Difference between revisions of "Paper - The lymphatic system in human embryos, with a consideration of the morphology of the system as a whole"

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==Introduction==
 
==Introduction==
When We consider the history of our knowledge of the lymphatic
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When We consider the history of our knowledge of the lymphatic system, it is clear that there have been two Wholly different lines of thought with regards to our general conceptions. To establish its general morphology is the fundamental task for each of the systems of the body, and upon such a general conception is based all future elaboration of the system. I need only to refer to the neurone theory as establishing such a foundation for our knowledge of the nervous system. In connection with the lymphatic system, the idea that it arises from mesenchyme spaces dominates anatomical and zoological literature as is evidenced by examining most of the text books. This conception is based on the work of Budge, Sala, Gulland and many others. It allies the lymphatic system with tissue spaces and serous cavities. The other theory, which seems in a fair Way to displace the earlier conception, is that the lymphatics are derived from the veins, that they are vascular rather than mesenchymal in origin. This theory, only recently crystallized, has had an interesting evolution; beginning with Langer and Ranvier, it has been formulated and developed by a group of American anatomists. In this paper I hope to add evidence for this theory and give a general picture of the primitive lymphatic system as a whole. The great usefulness of this theory, aside from the fact that we believe it to be true, is that it gives a key by which to work out the entire developmefit of the lymphatic system down to its ultimate capillaries, and it will be readily conceded that the old theory of the relation of the lymphatics to the tissue spaces gave us no such point of attack.
system, it is clear that there have been two Wholly different lines of
 
thought with regards to our general conceptions. To establish its
 
general morphology is the fundamental task for each of the systems
 
of the body, and upon such a general conception is based all future
 
elaboration of the system. I need only to refer to the neurone theory
 
as establishing such a foundation for our knowledge of the nervous
 
system. In connection with the lymphatic system, the idea that it
 
arises from mesenchyme spaces dominates anatomical and zoological
 
literature as is evidenced by examining most of the text books. This
 
conception is based on the work of Budge, Sala, Gulland and many
 
others. It allies the lymphatic system with tissue spaces and serous
 
cavities. The other theory, which seems in a fair Way to displace
 
the earlier conception, is that the lymphatics are derived from the
 
veins, that they are vascular rather than mesenchymal in origin.
 
This theory, only recently crystallized, has had an interesting evolution; beginning with Langer and Ranvier, it has been formulated
 
and developed by a group of American anatomists. In this paper I
 
hope to add evidence for this theory and give a general picture of the
 
primitive lymphatic system as a whole. The great usefulness of
 
this theory, aside from the fact that we believe it to be true, is that
 
it gives a key by which to work out the entire developmefit of the
 
lymphatic system down to its ultimate capillaries, and it will be
 
readily conceded that the old theory of the relation of the lymphatics
 
to the tissue spaces gave us no such point of attack.
 
  
  
The first theory, that the lymphatics arise from tissue spaces,
+
The first theory, that the lymphatics arise from tissue spaces, received its strongest support from Budge.‘
received its strongest support from Budge.‘
 
  
  
In his first paper Budge described injections of Berlin blue into
+
In his first paper Budge described injections of Berlin blue into the false amnion of threeday chick embryos. He found that the injection mass ran out into the area vasculosa in a series of irregular canals forming an abundant network immediately under the epiblast and hence dorsal to the vascular layer. This network of canals extended out to a marginal canal around the area vasculosa similar to the marginal vein. Budge interpreted this system of canals as a primitive lymphatic system which in his injections arose in connection with the coelom and its extra embryonal expansion, the false amnion. This primative lymphatic system he said never had any connection with the veins, so that the interchange of fluid must have been through the walls. Dr. Mal12 has studied B'udge’s specimens and is convinced that they are injections showing simply the extent of the extra embryonal coelom.
the false amnion of threeday chick embryos. He found that the
 
injection mass ran out into the area vasculosa in a series of irregular
 
canals forming an abundant network immediately under the epiblast
 
and hence dorsal to the vascular layer. This network of canals
 
extended out to a marginal canal around the area vasculosa similar
 
to the marginal vein. Budge interpreted this system of canals as
 
a primitive lymphatic system which in his injections arose in connection with the coelom and its extra embryonal expansion, the false
 
amnion. This primative lymphatic system he said never had any
 
connection with the veins, so that the interchange of fluid must have
 
been through the walls. Dr. Mal12 has studied B'udge’s specimens
 
and is convinced that they are injections showing simply the extent
 
of the extra embryonal coelom.
 
  
I repeated Budge’s experiments, using India ink instead of Prussian blue, as it flows more readily, and found that I could duplicate
+
I repeated Budge’s experiments, using India ink instead of Prussian blue, as it flows more readily, and found that I could duplicate Budge’s figures exactly?’ The fluid ran out in blunt processes simulating canals, but readily distinguished from the lymphatic injections. The fluid runs exactly as it would, if forced between two glass plates held closely together, that is, blunt processes push out which form an advancing network, but this network soon fills into a solid mass. lVith a careful injection of true lymphatics on the other hand the individual vessels often remain absolutely distinct from the very point of the needle as is shown in Fig. 4.-, of the article in Volume I, of the American Journal of Anatomy, where the needle was introduced into two places, one just over the shoulder and the other over the crest of the ilium. The injections in the area vasculosa of the chick are like the pictures obtained by injecting into a mass of embryonic connective tissue which has no lymphatics. The fluid runs out in the lines of least resistance, simulating performed canals but easily distinguished from true lymphatic capillaries, both in form and from the fact that as the injection proceeds the network fills into a solid mass. Serial sections of the area vasculosa showed no preformed channels, but rather that the space between the germ layers is bridged by delicate fibrils, the processes of mesenchyme cells. It seems certain then that Budge’s primitive lymphatic system is simply a study of the extent of the early coelom and morphologically has no relation to the lymphatic system.
Budge’s figures exactly?’ The fluid ran out in blunt processes
 
simulating canals, but readily distinguished from the lymphatic
 
injections. The fluid runs exactly as it would, if forced between
 
two glass plates held closely together, that is, blunt processes push
 
out which form an advancing network, but this network soon fills
 
into a solid mass. lVith a careful injection of true lymphatics on
 
the other hand the individual vessels often remain absolutely distinct
 
from the very point of the needle as is shown in Fig. 4.-, of the article
 
in Volume I, of the American Journal of Anatomy, where the
 
needle was introduced into two places, one just over the shoulder and
 
the other over the crest of the ilium. The injections in the area vasculosa of the chick are like the pictures obtained by injecting into a mass of embryonic connective tissue which has no lymphatics. The
 
fluid runs out in the lines of least resistance, simulating performed
 
canals but easily distinguished from true lymphatic capillaries, both in
 
form and from the fact that as the injection proceeds the network
 
fills into a solid mass. Serial sections of the area vasculosa showed
 
no preformed channels, but rather that the space between the germ
 
layers is bridged by delicate fibrils, the processes of mesenchyme
 
cells. It seems certain then that Budge’s primitive lymphatic system
 
is simply a study of the extent of the early coelom and morphologically has no relation to the lymphatic system.
 
  
  
Line 96: Line 41:
  
  
 +
In the understanding of the lymphatic system this point is of great importance, as will be shown later. None of the serous cavities, hollowed out of the mesenchyme, that is, the pleural and peritoneal cavities, the joints, the various bursae, and the chambers for the vitreous and aqueous ihumors in the eyes, though they contain serous fluid ever form a part of the true lymphatic system. In Budge’s second paper, which is unfortunately just a fragment of his work published from the notes after his death, are pictured beautiful figures of true lymphatic injections made at a much‘ later stage, namely in embryo chicks, 18 days old. These, the true lymphatics, Budge thought belonged to a second, the permanent system, distinguished from the first by the presence of the thoracic duct which emptied into the veins. Budge thought that the thoracic duct arose from spaces derived from the coelom. He also discovered the posterior lymph hearts in chick embryos between 10 and 20 days old.
  
In the understanding of the lymphatic system this point is of great
+
The theory of the origin of the lymphatic system from tissue spaces was further illustrated by Grullandf‘
importance, as will be shown later. None of the serous cavities,
 
hollowed out of the mesenchyme, that is, the pleural and peritoneal
 
cavities, the joints, the various bursae, and the chambers for the
 
vitreous and aqueous ihumors in the eyes, though they contain serous
 
fluid ever form a part of the true lymphatic system. In Budge’s
 
second paper, which is unfortunately just a fragment of his work
 
published from the notes after his death, are pictured beautiful
 
figures of true lymphatic injections made at a much‘ later stage,
 
namely in embryo chicks, 18 days old. These, the true lymphatics,
 
Budge thought belonged to a second, the permanent system, distinguished from the first by the presence of the thoracic duct which
 
emptied into the veins. Budge thought that the thoracic duct arose
 
from spaces derived from the coelom. He also discovered the posterior lymph hearts in chick embryos between 10 and 20 days old.
 
  
The theory of the origin of the lymphatic system from tissue
+
He found spaces hollowed out in the mesenchyme along the course of the blood vessels of the limbs and thought that these flowed together to form ducts.
spaces was further illustrated by Grullandf‘
 
  
He found spaces hollowed out in the mesenchyme along the course
+
The next exponent of the theory that the lymphatics arise from the tissue spaces in Salas‘
of the blood vessels of the limbs and thought that these flowed together to form ducts.
 
 
 
The next exponent of the theory that the lymphatics arise from
 
the tissue spaces in Salas‘
 
  
 
Sala has studied the origin and the development of the lymphatic
 
Sala has studied the origin and the development of the lymphatic
  
‘Gulland. Journal of Pathology and Bacteriology, Vol. II, 1894, p. 466.
+
‘Gulland. Journal of Pathology and Bacteriology, Vol. II, 1894, p. 466. ‘Sam. Ricerche Lab. di Anat. Norm. d. r. Univ. di Roma, Vol. VII, 1899-1900. 46 Florence R. Sabin. ( ,
‘Sam. Ricerche Lab. di Anat. Norm. d. r. Univ. di Roma, Vol. VII, 1899-1900.
 
46 Florence R. Sabin. ( ,
 
  
system in chick embryos. Basing his work on Budge’ s, he worked
+
system in chick embryos. Basing his work on Budge’ s, he worked out with care the origin of the posterior lymph hearts which Budge had discovered. He found that the posterior lymph hearts begin at the middle of the seventh day in connection with the lateral branches of the first five coccygeal veins. He says that corresponding to these veins there are excavations in the mesenchyme which soon enter into communication with the lateral branches, and in fact one would say that these fissures are simply dilatations of the veins themselves.
out with care the origin of the posterior lymph hearts which Budge
 
had discovered. He found that the posterior lymph hearts begin at
 
the middle of the seventh day in connection with the lateral branches
 
of the first five coccygeal veins. He says that corresponding to these
 
veins there are excavations in the mesenchyme which soon enter into
 
communication with the lateral branches, and in fact one would say that these fissures are simply dilatations of the veins themselves.
 
  
These two statements of course exclude one another, for the spaces can
+
These two statements of course exclude one another, for the spaces can not be both fissures in the mesenchyme and dilatations of the veins. (“Esaminando in serie le sezioni caudali di un emb. di g. 6 ~|— ore 18, si scorge che nel mesenchima che sta lateralmente ai miotomi ed in corrispondenza dei rami laterali delle prime cinque vene coccygei, si vanno scavando dei piccoli spazi o fessure che ben p-resto entrano in comunicazione cogli stessi rami laterali venosi: si direbbe anzi che esse non sono che semplici dilatazioni, ramificazioni delle stesse vene.”)
not be both fissures in the mesenchyme and dilatations of the veins.
 
(“Esaminando in serie le sezioni caudali di un emb. di g. 6 ~|— ore
 
18, si scorge che nel mesenchima che sta lateralmente ai miotomi ed
 
in corrispondenza dei rami laterali delle prime cinque vene coccygei,
 
si vanno scavando dei piccoli spazi o fessure che ben p-resto entrano
 
in comunicazione cogli stessi rami laterali venosi: si direbbe anzi che
 
esse non sono che semplici dilatazioni, ramificazioni delle stesse
 
vene.”)
 
  
Then he describes these fissures as becoming more abundant and
+
Then he describes these fissures as becoming more abundant and confluent. By opening up communications with each other they form a sac or lymph heart in the mesenchmye. This sac he says is lined with flattened mesenchyme cells, which, if it were so, would, according to our standpoint, exclude it from being a vein. He found muscle in the wall of the hearts on the ninth day and was able to inject the heart directly by the second half of the tenth day. Sala’ s description of the origin of the posterior lymph hearts in the chick is so clear and graphic that it is perfectly evident to those who are familiar with the method of origin of the lymph sacs in mammals, that the two processes are the same, that the sacs arise from the veins in both cases. The fact that Sala had the old conception of the lymphatic system as coming from the tissue spaces too firmly fixed in mind to really accept the evidence of his own material does not need to confuse the picture. .
confluent. By opening up communications with each other they
 
form a sac or lymph heart in the mesenchmye. This sac he says is lined
 
with flattened mesenchyme cells, which, if it were so, would, according
 
to our standpoint, exclude it from being a vein. He found muscle in
 
the wall of the hearts on the ninth day and was able to inject the
 
heart directly by the second half of the tenth day. Sala’ s description
 
of the origin of the posterior lymph hearts in the chick is so clear
 
and graphic that it is perfectly evident to those who are familiar
 
with the method of origin of the lymph sacs in mammals, that the
 
two processes are the same, that the sacs arise from the veins in both
 
cases. The fact that Sala had the old conception of the lymphatic
 
system as coming from the tissue spaces too firmly fixed in mind
 
to really accept the evidence of his own material does not need to
 
confuse the picture. .
 
  
The lymphatic ducts he thought began as fissures in the mesenchyme
+
The lymphatic ducts he thought began as fissures in the mesenchyme along the hypogastric veins on the ninth day. By the eleventh day these spaces communicated and formed a plexus of lymphatic ducts which connected with the lymph hearts and the thoracic duct. The Lymphatic System in Human Embryos. 47
along the hypogastric veins on the ninth day. By the eleventh day
 
these spaces communicated and formed a plexus of lymphatic
 
ducts which connected with the lymph hearts and the thoracic duct.
 
The Lymphatic System in Human Embryos. 47
 
  
The thoracic duct, which he found extended only from the beginning
+
The thoracic duct, which he found extended only from the beginning of the coeliac artery to the outlet of the superior vena cava, began on the eighth day in the following manner. First a series of mesenchyme spaces around which occur clumps of mesenchyme cells which develop into a solid cord. These solid cords become excavated and form the thoracic duct. There is nothing to correspond with this in connection with the lymphatic system in mammals.
of the coeliac artery to the outlet of the superior vena cava, began
 
on the eighth day in the following manner. First a series of mesenchyme spaces around which occur clumps of mesenchyme cells which
 
develop into a solid cord. These solid cords become excavated and
 
form the thoracic duct. There is nothing to correspond with this
 
in connection with the lymphatic system in mammals.
 
  
To trace the development of the idea that the lymphatic system
+
To trace the development of the idea that the lymphatic system is derived from the venous system it is necessary to begin with the work of Langerf published in 1868.
is derived from the venous system it is necessary to begin with the
 
work of Langerf published in 1868.
 
  
In this important paper, Langer makes clear a number of fundamental points. He distinguished the lymphatics in the tadpole’s tail
+
In this important paper, Langer makes clear a number of fundamental points. He distinguished the lymphatics in the tadpole’s tail from the arteries and the veins by injecting them. He found the two longitudinal lymphatic vessels of the tail, and the branches forming a plexus leading from them. He distinguished the lymphatic vessels clearly from the surrounding connective tissue, and determined that the lymphatics were closed tubes. He was studying a border zone of developing lymphatics and saw that the lymphatics here were really terminal blind ends. He noted the endothelial sprouts from the sides and ends of the vessels and interpreted these sprouts to mean that the lymphatic vessels grow by the same method as do blood capillaries.
from the arteries and the veins by injecting them. He found the
 
two longitudinal lymphatic vessels of the tail, and the branches
 
forming a plexus leading from them. He distinguished the lymphatic vessels clearly from the surrounding connective tissue, and
 
determined that the lymphatics were closed tubes. He was studying
 
a border zone of developing lymphatics and saw that the lymphatics
 
here were really terminal blind ends. He noted the endothelial
 
sprouts from the sides and ends of the vessels and interpreted
 
these sprouts to mean that the lymphatic vessels grow by the same
 
method as do blood capillaries.
 
  
Thus he says: “Ich zweifle nicht, dass Lymph und Blutcapillaren
+
Thus he says: “Ich zweifle nicht, dass Lymph und Blutcapillaren nach dem einen und demselben Bildungsmodus sich vermehren, die Elemente sind dieselben.” This in reality is his great contribution and upon this idea as a foundation rests the new conception of the lymphatic system as derived from the veins. Another of his observations must not be omitted, namely that in the course of a lymphatic capillary, a portion of the vessel may be greatly narrowed, that is to say, even completely collapsed. “Ich traf aber auch Rohrchen, welche sich ziemlich rash verengten und in der Mitte ihres Verlaufes einen diinnen, anseheinend ganz soliden Faden darstellten.” The meaning of this phenomenon and its relation to the general theory will be made clear later.
nach dem einen und demselben Bildungsmodus sich vermehren, die
 
Elemente sind dieselben.” This in reality is his great contribution
 
and upon this idea as a foundation rests the new conception of the
 
lymphatic system as derived from the veins. Another of his observations must not be omitted, namely that in the course of a lymphatic
 
capillary, a portion of the vessel may be greatly narrowed, that is to
 
say, even completely collapsed. “Ich traf aber auch Rohrchen,
 
welche sich ziemlich rash verengten und in der Mitte ihres Verlaufes
 
einen diinnen, anseheinend ganz soliden Faden darstellten.” The
 
meaning of this phenomenon and its relation to the general theory
 
will be made clear later.
 
  
°Langer. Ueber das Lymphgefiisssystem des Frosches. Sitzb. d. k. Akad.
+
°Langer. Ueber das Lymphgefiisssystem des Frosches. Sitzb. d. k. Akad. d. Wissenseh., LVIII Bd., I Abth., 1868.
d. Wissenseh., LVIII Bd., I Abth., 1868.
 
  
Between the years 1895 and 1897, Ranvier published a series of
+
Between the years 1895 and 1897, Ranvier published a series of articles on the development of the lymphatic system.7 He also studied the development of the lymphatic system in the frog and added an extensive study of the growth of the lymphatics in pig embryos from 9 to 18 cm. long. He observed endothelial sprouts in growing lymphatics and interpreted them as Langer had done 27 years before to mean that the growth of the lymphatic capillaries is by the process of sprouting. Some of the very large lymphatic vessels which he found in the mesentery he interpreted to mean degeneration or retrogression of the system. Ranvier suggested the theory that the lymphatic system comes from the veins, on the basis that the growth is from centre to periphery rather than from the connective tissue spaces to the veins——but he did not prove his theory, for he did not find lymphatics in embryos below 9 cm. in length, at which time the lymphatic capillaries have already covered the surface of the body.
articles on the development of the lymphatic system.7 He also
 
studied the development of the lymphatic system in the frog and
 
added an extensive study of the growth of the lymphatics in pig
 
embryos from 9 to 18 cm. long. He observed endothelial sprouts
 
in growing lymphatics and interpreted them as Langer had done
 
27 years before to mean that the growth of the lymphatic capillaries
 
is by the process of sprouting. Some of the very large lymphatic
 
vessels which he found in the mesentery he interpreted to mean
 
degeneration or retrogression of the system. Ranvier suggested the
 
theory that the lymphatic system comes from the veins, on the basis
 
that the growth is from centre to periphery rather than from the
 
connective tissue spaces to the veins——but he did not prove his theory,
 
for he did not find lymphatics in embryos below 9 cm. in length, at
 
which time the lymphatic capillaries have already covered the surface
 
of the body.
 
  
‘V. J. MacCallum was the next one to call attention to this method
+
‘V. J. MacCallum was the next one to call attention to this method of growth by sprouting and he has given graphic descriptions of the process. _He studied developing lymphatics in the skin of embryo pigs, 5 to 15 cm. long, watching the injection under the microscope in order to determine the relation of the lymphatic capillaries to the connective tissue cells and spaces? .
of growth by sprouting and he has given graphic descriptions of the
 
process. _He studied developing lymphatics in the skin of embryo
 
pigs, 5 to 15 cm. long, watching the injection under the microscope
 
in order to determine the relation of the lymphatic capillaries to the
 
connective tissue cells and spaces? .
 
  
In studying the growth of the lymphatic capillaries in the skin
+
In studying the growth of the lymphatic capillaries in the skin of the embryo pig, I found that the early lymphatics started from certain centres and gradually spread over the surface of the body.9 The first of these areas is in the neck, from which vessels grow over the head, shoulder and back. The second is over the crest of the ilium for the vessels over the back and hip, while subsequent centres form the axilla and inguinal region for vessels to the ventral aspects of the body wall and limbs. By studying the figures in Volume III,
of the embryo pig, I found that the early lymphatics started from
 
certain centres and gradually spread over the surface of the body.9
 
The first of these areas is in the neck, from which vessels grow over
 
the head, shoulder and back. The second is over the crest of the
 
ilium for the vessels over the back and hip, while subsequent centres
 
form the axilla and inguinal region for vessels to the ventral aspects of the body wall and limbs. By studying the figures in Volume III,
 
  
7Ranvier. Cvomptes Rendus de 1’Acad. d. Sciences, 189% to 1896, and
+
7Ranvier. Cvomptes Rendus de 1’Acad. d. Sciences, 189% to 1896, and Archives d’Anatomie microscopique. Paris, 1897.
Archives d’Anatomie microscopique. Paris, 1897.
 
  
8MacCa11un1. Die Beziehung der Lymphgefttsse zum Bindegewebe. Arch. f.
+
8MacCa11un1. Die Beziehung der Lymphgefttsse zum Bindegewebe. Arch. f. Anat. u. Phys., Anat. A1)th., 1902.
Anat. u. Phys., Anat. A1)th., 1902.
 
  
"Sabin American Journal of Anatomy, Vol. I, 1901-1902, Vol. III, 1904,
+
"Sabin American Journal of Anatomy, Vol. I, 1901-1902, Vol. III, 1904, and Vol. IV, 1905.
and Vol. IV, 1905.
 
  
of the American Journal of Anatomy, which show complete injections of the skin for each stage, it will be seen that the lymphatics invade non—lymphatic areas, even in the last figure of the series where all
+
of the American Journal of Anatomy, which show complete injections of the skin for each stage, it will be seen that the lymphatics invade non—lymphatic areas, even in the last figure of the series where all of the systems have anastomosed over the body there is a marked non-lymphatic area over the top of the head as well as over the feet. In pigs longer than 5.5 cm., it is diflicult to obtain such extensive injections because valves begin to develop and tend to make the lymph flow from periphery to centre. During this early period of the spread of the lymphatics‘ over the body there are no valves whatever, which accounts for the wide extent of the injection shown for a pig 5.5 cm. long.
of the systems have anastomosed over the body there is a marked
 
non-lymphatic area over the top of the head as well as over the feet.
 
In pigs longer than 5.5 cm., it is diflicult to obtain such extensive
 
injections because valves begin to develop and tend to make the lymph
 
flow from periphery to centre. During this early period of the
 
spread of the lymphatics‘ over the body there are no valves whatever,
 
which accounts for the wide extent of the injection shown for a pig
 
5.5 cm. long.
 
  
To trace these vessels back to their source was fundamental to an
+
To trace these vessels back to their source was fundamental to an understanding of the lymphatic system, and I began with the group in the neck as it was the primary group. The vessels in the neck converge to a sac which is readily demonstrated by injection as is shown in Fig. 1, Vol. IV, American Journal of Anatomy. This sac, which lies against the internal jugular vein, is the beginning or anlage of the lymphatic system. In embryo pigs from 14.5 to 16 cm. long there are symmetrical jugular sacs opening into the vein. Saxer made mention of these sacs as a part of the lymphatic system, but did not realize their fundamental significance.” These sacs are either empty or contain a few blood corpuscles. F. T. Lewis worked on the stages before this lymphatic sac is formed and carried our knowledge a step farther by showing that they are preceded by a plexus of veins opening into the jugular vein.“ This plexus of veins gradually becomes cut, off from the main vein and by the coalescence of the small veins a sac is formed which is entirely free fromthe jugular vein for a time. Subsequently the symmetrical sacs rejoin the veins. The endothelial lining of these sacs is thus derived from the endothelium of the veins. In studying the lymphatics Dr. Lewis used the method of graphic reconstruction. The fact that the jugular sacs are transformed venous capillaries, I was able to entirely confirm by the method of injectio-n in pig embryos.” In pig embryos
understanding of the lymphatic system, and I began with the group
 
in the neck as it was the primary group. The vessels in the neck
 
converge to a sac which is readily demonstrated by injection as is
 
shown in Fig. 1, Vol. IV, American Journal of Anatomy. This
 
sac, which lies against the internal jugular vein, is the beginning or
 
anlage of the lymphatic system. In embryo pigs from 14.5 to 16
 
cm. long there are symmetrical jugular sacs opening into the vein.
 
