cervical lymphatic complex, while the external jugular vein is, on the other hand, accompanied usually by two very slender lymphatic vessels.

In instances, however, in which the embryonic proportion between the two jugular veins is retained in the adult, so that the internal jugular appears as a large and functionally important vessel, while the external is correspondingly diminished, the internal jugular lymphatic trunk is reduced, while the double lymphatic vessel along the external jugular is enlarged, and evidently acts in compensation in the cervical lymphatic return.


Again, in the same way, in adult animals with normally placed right postcava, the main supracardinal lymphatic trunk, draining the abdomen and the posterior extremities, follows the left side of the large artery.

In the not infrequent instances, however, of left sided postcava or postcardinal vein in the adult the reverse obtains, and the periaortic lymphatic channels predominate on the right side and occupy the place usually filled by the large vein in normal venous development.

I have encountered in the adult series so far examined no instance of persistent left precava replacing functionally the normal right superior cava, but have no doubt that this venous variation would involve a transposition of the proximal end of the thoracic duct to the right side, or at least a marked increase in the size and functional importance of the usually insignificant preazygos segment of the adult right lymphatic duct.

The developmental outline just given describes the mutual ontogenetic relations of the venous and lymphatic systems throughout the greater part of the body.

Systemic lymphatic development in these regions is, however, by no menas confined to the immediate environment of degenerating embryonic veins. The same field, which shows the above described histogenetic processes in the development of extraintimal lymphatic spaces surrounding and replacing a decadent venule, will at the same time contain numerous equivalent lymphatic mesenchymal clefts and spaces which continue to develop independently of any association with retrograding veins. Naturally, these independently developed early lymphatic anlages are less striking than those above described as developing in association with a receding vein. They are smaller, because they lack the bulk of the contained venous core, and they are more difficult to clearly differentiate against the surrounding mesenchyme. They are, however, always present and their eventual connection with the larger perivenous lymphatic spaces can be ascertained definitely by following their development through the proper stages.


In additioD, in certain areas, a small group of the earliest lymphatic anlages appear to develop in the mesenchyme along definite Unes, and in distinct patterns, but v^ithout any preceding venous reticulum. They impress me, for example, in the area surrounding the omphalomesenteric artery, as systemic lymphatic channels developing ia the placental embryo in regions which are no longer ontogenetically the seat of venous development, although occupied by vei 3S in other mammalian types. Thus the cardinal collateral line of the marsupials^'^ and the correlated venous area of the monotremes" no longer develops as a permanent veoous plexus in placentalia'* but only partially appears in certain fonns as a temporary and evanescent component of the abdominal venous complex, as described above for certain stages in the development of the cat (pp. 29 to 33 and figs. 20 to 24) . Its place, however, is partially occupied by an early lymphatic plexus de\ eloped in the preaortic mesoderm from the omphalomesenteric anlages caudad. Here we are apparently dealing with an instance in which general phylogenetic venous lines have been almost or entirely abandoned in favor of other pathways. Such lines appear, however, to be retained under these conditions in the lymphatic organization. Thus, the spaces just referred to, as will be shown subsequently, form the first inception of the extensive network of lymphatic vessels which in the adtdt cat surrounds the aorta and the origin of the superior mesenteric artery, closely interwoven wdth the semilunar sympathetic and the adrenal plexus, and connecting on the one hand with the portal and intestinal lymphatics, and on the other with the beginning of the thoracic duct. This adult mammalian lymphatic plexus forms a perfect lymphatic shadow-picture of the lacertilian ontogenetic peri-omphalomesenteric venous ring.

In conclusion, I wish to give briefly a simunary of my reasons for regarding the structures described in this communication as the anlages of the systemic lymphatic vessels.

Except, as recently determined, in Tragulus, in wnich Ungulate the adult postcaval system is of the marsupial type, and in certain embryonic stages of the Cat (15.5-17 mm.) in which the channels appear as evanescent preaortic vessels, subsequently entirely replaced by lymphatics. (Cf. series 258; figs. 20 to 24.)