Saxer made mention of these sacs as a part of the lymphatic system,
 
but did not realize their fundamental significance.” These sacs are
 
either empty or contain a few blood corpuscles. F. T. Lewis worked
 
on the stages before this lymphatic sac is formed and carried our
 
knowledge a step farther by showing that they are preceded by a
 
plexus of veins opening into the jugular vein.“ This plexus of veins
 
gradually becomes cut, off from the main vein and by the coalescence
 
of the small veins a sac is formed which is entirely free fromthe
 
jugular vein for a time. Subsequently the symmetrical sacs rejoin
 
the veins. The endothelial lining of these sacs is thus derived from
 
the endothelium of the veins. In studying the lymphatics Dr. Lewis
 
used the method of graphic reconstruction. The fact that the jugular sacs are transformed venous capillaries, I was able to entirely
 
confirm by the method of injectio-n in pig embryos.” In pig embryos
 
  
“Anat. I-Iefte, Vol. VI, 1896. _
+
“Anat. I-Iefte, Vol. VI, 1896. _ “Lewis. The Development of the Lymphatic System in Rabbits. Amer. Jour. Anat, Vol. V, 1906. "Sabin. Anat. Record, Vol. II, 1908. .
“Lewis. The Development of the Lymphatic System in Rabbits. Amer.
 
Jour. Anat, Vol. V, 1906.
 
"Sabin. Anat. Record, Vol. II, 1908.
 
.
 
  
13 and 14 mm. long there is an abundant plexus of capillaries anterior
+
13 and 14 mm. long there is an abundant plexus of capillaries anterior to the junction of the primitive ulnar vein with the internal jugular vein, readily injected from the veins. In embryos slightly older this plexus of capillaries is being transformed into a sac, and these sacs are less readily injected from the veins. For example in an embryo 15 mm. long, the sac was injected on the side from the vein and not in the other. About this time then the primary connections with the vein become severed. In my specimens the sacs are filled with blood. When the secondary opening into the veins is formed the sacs become empty and this is true in pig embryos 16 mm. long. In connection with human embryos I shall show how to determine the presence of these secondary openings or valves.
to the junction of the primitive ulnar vein with the internal jugular
 
vein, readily injected from the veins. In embryos slightly older
 
this plexus of capillaries is being transformed into a sac, and these
 
sacs are less readily injected from the veins. For example in an
 
embryo 15 mm. long, the sac was injected on the side from the vein
 
and not in the other. About this time then the primary connections
 
with the vein become severed. In my specimens the sacs are filled
 
with blood. When the secondary opening into the veins is formed
 
the sacs become empty and this is true in pig embryos 16 mm. long.
 
In connection with human embryos I shall show how to determine
 
the presence of these secondary openings or valves.
 
  
This method of formation of the jugular sacs was also confirmed
+
This method of formation of the jugular sacs was also confirmed by Huntington and McClure in studying cat embryos.” They have followed all the details of the transformation of the simple veins to the abundant venous plexus and the sac formation by Born’s method of reconstruction. Thus the origin of the jugular sac has been Worked out in the pig, the rabbit and the cat by the methods of injection and of reconstruction both in two and in three dimensions. The formation of this ugular sac- will also be illustrated in the human embryos in this paper.
by Huntington and McClure in studying cat embryos.” They have
 
followed all the details of the transformation of the simple veins
 
to the abundant venous plexus and the sac formation by Born’s
 
method of reconstruction. Thus the origin of the jugular sac has
 
been Worked out in the pig, the rabbit and the cat by the methods of
 
injection and of reconstruction both in two and in three dimensions.
 
The formation of this ugular sac- will also be illustrated in the human
 
embryos in this paper.
 
  
Besides the jugular sacs two other paired sacs and two unpaired
+
Besides the jugular sacs two other paired sacs and two unpaired have been described. Lewis described symmetrical subclavian sacs in the rabbit, which in human embryos are, however, an extension of the jugular sacs; the other paired sac is the posterior or sciatic one, noted in the pig and more fully marked out in this paper for human embryos. The unpaired sacs are the cisterna chyli and the mesenteric or better retroperitoneal sac.
have been described. Lewis described symmetrical subclavian sacs
 
in the rabbit, which in human embryos are, however, an extension of
 
the jugular sacs; the other paired sac is the posterior or sciatic
 
one, noted in the pig and more fully marked out in this paper for
 
human embryos. The unpaired sacs are the cisterna chyli and the
 
mesenteric or better retroperitoneal sac.
 
  
This sac was discovered by Lewis its origin and development have
+
This sac was discovered by Lewis its origin and development have been worked out by Baetjer; its significance is brought out in Heuer’s work in connection with the lymphatics of the intestine. Mr. Baetjer” has shown conclusively that the retroperitoneal sac begins as a series of small veins which bud off from the renal veins.
been worked out by Baetjer; its significance is brought out in
 
Heuer’s work in connection with the lymphatics of the intestine.
 
Mr. Baetjer” has shown conclusively that the retroperitoneal sac
 
begins as a series of small veins which bud off from the renal veins.
 
  
13I-Iuntington and McClure. The Anatomical Record, Vol. II, 1908.
+
13I-Iuntington and McClure. The Anatomical Record, Vol. II, 1908. “Baetjer. Amer. Jour. Anat., Vol. VIII.
“Baetjer. Amer. Jour. Anat., Vol. VIII.
 
  
In his figures are shown the small veins in the root of the mesentery of a pig embryo 17 to 19 mm. long. It is readily noted that
+
In his figures are shown the small veins in the root of the mesentery of a pig embryo 17 to 19 mm. long. It is readily noted that these small veins are injected fro-m_the main veins as the drawings show the injected ink of the specimens. As the embryo develops, these small veins enlarge and coalesce to form a sac, which shows a few connections with the Veins, as proved by injection until the embryos are 23 mm. long. The sac is completely formed at 30 mm., when it is cut off from the Veins entirely and clearly connected with the cisterna chyli. Baetjer’s series of nine drawings show every stage in process of the transformation of the veins into the sac and its subsequent connection with the lymphatic system.
these small veins are injected fro-m_the main veins as the drawings
 
show the injected ink of the specimens. As the embryo develops, these
 
small veins enlarge and coalesce to form a sac, which shows a few
 
connections with the Veins, as proved by injection until the embryos
 
are 23 mm. long. The sac is completely formed at 30 mm., when
 
it is cut off from the Veins entirely and clearly connected with the
 
cisterna chyli. Baetjer’s series of nine drawings show every stage
 
in process of the transformation of the veins into the sac and its
 
subsequent connection with the lymphatic system.
 
  
Thus to sum up, it will be seen that the lymphatic system begins as
+
Thus to sum up, it will be seen that the lymphatic system begins as a series of sacs of which eight have been described; three paired, the jugular sacs, the subclavian and the posterior lymph sacs; and two unpaired, the retroperitoneal and the cisterna chyli. In the human embryo there are only six, for the subclavian sacs are extensions of the jugular sacs. All of the sacs are shown in Fig. 12, in a human embryo 30 mm. long. The method of origin of two of them, namely the jugular sacs and the retroperitoneal sacs, has been worked out with care showing that they are clearly derived from the Veins. The jugular sacs form a secondary connection with the jugular veins, the other sacs forming in regions where there is great shifting of veins do not form secondary communications with their own veins but join the other lymph sacs to make a primitive system.
a series of sacs of which eight have been described; three paired, the
 
jugular sacs, the subclavian and the posterior lymph sacs; and two
 
unpaired, the retroperitoneal and the cisterna chyli. In the human
 
embryo there are only six, for the subclavian sacs are extensions of
 
the jugular sacs. All of the sacs are shown in Fig. 12, in a human
 
embryo 30 mm. long. The method of origin of two of them, namely
 
the jugular sacs and the retroperitoneal sacs, has been worked out
 
with care showing that they are clearly derived from the Veins. The
 
jugular sacs form a secondary connection with the jugular veins, the
 
other sacs forming in regions where there is great shifting of veins
 
do not form secondary communications with their own veins but
 
join the other lymph sacs to make a primitive system.
 
  
The question now arises whether these sacs can be considered as
+
The question now arises whether these sacs can be considered as analogous with the amphibian lymph hearts. None of the mamma~ lian sacs studied develop any muscle in their walls; throughout their history they have a lining simply of endothelium, but they all are in regions from which ducts radiate out to drain wide areas, so that as the system begins to function the lymphatic stream converges to these sacs and in this sense they represent the lymph hearts. In the chick the posterior lymph sacs are true lymph hearts, for they develop a muscular wall, and from Sala’s description it is easy to see that these hearts really arise by exactly the same process as the mammalian sacs. The fate of the lymph sacs has some bearing on the subject.“ This has been followed for the jugular sac in the pig and
analogous with the amphibian lymph hearts. None of the mamma~
 
lian sacs studied develop any muscle in their walls; throughout their
 
history they have a lining simply of endothelium, but they all are in
 
regions from which ducts radiate out to drain wide areas, so that as
 
the system begins to function the lymphatic stream converges to
 
these sacs and in this sense they represent the lymph hearts. In the
 
chick the posterior lymph sacs are true lymph hearts, for they develop
 
a muscular wall, and from Sala’s description it is easy to see that
 
these hearts really arise by exactly the same process as the mammalian sacs. The fate of the lymph sacs has some bearing on the
 
subject.“ This has been followed for the jugular sac in the pig and
 
  
 
“Sabin. Amer. Jour. Anat., Vol. IV, 1905.
 
“Sabin. Amer. Jour. Anat., Vol. IV, 1905.
  
for all the sacs in the human. They all become completely transformed into a group of lymph nodes except the cisterna chyli, which
+
for all the sacs in the human. They all become completely transformed into a group of lymph nodes except the cisterna chyli, which is partially though to a varying degree transformed. The lymph sacs make the great primary gr.oups of nodes for each region through which lymph must pass before entering the veins. Thus for example in the intestines the preaortic nodes are the primary group and they come from the retroperitoneal sac, While the nodes of the mesentery are secondary, tertiary, etc. Thus we may define primary lymph nodes as those that are derived from the lymph sacs, and they are also primary in the sense of being the first to develop for a given region. It therefore seems to me that it is fair to conclude that the lymph sacs of the mammals, which represent the lymph nodes, take the place of the lymph hearts of the amphibia. They do not of course represent the same function, for they never have any muscle, so they never pulsate, and from the beginning they must cause a slowing of the lymph flow rather than a hastening of it and this slowing must become much more marked as they are transformed into lymph nodes. Thus they seem to me analogous to amphibian lymph hearts.
is partially though to a varying degree transformed. The lymph
 
sacs make the great primary gr.oups of nodes for each region through
 
which lymph must pass before entering the veins. Thus for example
 
in the intestines the preaortic nodes are the primary group and they
 
come from the retroperitoneal sac, While the nodes of the mesentery
 
are secondary, tertiary, etc. Thus we may define primary lymph
 
nodes as those that are derived from the lymph sacs, and they are
 
also primary in the sense of being the first to develop for a given
 
region. It therefore seems to me that it is fair to conclude that
 
the lymph sacs of the mammals, which represent the lymph nodes,
 
take the place of the lymph hearts of the amphibia. They do not
 
of course represent the same function, for they never have any
 
muscle, so they never pulsate, and from the beginning they must
 
cause a slowing of the lymph flow rather than a hastening of it and
 
this slowing must become much more marked as they are transformed
 
into lymph nodes. Thus they seem to me analogous to amphibian
 
lymph hearts.
 
 
 
From the preceding analysis of the literature, it is clear that
 
there is a general agreement among recent Workers that the mammalian lymph sacs precede the lymph vessels, and hence form a primary
 
lymphatic system and that these sacs are derived from the veins.
 
This position has been very greatly strengthened by the work of
 
Favarom and Allen,” on the lymphatic system in fishes, and by
 
Knowerls and Hoyer,” in the amphibia.
 
  
Favaro discovered that in fishes the lymphatics come from the veins,
+
From the preceding analysis of the literature, it is clear that there is a general agreement among recent Workers that the mammalian lymph sacs precede the lymph vessels, and hence form a primary lymphatic system and that these sacs are derived from the veins. This position has been very greatly strengthened by the work of Favarom and Allen,” on the lymphatic system in fishes, and by Knowerls and Hoyer,” in the amphibia.
and that here the relation of the lymphatics to the veins is much
 
more primitive than in mammals. Lymph hearts and vein hearts
 
may be present, moreover one and the same vessel may carry either
 
blood or lymph either at the same time or at different times. Thus he speaks of venae lymphaticze and vasa lymphaticw. The system
 
varies much in the different forms; in Urodeles he finds that the
 
lymph hearts begin as a swelling of one of the primitive lateral longitudinal veins. This abstract is taken from Schwalbe’s Jahres—
 
berichte.
 
  
1°FaVaro. Atti R. 1st Veneto di sc. lett. ed arti, 1905-06, T, 65, Parte seconda.
+
Favaro discovered that in fishes the lymphatics come from the veins, and that here the relation of the lymphatics to the veins is much more primitive than in mammals. Lymph hearts and vein hearts may be present, moreover one and the same vessel may carry either blood or lymph either at the same time or at different times. Thus he speaks of venae lymphaticze and vasa lymphaticw. The system varies much in the different forms; in Urodeles he finds that the lymph hearts begin as a swelling of one of the primitive lateral longitudinal veins. This abstract is taken from Schwalbe’s Jahres— berichte.
Appendice alla Dispensa 10. Octobre 1906. S. 279. Venezia 1906.
 
"Allen. Proceedings of the Washington Academy of Sciences, Vol. IX, 1907.
 
"“Knower. Anat. Record, Vol. II, 1908.
 
‘-“Hoyer. Bulletin de 1’Acad. d. Sciences d. Cracovie, 1908.
 
  
 +
1°FaVaro. Atti R. 1st Veneto di sc. lett. ed arti, 1905-06, T, 65, Parte seconda. Appendice alla Dispensa 10. Octobre 1906. S. 279. Venezia 1906. "Allen. Proceedings of the Washington Academy of Sciences, Vol. IX, 1907. "“Knower. Anat. Record, Vol. II, 1908. ‘-“Hoyer. Bulletin de 1’Acad. d. Sciences d. Cracovie, 1908.
  
  
  
Knower and Hoyer have shown independently that the fundamental points maintained for mammals are true also for the amphibia. They have found that the anterior lymph hearts arethe first
+
Knower and Hoyer have shown independently that the fundamental points maintained for mammals are true also for the amphibia. They have found that the anterior lymph hearts arethe first structures of the lymphatic system to appear in the embryo and have described their origin from the veins. They have found that the first lymph vessels are derived from the lymph hearts, this being stated by Hoyer on page 463 of his article as follows:
structures of the lymphatic system to appear in the embryo and have
 
described their origin from the veins. They have found that the
 
first lymph vessels are derived from the lymph hearts, this being
 
stated by Hoyer on page 463 of his article as follows:
 
  
“Beriicksichtigen wir weiterhin die Art und Weise, in weleher sich
+
“Beriicksichtigen wir weiterhin die Art und Weise, in weleher sich die Lymphgefasse entwickeln, namentlich das Auftreten der vorderen Lymphherzen an der vorderen Vertebralvene sowie der Lymphgefasse, welche aus dem Lymphherzen hervorgehen, so kann mansich clem Gredanken nicht verschlieszen, class das Lymphgefasssystem eben an diesen Stellen symmetrisch auf beiden Korperseiten seinen Anfang nimmt und sich Von dort aus iiber den ganzen Ktirper verbreitet. Als wichtige, diese Ansicht stiitzende Tatsachen hebe ich aus der vor liegenden Arbeit hervor: Die weite Kommunikation des sich entwichelnden Lymphherzens mit der Vene, die anfanglicli mit einer l{egelformigen Zelle endigende freie Spitze des spindelformigen Lymphherzens, welche sich spater zu einem Zellstrange verlangert und sich schlieszlich zu einem Lymphgefasse umbildet, ferner die rege Zell— vermehrung im Grebiete des sich cntwickclndcn Lymphherzens uncl schlieszlich die Entwieklung der zwei auf den Kanten der Myomeren einander parallel verlaufenden Lymphgefasse.” Both of them state that they will give further evidence of the central origin of the lymph vessels and their growth toward the periphery in their final papers.
die Lymphgefasse entwickeln, namentlich das Auftreten der vorderen
 
Lymphherzen an der vorderen Vertebralvene sowie der Lymphgefasse,
 
welche aus dem Lymphherzen hervorgehen, so kann mansich clem
 
Gredanken nicht verschlieszen, class das Lymphgefasssystem eben an
 
diesen Stellen symmetrisch auf beiden Korperseiten seinen Anfang
 
nimmt und sich Von dort aus iiber den ganzen Ktirper verbreitet.
 
Als wichtige, diese Ansicht stiitzende Tatsachen hebe ich aus der vor liegenden Arbeit hervor: Die weite Kommunikation des sich entwichelnden Lymphherzens mit der Vene, die anfanglicli mit einer l{egelformigen Zelle endigende freie Spitze des spindelformigen Lymphherzens, welche sich spater zu einem Zellstrange verlangert und sich
 
schlieszlich zu einem Lymphgefasse umbildet, ferner die rege Zell—
 
vermehrung im Grebiete des sich cntwickclndcn Lymphherzens uncl
 
schlieszlich die Entwieklung der zwei auf den Kanten der Myomeren
 
einander parallel verlaufenden Lymphgefasse.” Both of them state
 
that they will give further evidence of the central origin of the lymph
 
vessels and their growth toward the periphery in their final papers.
 
  
We come now to the relation of the peripheral lymphat.ics to the
+
We come now to the relation of the peripheral lymphat.ics to the sacs and to the origin of the thoracic duct. Here we have a diversity of opinion and certain unsettled points which for the sake of the development of the subject it is fundamental to have perfectly clear. In the first place, Sala, who, in connection with the origin of the posterior lymph hearts, really describes them as coming from the veins, though he confuses the picture by considering them as coming from tissue spaces at the same time, describes the thoracic duct as coming from solid cords of mesenchyme, and the peripheral vessels as derived from spaces in the mesenchyme. VVe find nothing to correspond to the solid cords of niesenchyme as an anlage of the thoracic duct in mammals, and believe that the lymph vessels grow out from the primitive sacs. That is, we believe that the conditions found by H. Hoyer for amphibia, that the vessels come from the hearts, is true also in mammals. This being the disputed point however, it will be necessary to review the literature in this connection with care.
sacs and to the origin of the thoracic duct. Here we have a diversity
 
of opinion and certain unsettled points which for the sake of the
 
development of the subject it is fundamental to have perfectly clear.
 
In the first place, Sala, who, in connection with the origin of the
 
posterior lymph hearts, really describes them as coming from the veins, though he confuses the picture by considering them as coming
 
from tissue spaces at the same time, describes the thoracic duct as
 
coming from solid cords of mesenchyme, and the peripheral vessels
 
as derived from spaces in the mesenchyme. VVe find nothing to
 
correspond to the solid cords of niesenchyme as an anlage of the
 
thoracic duct in mammals, and believe that the lymph vessels grow
 
out from the primitive sacs. That is, we believe that the conditions
 
found by H. Hoyer for amphibia, that the vessels come from the
 
hearts, is true also in mammals. This being the disputed point
 
however, it will be necessary to review the literature in this connection with care.
 
  
In 1901 I showed that the jugular lymph sacs are the primary
+
In 1901 I showed that the jugular lymph sacs are the primary lymphatics in mammals, that they are derived from the veins, that from these sacs, and others, vessels grow out to invade the body and that therefore there are non-lymphatic areas and one can study the invasion of these areas by lymphatic vessels. In the study of the skin this general law was found to hold, that there are areas which at first cannot be injected either directly or through the sacs. This I believe to be because there are no lymphatics to inject. That gradually lymphatics invade these areas and at first a primary subcutaneous plexus can be injected, later a secondary more superficial plexus, and finally terminal capillaries in the papillae. The same law holds for the lymphatics 0-f the intestine as shown by Dr. G. Heuer in the same number of this journal. In the intestine the lymphatics first form a plexus in the submucosa; secondarily a mucosal capillary plexus forms and from this mucosal plexus the lacteals grow out. In connection with the intestine the fundamental point that the lymphatics grow out from the sacs is also shown. In all the early work the injections of the intestine were made through the thoracic duct, but later it proved that by far the best place to inject is the retroperitoneal sac. This sac gives the key for working out the development of the lymphatics of the viscera. For years I have been trying to get injections of the lymphatics of the lungs and diaphragm and have never succeeded until I introduced the needle directly into the retroperitoneal sac. In connection with the intestine, injections into the retro-peritoneal sac at first show no vessels in the mesentery, next vessels inject from the sac into the mesentery and these vessels gradually extend to the bowel wall which they reach in embryos between 4 and 4.5 cm. long. Thus injections of the retroperitoneal sac make it possible to trace the development of the lymphatics to the viscera, and this is an important point in the proof of the general theory.
lymphatics in mammals, that they are derived from the veins, that
 
from these sacs, and others, vessels grow out to invade the body and
 
that therefore there are non-lymphatic areas and one can study the
 
invasion of these areas by lymphatic vessels. In the study of the
 
skin this general law was found to hold, that there are areas which
 
at first cannot be injected either directly or through the sacs. This
 
I believe to be because there are no lymphatics to inject. That
 
gradually lymphatics invade these areas and at first a primary
 
subcutaneous plexus can be injected, later a secondary more superficial plexus, and finally terminal capillaries in the papillae. The
 
same law holds for the lymphatics 0-f the intestine as shown by Dr. G.
 
Heuer in the same number of this journal. In the intestine the
 
lymphatics first form a plexus in the submucosa; secondarily a
 
mucosal capillary plexus forms and from this mucosal plexus the
 
lacteals grow out. In connection with the intestine the fundamental
 
point that the lymphatics grow out from the sacs is also shown.
 
In all the early work the injections of the intestine were made
 
through the thoracic duct, but later it proved that by far the best
 
place to inject is the retroperitoneal sac. This sac gives the key for
 
working out the development of the lymphatics of the viscera. For
 
years I have been trying to get injections of the lymphatics of the
 
lungs and diaphragm and have never succeeded until I introduced the needle directly into the retroperitoneal sac. In connection with the intestine, injections into the retro-peritoneal sac at first show no vessels in the mesentery, next vessels inject from the
 
sac into the mesentery and these vessels gradually extend to the bowel
 
wall which they reach in embryos between 4 and 4.5 cm. long. Thus
 
injections of the retroperitoneal sac make it possible to trace the
 
development of the lymphatics to the viscera, and this is an important point in the proof of the general theory.
 
  
In 1904 F. T. Lewis published an important contribution to our
+
In 1904 F. T. Lewis published an important contribution to our knowledge of the lymphatic system. He studied perfect serial sections of rabbit embryos, worked out the early history of the jugular sacs, and discovered the retroperitoneal sac as has been mentioned. In studying the peripheral lymphatics, Lewis pictured a series of small isolated vessels extending along the external mammary and umbilical veins. These isolated vessels are distinguished in sections by being slightly larger in caliber than the neighboring vein. In sections they are clearly isolated. I have had the privilege of examining Dr. Lewis’ specimens and can confirm his observations entirely. In one or two places there was evidently great difiiculty in, determining whether some of these vessels were isolated or were connected with the vein. Moreover, I can find some of these isolated vessels in pig and human embryos. These numerous lymphatic anlagen of Lewis are now the crucial point in connection with the lymphatic system. They exist undoubtedly in perfect sections, they are always lined by a perfectly formed endothelium and never ‘show any transitions toward tissue spaces. The question is simply, Are they lymphatic vessels which have grown from the sacs and are only apparently isolated or do they arise in situ? I believe them to be true lymphatics derived from the sacs and will give my reasons shortly.
knowledge of the lymphatic system. He studied perfect serial
 
sections of rabbit embryos, worked out the early history of the jugular sacs, and discovered the retroperitoneal sac as has been mentioned.
 
In studying the peripheral lymphatics, Lewis pictured a series of
 
small isolated vessels extending along the external mammary and
 
umbilical veins. These isolated vessels are distinguished in sections
 
by being slightly larger in caliber than the neighboring vein. In
 
sections they are clearly isolated. I have had the privilege of examining Dr. Lewis’ specimens and can confirm his observations entirely.
 
In one or two places there was evidently great difiiculty in, determining whether some of these vessels were isolated or were connected
 
with the vein. Moreover, I can find some of these isolated vessels
 
in pig and human embryos. These numerous lymphatic anlagen of
 
Lewis are now the crucial point in connection with the lymphatic
 
system. They exist undoubtedly in perfect sections, they are always
 
lined by a perfectly formed endothelium and never ‘show any transitions toward tissue spaces. The question is simply, Are they lymphatic vessels which have grown from the sacs and are only apparently
 
isolated or do they arise in situ? I believe them to be true lymphatics derived from the sacs and will give my reasons shortly.
 
  
In connection with Lewis’ observations it is important to make
+
In connection with Lewis’ observations it is important to make clear the work of Huntington and McClure.2° They have strengthened the theory that the lymphatics come from the veins the more because they began with a vigorous attack upon the theory.
clear the work of Huntington and McClure.2° They have strengthened the theory that the lymphatics come from the veins the more
 
because they began with a vigorous attack upon the theory.
 