These early lymphatic anlages, whether formed independently in mesoderm, or on the site of phylogenetically abandoned venous Unes, or, as is generally the case throughout the body, in close correlation to the embryonic venous pathways, always appear in the same situations and, in the average embryo, at the same developmental period. Their constant character, and regular occurrence and relations, repeated within very narrow limits of individual variation in every embryo of the proper stage, imparts to them a definite morphological character. In every series of the proper age in my collection I find the same spaces in the same place and in identical relationship to the adjacent veins. In some individuals, as above stated, they develop earlier than usual, in others their appearance is retarded, but this applies only to the achievement of the full development typical for the average embryo of a given stage. In the retarded individuals the same structures are always present, only they are less strikingly developed and less niunerous when compared with the average normal type characteristic of the period under consideration. With sufficient magnification it is not difficult to distinguish sharply between the perihaemal lymphatic spaces and the blood-vascular channels proper.

With sufficient material every stage of their development can be followed up to the confluence of the entire system and its final entrance into the jugular lymph sacs.

These spaces are neither artefacts due to embryonic shrinkage, nor are they the unfilled portions of the blood-vascular capillary network. They are, on the other hand, the well-defined earliest anlages of the systemic lymphatic vessels. The more perfect, as a matter of fact, the embryonic fixation is, the more clearly can these structures be indentified under the microscope. Their history, as will be shown presently, can be traced with the utmost accuracy, and they can be followed step by step in their development up to their inclusion in the completed and connected lymphatic channel system.

But even in their earliest stages they possess an unmistakable and definite morphological character, quite as distinct as that of the adjacent blood channels. They can be followed closely in good serial sections of the proper thickness and fixation, and can be reconstructed in the same manner and with the same accuracy and certainty as the blood channels with which they are for the most part so closely associated, although their lumen connects at no point with that of the vascular channels.

These statements are based, not on isolated observations, but on the close and repeated examination of a very large number of embryos of the same form. It seems curious to me that the presence of the first lymphatic anlages, as above described, should be denied, or, as has been recently done, that the isolated appearance of these spaces should be ascribed to the sudden collapsing " of a lymph vessel. At the time at which they make their first appearance there are no lymph vessels to "collapse," no more than there are in the homologous haemal ontogenetic stages bloodvessels in the sense of continuous channels. On the contrary, when they reach their period of most striking development (cat, 13-14 mm.) these perivenous lymphatic spaces are, if anything, distended, not only by their fluid contents, but by the remnant of the embryonic atrophying vein which they are in the process of replacing. The only structure showing any sign of "collapse is the empty endothelial bag of the decadent venule. The spaces become relatively reduced in. size in the later stages, after the multiple separate early anlages have fused into a more continuous lymphatic channel system.

These spaces are always present in embryos of the proper stages in the typical position and in constant relation to the venous channels. By following carefully and with suflBcient material their further growth and development in succeeding stages, a clear and consecutive picture of systemic lymphatic genesis is given.

It is noteworthy, in view of the incorrect statements published to the contrary, that these primary anlages of the systemic lymphatic system develop constantly in embryos of the cat before the definite organization of the jugular Jymph sacs. These latter structures, in the 10 mm. cat embryo, are still largely in the condition of a perivenous capillary plexus, at a time when the first lymphatic anlages can be distinctly recognized in the axial mesoderm.


2 The lymphatic endothelium is an independent modification of the mesodermal cells lining the first anlages of the lymphatic spaces, and is not derived from the haemal vascular endothelium.

3 I am obliged to deny the assumption that the mammahan systemic lymphatic vessels arise by the confluence of numerous elements detached in course of development from the embryonic veins.

4 I am obliged to put myself emphatically on record against the assumption that the mammalian systemic lymphatic vessels arise by a progressive sprouting from center to periphery fron) the endothelium of veins, or from that lining the jugular lymph sacs, or equivalent structures in other regions of the body. The mammalian embryo offers no evidence of such occurrences.