  
In 1906 they described elaborate models of the developing lymphatics in cat embryos which showed lymphatic vessels along the veins
+
In 1906 they described elaborate models of the developing lymphatics in cat embryos which showed lymphatic vessels along the veins previous to the formation of the lymph sacs. These early lymphatics which they termed subintimal, proved to be only tissue spaces and they withdrew this work in 1907.
previous to the formation of the lymph sacs. These early lymphatics which they termed subintimal, proved to be only tissue spaces and
 
they withdrew this work in 1907.
 
  
 
“Huntington and ;\IcCIure. Anat. Record, "01. 1, 1906-07, and Vol. II, 1908.
 
“Huntington and ;\IcCIure. Anat. Record, "01. 1, 1906-07, and Vol. II, 1908.
  
  
At this time they presented the development of the jugular lymph
+
At this time they presented the development of the jugular lymph sacs in the cat, agreeing entirely with the work of Lewis and myself; but in connection with the rest of the system they at that time agreed entirely with Sala, believing that the peripheral vessels were dilated tissue spaces. In the Anatomischer Anzeiger of 1908, McClure gives up entirely the theory of the origin of the lymphatics from tissue spaces and comes to agree with Lewis that sections show multiple anlagen. As I have already said, the multiple anlagen of Lewis are undoubtedly in sections and to interpret them is the crucial point. They cannot be interpreted through sections alone; «and merely repeating the observation of them in sections does not add to our knowledge of their interpretation. They must be subjected to some kind of an experiment. The inadequacy of simple observation to interpret them was clear to Lewis for he refrained from mak ing an interpretation. The experience of Huntington and HcClure serves to emphasize strongly" the inadequacy of sections alone, and the large part of that personal equation plays in interpretation, for from practically the same type of material they have taken successively three difierent standpoints.
sacs in the cat, agreeing entirely with the work of Lewis and myself;
 
but in connection with the rest of the system they at that time agreed
 
entirely with Sala, believing that the peripheral vessels were dilated
 
tissue spaces. In the Anatomischer Anzeiger of 1908, McClure gives
 
up entirely the theory of the origin of the lymphatics from tissue
 
spaces and comes to agree with Lewis that sections show multiple
 
anlagen. As I have already said, the multiple anlagen of Lewis
 
are undoubtedly in sections and to interpret them is the crucial
 
point. They cannot be interpreted through sections alone; «and
 
merely repeating the observation of them in sections does not add to
 
our knowledge of their interpretation. They must be subjected to
 
some kind of an experiment. The inadequacy of simple observation to interpret them was clear to Lewis for he refrained from mak
 
ing an interpretation. The experience of Huntington and HcClure serves to emphasize strongly" the inadequacy of sections alone, and the large part of that personal equation plays in interpretation, for from practically the same type of material they have taken successively three difierent standpoints.
 
  
In this laboratory under the direction of Professor Mall a group
+
In this laboratory under the direction of Professor Mall a group of people have ‘been subjecting these numerous anlagen of Lewis to some sort of experiment. Dr. Eliot K. Clark“ has been studying the blood vessels and lymphatics in the living tadpole’s tail. His specimens prove Langer’s suggestion that lymphatics grow by the sprouting of their endothelial lining cells by making it possible to watch them grow. His observations and descriptions of these lymphatic capillaries, sending out long sprouts that now move forward, now bend out of their course to pick up some stray blood corpuscle and now retreat, make one realize how little sections show us. Certain of his observations are exceedingly fundamental, first in the non—lymphatic zone in the living specimen there are no isolated anlagen. This you can never say with certainty in sections because as will be shortly proven lymphatics can be demonstrated by injection where they cannot be seen in sections. But in these specimens of the entire living tail, endothelium can be distinguished from mesenchyme, and the lymphatics grow out from their own endothelium and do not add any peripheral anlagen.
of people have ‘been subjecting these numerous anlagen of Lewis to
 
some sort of experiment. Dr. Eliot K. Clark“ has been studying the
 
blood vessels and lymphatics in the living tadpole’s tail. His specimens prove Langer’s suggestion that lymphatics grow by the sprouting
 
of their endothelial lining cells by making it possible to watch them
 
grow. His observations and descriptions of these lymphatic capillaries, sending out long sprouts that now move forward, now bend out
 
of their course to pick up some stray blood corpuscle and now retreat,
 
make one realize how little sections show us. Certain of his observations are exceedingly fundamental, first in the non—lymphatic zone
 
in the living specimen there are no isolated anlagen. This you can
 
never say with certainty in sections because as will be shortly proven
 
lymphatics can be demonstrated by injection where they cannot be seen in sections. But in these specimens of the entire living tail,
 
endothelium can be distinguished from mesenchyme, and the lymphatics grow out from their own endothelium and do not add any
 
peripheral anlagen.
 
  
 
"Clark, Anat. Record, Vol. III, 1909.
 
"Clark, Anat. Record, Vol. III, 1909.
  
  
 +
A second point which Dr. Clark observed, but did not publish, is the sudden collapsing of a part of a lymphatic vessel. Once or twice while a red blood cell was pushing its way into the vessel, its central end collapsed suddenly to an endothelial thread, while the peripheral end remained dilated. These collapsed lymphatics right in the middle of a vessel were noted and figured by Langer; they have been noted many times in blood capillaries, for example, see Fig. 49 of Stricker’s Handbuch der Histologie, but they have been interpreted as evidences of growth simply, while it may be that these collapsed vessels are a part of the functional activity of the lymphatic capillaries. The reverse of this process of collapsing of the vessels, namely the sudden opening up of tiny vessels during an injection, I have often observed and used as an argument in favor of continuous lymphatics rather than ‘isolated anlagen. (See Symposium on the Lymphatic System. Anat. Record, Vol. II, 1908.) It can be readily seen that in cross section these entirely collapsed vessels might be wholly lost and only the dilated portions shown, and thus the suggestion is that Lewis’ anlagen represent a transitory phase of the functional activity of the lymphatic capillaries.
  
A second point which Dr. Clark observed, but did not publish, is
+
The question of the multiple anlagen has resolved itself wholly into a question of method, with the study of the living lymphatics and injected lymphatics on the one hand and the method of serial sections on the other. Ludwig’ s famous phrase, “die Methode ist alles,” was never more apt than in this connection, for it sums up the whole situation. Having long worked with injections we are convinced that uninjected serial sections are wholly inadequate to show all the blood capillaries or lymph capillaries, moreover, we are convinced that Dr. Lewis has carried the observations as far as they can be carried with sections and that sections will always show these apparently isolated anlagen. To put the contention that serial sections are inadequate to the test, Dr. Clark has made the following experiment. He made a careful camera lucida drawing of the lymphatics in the living tadpole’ s tail, then killed the tadpole and cut it in serial sections and tried to reconstruct the lymphatics. The failure in reconstructing these amphibian lymphatics confirms similar attempts of my own on mammalian lymphatics and makes me feel sure that uninjected capillaries cannot be completely reconstructed.
the sudden collapsing of a part of a lymphatic vessel. Once
 
or twice while a red blood cell was pushing its way into the
 
vessel, its central end collapsed suddenly to an endothelial thread,
 
while the peripheral end remained dilated. These collapsed lymphatics right in the middle of a vessel were noted and figured by
 
Langer; they have been noted many times in blood capillaries, for
 
example, see Fig. 49 of Stricker’s Handbuch der Histologie, but
 
they have been interpreted as evidences of growth simply, while it
 
may be that these collapsed vessels are a part of the functional
 
activity of the lymphatic capillaries. The reverse of this process
 
of collapsing of the vessels, namely the sudden opening up of tiny
 
vessels during an injection, I have often observed and used as an
 
argument in favor of continuous lymphatics rather than ‘isolated
 
anlagen. (See Symposium on the Lymphatic System. Anat. Record,
 
Vol. II, 1908.) It can be readily seen that in cross section these entirely collapsed vessels might be wholly lost and only the dilated portions shown, and thus the suggestion is that Lewis’ anlagen represent a
 
transitory phase of the functional activity of the lymphatic capillaries.
 
  
The question of the multiple anlagen has resolved itself wholly
+
The same point in connection with the blood vascular system, namely that the blood capillaries cannot be reconstructed from uninjected specimens no matter how perfect, will be conceded, but has been brought out much more strikingly by the work of Dr. Evans, soon to be published from this laboratory, for he has shown that a blood capillary plexus can be demonstrated by injection where it was not known to exist before.
into a question of method, with the study of the living lymphatics
 
and injected lymphatics on the one hand and the method of serial
 
sections on the other. Ludwig’ s famous phrase, “die Methode ist
 
alles,” was never more apt than in this connection, for it sums up the
 
whole situation. Having long worked with injections we are convinced that uninjected serial sections are wholly inadequate to show
 
all the blood capillaries or lymph capillaries, moreover, we are convinced that Dr. Lewis has carried the observations as far as they
 
can be carried with sections and that sections will always show these
 
apparently isolated anlagen. To put the contention that serial
 
sections are inadequate to the test, Dr. Clark has made the following experiment. He made a careful camera lucida drawing of the lymphatics in the living tadpole’ s tail, then killed the tadpole and cut it
 
in serial sections and tried to reconstruct the lymphatics. The
 
failure in reconstructing these amphibian lymphatics confirms similar
 
attempts of my own on mammalian lymphatics and makes me feel
 
sure that uninjected capillaries cannot be completely reconstructed.
 
  
The same point in connection with the blood vascular system,
+
Thus the question of the relation of ‘the peripheral vessels to the sacs is becoming more and more clear. There is a primary lymphatic system which consists of sacs that are formed directly from the veins. These primary lymphatic sacs are transformed from a series of isolated sacs into a system by means of the thoracic duct and the right lymphatic duct. These two structures form a part of the primary system. The secondary system consists of the peripheral vessels which, it is becoming more and more sure, are an outgrowth from the sacs. Thus we can say that the primary system, as far as it is made up of sacs, comes from transformed veins, and that the secondary system, characterized by being formed of lymphatic ducts and capillaries, develops by endothelial sprouting from the sacs. It remains now to be determined whether the thoracic duct develops after the manner of the primary sacs as transformed branches of the azygos veins or whether it develops as the other lymphatic ducts of the body do, from endothelial sprouts from the sacs. No theorizing can decide between these two ideas. We must wait some decisive method of getting at the facts. The presumption seems to us to lie on the side that the thoracic duct develops in the same manner as all the other ducts, since wherever the isolated anlages of ducts can be tested, as, for example, in the living tadpole’s tail, they prove not to exist. Moreover, Dr. McClure, who is at present the advocate of the idea that the thoracic duct arises as a series of The Lymphatic System in Human Embryos. 59
namely that the blood capillaries cannot be reconstructed from uninjected specimens no matter how perfect, will be conceded, but has
 
been brought out much more strikingly by the work of Dr. Evans,
 
soon to be published from this laboratory, for he has shown that a
 
blood capillary plexus can be demonstrated by injection where it
 
was not known to exist before.
 
  
Thus the question of the relation of ‘the peripheral vessels to the
+
independent spindle spaces along the aygos vein, shows himself the’ Weakness of his own position. He says, referring to serial sections,” “These outgrowths, in the writer’s estimation, constitute the venolymphatic anlages of the thoracic and right lymphatic ducts.” That is to say, the entire argument rests on the interpretation of appearances in sections, and it is becoming more clear each year that interpretation of sections is not proof.
sacs is becoming more and more clear. There is a primary
 
lymphatic system which consists of sacs that are formed directly
 
from the veins. These primary lymphatic sacs are transformed
 
from a series of isolated sacs into a system by means of the thoracic
 
duct and the right lymphatic duct. These two structures form a part
 
of the primary system. The secondary system consists of the
 
peripheral vessels which, it is becoming more and more sure, are an
 
outgrowth from the sacs. Thus we can say that the primary system,
 
as far as it is made up of sacs, comes from transformed veins, and
 
that the secondary system, characterized by being formed of lymphatic
 
ducts and capillaries, develops by endothelial sprouting from the
 
sacs. It remains now to be determined whether the thoracic duct
 
develops after the manner of the primary sacs as transformed branches
 
of the azygos veins or whether it develops as the other lymphatic
 
ducts of the body do, from endothelial sprouts from the sacs. No
 
theorizing can decide between these two ideas. We must wait some
 
decisive method of getting at the facts. The presumption seems
 
to us to lie on the side that the thoracic duct develops in the same
 
manner as all the other ducts, since wherever the isolated anlages of
 
ducts can be tested, as, for example, in the living tadpole’s tail, they
 
prove not to exist. Moreover, Dr. McClure, who is at present the
 
advocate of the idea that the thoracic duct arises as a series of
 
The Lymphatic System in Human Embryos. 59
 
  
independent spindle spaces along the aygos vein, shows himself the’
 
Weakness of his own position. He says, referring to serial sections,”
 
“These outgrowths, in the writer’s estimation, constitute the venolymphatic anlages of the thoracic and right lymphatic ducts.” That
 
is to say, the entire argument rests on the interpretation of appearances in sections, and it is becoming more clear each year that interpretation of sections is not proof.
 
  
 +
Based upon these studies of the lymphatic system in the pig, rabbit and cat embryos, I have studied through the Mall collection of human embryos. - I do not believe that the subject could have been worked out with human embryos alone, for the real advances in the study of vascular problems have always come from the method of injection. The method cannot be well applied to human material on account of its scarcity, but the points determined in other mammalian embryos can be verified in serial sections of human embryos. Moreover, the Mall collection is sufficiently ample to illustrate all the essential points of the origin of the lymphatic system. In several points I think it adds new evidence to that already gained from other mammals; for example, in connection with the history of the thoracic duct, in gaining a conception of all of the primitive sacs as forming a primitive system, in tracing the posterior s.acs which had thus far been seen only in pig embryos among mammals, and in following the transformation of all the sacs into lymph nodes. It is a very great pleasure to thank Professor Mall for the privilege of studying his valuable collection and for many helpful suggestions during the progress of the work. V
  
Based upon these studies of the lymphatic system in the pig,
+
In the Mall collection no trace of a lymphatic system can be made out in embryos of the first four weeks, from 2 to 8 mm. long. In these there are certain spaces which might be confused with a lymphatic system, first certain areas where the meshes of the connective tissue are especially large, as, for example, around the developing coelom, and secondly spaces which follow the course of the nerves.
rabbit and cat embryos, I have studied through the Mall collection
 
of human embryos. - I do not believe that the subject could have been
 
worked out with human embryos alone, for the real advances in the
 
study of vascular problems have always come from the method of
 
injection. The method cannot be well applied to human material
 
on account of its scarcity, but the points determined in other mammalian embryos can be verified in serial sections of human embryos.
 
Moreover, the Mall collection is sufficiently ample to illustrate all
 
the essential points of the origin of the lymphatic system. In several
 
points I think it adds new evidence to that already gained from
 
other mammals; for example, in connection with the history of the
 
thoracic duct, in gaining a conception of all of the primitive sacs as
 
forming a primitive system, in tracing the posterior s.acs which had
 
thus far been seen only in pig embryos among mammals, and in following the transformation of all the sacs into lymph nodes. It is a very
 
great pleasure to thank Professor Mall for the privilege of studying
 
his valuable collection and for many helpful suggestions during the
 
progress of the work. V
 
  
In the Mall collection no trace of a lymphatic system can be made
+
”i\IcC1ure. Anat. Anz., XXXII Bd., 1908, p. 536. (30 I Florence R. Sabin.
out in embryos of the first four weeks, from 2 to 8 mm. long. In
 
these there are certain spaces which might be confused with a lymphatic system, first certain areas where the meshes of the connective
 
tissue are especially large, as, for example, around the developing
 
coelom, and secondly spaces which follow the course of the nerves.
 
  
”i\IcC1ure. Anat. Anz., XXXII Bd., 1908, p. 536.
+
These spaces along the nerves, which may be termed perineural spaces, are especially important to note both on account of their physiological significance and because they have been confused with lymphatics. They may be injected from the space around the spinal cord and they are especially large around the growing tips of the nerves. Their constancy, their presence in perfectly prepared specimens, and especially their size at the growing tips of the nerves, leads one to think that they are physiologically of great importance to the nerves, but they never form a part of the lymphatic system. No injections of these spaces ever run over into the lymphatic system. An injection into the developing arachnoid spaces around the spinal cord will often pass into the veins, entering them around the fourth ventricle, but I have never succeeded in injecting any lymphatic vessels from the arachnoid nor in tracing any lymphatic vessels to the arachnoid, so that I believe the older anatomist-s, for example Breschet, were right in believing that the lymphatic system does not drain the great arachnoid lymph space which rather retains its primitive relation to the veins while other parts of the body become drained by a new system of capillaries, namely the lymphatics, derived from the veins.
(30 I Florence R. Sabin.
 
  
These spaces along the nerves, which may be termed perineural spaces, are especially important to note both on account of their physiological significance and because they have been confused with
+
In studying Professor Mall’s collection it seems that there are two stages to be made out in the development of the system as a whole. This has been illustrated in the table 011 the next page. The first includes a study of the origin of all of the primitive sacs and their fusion into a primitive lymphatic system through two factors, namely the formation of the valves of the jugular sacs which make the per— manent openings into the veins, and secondly the connection of the various sacs by means of the cisterna chyli and thoracic duct. This period includes embryos up to 80 mm. in length, of which there are seventeen in the series. This first stage may be divided into two periods, one of which there are fourteen specimens, measuring up to 20 mm., which have the jugular sacs alone; the other shown in three specimens, which mark the time of origin of the other sacs and of the thoracic duct.
lymphatics. They may be injected from the space around the spinal
 
cord and they are especially large around the growing tips of the
 
nerves. Their constancy, their presence in perfectly prepared specimens, and especially their size at the growing tips of the nerves, leads
 
one to think that they are physiologically of great importance to the
 
nerves, but they never form a part of the lymphatic system. No
 
injections of these spaces ever run over into the lymphatic system.
 
An injection into the developing arachnoid spaces around the spinal
 
cord will often pass into the veins, entering them around the fourth
 
ventricle, but I have never succeeded in injecting any lymphatic
 
vessels from the arachnoid nor in tracing any lymphatic vessels to
 
the arachnoid, so that I believe the older anatomist-s, for example
 
Breschet, were right in believing that the lymphatic system does not
 
drain the great arachnoid lymph space which rather retains its
 
primitive relation to the veins while other parts of the body become
 
drained by a new system of capillaries, namely the lymphatics,
 
derived from the veins.
 
  
In studying Professor Mall’s collection it seems that there are two
+
The second stage involves the transformation of the sacs into the primary lymph nodes and the spread of the peripheral lymphatics.
stages to be made out in the development of the system as a whole.
 
This has been illustrated in the table 011 the next page. The first
 
includes a study of the origin of all of the primitive sacs and their
 
fusion into a primitive lymphatic system through two factors, namely
 
the formation of the valves of the jugular sacs which make the per—
 
manent openings into the veins, and secondly the connection of the
 
various sacs by means of the cisterna chyli and thoracic duct. This
 
period includes embryos up to 80 mm. in length, of which there
 
are seventeen in the series. This first stage may be divided into
 
two periods, one of which there are fourteen specimens, measuring up
 
to 20 mm., which have the jugular sacs alone; the other shown in
 
three specimens, which mark the time of origin of the other sacs
 
and of the thoracic duct.
 
  
The second stage involves the transformation of the sacs into the
 
primary lymph nodes and the spread of the peripheral lymphatics.
 
  
 +
The first point is well illustrated in the Mall collection; the second, namely the spread of the peripheral lymphatics, needs ample material foriinjection. It has been worked out only for the lymphatics of the intestine and skin in the pig. T
  
The first point is well illustrated in the Mall collection; the second,
+
To return to the first stage, namely that of the origin of the sacs, one can outline the course of development as follows. The jugular lymph sacs begin in an embryo 8 mm. long, the valves are first seen at 10.5 mm. The sac reaches its maximum development at 30 mm. when it attains a size of 5 X 3.6 mm. The beginning of the process of the bridging of the sac, which is the process by which the sac is ultimately turned into a chain of lymph nodes comes early, namely in an embryo 14 mm. long. The process of the transformation of the jugular. sac into nodes is about complete in an embryo of 80 mm. At 20 mm. there begin to be signs of the formation of the other sacs in the presence of a plexus of veins in the region of the mesenteric sac and the posterior lymph sacs, and at 23 mm. there is a definite retroperitoneal sac and a cisterna chyli. By 24 mm. all three of the sacs are well formed, namely the mesenteric, the cisterna chyli and the posterior lymph sacs. All the sacs together with the thoracic duct are illustrated in Fig. 12, for an embryo of 30 mm., which marks the stageof the completion of the primitive system. The posterior lymph sac which is second in size to t-he jugular apparently reaches its maximum in an embryo 80 mm. where it measures 2.8 x 2 x 3.5 mm. I have no higher stages but judge from its appearance that it will soon be entirely cut into lymph nodes. The retroperitoneal sac, so large in the pig embryos, is always small in the human, and the cisterna chyli is the smallest of all. The thoracic duct is complete in an embryo 30 mm. long. These facts are summed up in the accompanying table. In the table, where one measurement is given, it represents the length o-f the sac or its ante.ro—posterior diameter; where two measurements are given the first is the length, the second the width or lateral diameter.
namely the spread of the peripheral lymphatics, needs ample material
 
foriinjection. It has been worked out only for the lymphatics of
 
the intestine and skin in the pig. T
 
  
To return to the first stage, namely that of the origin of the sacs,
+
I shall now describe in detail the lymphatics in each of the 22 embryos listed in the table. The earliest specimen in the Mall collection to show any traces of the beginning lymphatic system is an embryo (No. 397) 8 mm. long. In this embryo, as shown in Cb L0
one can outline the course of development as follows. The jugular
 
lymph sacs begin in an embryo 8 mm. long, the valves are first seen
 
at 10.5 mm. The sac reaches its maximum development at 30 mm.
 
when it attains a size of 5 X 3.6 mm. The beginning of the process
 
of the bridging of the sac, which is the process by which the sac is
 
ultimately turned into a chain of lymph nodes comes early, namely
 
in an embryo 14 mm. long. The process of the transformation of
 
the jugular. sac into nodes is about complete in an embryo of 80 mm.
 
At 20 mm. there begin to be signs of the formation of the other sacs
 
in the presence of a plexus of veins in the region of the mesenteric
 
sac and the posterior lymph sacs, and at 23 mm. there is a definite
 
retroperitoneal sac and a cisterna chyli. By 24 mm. all three of the
 
sacs are well formed, namely the mesenteric, the cisterna chyli and
 
the posterior lymph sacs. All the sacs together with the thoracic
 
duct are illustrated in Fig. 12, for an embryo of 30 mm., which
 
marks the stageof the completion of the primitive system. The
 
posterior lymph sac which is second in size to t-he jugular apparently
 
reaches its maximum in an embryo 80 mm. where it measures
 
2.8 x 2 x 3.5 mm. I have no higher stages but judge from its appearance that it will soon be entirely cut into lymph nodes. The retroperitoneal sac, so large in the pig embryos, is always small in the
 
human, and the cisterna chyli is the smallest of all. The thoracic
 
duct is complete in an embryo 30 mm. long. These facts are summed
 
up in the accompanying table. In the table, where one measurement
 
is given, it represents the length o-f the sac or its ante.ro—posterior
 
diameter; where two measurements are given the first is the length,
 
the second the width or lateral diameter.
 
  
I shall now describe in detail the lymphatics in each of the 22
+
x x r
embryos listed in the table. The earliest specimen in the Mall
 
collection to show any traces of the beginning lymphatic system is
 
an embryo (No. 397) 8 mm. long. In this embryo, as shown in
 
Cb
 
L0
 
  
x
+
l l I
x
 
r
 
  
l
+
Florence R. Sabin.
l
 
I
 
  
Florence R. Sabin.
 
  
 
 
  
 
l.
 
l.
  
6 .2 ,; 1 in 1
+
6 .2 ,; 1 in 1 “6 E 3% '5 .. l '1 5.1:.‘ ‘E; Direcftion § 5 J I L h S l we , o o_- ‘-' s ugu at mp ac. ; E; 5153 Section. 1 y 3
“6 E 3% '5 .. l '1
 
5.1:.‘ ‘E; Direcftion § 5 J I L h S l
 
we , o o_- ‘-' s ugu at mp ac. ;
 
E; 5153 Section. 1 y 3
 
  
E -3 E-4 ‘
+
E -3 E-4 ‘ "4 £2 v. I I ‘ Size in mm. 8 397 Trans- 10 ‘I .3 X .19 Prelymphatic . verse ‘ plexus of veins. 9 , 163 Trans- i 20 .36 X .14 Same. 1 verse ' . 10.5 109 Trans- 20 .7 X .28 Symmetri call E verse sacs,empty,§ l . | 5 with valves. 5 11 :1 353 Coronal 1 10 1.2 Sac full of blood.‘ ‘ '(Ant.post.) Extensive plex—§
"4 £2 v.
 
I I ‘ Size in mm.  
 
8 397 Trans- 10 ‘I .3 X .19 Prelymphatic  
 
. verse ‘ plexus of veins.
 
9 , 163 Trans- i 20 .36 X .14 Same.
 
1 verse ' .
 