PART I, PLATES

FIGURES 1 TO 28

The series here figured and de«oribed are in the embryological collection of Columbia University, with the exception of series 34, which belongs to the embryological collection of Princeton University. I am greatly indebted to Prof. C. F. W. McClure for the opportunity of studying this series and publishing the eight sections shown in figs. 245 to 251.


FIGURE 1

1 Transverse section of 10 mm. cat embryo (series HI, slide VIII, section 4), X 175*— Topographical picture of site of earliest lymphatic space development.

1 Sympathetic nervo.

8 Oesophagus.

S8 Left postcardinal vein.

69 Lungs.

72 Right dorsal aorta.

73 Left dorsal aorta.

77 Mesenchymal intorccllular lymphatic anlages.

78 Coelom.


FIGURE 2

2 Tranfiverre Mv-tion of 10 mm. cat embr>*o series 111. :«lide VIII. section 4) y 30O — left .siile of embrj'O.

GS I^eft iK>sicarrlinal vein.

73 I^ft dorsal aorta.

77 Mesench\-mal intercellular h-mphatic anlafces.

7S C'oelom.

79 Coelomic stoma.


FIGURE 3


3 Same. X 600.


FIGI'KES 4 AND 5

4 Transverse section of 10 mm. cat embryo (series 111. slide VIII. section 6), X 300.

5 Same, section 7,


FIGURES 6 AND 7


6 Same, section 8.

7 Same, section 9.


FKJl'RKS 8 AND {)

S Trafisvprsc sorti<»n of 10 inni. cat embryo (series 120, slide IX, section 25) X .WO. Saiiie, seel ion 2r>.

1 Syinpiithetic nerve.

(iS Left posteanlinal vein.

7.') Left dorsal aorta.

77 Mesenehynial int<'reelliilar lymphatic anlages.

78 Coeloni.


FIGURES 10 AND 11

10 Transverse section of anterior thoracic region of 12 mm. cat embryo (series 217. slide X, section 12). X 225 — showing early extraintimal lymphatic development.

11 Transverse section of anterior thoracic region in a 12 mm. cat embryo (series 211. slide X. section 15). X 225.

3 Prci-ardinal or precava. resp. azygos of right side.

4 Atrophying embryonal vein, forming kernel in interior of developing

and replacing lymphatic space.

5 E.Ytraintimal or perivenous lymphatic space surrounding degenerating

embryonal vein. Precardinal or precava, resp. azygos of left side.

7 Aorta.

8 Oesophagus.

9 Trachea.

10 Pulmonarv arterv. 22 Vagus.


FIGURE 12

12 Transverse section of anterior thoracic region in a 14 mm. embryo (series 127, slide VIII, section 12), X 225.

4 Atrophying embryonal vein, forming kernel in interior of develop ing and replacing lymphatic space.

5 Ex train timal or perivenous lymphatic space surrounding degen erating embryonal vein.

6 Precardinal or precava, reap, azygos of left side. 6' Left azygos vein, thoracic portion.

7 Aorta.

8 OosophagiLs.


FIGURES 6 AND 7


6 Same, section 8.

7 Same, section 9.


FIGURE 15

16 Transverse section through lower cervical region of a 14 mm. cat embryo (series 222, slide VII, section 26), X 150.

11 Jugular lymph sac.

25 Internal jugular vein.

27 External jugular vein.

27' External jugular lymphatics.


riGURE 10 . Ill Same, slide VIII, section 4.

11 Jugular lymph sac.

25 Internal jugular vein.

27 External jugular vein.

27' External jugular lymphatics.