10.5 109 Trans- 20 .7 X .28 Symmetri call
 
E verse sacs,empty,§
 
l . |
 
5   with valves. 5
 
11 :1 353 Coronal 1 10 1.2 Sac full of blood.‘
 
‘ '(Ant.post.) Extensive plex—§
 
: 3 us of veins along?
 
{ jugular vein. ’
 
3 . Valve formed-1
 
I 2 but apparently'
 
: not open. Ex1 tension of jug—§
 
3 ular sac along}
 
. primitive ulnar;
 
; ; vein.
 
12.5 ‘ 317 Coronal  20 1.5 Definite longsac
 
1  out of preceding
 
z plexus of veins»
 
; Valve.
 
14 1 144 Sagittall 40 1.5 Sac empty, be: ‘ ginning of bridg' _ ing. '
 
15  350 Coronal '. 10 Very abortive =
 
‘ sac.
 
15  423 Trans- 50 .9 Very small sac. I
 
1 verse i
 
17  106 Trans-  50 Very abortive
 
5 verse ‘ sac. .
 
17 ; 424 ‘ Region damag’d.
 
17  296 Coronal  20 1 .5 Sacs large,valve
 
u ndc/‘u b t ed ly
 
g open. Small ex‘ ‘ tension along
 
E primitive ulnar
 
vein. I
 
  
Other Lymph Sacs.
+
3 us of veins along?
The Lymphatic System in Human Embryos.
+
{ jugular vein. ’ 3 . Valve formed-1 I 2 but apparently'
 +
 
 +
not open. Ex1 tension of jug—§
 +
3 ular sac along} . primitive ulnar;
 +
 
 +
; vein.
 +
12.5 ‘ 317 Coronal 20 1.5 Definite longsac 1 out of preceding
 +
 
 +
z plexus of veins»
 +
; Valve.
 +
14 1 144 Sagittall 40 1.5 Sac empty, be: ‘ ginning of bridg' _ ing. ' 15 350 Coronal '. 10 Very abortive = ‘ sac. 15 423 Trans- 50 .9 Very small sac. I 1 verse i 17 106 Trans- 50 Very abortive 5 verse ‘ sac. . 17 ; 424 ‘ Region damag’d. 17 296 Coronal 20 1 .5 Sacs large,valve
 +
 
 +
u ndc/‘u b t ed ly
 +
g open. Small ex‘ ‘ tension along E primitive ulnar vein. I
 +
 
 +
Other Lymph Sacs. The Lymphatic System in Human Embryos.
  
Length of
+
Length of l Embryo in mm. I
l Embryo in mm.
 
I
 
  
I»-4
+
I»-4 O2
O2
 
  
 
20
 
20
Line 776: Line 211:
 
20
 
20
  
23
+
23 24
24
 
  
 
30
 
30
  
46
+
46 50 50 50
50
 
50
 
50
 
  
 
80
 
80
  
E No. of Emb
+
E No. of Emb I
I
 
  
O .
+
O . 3 Mall colleéionln
3 Mall colleéionln
 
  
 
22
 
22
Line 814: Line 243:
 
Jugular Lymph Sac.
 
Jugular Lymph Sac.
  
E .
+
E . Diregftion § 5 Section. 5 -= 1 E: u lSize in mm. Trans- 50 g 1.8 verse ‘ 3 1 Trans- 50 1 1.6 verse l l 1 V Coronal‘ 50 .75 i Sagittal - 50 2 x 1 Trans- 20 verse Coronal 50 5 x 3. 6 I Sagittali 1o ‘ 3.75 x 1.5 Sagittal l 100 4 x 1.5 l Trans-l 50 _ 3x1:5 verse [ Sagittal :50 and.’ 4 x 1.75
Diregftion § 5  
+
 
Section. 5
+
100
-= 1
+
!Trans~.l 100 1.75x1 ! verse ? 1 I , . I
E: u
 
lSize in mm.
 
Trans- 50 g 1.8
 
verse ‘
 
3 1
 
Trans- 50 1 1.6
 
verse  
 
l
 
l
 
1 V
 
Coronal‘ 50 .75
 
i
 
Sagittal - 50 2 x 1
 
Trans- 20
 
verse  
 
Coronal 50 5 x 3. 6
 
I
 
Sagittali 1o ‘ 3.75 x 1.5
 
Sagittal l 100 4 x 1.5
 
l
 
Trans-l 50 _ 3x1:5
 
verse [  
 
Sagittal :50 and.’ 4 x 1.75
 
100
 
!Trans~.l 100 1.75x1
 
! verse ?  
 
1 I
 
, .
 
I
 
  
 
S'y mm at rical
 
S'y mm at rical
Line 852: Line 252:
 
‘jugular sacs. No
 
‘jugular sacs. No
  
extension along
+
extension along primitive ulnar vein.
primitive ulnar
 
vein.
 
  
Sacs wider, cut
+
Sacs wider, cut by developing nerve. F i r s t vessels from the sac to the skin. Abortive.
by developing
 
nerve. F i r s t
 
vessels from the
 
sac to the skin.
 
Abortive.
 
  
Sacs and valves
+
Sacs and valves ‘Large.
‘Large.
 
  
Maximum size,
+
Maximum size, ‘begin’g lymphn o d e s a l on g jugular sac and subclavian vein. Sac with few lymph nodes. Sac turning into lymph nodes. Many follicles.
‘begin’g lymphn o d e s a l on g
 
jugular sac and
 
subclavian vein.
 
Sac with few
 
lymph nodes.
 
Sac turning into
 
lymph nodes.
 
Many follicles.
 
  
 
Fine bridges all
 
Fine bridges all
Line 880: Line 264:
 
thin.
 
thin.
  
Chains of lymph
+
Chains of lymph nodes.
nodes.
 
  
 
63
 
63
Line 887: Line 270:
 
Other Lymph Sacs.
 
Other Lymph Sacs.
  
Small groups of vessels along
+
Small groups of vessels along renal anastomosis.
renal anastomosis.
 
  
Large median anastomosis of
+
Large median anastomosis of sciatic veins. Groups of veins along sciatic vein, anlage of posterior lymph sacs. Median anastomosis of renal veins.
sciatic veins. Groups of veins
 
along sciatic vein, anlage of
 
posterior lymph sacs. Median
 
anastomosis of renal veins.
 
  
Cisterna Retroperi- : Posterior
+
Cisterna Retroperi- : Posterior Chyli. toneal Sam: Lymph Sac. l
Chyli. toneal Sam: Lymph Sac.
 
l
 
  
 
Present Present ;
 
Present Present ;
  
Present Present Present
+
Present Present Present Present, Present i 4. 6 x 1 thoracic with beginduct com- ni’g lymphplete. hnode.
Present, Present i 4. 6 x 1
 
thoracic with beginduct com- ni’g lymphplete. hnode.
 
  
I
+
I Not Present, ‘ Present found. no nodes. * 2.5 x .75 Not Present, l 3 x 1.75 ‘ found no nodes; 1.2 Large 1.7x2.5 1 . 6 x 1 Darn aged ‘ 2 x 1 Present, Mass of Sac with surround- 1ymph— nodesmeased by nodes. ‘uring 2.8 x nodes 2 X 3. 5 64 Florence R. Sabin.
Not Present, ‘ Present
 
found. no nodes. * 2.5 x .75
 
Not Present, l 3 x 1.75
 
‘ found no nodes;
 
1.2 Large 1.7x2.5
 
1 . 6 x 1  
 
Darn aged ‘ 2 x 1
 
Present, Mass of Sac with
 
surround- 1ymph— nodesmeased by nodes. ‘uring 2.8 x
 
nodes 2 X 3. 5
 
64 Florence R. Sabin.
 
  
diagrammatic form in Fig. 1, there is a group of vessels lying
+
diagrammatic form in Fig. 1, there is a group of vessels lying external to the internal jugular vein near its junction with the primitive ulnar vein. The figure can be interpreted by reference to Fig. 4. These vessels are completely filled with blood and yet I cannot find any openings from them into the veins, or into each other, and thus interpret them after a study of corresponding stages in other mammalian embryos as a plexus of veins which have separated from the jugular vein preparatory to the formation of the anterior or jugular lymph sac. These vessels are small, the largest measuring
external to the internal jugular vein near its junction with the
 
primitive ulnar vein. The figure can be interpreted by reference
 
to Fig. 4. These vessels are completely filled with blood and yet I
 
cannot find any openings from them into the veins, or into each other,
 
and thus interpret them after a study of corresponding stages in
 
other mammalian embryos as a plexus of veins which have separated
 
from the jugular vein preparatory to the formation of the anterior or
 
jugular lymph sac. These vessels are small, the largest measuring
 
  
 
  
FIG. 1. Reconstruction of the plexus of small veins lateral to the V.
+
FIG. 1. Reconstruction of the plexus of small veins lateral to the V. jugularis interna in a human embryo, 8 mm. long, (crown rump). Mall collection, No. 397. X about 50. The plexus of veins is shaded. D. C., ductus Cuvier; V. j. i., vena jugularis interna; V. u. p., vena ulnaris priinitiva.
jugularis interna in a human embryo, 8 mm. long, (crown rump). Mall
 
collection, No. 397. X about 50. The plexus of veins is shaded. D. C.,
 
ductus Cuvier; V. j. i., vena jugularis interna; V. u. p., vena ulnaris priinitiva.
 
  
FIG. 2. Reconstruction of the small veins lateral to the right V. jugularis
+
FIG. 2. Reconstruction of the small veins lateral to the right V. jugularis interna in a human embryo 9 mm. long. Mall collection, No. 163. ){ about 50. Of the veins, six are shaded, indicating that they are full of blood, while the two with heavy outlines are nearly empty. Lettering same as Fig. 10. approximately .3 mm. in the antero—posterior diameter, by .19 mm. laterally.
interna in a human embryo 9 mm. long. Mall collection, No. 163. ){ about 50.
 
Of the veins, six are shaded, indicating that they are full of blood, while
 
the two with heavy outlines are nearly empty. Lettering same as Fig. 10. approximately .3 mm. in the antero—posterior diameter, by .19 mm. laterally.
 
  
The next specimen in the series is an embryo (No. 163) measuring
+
The next specimen in the series is an embryo (No. 163) measuring 9 mm. This specimen shows a similar condition but with certain differences. In the first place the plexus of isolated Vessels occupies a slightly different place, as seen in Fig. 2. They lie farther ventralWard, extending over the body wall external to the heart. Most of these vessels are well filled with blood, while two are nearly empty. This embryo differs also in having an asymmetrical development, the vessels representing the forerunners of the lymphatics being much larger on the right side than on the left. The three largest sacs of this series measure .27 x .19 mm., .36 x .14 mm. and .27 x .14 mm. respectively.
9 mm. This specimen shows a similar condition but with certain
 
differences. In the first place the plexus of isolated Vessels occupies
 
a slightly different place, as seen in Fig. 2. They lie farther ventralWard, extending over the body wall external to the heart. Most of
 
these vessels are well filled with blood, while two are nearly empty.
 
This embryo differs also in having an asymmetrical development, the vessels representing the forerunners of the lymphatics being much
 
larger on the right side than on the left. The three largest sacs of
 
this series measure .27 x .19 mm., .36 x .14 mm. and .27 x .14 mm.
 
respectively.
 
  
The next specimen is an embryo (No. 109) measuring 10.5 mm.
+
The next specimen is an embryo (No. 109) measuring 10.5 mm. In this embryo there are symmetrical jugular sacs as seen in Fig. 3, just external to the internal jugular vein. The relation of the sac to the venous system as a whole is shown in Fig. 4, which is a reconstruction from serial sections. This embryo has been figured
In this embryo there are symmetrical jugular sacs as seen in Fig. 3,
 
just external to the internal jugular vein. The relation of the sac
 
to the venous system as a whole is shown in Fig. 4, which is a
 
reconstruction from serial sections. This embryo has been figured
 
  
  
FIG. 3. Transverse section through the neck of a human embryo, 10.5 mm.
+
FIG. 3. Transverse section through the neck of a human embryo, 10.5 mm. long, showing the symmetrical jugular lymph sacs. Mall collection, No. 109. A., artery; N. X., n. vagus; m. s., 11. sympatheticus; Oe., oesophagus; P., pericardium; S. 1. j., saccus lymphaticus jugularis; T. trachea. The V. jugularis are filled with blood and lie just medial to the sacs.
long, showing the symmetrical jugular lymph sacs. Mall collection, No.
 
109. A., artery; N. X., n. vagus; m. s., 11. sympatheticus; Oe., oesophagus;
 
P., pericardium; S. 1. j., saccus lymphaticus jugularis; T. trachea. The V.
 
jugularis are filled with blood and lie just medial to the sacs.
 
  
by Bardeen and Lewis, American J our. of Anat., Vol. I, 1901-1902,
+
by Bardeen and Lewis, American J our. of Anat., Vol. I, 1901-1902, and by Dr. Mall, American J our. of Anat., Vol. IV, 1905; the outline and some of the details of the figure are taken from their reconstructions. As will be seen in Fig. 4, the sac lies external to the jugular vein and anterior to the primitive ulnar. In this embryo the question of a valve is an interesting one.
and by Dr. Mall, American J our. of Anat., Vol. IV, 1905; the
 
outline and some of the details of the figure are taken from their
 
reconstructions. As will be seen in Fig. 4, the sac lies external to
 
the jugular vein and anterior to the primitive ulnar. In this embryo
 
the question of a valve is an interesting one.
 
  
In studying through Dr. Mall’s collection it has proved that the
+
In studying through Dr. Mall’s collection it has proved that the finding of the valves depends wholly on the plane of the section. There is only one plane which is at all adequate for determining the FIG. 4. Reconstruction of the right jugular lymph sacs, shown in solid black, in a human 10.5 mm. long. Mall collection, No. 109. X about 14. G. N., gasserian ganglion; S. v., sinus venosus; V. c., V. cephalica: V. c. 1., vena cava inferior; V. 13., vena hepatica; V. 5. i., vena jugularls interna; V. p., vena porta; V. p. c., vena cardinalis posterior; V. s. c., vena subcardinalis;
finding of the valves depends wholly on the plane of the section.
 
There is only one plane which is at all adequate for determining the
 
FIG. 4. Reconstruction of the right jugular lymph sacs, shown in solid
 
black, in a human 10.5 mm. long. Mall collection, No. 109. X about 14.
 
G. N., gasserian ganglion; S. v., sinus venosus; V. c., V. cephalica: V. c. 1.,
 
vena cava inferior; V. 13., vena hepatica; V. 5. i., vena jugularls interna; V. p.,
 
vena porta; V. p. c., vena cardinalis posterior; V. s. c., vena subcardinalis;
 
  
V. u. (p.), Vena ulnaris (primitiva) ; V. u., vena umbilicalis; W. b, Wolflian
+
V. u. (p.), Vena ulnaris (primitiva) ; V. u., vena umbilicalis; W. b, Wolflian body.
body.
 
  
valves, namely the coronal. This will be readily seen in Fig. 10,
+
valves, namely the coronal. This will be readily seen in Fig. 10, which shows that the valve is made by along projection of the lymphatic duct into the angle of the internal jugular vein with the cephalic Vein. Imaginary cross sections through this figure will show that the place of the valve would be represented by a small duct in the angle between two veins and this is exactly what is seen in Fig. 5 for this embryo. A -study of Fig. 10 will also show that there could be nothing distinctive of the actual opening of the lymphatic to the vein in cross sections, for they would consist simply of a double layer of endothelium between the veins. In like manner sagittal sections are still more diflicult than transverse ones for locat ing the valves and indeed only in an occasional, fortunate section can it be accurately done.
which shows that the valve is made by along projection of the
 
lymphatic duct into the angle of the internal jugular vein with the
 
cephalic Vein. Imaginary cross sections through this figure will show
 
that the place of the valve would be represented by a small duct in
 
the angle between two veins and this is exactly what is seen in Fig.
 
5 for this embryo. A -study of Fig. 10 will also show that there
 
could be nothing distinctive of the actual opening of the lymphatic
 
to the vein in cross sections, for they would consist simply of a
 
double layer of endothelium between the veins. In like manner
 
sagittal sections are still more diflicult than transverse ones for locat
 
ing the valves and indeed only in an occasional, fortunate section can
 
it be accurately done.
 
  
  
FIG. 5. Transverse section through the jugular sacs of a human embryo,
+
FIG. 5. Transverse section through the jugular sacs of a human embryo, 10.5 mm. long. Mall collection, No. 109, to show the left valve. X 28. A., artery; N., nerve; Oe., oesophagus; P., pericardium; S. 1, j., vena jugularis; V. j. i., vena jugularis interna.
10.5 mm. long. Mall collection, No. 109, to show the left valve. X 28. A.,
 
artery; N., nerve; Oe., oesophagus; P., pericardium; S. 1, j., vena jugularis;
 
V. j. i., vena jugularis interna.
 
  
To return to the embryo 10.5 mm. long, I think that the valve is
+
To return to the embryo 10.5 mm. long, I think that the valve is present, for, as is seen in Fig. 5, there is a small duct in the angle between two Veins and the duct connects with the sac as traced in serial sections. Secondly, the lateral vein in this section is the cephalic, see Fig. 4, and is therefore in the exact position of the undoubted valves seen later in Figs. 10 and 13. Whether this valve is open or not it is impossible to say. The sacs are both empty,’ and in the earlier stages where there are no valves they are often, though not always, full of blood. They measure .7 X .28 mm., showing a considerable increase over the two preceding specimens. This embryo shows. one further point of interest, namely a possible beginning of the thoracic duct in the shape of a duct running over toward the aorta as shown in Fig. 6. The entire question of a thoracic duct will be discussed later, on page 7 7 .l
present, for, as is seen in Fig. 5, there is a small duct in the angle
 
between two Veins and the duct connects with the sac as traced in
 
serial sections. Secondly, the lateral vein in this section is the
 
cephalic, see Fig. 4, and is therefore in the exact position of the
 
undoubted valves seen later in Figs. 10 and 13. Whether this valve
 
is open or not it is impossible to say. The sacs are both empty,’ and
 
in the earlier stages where there are no valves they are often, though
 
not always, full of blood. They measure .7 X .28 mm., showing a considerable increase over the two preceding specimens. This embryo shows. one further point of interest, namely a possible beginning of
 
the thoracic duct in the shape of a duct running over toward the
 
aorta as shown in Fig. 6. The entire question of a thoracic duct
 
will be discussed later, on page 7 7 .l
 
  
The next embryo of the series (No. 353) is 11 mm. in length.
+
The next embryo of the series (No. 353) is 11 mm. in length. This embryo is cut in coronal sections which proves to be the best plain not only for seeing the valves but for understanding all of the cervical lymphatics. This embryo is represented in a series of three figures, 7, 8 and 9, two of them sections and the third a diagram
This embryo is cut in coronal sections which proves to be the best
 
plain not only for seeing the valves but for understanding all of
 
the cervical lymphatics. This embryo is represented in a series of
 
three figures, 7, 8 and 9, two of them sections and the third a diagram
 
  
 
  
FIG. 6. Transverse section through the left jugular sac to show the possible
+
FIG. 6. Transverse section through the left jugular sac to show the possible beginning of a vessel growing down to form the upper part of the thoracic duct. X 40. A., aorta; N. X., N. vagus; Oe., oesophagus; S. 1. j., saccus lymphaticus jugularis; V. j. i., vena jugularis interna.
beginning of a vessel growing down to form the upper part of the thoracic
 
duct. X 40. A., aorta; N. X., N. vagus; Oe., oesophagus; S. 1. j., saccus
 
lymphaticus jugularis; V. j. i., vena jugularis interna.
 
  
from the same series. In Figs. 7 and 8 will be seen the extension of the lymphatic plexus along the external border of the jugular
+
from the same series. In Figs. 7 and 8 will be seen the extension of the lymphatic plexus along the external border of the jugular vein. These two figures show a number of important things, first in connection with the veins, they show the relations of the primitive ulnar and the cephalic to the jugular vein; for the lymphatics they show the relation of the lymphatics to the cephalic vein and in general to the arm bud. These relations are all brought together in the diagram of Fig. 9. Here it will be seen that this plexus which appears isolated in Fig. 7 is really continuous. The plexus is actually much more complex than is shown in Fig. 9. Measuring from the valve, which is in the angle between the cephalic and internal jugular veins, it extends 1.2 mm. along the jugular vein. By a comparison with the reconstruction of the preceding stage, Fig. 4, I think that the sections shown in Fig. 7 and 8 suggest that the sac is extending along the jugular vein by means of a plexus of veins.
vein. These two figures show a number of important things, first
 
in connection with the veins, they show the relations of the primitive
 
ulnar and the cephalic to the jugular vein; for the lymphatics they
 
show the relation of the lymphatics to the cephalic vein and in general
 
to the arm bud. These relations are all brought together in the
 
diagram of Fig. 9. Here it will be seen that this plexus which
 
appears isolated in Fig. 7 is really continuous. The plexus is
 
actually much more complex than is shown in Fig. 9. Measuring from the valve, which is in the angle between the cephalic and internal
 
jugular veins, it extends 1.2 mm. along the jugular vein. By a
 
comparison with the reconstruction of the preceding stage, Fig. 4,
 
I think that the sections shown in Fig. 7 and 8 suggest that the sac
 
is extending along the jugular vein by means of a plexus of veins.
 
  
The next point of interest is the location of the Valve. In Figs.
+
The next point of interest is the location of the Valve. In Figs. 7 and 8, it will be seen that the beginning cephalic vein is easily recognized by its position opposite the upper curve of the arm bud. The lymphatic sac runs deep into the angle between the cephalic and the internal jugular veins, Fig. 7, but in no section is there any break in the endothelium of the sac, which leads one to think that the valve may not yet be open and that this fact may account for the complete filling of the lymphatic sacs with blood. The internal jugular vein is only partially filled with blood. The blood of the vein itself was omitted in the drawing.
7 and 8, it will be seen that the beginning cephalic vein is easily
 
recognized by its position opposite the upper curve of the arm bud.
 
The lymphatic sac runs deep into the angle between the cephalic
 
and the internal jugular veins, Fig. 7, but in no section is there
 
any break in the endothelium of the sac, which leads one to think
 
that the valve may not yet be open and that this fact may account
 
for the complete filling of the lymphatic sacs with blood. The internal jugular vein is only partially filled with blood. The blood
 
of the vein itself was omitted in the drawing.
 
  
In this embryo there is an extension of the jugular sac along the
+
In this embryo there is an extension of the jugular sac along the primitive ulnar and lateral thoracic veins. This extension forms the subclavian sac which gives rise to the lymphatics of the arm, Fig. 9. This is especially interesting in connection with F. T. Lewis’ s observations on the subclavian sac inrabbits where it begins as an isolated sac. I was able to confirm Lewis’ observations on his specimens of rabbit embryos, but feel sure that in human embryos the sac in the arm bud is an extension of the jugular sac. The sac along the ulnar veins measures .8 mm. beginning from the valve. This makes 2 mm. the total extent of the lymphatics in this embryo.
primitive ulnar and lateral thoracic veins. This extension forms
 
the subclavian sac which gives rise to the lymphatics of the arm,
 
Fig. 9. This is especially interesting in connection with F. T.
 
Lewis’ s observations on the subclavian sac inrabbits where it begins
 
as an isolated sac. I was able to confirm Lewis’ observations on
 
his specimens of rabbit embryos, but feel sure that in human embryos
 
the sac in the arm bud is an extension of the jugular sac. The sac
 
along the ulnar veins measures .8 mm. beginning from the valve.
 
This makes 2 mm. the total extent of the lymphatics in this embryo.
 
  
By putting together Figs. 7 and 8, relating them by the position
+
By putting together Figs. 7 and 8, relating them by the position of the cephalic veins, it will be noted that following along the ex— ternal border of the internal jugular vein there are a series of branches which we might call segmental, some of them, as for example above the lymphatics in Fig. 7 0-r between the lymphatics and the primitive ulnar vein in Fig. 8, are obviously small veins, others like the cephalic and primitive ulnar are large veins, while still others are being transformed into lymphatics. This suggests the process of transformation of the various branches of the internal jugular vein from the original simple segmental type into the adult system. In these transformations some of the branches become enlarged, others reduced and dropped out, while still others are changed into lymphatic sacs.
of the cephalic veins, it will be noted that following along the ex—
 
ternal border of the internal jugular vein there are a series of
 
branches which we might call segmental, some of them, as for
 
example above the lymphatics in Fig. 7 0-r between the lymphatics
 
and the primitive ulnar vein in Fig. 8, are obviously small veins,
 
others like the cephalic and primitive ulnar are large veins, while still
 
others are being transformed into lymphatics. This suggests the
 
process of transformation of the various branches of the internal
 
jugular vein from the original simple segmental type into the adult
 
system. In these transformations some of the branches become enlarged, others reduced and dropped out, while still others are
 
changed into lymphatic sacs.
 
  
The next embryo of the series (No. 317 ), measuring 121/2 cm.,
+
The next embryo of the series (No. 317 ), measuring 121/2 cm., has not been illustrated because it is exactly like the preceding except that the lymphatics have much less blood, and the plexus along the
has not been illustrated because it is exactly like the preceding except
 
that the lymphatics have much less blood, and the plexus along the
 
  
  
FIG. 7. Coronal section through the arm bud of a human embryo, 11 mm.
+
FIG. 7. Coronal section through the arm bud of a human embryo, 11 mm. long. Mall collection, No. 353, to show the plexus of veins or lymphatic sacs along the internal vein. This section is to be related to Fig. 8 by means of the composite section, Fig. 9. X about 36. S. 1. j., saccus lymphaticus jugularis; V. c., vena cephalica; V. j. i., vena jugularis interna.
long. Mall collection, No. 353, to show the plexus of veins or lymphatic
 
sacs along the internal vein. This section is to be related to Fig. 8 by means
 
of the composite section, Fig. 9. X about 36. S. 1. j., saccus lymphaticus
 
jugularis; V. c., vena cephalica; V. j. i., vena jugularis interna.
 
  
FIG. 8. Coronal section through the arm bud of the same embryo as Fig.
+
FIG. 8. Coronal section through the arm bud of the same embryo as Fig. 7, to show the relation of the lymphatic sac to the primitive ulnar vein. The larger lymphatic sac is the upper part of the extension along the primitive ulnar vein, shown in Fig. 18. X about 36. S. l. j., saccus lymphaticus jugularis; V. c., vena cephalica; V. j. i., vena jugularis interna; V. t. l.. vena thoracicus lateralis; V. u. (p.), vena ulnaris (primitiva).
7, to show the relation of the lymphatic sac to the primitive ulnar vein.
 
The larger lymphatic sac is the upper part of the extension along the primitive ulnar vein, shown in Fig. 18. X about 36. S. l. j., saccus lymphaticus
 
jugularis; V. c., vena cephalica; V. j. i., vena jugularis interna; V. t. l..
 
vena thoracicus lateralis; V. u. (p.), vena ulnaris (primitiva).
 
  
jugular vein has been definitely transformed into a single sac. The
+
jugular vein has been definitely transformed into a single sac. The extent of the lymphatics along the jugular vein is practically the same. The Valve is definite, showing the same type as seen in Fig. The Lymphatic System in Human Embryos. 71
extent of the lymphatics along the jugular vein is practically the
 
same. The Valve is definite, showing the same type as seen in Fig.
 
The Lymphatic System in Human Embryos. 71
 
  
FIG. 9. A composite diagram made by superimposing the sections showing
+
FIG. 9. A composite diagram made by superimposing the sections showing the jugular sacs, as shown in Figs. 16 and 17, of human embryo, 11 mm. long, Mall collection. X about 36. D. 0., ductus Cuvier; V., position of valve; V. j. i., vena jugularis interna; V. t. 1., vena thoracicus lateralis; V. u. (p.) vena nlnaris (primitiva).
the jugular sacs, as shown in Figs. 16 and 17, of human embryo, 11 mm.
 
long, Mall collection. X about 36. D. 0., ductus Cuvier; V., position of
 
valve; V. j. i., vena jugularis interna; V. t. 1., vena thoracicus lateralis; V. u. (p.) vena nlnaris (primitiva).
 
  
10, except that an opening cannot be made out. It is impossible to
+
10, except that an opening cannot be made out. It is impossible to say whether the opening is not pre-sent or whether the shrinkage of preservative is sufiicient to conceal it.
say whether the opening is not pre-sent or whether the shrinkage of
 
preservative is sufiicient to conceal it.
 
  
The sixth embryo of the series (No. 144), 14 mm. long, shows
+
The sixth embryo of the series (No. 144), 14 mm. long, shows only one new point in the formation of the jugular sac, namely the beginning of the process of bridging of the sac which is illustrated for a later stage in Fig. 14. This cutting of the sacs by slender connective tissue bridges, which has already been described in the development of the jugular lymph sacs in the pig, is, believe, the beginning of the transformation of the sac into a lymph node.” This’ will be considered later.
only one new point in the formation of the jugular sac, namely the
 
beginning of the process of bridging of the sac which is illustrated
 
for a later stage in Fig. 14. This cutting of the sacs by slender connective tissue bridges, which has already been described in the development of the jugular lymph sacs in the pig, is, believe, the
 
beginning of the transformation of the sac into a lymph node.” This’
 
will be considered later.
 
  
Two of the embryos of the series, one (No. 350) measuring 15 mm.
+
Two of the embryos of the series, one (No. 350) measuring 15 mm. and the other (No. 106) measuring 17 mm., have very abortive sacs near the junction of the primitive ulnar with the jugular vein. In both instances the preservative is not good enough to show the endothelium, so there is no way of telling these small sacs, which measure less than half a millimeter in their longest diameter, from mcscnchyme spaces except by their position in coniparisoan with other embryos. They certainly are an evidence that there are marked irregularities in the development of the lymphatic system. _
and the other (No. 106) measuring 17 mm., have very abortive sacs
 
near the junction of the primitive ulnar with the jugular vein. In
 
both instances the preservative is not good enough to show the endothelium, so there is no way of telling these small sacs, which
 
measure less than half a millimeter in their longest diameter, from
 
mcscnchyme spaces except by their position in coniparisoan with other
 
embryos. They certainly are an evidence that there are marked
 
irregularities in the development of the lymphatic system. _
 
  
Another embryo of 15 mm. (No. 423) has also only a small sac,
+
Another embryo of 15 mm. (No. 423) has also only a small sac, this one measuring .9 mm. In the collection there are some embryos in which the preservative is too poor to admit determining the lymphatics at all, but out of the series of 22 which have been studied there are four cases of abortive jugular sacs, or 18. per cent. These embryos measure 15, 17 and 20 mm.
this one measuring .9 mm. In the collection there are some embryos
 
in which the preservative is too poor to admit determining the
 
lymphatics at all, but out of the series of 22 which have been studied
 
there are four cases of abortive jugular sacs, or 18. per cent. These
 
embryos measure 15, 17 and 20 mm.
 
  
The next specimen (No. 424), measuring 17 mm., is valuable,
+
The next specimen (No. 424), measuring 17 mm., is valuable, for it has a double vascular injection. An extravasation along the jugular region interferes with a study of the jugular lymph sacs, but the vascular injection of the posterior part of the embryo gives conclusive evidence that the other sacs, namely the retroperitoneal, the posterior and the receptaculum chyli have not begun.
for it has a double vascular injection. An extravasation along the
 
jugular region interferes with a study of the jugular lymph sacs,
 
but the vascular injection of the posterior part of the embryo gives
 
conclusive evidence that the other sacs, namely the retroperitoneal, the
 
posterior and the receptaculum chyli have not begun.
 
  
Embryo (No. 296) measuring 17 mm. is the earliest specimen in
+
Embryo (No. 296) measuring 17 mm. is the earliest specimen in which I have found a valve undoubtedly open. This is shown in
which I have found a valve undoubtedly open. This is shown in
 
  
 
"Sabin. Amer. Jour. Anat., Vol. IV, 1905.
 
"Sabin. Amer. Jour. Anat., Vol. IV, 1905.
  
10. It is in exactly the position found in the embryo 11 mm.
+
10. It is in exactly the position found in the embryo 11 mm. long (Fig. 7) and in No. 317 which is 12.5 mm., which are cut in coronal sections, but in the two earlier embryos I could not make out the break in the endothelium. The extent of the lymph sac in the section is 1.5 mm. and there is a slight extension along the primitive ulnar vein.
long (Fig. 7) and in No. 317 which is 12.5 mm., which are cut in
 
coronal sections, but in the two earlier embryos I could not make
 
out the break in the endothelium. The extent of the lymph sac in
 
the section is 1.5 mm. and there is a slight extension along the primitive ulnar vein.
 
  
The next embryo of the series (No. 7 4) measures 16 mm. In
+
The next embryo of the series (No. 7 4) measures 16 mm. In Dr. Mall’s catalogue it is placed after those measuring 17 mm., for
Dr. Mall’s catalogue it is placed after those measuring 17 mm., for
 
  
 
  
FIG. 10. Coronal section through the arm bud of a human embryo, 17 mm.
+
FIG. 10. Coronal section through the arm bud of a human embryo, 17 mm. long, Mall collection, No. 296, to show the open valve of the jugular lymph sac in relation to the veins. X about 26. S. 1. j., saccus lymphaticus jugularis; V. c., vena cephalica; V. j. i., vena jugularis interna; V. 11. (p.). vena ulnaris (primitiva).
long, Mall collection, No. 296, to show the open valve of the jugular lymph
 
sac in relation to the veins. X about 26. S. 1. j., saccus lymphaticus jugularis; V. c., vena cephalica; V. j. i., vena jugularis interna; V. 11. (p.). vena
 
ulnaris (primitiva).
 
  
it is undoubtedly further developed. This embryo, 'in which the sections are 50 microns thick, is a very satisfactory one for determining
+
it is undoubtedly further developed. This embryo, 'in which the sections are 50 microns thick, is a very satisfactory one for determining the sacs, for the veins are unusually distended with blood and the lymph sacs are filled with a serum which takes a definite stain. The sacs extend a distance of 1.8 mm. along the internal jugular vein. There is no sac on the primitive ulnar vein and there are 74 Florence R. Sabin.
the sacs, for the veins are unusually distended with blood and the
 
lymph sacs are filled with a serum which takes a definite stain.
 
The sacs extend a distance of 1.8 mm. along the internal jugular
 
vein. There is no sac on the primitive ulnar vein and there are
 
74 Florence R. Sabin.
 
  
no traces of the other sacs in the posterior part of the body. The
+
no traces of the other sacs in the posterior part of the body. The veins are especially large in the posterior part of the body. The sections are too thick to show the valves well. The sacs appear as in Fig. 3 except that they are larger.
veins are especially large in the posterior part of the body. The
 
sections are too thick to show the valves well. The sacs appear as in
 
Fig. 3 except that they are larger.
 
  
The next embryo of the series (No. 22) measures 20 mm. and
+
The next embryo of the series (No. 22) measures 20 mm. and shows several interesting points. The series is cut transversely and the sacs also appear much as they are shown in Fig. 3 for an embryo 10.5 long except that they are much wider. The sacs measure 1.6 x 7. The new point of interest is, that in this series the third nerve cuts through the sac; in a later stage, in an embryo measuring 30 mm., Fig. 12, three nerves cut through the sac, namely the third, fourth and fifth. For the first t.ime, in this stage, there are vessels extending from the sac toward the skin. It will be remembered that this is the point in.which the recent American workers on the lymphatic system differ.
shows several interesting points. The series is cut transversely and
 
the sacs also appear much as they are shown in Fig. 3 for an embryo
 
10.5 long except that they are much wider. The sacs measure
 
1.6 x 7. The new point of interest is, that in this series the third
 
nerve cuts through the sac; in a later stage, in an embryo measuring
 
30 mm., Fig. 12, three nerves cut through the sac, namely the third,
 
fourth and fifth. For the first t.ime, in this stage, there are vessels
 
extending from the sac toward the skin. It will be remembered that
 
this is the point in.which the recent American workers on the
 
lymphatic system differ.
 
  
A further point of interest in this series is a group of small vessels along the renal anastomosing vein. These vessels, I think, are
+
A further point of interest in this series is a group of small vessels along the renal anastomosing vein. These vessels, I think, are forerunners of the mesenteric sacs. The indications of lymphatics for the posterior part of the body appear at this stage.
forerunners of the mesenteric sacs. The indications of lymphatics
 
for the posterior part of the body appear at this stage.
 
  
In another embryo (No. 128) measuring 20 mm. the jugular
+
In another embryo (No. 128) measuring 20 mm. the jugular sacs are again abortive, measuring only .75 mm. The specimen is, however, very interesting in connection with the lymphatics for the posterior part of the body. In the neck, as we have seen, the early lymphatics are the two jugular sacs, with either an extension or a supplementary sac along the primitive ulnar vein, in the arm bud. In the posterior part of the body three sacs have been found, two of them median, the mesenteric sac and the cisterna chyli; and one paired, namely the posterior lymph sac. In this embryo, in the place of the future cisterna chyli, there is an extensive median vein connecting the two sciatic veins. Just ventral to this, compare with Fig. 12, is the renal anastomosis running through the great mass of the sympathetic system in the hilum of the two adrenal bodies. Around these two large median anastomosing veins there is as yet no evidence of the future median lymphatic sac. However, to the side of the two sciatic veins, just posterior to the median anastomosis, is an abundant plexus of veins on the one side and a possible beginning posterior lymph sac on the other, making a definite indication of the posterior lymphatic sacs. This stage is, I believe, just preliminary to the ’formation of the three abdominal sacs. In the next specimen these sacs become definite.
sacs are again abortive, measuring only .75 mm. The specimen is,
 
however, very interesting in connection with the lymphatics for the
 
posterior part of the body. In the neck, as we have seen, the early
 
lymphatics are the two jugular sacs, with either an extension or
 
a supplementary sac along the primitive ulnar vein, in the arm bud.
 
In the posterior part of the body three sacs have been found, two
 
of them median, the mesenteric sac and the cisterna chyli; and one
 
paired, namely the posterior lymph sac. In this embryo, in the
 
place of the future cisterna chyli, there is an extensive median vein
 
connecting the two sciatic veins. Just ventral to this, compare with
 
Fig. 12, is the renal anastomosis running through the great mass
 
of the sympathetic system in the hilum of the two adrenal bodies.
 
Around these two large median anastomosing veins there is as yet
 
no evidence of the future median lymphatic sac. However, to the side
 
of the two sciatic veins, just posterior to the median anastomosis, is an
 
abundant plexus of veins on the one side and a possible beginning posterior lymph sac on the other, making a definite indication of the posterior lymphatic sacs. This stage is, I believe, just preliminary to the
 
’formation of the three abdominal sacs. In the next specimen these sacs become definite.
 
  
Thus in the first fourteen specimens of the series, measuring from
+
Thus in the first fourteen specimens of the series, measuring from 38 to 20 mm., simply the jugular sacs are present. From now on, that is in embryos above 20 mm., we shall have to follow no-t only the jugular sacs but the mesenteric sac, the cisterna chyli and the posterior lymph sacs as well.
38 to 20 mm., simply the jugular sacs are present. From now on,
 
that is in embryos above 20 mm., we shall have to follow no-t only
 
the jugular sacs but the mesenteric sac, the cisterna chyli and the
 
posterior lymph sacs as well.
 
  
The first embryo above 20 mm. in the series, is one (No. 382)
+
The first embryo above 20 mm. in the series, is one (No. 382) measuring 23 mm. This series is cut in sagittal sections. It shows the jugular sac beautifully, which has now reached a size of 2 x1 'mm., and lies opposite the third, fourth and fifth cervical vertebrae. The series, however, is much more important in connection with the other. lymphatic sacs. I cannot find the posterior lymph sac, but both the mesenteric sac and the cisterna chyli are present. For these two median sacs the sagittal plane proves to be by far the best. In Fig. 11,. which was made by graphic reconstruction, is shown the retroperitoneal sac in its relation to the renal vein and the suprarenal body. It is designed to relate the mesenteric sac and cisterna chyli to the -surrounding structures. The point at which the vena cava turns ventralward, opposite the second lumbar vertebra, marks the position both of the renal veins and also the suprarenal branch which is a large vein running anteriorly along the ventral surface of the suprarenal body. The retroperitoneal sac extends along the renal and suprarenal veins, the latter being hidden in the diagram by the venacava. In following the suprarenal veins the lymphatic vessels approach the superior mesenteric artery, along which they subsequently grow out into the mesentery, as has been shown by Heuer.“ The line of mesentery is shown in the diagram. The diagram shows the mass of sympathetic ganglia closely related to the suprarenal body. In this early stage the lymphatic ducts are not likely to be confused with the sympathetic ganglia, but later when nodes begin to develop care must be exercised to distinguish them. The diagram also shows
measuring 23 mm. This series is cut in sagittal sections. It shows
 
the jugular sac beautifully, which has now reached a size of 2 x1
 
'mm., and lies opposite the third, fourth and fifth cervical vertebrae.
 
The series, however, is much more important in connection with the
 
other. lymphatic sacs. I cannot find the posterior lymph sac, but both
 
the mesenteric sac and the cisterna chyli are present. For these two
 
median sacs the sagittal plane proves to be by far the best. In Fig.
 
11,. which was made by graphic reconstruction, is shown the retroperitoneal sac in its relation to the renal vein and the suprarenal body.
 
It is designed to relate the mesenteric sac and cisterna chyli to the
 
-surrounding structures. The point at which the vena cava turns
 
ventralward, opposite the second lumbar vertebra, marks the position
 
both of the renal veins and also the suprarenal branch which is a
 
large vein running anteriorly along the ventral surface of the suprarenal body. The retroperitoneal sac extends along the renal and
 
suprarenal veins, the latter being hidden in the diagram by the venacava. In following the suprarenal veins the lymphatic vessels approach the superior mesenteric artery, along which they subsequently
 
grow out into the mesentery, as has been shown by Heuer.“ The
 
line of mesentery is shown in the diagram. The diagram shows the
 
mass of sympathetic ganglia closely related to the suprarenal body.
 
In this early stage the lymphatic ducts are not likely to be confused
 
with the sympathetic ganglia, but later when nodes begin to develop
 
care must be exercised to distinguish them. The diagram also shows
 
  
”Heuer. Amer. Jour. Anat, Vol. IX, N0. 1.
+
”Heuer. Amer. Jour. Anat, Vol. IX, N0. 1. FIG. 11. A composite diagram made by superimposing the ections showing the relatlons of the mesenteric sac and cisterna chyli to the veins, in 9. human embryo measuring 23 mm., Mall collection, No. 382. X about 8. A. m. s., A. mesenterica su perior; C. c., cisterns. chyli; G. s., gangli sympathetica; S. 1. m., saccus Iymphaticus:
FIG. 11. A composite diagram made by superimposing the ections showing the
 
relatlons of the mesenteric sac and cisterna chyli to the veins, in 9. human embryo
 
measuring 23 mm., Mall collection, No. 382. X about 8. A. m. s., A. mesenterica su
 
perior; C. c., cisterns. chyli; G. s., gangli sympathetica; S. 1. m., saccus Iymphaticus:
 
  
 
mesentericus; 8., suprarenal body; V. a., v. azygos; v. c. i.. vena cava inferior.
 
mesentericus; 8., suprarenal body; V. a., v. azygos; v. c. i.. vena cava inferior.
  
  
nteresting relations of the cisterna chyli. It arises opposite the
+
nteresting relations of the cisterna chyli. It arises opposite the second, third and fourth lumbar vertebrae, closely adjacent to the inferior vena cava where it anastomoses with the azygos veins. In studying through Dr. Mall’s collection I have become convinced that the cisterna chyli forms one of the primitive sacs and that the thoracic duct may grow forward, '5. e., anteriorly from it. Baetjer has shown that the mesenteric sac soon becomes connected with the cisterna chyli. In this series I cannot find any evidence of a thoracic duct. The cisterna chyli differs from the other sacs simply in not being completely transformed into lymph nodes, though its lower border develops into a large group of them, as will be shown in the last series.
second, third and fourth lumbar vertebrae, closely adjacent to the
 
inferior vena cava where it anastomoses with the azygos veins. In
 
studying through Dr. Mall’s collection I have become convinced that
 
the cisterna chyli forms one of the primitive sacs and that the thoracic
 
duct may grow forward, '5. e., anteriorly from it. Baetjer has shown
 
that the mesenteric sac soon becomes connected with the cisterna
 
chyli. In this series I cannot find any evidence of a thoracic duct.
 
The cisterna chyli differs from the other sacs simply in not being
 
completely transformed into lymph nodes, though its lower border
 
develops into a large group of them, as will be shown in the last
 
series.
 
  
The next embryo of the series (No. 6), measuring 24 mm., has a
+
The next embryo of the series (No. 6), measuring 24 mm., has a large jugular sac. The series is incomplete so that I cannot get the length of the sac, but its width is the same as the preceding, namely 1 mm. The valves are present and the sac shows much bridging. There is a well defined subclavian sac. This series is also more interesting in connection with the other sacs. It shows three things, the retroperitoneal sac, the cisterna chyli, the beginning thoracic duct and the anlage of the posterior lymph sacs. A point of especial interest in this series is in connection with the cisterna chyli. This sac is present as a few vessels dorsal to the aorta; and from the sac ducts extend anteriorly immediately adjacent to the azygos veins. On the left side, this duct extends into the thoracic cavity almost to the neck. I cannot trace it to the jugular sac nor is the series perfect enough to enable one to say whether it is present in every section or not, but there is sufficient evidence to indicate that the thoracic duct may be an outgrowth of the cisterna chyli.
large jugular sac. The series is incomplete so that I cannot get the
 
length of the sac, but its width is the same as the preceding, namely
 
1 mm. The valves are present and the sac shows much bridging.
 
There is a well defined subclavian sac. This series is also more interesting in connection with the other sacs. It shows three things,
 
the retroperitoneal sac, the cisterna chyli, the beginning thoracic
 
duct and the anlage of the posterior lymph sacs. A point of especial
 
interest in this series is in connection with the cisterna chyli. This
 
sac is present as a few vessels dorsal to the aorta; and from the sac
 
ducts extend anteriorly immediately adjacent to the azygos veins.
 
On the left side, this duct extends into the thoracic cavity almost
 
to the neck. I cannot trace it to the jugular sac nor is the series
 
perfect enough to enable one to say whether it is present in every
 
section or not, but there is sufficient evidence to indicate that the
 
thoracic duct may be an outgrowth of the cisterna chyli.
 
  
The thoracic duct has proved to be the most difficult part of the
+
The thoracic duct has proved to be the most difficult part of the lymphatic system to work out for this reason, we have not yet found a way to inject it in early stages and uninjected sections are not adequate. The evidence of sections is as follows, the jugular sac and the cisterna chyli, which the duct subsequently connects, develop before the duct. The question is, does the duct develop from multiple anlagen from the azygos veins for which there is no proof except that lymphatic vessels can be seen in sections adjacent to FIG. 12. Flat reconstruction of the primitive lymphatic system in a human embryo, 30 mm. long, Mall collection. No. 86. X about 5.4. C. c., cisterna chyli; L. g., lymphoglandula; N. III., N. IV., and N. V., Nn. cervicales; S. 1. jug., saccus lymphaticus jugularis; S. 1. 1119s., saccus lymphaticus mesentericus; S. 1. post, saccus lymphaticus posterior; S. 1. 5., saccus lymphaticus subclavius; V. c., vena cephalica; V. <3. i., vena cava inferior; V. f.. vena femoralis: V. j. i. vena jugularis inferior; V. 1. p., vasa lymphatica profunda; V. l. s., vasa lymphatica superficialis; V. 1-., vena renalis; v. s., vena sciatica; V. u. (1).), vena ulnai-is (primitiva).
lymphatic system to work out for this reason, we have not yet found
 
a way to inject it in early stages and uninjected sections are not
 
adequate. The evidence of sections is as follows, the jugular sac
 
and the cisterna chyli, which the duct subsequently connects, develop
 
before the duct. The question is, does the duct develop from
 
multiple anlagen from the azygos veins for which there is no proof
 
except that lymphatic vessels can be seen in sections adjacent to
 
FIG. 12. Flat reconstruction of the primitive lymphatic system in a human embryo,
 
30 mm. long, Mall collection. No. 86. X about 5.4. C. c., cisterna chyli; L. g.,
 
lymphoglandula; N. III., N. IV., and N. V., Nn. cervicales; S. 1. jug., saccus lymphaticus jugularis; S. 1. 1119s., saccus lymphaticus mesentericus; S. 1. post, saccus
 
lymphaticus posterior; S. 1. 5., saccus lymphaticus subclavius; V. c., vena cephalica;
 
V. <3. i., vena cava inferior; V. f.. vena femoralis: V. j. i. vena jugularis inferior;
 
V. 1. p., vasa lymphatica profunda; V. l. s., vasa lymphatica superficialis; V. 1-.,
 
vena renalis; v. s., vena sciatica; V. u. (1).), vena ulnai-is (primitiva).
 
  
these veins, or does the duct grow from the two sacs, the cisterna
+
these veins, or does the duct grow from the two sacs, the cisterna chyli and the jugular one. For this second view the evidence is also weak, it consists in this, that other lymph ducts wherever we can study them grow from the sacs; and secondly in pig embryos and in human embryos one can trace a duct forward from the cisterna chyli and caudalward from the jugular sac, and in later stages these two ducts have joined. The weakness of this evidence lies in the fact that in the earlier stages the picture is always liable to be confused by Lewis’ multiple anlagen. In both pig and human embryos the stages to be studied for the thoracic duct lie between 20 and 30 mm. In an embryo pig the complete thoracic duct can be injected at 27 mm. It should be quite clearly noted that whichever method of formation of the thoracic duct proves ultimately to be correct, that is whether it arises from the azygos veins in situ or from an outgrowth of the lymphatic sacs, the most fundamental point remains the same, that its endothelium is vascular.
chyli and the jugular one. For this second view the evidence is
 
also weak, it consists in this, that other lymph ducts wherever we
 
can study them grow from the sacs; and secondly in pig embryos and
 
in human embryos one can trace a duct forward from the cisterna
 
chyli and caudalward from the jugular sac, and in later stages these
 
two ducts have joined. The weakness of this evidence lies in the
 
fact that in the earlier stages the picture is always liable to be confused by Lewis’ multiple anlagen. In both pig and human embryos
 
the stages to be studied for the thoracic duct lie between 20 and 30
 
mm. In an embryo pig the complete thoracic duct can be injected at
 
27 mm. It should be quite clearly noted that whichever method
 
of formation of the thoracic duct proves ultimately to be correct,
 
that is whether it arises from the azygos veins in situ or from an outgrowth of the lymphatic sacs, the most fundamental point remains
 
the same, that its endothelium is vascular.
 