I


FIGURE 17

17 Transverse section of upper thoracic region of 14 mm. embryo (series 37, slide XIII, section 12), X 150.

1 Sympathetic nerve.

3 Frecardinal or precava, resp. azygos of right side.

6 Frecardinal or precava, resp. azygos of left side.

7 Aorta.

8 Oesophagus.

9 Trachea. 22 Vagus.

53 Precaval lymphatics.


FIGURES 18 AXD 19

18 Transverse section of middle thoracic region in a 17 mm. cat embryo (series 258, slide XVIII, section 9), X 225.

19 Transverse section through mid-thoracic region of a 19 mm. cat embryo (series 253, slide XXIV, section 9), X 225.

1 Sympathetic nerve.

2 Intersegmental arteries.

3 Right azygos.

4 Atrophying embryonal vein.

5 Extraintimal or perivenous l>Tnphatic space.

6 Left azygos.

7 Aorta.

15 Interazygos venous ple.xus.

36 Azygos segment of thoracic duct.


FIGURE 20

20 Transverse section of upper abdominal region of a 17 mm. cat embryo, showing developing components of ascending Imnbar l3anphatic trunks and of mesenteric sac in relation to embryonic veins in the root of the dorsal mesentery and their relation to the cardinal collateral venous channels (series 258, slide XXIII, section

•M), X 75.

1 Sympathetic nerve.

7 Aorta.

51 Mesenteric lymphatics.

58 Ureters.

61 Iliac vessels.

62 End gut.

63 Ventral division of cloaca (urinary bladder).

64 Wolffian ducts.

66 Umbilical arteries.

67 Right postcardinal vein.

68 Left postcardinal vein.

74 Cardinal collateral veins.

75 Ascending lumbar hmphatic trunks.


FIGURE 21 21 Same section, X 150.

7 Aorta.

51 Mesenteric lymphatics.

58 Ureters.

67 Right postcardinal vein.

68 Left postcardinal vein.

74 Cardinal collateral veins.

75 Ascending lumbar lymphatic trunks.


FIGURE322 22 Same, section 33.

1 Sympathetic nerve.

7 Aorta.

51 Mesenteric lymphatics.

68 Ureters;

67 Right postcardinal vein.

68 Left postcardinal vein.

74 Cardinal collateral veins.

75 Ascending lumbar lymphatic trunks.


FRJURES 23 AND 24


23 Same, section 32.

24 Same, section 31.

7 Aorta.

61 Mesenteric lymphatics.

67 Right postcardinal vein.

68 Left postcardinal vein.

74 Cardinal collateral veins.

75 A.«<cending lumbar lymphatic trunks*


25 Transverse section of posterior end of a 2() mm. cat eml)ryo (series 241, sli(ie XXX, section 4), X 75 — showing extraintimal replacement of left supra cardinal vein (59) by ascending lumbar relroaortic lymphatic channel (76).

1 Sympathetic nerve.

7 Aorta.

58 Ureters.

59 Left supracardinal vein.

60 Right supracardinal vein.

62 End gut.

63 Ventral division of cloaca (urinary bladder).

64 Wolffian ducts.

65 Metanephros.

66 Umbilical arteries.

67 Right post cardinal vein. 6S Left postcardinal vein.

76 Hetroaortic supracardinal lyin])hatic trunks.


FKJUUE 26 26 Same, section 14, X 150.

1 Sympathetic nerve.

58 Ureters. .

59 Left supracardinal vein.

60 Right supracardinal vein.

67 Right postcardinal vein.

68 Left postcardinal vein.

75 Ascending lumbar lymphatic trunks.

76 Retroaortic supracardinal lymphatic trunks.


FIGURE 27


27 Reconstruction of anterior vascular complex in an IS mm. cat embrj^o (serie»< 88), X oO. Ventral view.


FIGUUK 28 28 Same, lateral view of left side.


it increasingly turns to the left and continues to develop cephalad along the ventral surface of the inter-azygos plexus, by extraintimal replacement of elements belonging to the latter. (Compare the series of six reconstructions shown in figs. 188, 189, 190, 191, 192, 193.)


Huntington1911: Part I. The development of the systemic lymphatic vessels in their relation to the blood-vascular system | Part II. The development of the preazygos and azygos segments of the thoracic ducts | Bibliography


Huntington GS. The anatomy and development of the systemic lymphatic vessels in the domestic cat. (1911) Memoirs of the Wistar Institute of Anatomy and Biology No. 1.

Cite this page: Hill, M.A. (2024, April 18) Embryology Huntington1911 - 1. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Huntington1911_-_1

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