  
However, it should be stated here that wherever growing lymphatic capillaries have been absolutely tested, they grow by the
+
However, it should be stated here that wherever growing lymphatic capillaries have been absolutely tested, they grow by the sprouting of their own endothelium rather than by additions of new anlagen from the veins. This has already been noted for the living lymphatics; it is also shown by the work of Dr. H. M. Evans” on the growth of new lymphatic capillaries into a sarcoma of the intestine. His injections show that theinew lymphatic capillaries are derived from the mucosal plexus and that these new vessels are analogous with the central lacteals of the villi. In the tumor, however, they are developing beyond the normal limits of the terminal lacteals into a spreading plexus. This plexus shows all gradations as seen in Evans’ figure to the normal lacteal.
sprouting of their own endothelium rather than by additions of new
 
anlagen from the veins. This has already been noted for the living
 
lymphatics; it is also shown by the work of Dr. H. M. Evans”
 
on the growth of new lymphatic capillaries into a sarcoma of the
 
intestine. His injections show that theinew lymphatic capillaries
 
are derived from the mucosal plexus and that these new vessels are
 
analogous with the central lacteals of the villi. In the tumor, however, they are developing beyond the normal limits of the terminal
 
lacteals into a spreading plexus. This plexus shows all gradations
 
as seen in Evans’ figure to the normal lacteal.
 
  
From the next specimen (No. 86), measuring 30 mm., a graphic
+
From the next specimen (No. 86), measuring 30 mm., a graphic reconstruction has been made of the entire primitive lymphatic system, Fig. 12. It does not show the extent of the peripheral lymphatics, but does show the relations of the primitive system. At this stage, as will be seen in the reconstruction, the lymphatic system consists of the large jugular sac, measuring 5 X 3.6 mm., with its large extension along the ulnar vein to the arm bud. Emptying into the jugular sac on one side is the thoracic duct which connects
reconstruction has been made of the entire primitive lymphatic system, Fig. 12. It does not show the extent of the peripheral lymphatics, but does show the relations of the primitive system. At
 
this stage, as will be seen in the reconstruction, the lymphatic system consists of the large jugular sac, measuring 5 X 3.6 mm., with its
 
large extension along the ulnar vein to the arm bud. Emptying
 
into the jugular sac on one side is the thoracic duct which connects
 
  
  
"Evans. On the occurrence of newly-formed lymphatic vessels in malignant
+
"Evans. On the occurrence of newly-formed lymphatic vessels in malignant growths. Johns Hopkins Hospital Bulletin, 1908.
growths. Johns Hopkins Hospital Bulletin, 1908.
 
  
  
FIG. 13. Coronal section through the jugular lymph sacs in a human
+
FIG. 13. Coronal section through the jugular lymph sacs in a human embryo of 30 mm., Mall collection, No. 86. X about 11. The level of the section is shown on the reconstruction of Fig. 21. The section shows the complete lymph sac on the right side and is cut to show the valve on the left. S. 1. j., saccus Iymphaticus jugularis; V. i., V. innominata; V. j. i., V. jugularis interna; V. I. s., vasa Iymphatica superficialis.
embryo of 30 mm., Mall collection, No. 86. X about 11. The level of the section is shown on the reconstruction of Fig. 21. The section shows the
 
complete lymph sac on the right side and is cut to show the valve on the
 
left. S. 1. j., saccus Iymphaticus jugularis; V. i., V. innominata; V. j. i., V.
 
jugularis interna; V. I. s., vasa Iymphatica superficialis.
 
  
ond median sac, the retroperitoneal, which is adjacent to the renal
+
ond median sac, the retroperitoneal, which is adjacent to the renal veins. At this stage a connection between the cisterna chyli and the mesenteric sac, which has been so well shown by Baetjer for. the_ pig of the same size, could not be made out. The posterior sac has now become a long narrow sac, along the course of the primitive sciatic veins and inferior vena cava. It measures 4.6 X .5 x .96 (dorso—ventral), and runs almost to the cisterna chyli, with which a connection cannot be made out. The plane of the section, coronal, is not especially advantageous for determining whether the connection has been made or not-.
veins. At this stage a connection between the cisterna chyli
 
and the mesenteric sac, which has been so well shown by Baetjer
 
for. the_ pig of the same size, could not be made out. The posterior
 
sac has now become a long narrow sac, along the course of the primitive sciatic veins and inferior vena cava. It measures 4.6 X .5 x .96
 
(dorso—ventral), and runs almost to the cisterna chyli, with which
 
a connection cannot be made out. The plane of the section, coronal,
 
is not especially advantageous for determining whether the connection
 
has been made or not-.
 
  
  
FIG. 14. Coronal section through the jugular lymph sac of the same
+
FIG. 14. Coronal section through the jugular lymph sac of the same embryo, at the level shown in Fig. 21, to show the simple bridging of the sac which is the anlage of the first lymph node. X about 19. S. I. j.,
embryo, at the level shown in Fig. 21, to show the simple bridging of
 
the sac which is the anlage of the first lymph node. X about 19. S. I. j.,
 
  
 
saccus lymphaticus jugularis.
 
saccus lymphaticus jugularis.
  
The jugular sacs show a number of points of interest. First
+
The jugular sacs show a number of points of interest. First their increase in size, this being the stage of the maximum size. The valve is very beautifully shown, as is seen in Fig. 13. The level of this section is shown on the diagram. A second point of interest is the extensive bridging of the sac. This occurs especially near the dorsal border, as is shown in Fig. 14. At this stage the bridges of connective tissue, which cut the sac, show more connective tissue cells than the surrounding mesenchyme. This thickening of the mesenchyme around a plexus of lymph ducts makes the anlage of a lymph node.
their increase in size, this being the stage of the maximum size.
+
 
The valve is very beautifully shown, as is seen in Fig. 13. The
+
A third point of interest is the spreading of the ducts from the jugular sac to the skin. I want to call especial attention to the great size of these ducts, one especially which leaves the lateral surface of the sac. These ducts are the first lymphatics to reach the skin; as has been said, they first reach the skin in a human embryo of about 20 mm., and by this stage they have grown over the head and down over the shoulders. These peripheral vessels have not been reconstructed.
level of this section is shown on the diagram. A second point of
+
 
interest is the extensive bridging of the sac. This occurs especially
+
Fig. 12 shows that the sac has now been cut through by three of the cervical nerves, the third, fourth and fifth. This is interesting in connection with the shifting of the structures in the neck and in the placing of the sacs. Just at the edge of the subclavian sac is a second small beginning lymph node.— This lymph node is like the jugular one, consisting of bridges of thickened connective tissue between a rich plexus of lymphatic capillaries. The beginning of the deep lymphatics for the arm is also shown. I could not trace them farther in the sections.
near the dorsal border, as is shown in Fig. 14. At this stage the
 
bridges of connective tissue, which cut the sac, show more connective tissue cells than the surrounding mesenchyme. This thickening of
 
the mesenchyme around a plexus of lymph ducts makes the anlage
 
of a lymph node.
 
  
A third point of interest is the spreading of the ducts from the
+
The thoracic duct shows beautifully in the sections. It begins at the cisterna chyli as a double duct, but the right one soon crosses obliquely in the plane of the coronal section to the left side and joins its fellow. The duct lies adjacent to the azygos veins and has many irregularities. At this stage, the duct reaches the jugular sac, an advance from embryo No. 6, of 24 mm., in which it only extended into the thoracic cavity.
jugular sac to the skin. I want to call especial attention to the
 
great size of these ducts, one especially which leaves the lateral surface of the sac. These ducts are the first lymphatics to reach the
 
skin; as has been said, they first reach the skin in a human embryo
 
of about 20 mm., and by this stage they have grown over the head
 
and down over the shoulders. These peripheral vessels have not
 
been reconstructed.
 
  
Fig. 12 shows that the sac has now been cut through by three of
+
In the angle of the bifurcation of the trachea in this embryo is a clump of lymphatic vessels which possibly connect with the thoracic duct, though the connection could not be made out in the sections. These vessels extend a short distance along the bronchi and are the first visceral lymphatics I have found in the series.
the cervical nerves, the third, fourth and fifth. This is interesting
 
in connection with the shifting of the structures in the neck and
 
in the placing of the sacs. Just at the edge of the subclavian sac
 
is a second small beginning lymph node.— This lymph node is like
 
the jugular one, consisting of bridges of thickened connective tissue
 
between a rich plexus of lymphatic capillaries. The beginning of
 
the deep lymphatics for the arm is also shown. I could not trace
 
them farther in the sections.
 
  
The thoracic duct shows beautifully in the sections. It begins
+
The retroperitoneal sac is shown in Fig. 15, which corresponds with the line on Fig. 12. The section shows the relation of the sac to the renal vein and brings out the especially large masses of the sympathetic ganglia in this region.
at the cisterna chyli as a double duct, but the right one soon crosses
 
obliquely in the plane of the coronal section to the left side and
 
joins its fellow. The duct lies adjacent to the azygos veins and
 
has many irregularities. At this stage, the duct reaches the jugular
 
sac, an advance from embryo No. 6, of 24 mm., in which it only
 
extended into the thoracic cavity.
 
  
In the angle of the bifurcation of the trachea in this embryo is
+
The posterior lymph sac shows on one side in Fig. 15, but much better in Fig. 16. The posterior lymph sac is a double sac extending
a clump of lymphatic vessels which possibly connect with the thoracic
 
duct, though the connection could not be made out in the sections.
 
These vessels extend a short distance along the bronchi and are the
 
first visceral lymphatics I have found in the series.
 
  
The retroperitoneal sac is shown in Fig. 15, which corresponds
 
with the line on Fig. 12. The section shows the relation of the
 
sac to the renal vein and brings out the especially large masses of the
 
sympathetic ganglia in this region.
 
  
The posterior lymph sac shows on one side in Fig. 15, but much
 
better in Fig. 16. The posterior lymph sac is a double sac extending
 
  
   
+
FIG. 15. Coronal section through the retroperitoneai sac of the human embryo, at a level indicated on Fig. 21. X about 39. A., aorta; K., kidney; S. I. m., saccus lymphaticus mesenterica; S. 1. p., saccus lymphatica posterior; V. c. i., vena cava inferior; V. r., vena renalis.
 
  
FIG. 15. Coronal section through the retroperitoneai sac of the human
+
along the primitive sciatic veins. The reconstruction is made of the left side, but shows where the left primitive sciatic vein joins the 84 Florence R. Sabin.
embryo, at a level indicated on Fig. 21. X about 39. A., aorta; K., kidney;
 
S. I. m., saccus lymphaticus mesenterica; S. 1. p., saccus lymphatica posterior;
 
V. c. i., vena cava inferior; V. r., vena renalis.
 
  
along the primitive sciatic veins. The reconstruction is made of the
+
right to form the inferior vena cava, and shows that the sacs now extend forward almost to the cisterna chyli. The cisterna chyli being median and the posterior sacs being lateral, the plane of the section made it impossible to trace whether the connection has been made or no-t. The two sacs, however, run to the same level and probably do connect. The posterior sac measures 4.6x.2 (lateral X .9 (dorso-ventral). In the angle where the femoral vein branches
left side, but shows where the left primitive sciatic vein joins the
 
84 Florence R. Sabin.
 
  
right to form the inferior vena cava, and shows that the sacs now
 
extend forward almost to the cisterna chyli. The cisterna chyli
 
being median and the posterior sacs being lateral, the plane of the
 
section made it impossible to trace whether the connection has been
 
made or no-t. The two sacs, however, run to the same level and
 
probably do connect. The posterior sac measures 4.6x.2 (lateral
 
X .9 (dorso-ventral). In the angle where the femoral vein branches
 
  
+
FIG. 16. Coronal section through the posterior lymph sacs as they lie along the primitive sciatic veins, of the same embryo, at a level shown i! Fig. 21. X about 49. S. 1. p., saccus lymphaticus posterior; V. c., vena candalis; V. s., vena sciatica primitiva.
  
FIG. 16. Coronal section through the posterior lymph sacs as they lie
+
oil from the primitive sciatic is a lymph node and it will be seen that deep lymphatic vessels follow both the sciatic and femoral veins. There is also a group of superficial lymphatics covering the skin of the hip in the groove between the body wall and the leg. These superficial lymphatics could be traced to a connection with the sac on the opposite side, but not on the side reconstructed. This gap is probably due to the accidental plane of the section; it comes where the vessels turn directly outward and are so cut in cross section. These gaps to be found in serial sections have already been discussed, they occur in thin sections, but much more often in thick ones like these, this embryo being cut at 50 microns, where the slender lymphatics must often be missed. The extent of these superficial lymphatics has not been shown in the reconstruction, they are readily made out in the skin over the back and hip. There is no difliculty in telling them, they are so sharply lined by endothelium, are empty and about three times the size of the blood capillary. This specimen then shows all the primitive sacs; and their relations to the thoracic duct. It marks also the beginning of the peripheral lymphatic system, both visceral, to the lungs, and superficial to the skin.
along the primitive sciatic veins, of the same embryo, at a level shown i!
 
Fig. 21. X about 49. S. 1. p., saccus lymphaticus posterior; V. c., vena
 
candalis; V. s., vena sciatica primitiva.
 
  
oil from the primitive sciatic is a lymph node and it will be seen
+
The next specimens consist of a group of four embryos of about the same stage, No. 95 measuring 46 mm. and three others (No. 96, No. 84 and No. 224;) all measuring 50 mm. They all prove to be especially interesting in connection with the development of the posterior lymph sac. In connection with the jugular sac the measurements are given in the table. These sacs show certain differences. In No. 95 the transformation into lymph nodes is not extensive and is chiefly at the upper end. No. 224.», on the other hand, shows a fine bridging throughout the sac. The other two specimens show an important stage in the evolution of lymph nodes. By referring back to Fig. 14 it will be seen that when the nodes first begin in an embryo, 30 mm. long, they consist simply of a thickened connective tissue between a plexus of ducts. But at this stage, 50 mm., there appear round clumps of lymphocytes in the connective tissue bridges. These clumps of lymphocytes are the primary lymph follicles and they occur around the blood vessels of the connective tissue bridges. These primary follicles are well illustrated in Fig. 17, in the femoral lymph node, or in Fig." 18. The evolution of the lymph node depends on the balance between the two elements; the lymph ducts which multiply until they are sinuses and the vascular part with its attendant lymphocytes which make the follicles and cords. It will be seen in the figures of these embryos, that in early stages the lymphatic element by far predominates.
that deep lymphatic vessels follow both the sciatic and femoral veins.
 
There is also a group of superficial lymphatics covering the skin
 
of the hip in the groove between the body wall and the leg. These
 
superficial lymphatics could be traced to a connection with the sac on
 
the opposite side, but not on the side reconstructed. This gap
 
is probably due to the accidental plane of the section; it comes where the vessels turn directly outward and are so cut in cross section.
 
These gaps to be found in serial sections have already been discussed,
 
they occur in thin sections, but much more often in thick ones like
 
these, this embryo being cut at 50 microns, where the slender lymphatics must often be missed. The extent of these superficial lymphatics has not been shown in the reconstruction, they are readily
 
made out in the skin over the back and hip. There is no difliculty
 
in telling them, they are so sharply lined by endothelium, are empty
 
and about three times the size of the blood capillary. This specimen
 
then shows all the primitive sacs; and their relations to the thoracic
 
duct. It marks also the beginning of the peripheral lymphatic
 
system, both visceral, to the lungs, and superficial to the skin.
 
  
The next specimens consist of a group of four embryos of about
+
In embryo No. 84, the size of the lymph ducts coming from the jugular sac is particularly striking. In one section, one of these ducts measures 2.7 5 X .5 mm. VVhen it is considered that these vessels are really capillaries, being lined by a single layer of endothelium, one sees that they are really enormous in size, almost as
the same stage, No. 95 measuring 46 mm. and three others (No. 96,
 
No. 84 and No. 224;) all measuring 50 mm. They all prove to be
 
especially interesting in connection with the development of the
 
posterior lymph sac. In connection with the jugular sac the measurements are given in the table. These sacs show certain differences.
 
In No. 95 the transformation into lymph nodes is not extensive and is
 
chiefly at the upper end. No. 224.», on the other hand, shows a fine
 
bridging throughout the sac. The other two specimens show an
 
important stage in the evolution of lymph nodes. By referring back
 
to Fig. 14 it will be seen that when the nodes first begin in an embryo,
 
30 mm. long, they consist simply of a thickened connective tissue
 
between a plexus of ducts. But at this stage, 50 mm., there appear
 
round clumps of lymphocytes in the connective tissue bridges. These
 
clumps of lymphocytes are the primary lymph follicles and they
 
occur around the blood vessels of the connective tissue bridges.
 
These primary follicles are well illustrated in Fig. 17, in the femoral
 
lymph node, or in Fig." 18. The evolution of the lymph node depends
 
on the balance between the two elements; the lymph ducts which
 
multiply until they are sinuses and the vascular part with its attendant lymphocytes which make the follicles and cords. It will be
 
seen in the figures of these embryos, that in early stages the
 
lymphatic element by far predominates.
 
  
In embryo No. 84, the size of the lymph ducts coming from the
 
jugular sac is particularly striking. In one section, one of these
 
ducts measures 2.7 5 X .5 mm. VVhen it is considered that these
 
vessels are really capillaries, being lined by a single layer of endothelium, one sees that they are really enormous in size, almost as
 
 
  
FIG. 17. Sagittal section of a human embryo measuring 50 mm., Mall
+
FIG. 17. Sagittal section of a human embryo measuring 50 mm., Mall collection, No. 96, showing the posterior lymph sac within the pelvis and its extension along the femoral vein. )( about 8. F., femur; Lg., lymphoglandula (femoralis) ; O. s., os sacrum; S. 1. p., saccus lymphaticus posterior with lymph node in the border; V. s., vena sciatica; V. l. v., vertebra lumbalis v.
collection, No. 96, showing the posterior lymph sac within the pelvis and
 
its extension along the femoral vein. )( about 8. F., femur; Lg., lymphoglandula (femoralis) ; O. s., os sacrum; S. 1. p., saccus lymphaticus posterior
 
with lymph node in the border; V. s., vena sciatica; V. l. v., vertebra lumbalis v.
 
  
big as the inferior vena cava itself. In general, the lymphatic
+
big as the inferior vena cava itself. In general, the lymphatic vessels are considerably larger than the blood capillaries.
vessels are considerably larger than the blood capillaries.
 
  
The cisterna chyli could not be found in No. 95, but there is a
+
The cisterna chyli could not be found in No. 95, but there is a small lymph node near its usual location and there is a thoracic duct. The second embryo (No. 96) was damaged at the area; the other two show the cisterna chyli well with large connections with the mesenteric sac. This is especially true in No. 84, when the series is transverse, the sections looking like Fig. 9 of Mr. Baetjer’s series. Both the cisterna chyli and the retroperitoneal sac are easily located from Fig. 11. They are bridged from the very beginning.
small lymph node near its usual location and there is a thoracic
 
duct. The second embryo (No. 96) was damaged at the area; the other two show the cisterna chyli well with large connections with the
 
mesenteric sac. This is especially true in No. 84, when the series
 
is transverse, the sections looking like Fig. 9 of Mr. Baetjer’s series.
 
Both the cisterna chyli and the retroperitoneal sac are easily located
 
from Fig. 11. They are bridged from the very beginning.
 
  
These four series, however, are much more interesting in connection with the posterior lymph sacs. As we have seen, these sacs
+
These four series, however, are much more interesting in connection with the posterior lymph sacs. As we have seen, these sacs begin in an embryo about 24: mm. long as sacs along the primitive sciatic veins. In an embryo of 30 mm. they are long, narrow sacs. In Fig. 17 it will be seen that in an embryo 50 mm. long they have become large sacs lying in the side of the pelvis opposite the first three sacral vertebrae. The entire dorsal wall of the sac is occupied by a lymph node. In one of the other series it is plain that the sac is opposite the bifurcation of the vein into the sciatic and femoral veins, and that there is a large lymph node in the angle of these two veins. From the sacs extend vessels, both along the femoral vein, as shown in the figure and along the sciatic; both of these groups of vessels have developing lymph nodes. These are secondary nodes in contrast with the primary nodes which come from the sacs. The primary groups of nodes are the jugular, subclavian, retroperitoneal and posterior. The early secondary nodes are near the sacs, a point also in support of the outgrowth of lymphatics from centre to periphery.
begin in an embryo about 24: mm. long as sacs along the primitive
 
sciatic veins. In an embryo of 30 mm. they are long, narrow sacs.
 
In Fig. 17 it will be seen that in an embryo 50 mm. long they have
 
become large sacs lying in the side of the pelvis opposite the first
 
three sacral vertebrae. The entire dorsal wall of the sac is occupied
 
by a lymph node. In one of the other series it is plain that the sac
 
is opposite the bifurcation of the vein into the sciatic and femoral
 
veins, and that there is a large lymph node in the angle of these two
 
veins. From the sacs extend vessels, both along the femoral vein, as
 
shown in the figure and along the sciatic; both of these groups of
 
vessels have developing lymph nodes. These are secondary nodes
 
in contrast with the primary nodes which come from the sacs. The
 
primary groups of nodes are the jugular, subclavian, retroperitoneal
 
and posterior. The early secondary nodes are near the sacs, a point
 
also in support of the outgrowth of lymphatics from centre to
 
periphery.
 
  
The last embryo of the series (No. 172), measuring 80 mm., is
+
The last embryo of the series (No. 172), measuring 80 mm., is especially valuable in connection with the fate of the jugular lymph sacs, the development of lymph nodes and the spread of the peripheral lymphatics. The jugular sac is fast becoming transformed into a large group of lymph nodes. In a few sections there are remnants of the sac measuring 1.75 x .5 or even 1.75 x 1 mm., but most of the sac has disappeared. There are also secondary lymph nodes along the other veins of the neck, for example along the external jugular vein next the parotid gland, and along the facial vein ,at the angle of the aw.
especially valuable in connection with the fate of the jugular lymph
 
sacs, the development of lymph nodes and the spread of the peripheral
 
lymphatics. The jugular sac is fast becoming transformed into a
 
large group of lymph nodes. In a few sections there are remnants
 
of the sac measuring 1.75 x .5 or even 1.75 x 1 mm., but most of the
 
sac has disappeared. There are also secondary lymph nodes along
 
the other veins of the neck, for example along the external jugular
 
vein next the parotid gland, and along the facial vein ,at the angle
 
of the aw.
 
  
In connection with the arm there is an extensive group of nodes
+
In connection with the arm there is an extensive group of nodes over the shoulder.. In the axilla there are four groups—one posterior to the vessels and nerves, one along the subclavian vein, and two groups anterior to the pectoralis minor muscle.
over the shoulder.. In the axilla there are four groups—one posterior
 
to the vessels and nerves, one along the subclavian vein, and two
 
groups anterior to the pectoralis minor muscle.
 
  
Along the trachea is a group of nodes, of which the mass at the
+
Along the trachea is a group of nodes, of which the mass at the bifurcation is especially large. Nodes are also seen along the bronchi within the hilum of the lung, and large lymph vessels extend into the pleura while smaller ones are to be seen in the septa of the lung itself. No nodes are to be made out within the lung.
bifurcation is especially large. Nodes are also seen along the bronchi
 
within the hilum of the lung, and large lymph vessels extend into
 
the pleura while smaller ones are to be seen in the septa of the lung
 
itself. No nodes are to be made out within the lung.
 
  
The thoracic duct is easy to follow as a plexus of vessels along
+
The thoracic duct is easy to follow as a plexus of vessels along the aorta. Along the vertebral column there are three chains of lymph no-des—o«ne on either side of the bodies of the vertebra not far from the mid-line and closely associated with the thoracic duct. The other two sets are farther to the side, against the body of the vertebrae near the base of the transverseiprocesses. These drain the body walls. So abundant are these vertebral lymph nodes that scarcely a section lacks them, the sections being 100 microns thick.
the aorta. Along the vertebral column there are three chains of
 
lymph no-des—o«ne on either side of the bodies of the vertebra not
 
far from the mid-line and closely associated with the thoracic duct.
 
The other two sets are farther to the side, against the body of the
 
vertebrae near the base of the transverseiprocesses. These drain the
 
body walls. So abundant are these vertebral lymph nodes that
 
scarcely a section lacks them, the sections being 100 microns thick.
 
  
In passing into the abdominal cavity the cisterna chyli is readily
+
In passing into the abdominal cavity the cisterna chyli is readily located. Along its lateral borders is a complete chain of nodes, and at the lower end is a large clump of similar nodes.
located. Along its lateral borders is a complete chain of nodes,
 
and at the lower end is a large clump of similar nodes.
 
  
The retroperitoneal sac has been transformed into a group of
+
The retroperitoneal sac has been transformed into a group of nodes except at the upper end, just below the superior mesenteric artery where the sac still persists. Fig. 18 is taken just below the more open part of the sac and shows the bridging and some extension of the sac to the right. The retroperitoneal sac then becomes the group of nodes ventral to the aorta. It will be remembered that at the beginning, the sac extended along the veins of the adrenal bodies. At this stage there is an extensive mass of lymphatic tissue continuous with the mesenteric sac, extending along the hilum of the suprarenal bodies. The same mass of lymphatic tissue lies at the base of the mesentery at the portal of the liver. In no section, however, are there any nodes within the hilnm of the liver.
nodes except at the upper end, just below the superior mesenteric
 
artery where the sac still persists. Fig. 18 is taken just below the
 
more open part of the sac and shows the bridging and some extension
 
of the sac to the right. The retroperitoneal sac then becomes the
 
group of nodes ventral to the aorta. It will be remembered that at
 
the beginning, the sac extended along the veins of the adrenal bodies.
 
At this stage there is an extensive mass of lymphatic tissue continuous with the mesenteric sac, extending along the hilum of the
 
suprarenal bodies. The same mass of lymphatic tissue lies at the
 
base of the mesentery at the portal of the liver. In no section,
 
however, are there any nodes within the hilnm of the liver.
 
  
The most extraordinary development has taken place in the
+
The most extraordinary development has taken place in the mesentery. A group of nodes follows the pancreas and there is a small node at the hilum of the spleen. A similar node lies against the stomach. , In the center of the mesentery is an exceedingly large node, measuring 2 mm. on a side, see Fig. 18. This large central lymphatic mass in the mesentery is connected with the mesenteric sac by a chain of nodes running along the superior mesenteric artery. From this central mass vessels run out in the mesentery toward the intestine.
mesentery. A group of nodes follows the pancreas and there is a
 
small node at the hilum of the spleen. A similar node lies against
 
the stomach. , In the center of the mesentery is an exceedingly large
 
node, measuring 2 mm. on a side, see Fig. 18. This large central
 
lymphatic mass in the mesentery is connected with the mesenteric
 
sac by a chain of nodes running along the superior mesenteric
 
artery. From this central mass vessels run out in the mesentery
 
toward the intestine.
 
  
The only structures with which the developing lymph nodes
+
The only structures with which the developing lymph nodes could be confused are the sympathetic ganglia. On this account care must be exercised, especially around the retroperitoneal sac, where both structures are very abundant. The sections of these stages are thick (50 to 100 microns) and the low powers of the microscope are inadequate to distinguish them, especially when the connective tissue around the ganglia is broken. With cane and serial sections the lymph nodes can be absolutely determined.
could be confused are the sympathetic ganglia. On this account
 
care must be exercised, especially around the retroperitoneal sac,
 
where both structures are very abundant. The sections of these
 
stages are thick (50 to 100 microns) and the low powers of the microscope are inadequate to distinguish them, especially when the
 
connective tissue around the ganglia is broken. With cane and serial
 
sections the lymph nodes can be absolutely determined.
 
  
  
FIG. 18. Transverse section through the abdominal cavity of a human
+
FIG. 18. Transverse section through the abdominal cavity of a human embryo, 80 mm. long, Mall collection, No. 172. It shows the kidneys, a little of the liver, and many loops of the intestine. X about 8. A. in. s., arteria mesenterica superior; C. c., cisterna chyli at its lower border; Lg. m., lymphoglandulae mesentericae; S. l. m., saccus Iymphaticus mesenterica.
embryo, 80 mm. long, Mall collection, No. 172. It shows the kidneys, a
 
little of the liver, and many loops of the intestine. X about 8. A. in. s.,
 
arteria mesenterica superior; C. c., cisterna chyli at its lower border; Lg. m.,
 
lymphoglandulae mesentericae; S. l. m., saccus Iymphaticus mesenterica.
 
  
  
The significance of this retroperitoneal sac is brought out in the
+
The significance of this retroperitoneal sac is brought out in the injected specimens in Dr. Heuer’s paper. It will be noted that in the injected pig embryos the sac seems much larger than in the sections of human embryos. Its importance is that it is the anlage of the visceral lymphatics; it is transformed into the preaortic nodes of which the most anterior group is around the coeliao axis.
injected specimens in Dr. Heuer’s paper. It will be noted that in the injected pig embryos the sac seems much larger than in the
 
sections of human embryos. Its importance is that it is the anlage
 
of the visceral lymphatics; it is transformed into the preaortic
 
nodes of which the most anterior group is around the coeliao axis.
 
  
  
 +
FIG. 19. Transverse section through the pelvis of a human embryo, 80 mm. long. Mall collection, No. 172, to show the posterior lymph sacs. X about 9. B., bladder; Lg., 1ymph0g1andu1a;‘R., rectum; S. 1. post, saccus Iymphaticus posterior.
  
FIG. 19. Transverse section through the pelvis of a human embryo, 80
 
mm. long. Mall collection, No. 172, to show the posterior lymph sacs. X about 9. B., bladder; Lg., 1ymph0g1andu1a;‘R., rectum; S. 1. post, saccus
 
Iymphaticus posterior.
 
  
 +
In Fig. 18 is shown the lower part of the cisterna chyli; here the sac is being transformed into lymph nodes while farther anLymphatics in Small Intestine of the Pig. 91
  
In Fig. 18 is shown the lower part of the cisterna chyli; here
+
terior the sac itself persists. In tracing the series caudalward, the central mass of lymph nodes corresponding with the cisterna chyli, can be traced to the pelvis, where the mass turns a little to the side and joins the posterior lymph sacs. The posterior lymph sacs are really enormous in size, measuring 2.8 x 2 x 3.5 mm. (dorscrirentral). These measurements include the glandular masses in the edge of the sac. The sacs are Well shown in Fig. 19, which illustrates that the posterior sacs are being transformed into lymph nodes. In some sections of the pelvis these masses of lymphatic tissue seem to take up almost two thirds of the area of the cross section. From the posterior sac two sets of vessels extend, one along the sciatic vein and the other along the femoral. There is one lymph no-de along the sciatic vessels and a chain of nodes along the femoral. In Fig. 19 is a tiny lymph node, labeled Lg., which illustrates well the simplest form of a lymph node, a central mass of lymphocytes with a plexus of lymph ducts around. This plexus of ducts is so close that it may already be termed a sinus, so the node consists ‘ of a single follicle with its peripheral sinus. It is the structural unit of the lymph node. '
the sac is being transformed into lymph nodes while farther anLymphatics in Small Intestine of the Pig. 91
 
  
terior the sac itself persists. In tracing the series caudalward, the
+
From the description of this specimen it will be seen that. the foundations of the lymphatic system as it is found in the adult have been laid down in an embryo of 80 mm. ‘
central mass of lymph nodes corresponding with the cisterna chyli,
 
can be traced to the pelvis, where the mass turns a little to the side
 
and joins the posterior lymph sacs. The posterior lymph sacs are
 
really enormous in size, measuring 2.8 x 2 x 3.5 mm. (dorscrirentral).
 
These measurements include the glandular masses in the edge of the
 
sac.
 
The sacs are Well shown in Fig. 19, which illustrates that the
 
posterior sacs are being transformed into lymph nodes. In some
 
sections of the pelvis these masses of lymphatic tissue seem to
 
take up almost two thirds of the area of the cross section. From
 
the posterior sac two sets of vessels extend, one along the sciatic
 
vein and the other along the femoral. There is one lymph no-de along
 
the sciatic vessels and a chain of nodes along the femoral. In Fig.
 
19 is a tiny lymph node, labeled Lg., which illustrates well the
 
simplest form of a lymph node, a central mass of lymphocytes
 
with a plexus of lymph ducts around. This plexus of ducts is so
 
close that it may already be termed a sinus, so the node consists
 
of a single follicle with its peripheral sinus. It is the structural
 
unit of the lymph node. '
 
  
From the description of this specimen it will be seen that. the
+
The primitive system is complete, and the sacs are forming the primary nodes. The peripheral vessels have extended to the skin and to the viscera, and secondary nodes are forming along these vessels. I think that we have the key for working out the peripheral spread of the lymphatics and carrying them to their capillary bed. Injections of the retroperitoneal sac give us the material for tracing this development.
foundations of the lymphatic system as it is found in the adult have
 
been laid down in an embryo of 80 mm.
 
  
The primitive system is complete, and the sacs are forming the
 
primary nodes. The peripheral vessels have extended to the skin
 
and to the viscera, and secondary nodes are forming along these
 
vessels. I think that we have the key for working out the peripheral
 
spread of the lymphatics and carrying them to their capillary bed.
 
Injections of the retroperitoneal sac give us the material for tracing
 
this development.
 
  
 
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Sabin FR. The lymphatic system in human embryos, with a consideration of the morphology of the system as a whole. (1909) Amer. J Anat. 9(1): 43–91.

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This historic 1909 paper by Sabin described human lymphatic system development.


Sabin FR. Description of a model showing the tracts of fibres medullated in a new-born baby’s brain. (1911) Amer. J Anat. 11(2): 114- .

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The Lymphatid System in Human Embryos, with a Consideration of the Morphology of the System as a Whole

By

Florence R. Sabin.

From the Anatomical Laboratory of the Johns Hopkins University.

Introduction

When We consider the history of our knowledge of the lymphatic system, it is clear that there have been two Wholly different lines of thought with regards to our general conceptions. To establish its general morphology is the fundamental task for each of the systems of the body, and upon such a general conception is based all future elaboration of the system. I need only to refer to the neurone theory as establishing such a foundation for our knowledge of the nervous system. In connection with the lymphatic system, the idea that it arises from mesenchyme spaces dominates anatomical and zoological literature as is evidenced by examining most of the text books. This conception is based on the work of Budge, Sala, Gulland and many others. It allies the lymphatic system with tissue spaces and serous cavities. The other theory, which seems in a fair Way to displace the earlier conception, is that the lymphatics are derived from the veins, that they are vascular rather than mesenchymal in origin. This theory, only recently crystallized, has had an interesting evolution; beginning with Langer and Ranvier, it has been formulated and developed by a group of American anatomists. In this paper I hope to add evidence for this theory and give a general picture of the primitive lymphatic system as a whole. The great usefulness of this theory, aside from the fact that we believe it to be true, is that it gives a key by which to work out the entire developmefit of the lymphatic system down to its ultimate capillaries, and it will be readily conceded that the old theory of the relation of the lymphatics to the tissue spaces gave us no such point of attack.


The first theory, that the lymphatics arise from tissue spaces, received its strongest support from Budge.‘


In his first paper Budge described injections of Berlin blue into the false amnion of threeday chick embryos. He found that the injection mass ran out into the area vasculosa in a series of irregular canals forming an abundant network immediately under the epiblast and hence dorsal to the vascular layer. This network of canals extended out to a marginal canal around the area vasculosa similar to the marginal vein. Budge interpreted this system of canals as a primitive lymphatic system which in his injections arose in connection with the coelom and its extra embryonal expansion, the false amnion. This primative lymphatic system he said never had any connection with the veins, so that the interchange of fluid must have been through the walls. Dr. Mal12 has studied B'udge’s specimens and is convinced that they are injections showing simply the extent of the extra embryonal coelom.

I repeated Budge’s experiments, using India ink instead of Prussian blue, as it flows more readily, and found that I could duplicate Budge’s figures exactly?’ The fluid ran out in blunt processes simulating canals, but readily distinguished from the lymphatic injections. The fluid runs exactly as it would, if forced between two glass plates held closely together, that is, blunt processes push out which form an advancing network, but this network soon fills into a solid mass. lVith a careful injection of true lymphatics on the other hand the individual vessels often remain absolutely distinct from the very point of the needle as is shown in Fig. 4.-, of the article in Volume I, of the American Journal of Anatomy, where the needle was introduced into two places, one just over the shoulder and the other over the crest of the ilium. The injections in the area vasculosa of the chick are like the pictures obtained by injecting into a mass of embryonic connective tissue which has no lymphatics. The fluid runs out in the lines of least resistance, simulating performed canals but easily distinguished from true lymphatic capillaries, both in form and from the fact that as the injection proceeds the network fills into a solid mass. Serial sections of the area vasculosa showed no preformed channels, but rather that the space between the germ layers is bridged by delicate fibrils, the processes of mesenchyme cells. It seems certain then that Budge’s primitive lymphatic system is simply a study of the extent of the early coelom and morphologically has no relation to the lymphatic system.


‘Budge. Ueber ein Canalsystem im Mesoderm Von Hiihnerembryonen. Arch. f. Anat. u. Phys, Anat. Abth., 1880, S. 320.

Unterslfchungen iiber die Entwickelung des Lymphsystems beim H1'ihnerembryo. Arch. f. Anat. u. Phys, Anat. Abth., 1887, s. 59.

’Buek’s Handbook of Medical Sciences. The Coelom.


In the understanding of the lymphatic system this point is of great importance, as will be shown later. None of the serous cavities, hollowed out of the mesenchyme, that is, the pleural and peritoneal cavities, the joints, the various bursae, and the chambers for the vitreous and aqueous ihumors in the eyes, though they contain serous fluid ever form a part of the true lymphatic system. In Budge’s second paper, which is unfortunately just a fragment of his work published from the notes after his death, are pictured beautiful figures of true lymphatic injections made at a much‘ later stage, namely in embryo chicks, 18 days old. These, the true lymphatics, Budge thought belonged to a second, the permanent system, distinguished from the first by the presence of the thoracic duct which emptied into the veins. Budge thought that the thoracic duct arose from spaces derived from the coelom. He also discovered the posterior lymph hearts in chick embryos between 10 and 20 days old.

The theory of the origin of the lymphatic system from tissue spaces was further illustrated by Grullandf‘

He found spaces hollowed out in the mesenchyme along the course of the blood vessels of the limbs and thought that these flowed together to form ducts.

The next exponent of the theory that the lymphatics arise from the tissue spaces in Salas‘

Sala has studied the origin and the development of the lymphatic

‘Gulland. Journal of Pathology and Bacteriology, Vol. II, 1894, p. 466. ‘Sam. Ricerche Lab. di Anat. Norm. d. r. Univ. di Roma, Vol. VII, 1899-1900. 46 Florence R. Sabin. ( ,

system in chick embryos. Basing his work on Budge’ s, he worked out with care the origin of the posterior lymph hearts which Budge had discovered. He found that the posterior lymph hearts begin at the middle of the seventh day in connection with the lateral branches of the first five coccygeal veins. He says that corresponding to these veins there are excavations in the mesenchyme which soon enter into communication with the lateral branches, and in fact one would say that these fissures are simply dilatations of the veins themselves.

These two statements of course exclude one another, for the spaces can not be both fissures in the mesenchyme and dilatations of the veins. (“Esaminando in serie le sezioni caudali di un emb. di g. 6 ~|— ore 18, si scorge che nel mesenchima che sta lateralmente ai miotomi ed in corrispondenza dei rami laterali delle prime cinque vene coccygei, si vanno scavando dei piccoli spazi o fessure che ben p-resto entrano in comunicazione cogli stessi rami laterali venosi: si direbbe anzi che esse non sono che semplici dilatazioni, ramificazioni delle stesse vene.”)

Then he describes these fissures as becoming more abundant and confluent. By opening up communications with each other they form a sac or lymph heart in the mesenchmye. This sac he says is lined with flattened mesenchyme cells, which, if it were so, would, according to our standpoint, exclude it from being a vein. He found muscle in the wall of the hearts on the ninth day and was able to inject the heart directly by the second half of the tenth day. Sala’ s description of the origin of the posterior lymph hearts in the chick is so clear and graphic that it is perfectly evident to those who are familiar with the method of origin of the lymph sacs in mammals, that the two processes are the same, that the sacs arise from the veins in both cases. The fact that Sala had the old conception of the lymphatic system as coming from the tissue spaces too firmly fixed in mind to really accept the evidence of his own material does not need to confuse the picture. .

The lymphatic ducts he thought began as fissures in the mesenchyme along the hypogastric veins on the ninth day. By the eleventh day these spaces communicated and formed a plexus of lymphatic ducts which connected with the lymph hearts and the thoracic duct. The Lymphatic System in Human Embryos. 47

The thoracic duct, which he found extended only from the beginning of the coeliac artery to the outlet of the superior vena cava, began on the eighth day in the following manner. First a series of mesenchyme spaces around which occur clumps of mesenchyme cells which develop into a solid cord. These solid cords become excavated and form the thoracic duct. There is nothing to correspond with this in connection with the lymphatic system in mammals.

To trace the development of the idea that the lymphatic system is derived from the venous system it is necessary to begin with the work of Langerf published in 1868.

In this important paper, Langer makes clear a number of fundamental points. He distinguished the lymphatics in the tadpole’s tail from the arteries and the veins by injecting them. He found the two longitudinal lymphatic vessels of the tail, and the branches forming a plexus leading from them. He distinguished the lymphatic vessels clearly from the surrounding connective tissue, and determined that the lymphatics were closed tubes. He was studying a border zone of developing lymphatics and saw that the lymphatics here were really terminal blind ends. He noted the endothelial sprouts from the sides and ends of the vessels and interpreted these sprouts to mean that the lymphatic vessels grow by the same method as do blood capillaries.

Thus he says: “Ich zweifle nicht, dass Lymph und Blutcapillaren nach dem einen und demselben Bildungsmodus sich vermehren, die Elemente sind dieselben.” This in reality is his great contribution and upon this idea as a foundation rests the new conception of the lymphatic system as derived from the veins. Another of his observations must not be omitted, namely that in the course of a lymphatic capillary, a portion of the vessel may be greatly narrowed, that is to say, even completely collapsed. “Ich traf aber auch Rohrchen, welche sich ziemlich rash verengten und in der Mitte ihres Verlaufes einen diinnen, anseheinend ganz soliden Faden darstellten.” The meaning of this phenomenon and its relation to the general theory will be made clear later.

°Langer. Ueber das Lymphgefiisssystem des Frosches. Sitzb. d. k. Akad. d. Wissenseh., LVIII Bd., I Abth., 1868.

Between the years 1895 and 1897, Ranvier published a series of articles on the development of the lymphatic system.7 He also studied the development of the lymphatic system in the frog and added an extensive study of the growth of the lymphatics in pig embryos from 9 to 18 cm. long. He observed endothelial sprouts in growing lymphatics and interpreted them as Langer had done 27 years before to mean that the growth of the lymphatic capillaries is by the process of sprouting. Some of the very large lymphatic vessels which he found in the mesentery he interpreted to mean degeneration or retrogression of the system. Ranvier suggested the theory that the lymphatic system comes from the veins, on the basis that the growth is from centre to periphery rather than from the connective tissue spaces to the veins——but he did not prove his theory, for he did not find lymphatics in embryos below 9 cm. in length, at which time the lymphatic capillaries have already covered the surface of the body.

‘V. J. MacCallum was the next one to call attention to this method of growth by sprouting and he has given graphic descriptions of the process. _He studied developing lymphatics in the skin of embryo pigs, 5 to 15 cm. long, watching the injection under the microscope in order to determine the relation of the lymphatic capillaries to the connective tissue cells and spaces? .

In studying the growth of the lymphatic capillaries in the skin of the embryo pig, I found that the early lymphatics started from certain centres and gradually spread over the surface of the body.9 The first of these areas is in the neck, from which vessels grow over the head, shoulder and back. The second is over the crest of the ilium for the vessels over the back and hip, while subsequent centres form the axilla and inguinal region for vessels to the ventral aspects of the body wall and limbs. By studying the figures in Volume III,

7Ranvier. Cvomptes Rendus de 1’Acad. d. Sciences, 189% to 1896, and Archives d’Anatomie microscopique. Paris, 1897.

8MacCa11un1. Die Beziehung der Lymphgefttsse zum Bindegewebe. Arch. f. Anat. u. Phys., Anat. A1)th., 1902.

"Sabin American Journal of Anatomy, Vol. I, 1901-1902, Vol. III, 1904, and Vol. IV, 1905.

of the American Journal of Anatomy, which show complete injections of the skin for each stage, it will be seen that the lymphatics invade non—lymphatic areas, even in the last figure of the series where all of the systems have anastomosed over the body there is a marked non-lymphatic area over the top of the head as well as over the feet. In pigs longer than 5.5 cm., it is diflicult to obtain such extensive injections because valves begin to develop and tend to make the lymph flow from periphery to centre. During this early period of the spread of the lymphatics‘ over the body there are no valves whatever, which accounts for the wide extent of the injection shown for a pig 5.5 cm. long.

To trace these vessels back to their source was fundamental to an understanding of the lymphatic system, and I began with the group in the neck as it was the primary group. The vessels in the neck converge to a sac which is readily demonstrated by injection as is shown in Fig. 1, Vol. IV, American Journal of Anatomy. This sac, which lies against the internal jugular vein, is the beginning or anlage of the lymphatic system. In embryo pigs from 14.5 to 16 cm. long there are symmetrical jugular sacs opening into the vein. Saxer made mention of these sacs as a part of the lymphatic system, but did not realize their fundamental significance.” These sacs are either empty or contain a few blood corpuscles. F. T. Lewis worked on the stages before this lymphatic sac is formed and carried our knowledge a step farther by showing that they are preceded by a plexus of veins opening into the jugular vein.“ This plexus of veins gradually becomes cut, off from the main vein and by the coalescence of the small veins a sac is formed which is entirely free fromthe jugular vein for a time. Subsequently the symmetrical sacs rejoin the veins. The endothelial lining of these sacs is thus derived from the endothelium of the veins. In studying the lymphatics Dr. Lewis used the method of graphic reconstruction. The fact that the jugular sacs are transformed venous capillaries, I was able to entirely confirm by the method of injectio-n in pig embryos.” In pig embryos

“Anat. I-Iefte, Vol. VI, 1896. _ “Lewis. The Development of the Lymphatic System in Rabbits. Amer. Jour. Anat, Vol. V, 1906. "Sabin. Anat. Record, Vol. II, 1908. .

13 and 14 mm. long there is an abundant plexus of capillaries anterior to the junction of the primitive ulnar vein with the internal jugular vein, readily injected from the veins. In embryos slightly older this plexus of capillaries is being transformed into a sac, and these sacs are less readily injected from the veins. For example in an embryo 15 mm. long, the sac was injected on the side from the vein and not in the other. About this time then the primary connections with the vein become severed. In my specimens the sacs are filled with blood. When the secondary opening into the veins is formed the sacs become empty and this is true in pig embryos 16 mm. long. In connection with human embryos I shall show how to determine the presence of these secondary openings or valves.

This method of formation of the jugular sacs was also confirmed by Huntington and McClure in studying cat embryos.” They have followed all the details of the transformation of the simple veins to the abundant venous plexus and the sac formation by Born’s method of reconstruction. Thus the origin of the jugular sac has been Worked out in the pig, the rabbit and the cat by the methods of injection and of reconstruction both in two and in three dimensions. The formation of this ugular sac- will also be illustrated in the human embryos in this paper.

Besides the jugular sacs two other paired sacs and two unpaired have been described. Lewis described symmetrical subclavian sacs in the rabbit, which in human embryos are, however, an extension of the jugular sacs; the other paired sac is the posterior or sciatic one, noted in the pig and more fully marked out in this paper for human embryos. The unpaired sacs are the cisterna chyli and the mesenteric or better retroperitoneal sac.

This sac was discovered by Lewis its origin and development have been worked out by Baetjer; its significance is brought out in Heuer’s work in connection with the lymphatics of the intestine. Mr. Baetjer” has shown conclusively that the retroperitoneal sac begins as a series of small veins which bud off from the renal veins.

13I-Iuntington and McClure. The Anatomical Record, Vol. II, 1908. “Baetjer. Amer. Jour. Anat., Vol. VIII.

In his figures are shown the small veins in the root of the mesentery of a pig embryo 17 to 19 mm. long. It is readily noted that these small veins are injected fro-m_the main veins as the drawings show the injected ink of the specimens. As the embryo develops, these small veins enlarge and coalesce to form a sac, which shows a few connections with the Veins, as proved by injection until the embryos are 23 mm. long. The sac is completely formed at 30 mm., when it is cut off from the Veins entirely and clearly connected with the cisterna chyli. Baetjer’s series of nine drawings show every stage in process of the transformation of the veins into the sac and its subsequent connection with the lymphatic system.

Thus to sum up, it will be seen that the lymphatic system begins as a series of sacs of which eight have been described; three paired, the jugular sacs, the subclavian and the posterior lymph sacs; and two unpaired, the retroperitoneal and the cisterna chyli. In the human embryo there are only six, for the subclavian sacs are extensions of the jugular sacs. All of the sacs are shown in Fig. 12, in a human embryo 30 mm. long. The method of origin of two of them, namely the jugular sacs and the retroperitoneal sacs, has been worked out with care showing that they are clearly derived from the Veins. The jugular sacs form a secondary connection with the jugular veins, the other sacs forming in regions where there is great shifting of veins do not form secondary communications with their own veins but join the other lymph sacs to make a primitive system.

The question now arises whether these sacs can be considered as analogous with the amphibian lymph hearts. None of the mamma~ lian sacs studied develop any muscle in their walls; throughout their history they have a lining simply of endothelium, but they all are in regions from which ducts radiate out to drain wide areas, so that as the system begins to function the lymphatic stream converges to these sacs and in this sense they represent the lymph hearts. In the chick the posterior lymph sacs are true lymph hearts, for they develop a muscular wall, and from Sala’s description it is easy to see that these hearts really arise by exactly the same process as the mammalian sacs. The fate of the lymph sacs has some bearing on the subject.“ This has been followed for the jugular sac in the pig and

“Sabin. Amer. Jour. Anat., Vol. IV, 1905.

for all the sacs in the human. They all become completely transformed into a group of lymph nodes except the cisterna chyli, which is partially though to a varying degree transformed. The lymph sacs make the great primary gr.oups of nodes for each region through which lymph must pass before entering the veins. Thus for example in the intestines the preaortic nodes are the primary group and they come from the retroperitoneal sac, While the nodes of the mesentery are secondary, tertiary, etc. Thus we may define primary lymph nodes as those that are derived from the lymph sacs, and they are also primary in the sense of being the first to develop for a given region. It therefore seems to me that it is fair to conclude that the lymph sacs of the mammals, which represent the lymph nodes, take the place of the lymph hearts of the amphibia. They do not of course represent the same function, for they never have any muscle, so they never pulsate, and from the beginning they must cause a slowing of the lymph flow rather than a hastening of it and this slowing must become much more marked as they are transformed into lymph nodes. Thus they seem to me analogous to amphibian lymph hearts.

From the preceding analysis of the literature, it is clear that there is a general agreement among recent Workers that the mammalian lymph sacs precede the lymph vessels, and hence form a primary lymphatic system and that these sacs are derived from the veins. This position has been very greatly strengthened by the work of Favarom and Allen,” on the lymphatic system in fishes, and by Knowerls and Hoyer,” in the amphibia.

Favaro discovered that in fishes the lymphatics come from the veins, and that here the relation of the lymphatics to the veins is much more primitive than in mammals. Lymph hearts and vein hearts may be present, moreover one and the same vessel may carry either blood or lymph either at the same time or at different times. Thus he speaks of venae lymphaticze and vasa lymphaticw. The system varies much in the different forms; in Urodeles he finds that the lymph hearts begin as a swelling of one of the primitive lateral longitudinal veins. This abstract is taken from Schwalbe’s Jahres— berichte.

1°FaVaro. Atti R. 1st Veneto di sc. lett. ed arti, 1905-06, T, 65, Parte seconda. Appendice alla Dispensa 10. Octobre 1906. S. 279. Venezia 1906. "Allen. Proceedings of the Washington Academy of Sciences, Vol. IX, 1907. "“Knower. Anat. Record, Vol. II, 1908. ‘-“Hoyer. Bulletin de 1’Acad. d. Sciences d. Cracovie, 1908.


Knower and Hoyer have shown independently that the fundamental points maintained for mammals are true also for the amphibia. They have found that the anterior lymph hearts arethe first structures of the lymphatic system to appear in the embryo and have described their origin from the veins. They have found that the first lymph vessels are derived from the lymph hearts, this being stated by Hoyer on page 463 of his article as follows:

“Beriicksichtigen wir weiterhin die Art und Weise, in weleher sich die Lymphgefasse entwickeln, namentlich das Auftreten der vorderen Lymphherzen an der vorderen Vertebralvene sowie der Lymphgefasse, welche aus dem Lymphherzen hervorgehen, so kann mansich clem Gredanken nicht verschlieszen, class das Lymphgefasssystem eben an diesen Stellen symmetrisch auf beiden Korperseiten seinen Anfang nimmt und sich Von dort aus iiber den ganzen Ktirper verbreitet. Als wichtige, diese Ansicht stiitzende Tatsachen hebe ich aus der vor liegenden Arbeit hervor: Die weite Kommunikation des sich entwichelnden Lymphherzens mit der Vene, die anfanglicli mit einer l{egelformigen Zelle endigende freie Spitze des spindelformigen Lymphherzens, welche sich spater zu einem Zellstrange verlangert und sich schlieszlich zu einem Lymphgefasse umbildet, ferner die rege Zell— vermehrung im Grebiete des sich cntwickclndcn Lymphherzens uncl schlieszlich die Entwieklung der zwei auf den Kanten der Myomeren einander parallel verlaufenden Lymphgefasse.” Both of them state that they will give further evidence of the central origin of the lymph vessels and their growth toward the periphery in their final papers.

We come now to the relation of the peripheral lymphat.ics to the sacs and to the origin of the thoracic duct. Here we have a diversity of opinion and certain unsettled points which for the sake of the development of the subject it is fundamental to have perfectly clear. In the first place, Sala, who, in connection with the origin of the posterior lymph hearts, really describes them as coming from the veins, though he confuses the picture by considering them as coming from tissue spaces at the same time, describes the thoracic duct as coming from solid cords of mesenchyme, and the peripheral vessels as derived from spaces in the mesenchyme. VVe find nothing to correspond to the solid cords of niesenchyme as an anlage of the thoracic duct in mammals, and believe that the lymph vessels grow out from the primitive sacs. That is, we believe that the conditions found by H. Hoyer for amphibia, that the vessels come from the hearts, is true also in mammals. This being the disputed point however, it will be necessary to review the literature in this connection with care.

In 1901 I showed that the jugular lymph sacs are the primary lymphatics in mammals, that they are derived from the veins, that from these sacs, and others, vessels grow out to invade the body and that therefore there are non-lymphatic areas and one can study the invasion of these areas by lymphatic vessels. In the study of the skin this general law was found to hold, that there are areas which at first cannot be injected either directly or through the sacs. This I believe to be because there are no lymphatics to inject. That gradually lymphatics invade these areas and at first a primary subcutaneous plexus can be injected, later a secondary more superficial plexus, and finally terminal capillaries in the papillae. The same law holds for the lymphatics 0-f the intestine as shown by Dr. G. Heuer in the same number of this journal. In the intestine the lymphatics first form a plexus in the submucosa; secondarily a mucosal capillary plexus forms and from this mucosal plexus the lacteals grow out. In connection with the intestine the fundamental point that the lymphatics grow out from the sacs is also shown. In all the early work the injections of the intestine were made through the thoracic duct, but later it proved that by far the best place to inject is the retroperitoneal sac. This sac gives the key for working out the development of the lymphatics of the viscera. For years I have been trying to get injections of the lymphatics of the lungs and diaphragm and have never succeeded until I introduced the needle directly into the retroperitoneal sac. In connection with the intestine, injections into the retro-peritoneal sac at first show no vessels in the mesentery, next vessels inject from the sac into the mesentery and these vessels gradually extend to the bowel wall which they reach in embryos between 4 and 4.5 cm. long. Thus injections of the retroperitoneal sac make it possible to trace the development of the lymphatics to the viscera, and this is an important point in the proof of the general theory.

In 1904 F. T. Lewis published an important contribution to our knowledge of the lymphatic system. He studied perfect serial sections of rabbit embryos, worked out the early history of the jugular sacs, and discovered the retroperitoneal sac as has been mentioned. In studying the peripheral lymphatics, Lewis pictured a series of small isolated vessels extending along the external mammary and umbilical veins. These isolated vessels are distinguished in sections by being slightly larger in caliber than the neighboring vein. In sections they are clearly isolated. I have had the privilege of examining Dr. Lewis’ specimens and can confirm his observations entirely. In one or two places there was evidently great difiiculty in, determining whether some of these vessels were isolated or were connected with the vein. Moreover, I can find some of these isolated vessels in pig and human embryos. These numerous lymphatic anlagen of Lewis are now the crucial point in connection with the lymphatic system. They exist undoubtedly in perfect sections, they are always lined by a perfectly formed endothelium and never ‘show any transitions toward tissue spaces. The question is simply, Are they lymphatic vessels which have grown from the sacs and are only apparently isolated or do they arise in situ? I believe them to be true lymphatics derived from the sacs and will give my reasons shortly.

In connection with Lewis’ observations it is important to make clear the work of Huntington and McClure.2° They have strengthened the theory that the lymphatics come from the veins the more because they began with a vigorous attack upon the theory.

In 1906 they described elaborate models of the developing lymphatics in cat embryos which showed lymphatic vessels along the veins previous to the formation of the lymph sacs. These early lymphatics which they termed subintimal, proved to be only tissue spaces and they withdrew this work in 1907.

“Huntington and ;\IcCIure. Anat. Record, "01. 1, 1906-07, and Vol. II, 1908.


At this time they presented the development of the jugular lymph sacs in the cat, agreeing entirely with the work of Lewis and myself; but in connection with the rest of the system they at that time agreed entirely with Sala, believing that the peripheral vessels were dilated tissue spaces. In the Anatomischer Anzeiger of 1908, McClure gives up entirely the theory of the origin of the lymphatics from tissue spaces and comes to agree with Lewis that sections show multiple anlagen. As I have already said, the multiple anlagen of Lewis are undoubtedly in sections and to interpret them is the crucial point. They cannot be interpreted through sections alone; «and merely repeating the observation of them in sections does not add to our knowledge of their interpretation. They must be subjected to some kind of an experiment. The inadequacy of simple observation to interpret them was clear to Lewis for he refrained from mak ing an interpretation. The experience of Huntington and HcClure serves to emphasize strongly" the inadequacy of sections alone, and the large part of that personal equation plays in interpretation, for from practically the same type of material they have taken successively three difierent standpoints.

In this laboratory under the direction of Professor Mall a group of people have ‘been subjecting these numerous anlagen of Lewis to some sort of experiment. Dr. Eliot K. Clark“ has been studying the blood vessels and lymphatics in the living tadpole’s tail. His specimens prove Langer’s suggestion that lymphatics grow by the sprouting of their endothelial lining cells by making it possible to watch them grow. His observations and descriptions of these lymphatic capillaries, sending out long sprouts that now move forward, now bend out of their course to pick up some stray blood corpuscle and now retreat, make one realize how little sections show us. Certain of his observations are exceedingly fundamental, first in the non—lymphatic zone in the living specimen there are no isolated anlagen. This you can never say with certainty in sections because as will be shortly proven lymphatics can be demonstrated by injection where they cannot be seen in sections. But in these specimens of the entire living tail, endothelium can be distinguished from mesenchyme, and the lymphatics grow out from their own endothelium and do not add any peripheral anlagen.

"Clark, Anat. Record, Vol. III, 1909.


A second point which Dr. Clark observed, but did not publish, is the sudden collapsing of a part of a lymphatic vessel. Once or twice while a red blood cell was pushing its way into the vessel, its central end collapsed suddenly to an endothelial thread, while the peripheral end remained dilated. These collapsed lymphatics right in the middle of a vessel were noted and figured by Langer; they have been noted many times in blood capillaries, for example, see Fig. 49 of Stricker’s Handbuch der Histologie, but they have been interpreted as evidences of growth simply, while it may be that these collapsed vessels are a part of the functional activity of the lymphatic capillaries. The reverse of this process of collapsing of the vessels, namely the sudden opening up of tiny vessels during an injection, I have often observed and used as an argument in favor of continuous lymphatics rather than ‘isolated anlagen. (See Symposium on the Lymphatic System. Anat. Record, Vol. II, 1908.) It can be readily seen that in cross section these entirely collapsed vessels might be wholly lost and only the dilated portions shown, and thus the suggestion is that Lewis’ anlagen represent a transitory phase of the functional activity of the lymphatic capillaries.

The question of the multiple anlagen has resolved itself wholly into a question of method, with the study of the living lymphatics and injected lymphatics on the one hand and the method of serial sections on the other. Ludwig’ s famous phrase, “die Methode ist alles,” was never more apt than in this connection, for it sums up the whole situation. Having long worked with injections we are convinced that uninjected serial sections are wholly inadequate to show all the blood capillaries or lymph capillaries, moreover, we are convinced that Dr. Lewis has carried the observations as far as they can be carried with sections and that sections will always show these apparently isolated anlagen. To put the contention that serial sections are inadequate to the test, Dr. Clark has made the following experiment. He made a careful camera lucida drawing of the lymphatics in the living tadpole’ s tail, then killed the tadpole and cut it in serial sections and tried to reconstruct the lymphatics. The failure in reconstructing these amphibian lymphatics confirms similar attempts of my own on mammalian lymphatics and makes me feel sure that uninjected capillaries cannot be completely reconstructed.

The same point in connection with the blood vascular system, namely that the blood capillaries cannot be reconstructed from uninjected specimens no matter how perfect, will be conceded, but has been brought out much more strikingly by the work of Dr. Evans, soon to be published from this laboratory, for he has shown that a blood capillary plexus can be demonstrated by injection where it was not known to exist before.

Thus the question of the relation of ‘the peripheral vessels to the sacs is becoming more and more clear. There is a primary lymphatic system which consists of sacs that are formed directly from the veins. These primary lymphatic sacs are transformed from a series of isolated sacs into a system by means of the thoracic duct and the right lymphatic duct. These two structures form a part of the primary system. The secondary system consists of the peripheral vessels which, it is becoming more and more sure, are an outgrowth from the sacs. Thus we can say that the primary system, as far as it is made up of sacs, comes from transformed veins, and that the secondary system, characterized by being formed of lymphatic ducts and capillaries, develops by endothelial sprouting from the sacs. It remains now to be determined whether the thoracic duct develops after the manner of the primary sacs as transformed branches of the azygos veins or whether it develops as the other lymphatic ducts of the body do, from endothelial sprouts from the sacs. No theorizing can decide between these two ideas. We must wait some decisive method of getting at the facts. The presumption seems to us to lie on the side that the thoracic duct develops in the same manner as all the other ducts, since wherever the isolated anlages of ducts can be tested, as, for example, in the living tadpole’s tail, they prove not to exist. Moreover, Dr. McClure, who is at present the advocate of the idea that the thoracic duct arises as a series of The Lymphatic System in Human Embryos. 59

independent spindle spaces along the aygos vein, shows himself the’ Weakness of his own position. He says, referring to serial sections,” “These outgrowths, in the writer’s estimation, constitute the venolymphatic anlages of the thoracic and right lymphatic ducts.” That is to say, the entire argument rests on the interpretation of appearances in sections, and it is becoming more clear each year that interpretation of sections is not proof.


Based upon these studies of the lymphatic system in the pig, rabbit and cat embryos, I have studied through the Mall collection of human embryos. - I do not believe that the subject could have been worked out with human embryos alone, for the real advances in the study of vascular problems have always come from the method of injection. The method cannot be well applied to human material on account of its scarcity, but the points determined in other mammalian embryos can be verified in serial sections of human embryos. Moreover, the Mall collection is sufficiently ample to illustrate all the essential points of the origin of the lymphatic system. In several points I think it adds new evidence to that already gained from other mammals; for example, in connection with the history of the thoracic duct, in gaining a conception of all of the primitive sacs as forming a primitive system, in tracing the posterior s.acs which had thus far been seen only in pig embryos among mammals, and in following the transformation of all the sacs into lymph nodes. It is a very great pleasure to thank Professor Mall for the privilege of studying his valuable collection and for many helpful suggestions during the progress of the work. V

In the Mall collection no trace of a lymphatic system can be made out in embryos of the first four weeks, from 2 to 8 mm. long. In these there are certain spaces which might be confused with a lymphatic system, first certain areas where the meshes of the connective tissue are especially large, as, for example, around the developing coelom, and secondly spaces which follow the course of the nerves.

”i\IcC1ure. Anat. Anz., XXXII Bd., 1908, p. 536. (30 I Florence R. Sabin.

These spaces along the nerves, which may be termed perineural spaces, are especially important to note both on account of their physiological significance and because they have been confused with lymphatics. They may be injected from the space around the spinal cord and they are especially large around the growing tips of the nerves. Their constancy, their presence in perfectly prepared specimens, and especially their size at the growing tips of the nerves, leads one to think that they are physiologically of great importance to the nerves, but they never form a part of the lymphatic system. No injections of these spaces ever run over into the lymphatic system. An injection into the developing arachnoid spaces around the spinal cord will often pass into the veins, entering them around the fourth ventricle, but I have never succeeded in injecting any lymphatic vessels from the arachnoid nor in tracing any lymphatic vessels to the arachnoid, so that I believe the older anatomist-s, for example Breschet, were right in believing that the lymphatic system does not drain the great arachnoid lymph space which rather retains its primitive relation to the veins while other parts of the body become drained by a new system of capillaries, namely the lymphatics, derived from the veins.

In studying Professor Mall’s collection it seems that there are two stages to be made out in the development of the system as a whole. This has been illustrated in the table 011 the next page. The first includes a study of the origin of all of the primitive sacs and their fusion into a primitive lymphatic system through two factors, namely the formation of the valves of the jugular sacs which make the per— manent openings into the veins, and secondly the connection of the various sacs by means of the cisterna chyli and thoracic duct. This period includes embryos up to 80 mm. in length, of which there are seventeen in the series. This first stage may be divided into two periods, one of which there are fourteen specimens, measuring up to 20 mm., which have the jugular sacs alone; the other shown in three specimens, which mark the time of origin of the other sacs and of the thoracic duct.

The second stage involves the transformation of the sacs into the primary lymph nodes and the spread of the peripheral lymphatics.


The first point is well illustrated in the Mall collection; the second, namely the spread of the peripheral lymphatics, needs ample material foriinjection. It has been worked out only for the lymphatics of the intestine and skin in the pig. T

To return to the first stage, namely that of the origin of the sacs, one can outline the course of development as follows. The jugular lymph sacs begin in an embryo 8 mm. long, the valves are first seen at 10.5 mm. The sac reaches its maximum development at 30 mm. when it attains a size of 5 X 3.6 mm. The beginning of the process of the bridging of the sac, which is the process by which the sac is ultimately turned into a chain of lymph nodes comes early, namely in an embryo 14 mm. long. The process of the transformation of the jugular. sac into nodes is about complete in an embryo of 80 mm. At 20 mm. there begin to be signs of the formation of the other sacs in the presence of a plexus of veins in the region of the mesenteric sac and the posterior lymph sacs, and at 23 mm. there is a definite retroperitoneal sac and a cisterna chyli. By 24 mm. all three of the sacs are well formed, namely the mesenteric, the cisterna chyli and the posterior lymph sacs. All the sacs together with the thoracic duct are illustrated in Fig. 12, for an embryo of 30 mm., which marks the stageof the completion of the primitive system. The posterior lymph sac which is second in size to t-he jugular apparently reaches its maximum in an embryo 80 mm. where it measures 2.8 x 2 x 3.5 mm. I have no higher stages but judge from its appearance that it will soon be entirely cut into lymph nodes. The retroperitoneal sac, so large in the pig embryos, is always small in the human, and the cisterna chyli is the smallest of all. The thoracic duct is complete in an embryo 30 mm. long. These facts are summed up in the accompanying table. In the table, where one measurement is given, it represents the length o-f the sac or its ante.ro—posterior diameter; where two measurements are given the first is the length, the second the width or lateral diameter.

I shall now describe in detail the lymphatics in each of the 22 embryos listed in the table. The earliest specimen in the Mall collection to show any traces of the beginning lymphatic system is an embryo (No. 397) 8 mm. long. In this embryo, as shown in Cb L0

x x r

l l I

Florence R. Sabin.


l.

6 .2 ,; 1 in 1 “6 E 3% '5 .. l '1 5.1:.‘ ‘E; Direcftion § 5 J I L h S l we , o o_- ‘-' s ugu at mp ac. ; E; 5153 Section. 1 y 3

E -3 E-4 ‘ "4 £2 v. I I ‘ Size in mm. 8 397 Trans- 10 ‘I .3 X .19 Prelymphatic . verse ‘ plexus of veins. 9 , 163 Trans- i 20 .36 X .14 Same. 1 verse ' . 10.5 109 Trans- 20 .7 X .28 Symmetri call E verse sacs,empty,§ l . | 5 with valves. 5 11 :1 353 Coronal 1 10 1.2 Sac full of blood.‘ ‘ '(Ant.post.) Extensive plex—§

3 us of veins along? { jugular vein. ’ 3 . Valve formed-1 I 2 but apparently'

not open. Ex1 tension of jug—§ 3 ular sac along} . primitive ulnar;

; vein.

12.5 ‘ 317 Coronal 20 1.5 Definite longsac 1 out of preceding

z plexus of veins»

Valve.

14 1 144 Sagittall 40 1.5 Sac empty, be: ‘ ginning of bridg' _ ing. ' 15 350 Coronal '. 10 Very abortive = ‘ sac. 15 423 Trans- 50 .9 Very small sac. I 1 verse i 17 106 Trans- 50 Very abortive 5 verse ‘ sac. . 17 ; 424 ‘ Region damag’d. 17 296 Coronal 20 1 .5 Sacs large,valve

u ndc/‘u b t ed ly g open. Small ex‘ ‘ tension along E primitive ulnar vein. I

Other Lymph Sacs. The Lymphatic System in Human Embryos.

Length of l Embryo in mm. I

I»-4 O2

20

20

23 24

30

46 50 50 50

80

E No. of Emb I

O . 3 Mall colleéionln

22

128

382

86

95

96

84

224

172

Jugular Lymph Sac.

E . Diregftion § 5 Section. 5 -= 1 E: u lSize in mm. Trans- 50 g 1.8 verse ‘ 3 1 Trans- 50 1 1.6 verse l l 1 V Coronal‘ 50 .75 i Sagittal - 50 2 x 1 Trans- 20 verse Coronal 50 5 x 3. 6 I Sagittali 1o ‘ 3.75 x 1.5 Sagittal l 100 4 x 1.5 l Trans-l 50 _ 3x1:5 verse [ Sagittal :50 and.’ 4 x 1.75

100 !Trans~.l 100 1.75x1 ! verse ? 1 I , . I

S'y mm at rical

‘jugular sacs. No

extension along primitive ulnar vein.

Sacs wider, cut by developing nerve. F i r s t vessels from the sac to the skin. Abortive.

Sacs and valves ‘Large.

Maximum size, ‘begin’g lymphn o d e s a l on g jugular sac and subclavian vein. Sac with few lymph nodes. Sac turning into lymph nodes. Many follicles.

Fine bridges all

thin.

Chains of lymph nodes.

63

Other Lymph Sacs.

Small groups of vessels along renal anastomosis.

Large median anastomosis of sciatic veins. Groups of veins along sciatic vein, anlage of posterior lymph sacs. Median anastomosis of renal veins.

Cisterna Retroperi- : Posterior Chyli. toneal Sam: Lymph Sac. l

Present Present ;

Present Present Present Present, Present i 4. 6 x 1 thoracic with beginduct com- ni’g lymphplete. hnode.

I Not Present, ‘ Present found. no nodes. * 2.5 x .75 Not Present, l 3 x 1.75 ‘ found no nodes; 1.2 Large 1.7x2.5 1 . 6 x 1 Darn aged ‘ 2 x 1 Present, Mass of Sac with surround- 1ymph— nodesmeased by nodes. ‘uring 2.8 x nodes 2 X 3. 5 64 Florence R. Sabin.

diagrammatic form in Fig. 1, there is a group of vessels lying external to the internal jugular vein near its junction with the primitive ulnar vein. The figure can be interpreted by reference to Fig. 4. These vessels are completely filled with blood and yet I cannot find any openings from them into the veins, or into each other, and thus interpret them after a study of corresponding stages in other mammalian embryos as a plexus of veins which have separated from the jugular vein preparatory to the formation of the anterior or jugular lymph sac. These vessels are small, the largest measuring


FIG. 1. Reconstruction of the plexus of small veins lateral to the V. jugularis interna in a human embryo, 8 mm. long, (crown rump). Mall collection, No. 397. X about 50. The plexus of veins is shaded. D. C., ductus Cuvier; V. j. i., vena jugularis interna; V. u. p., vena ulnaris priinitiva.

FIG. 2. Reconstruction of the small veins lateral to the right V. jugularis interna in a human embryo 9 mm. long. Mall collection, No. 163. ){ about 50. Of the veins, six are shaded, indicating that they are full of blood, while the two with heavy outlines are nearly empty. Lettering same as Fig. 10. approximately .3 mm. in the antero—posterior diameter, by .19 mm. laterally.

The next specimen in the series is an embryo (No. 163) measuring 9 mm. This specimen shows a similar condition but with certain differences. In the first place the plexus of isolated Vessels occupies a slightly different place, as seen in Fig. 2. They lie farther ventralWard, extending over the body wall external to the heart. Most of these vessels are well filled with blood, while two are nearly empty. This embryo differs also in having an asymmetrical development, the vessels representing the forerunners of the lymphatics being much larger on the right side than on the left. The three largest sacs of this series measure .27 x .19 mm., .36 x .14 mm. and .27 x .14 mm. respectively.

The next specimen is an embryo (No. 109) measuring 10.5 mm. In this embryo there are symmetrical jugular sacs as seen in Fig. 3, just external to the internal jugular vein. The relation of the sac to the venous system as a whole is shown in Fig. 4, which is a reconstruction from serial sections. This embryo has been figured


FIG. 3. Transverse section through the neck of a human embryo, 10.5 mm. long, showing the symmetrical jugular lymph sacs. Mall collection, No. 109. A., artery; N. X., n. vagus; m. s., 11. sympatheticus; Oe., oesophagus; P., pericardium; S. 1. j., saccus lymphaticus jugularis; T. trachea. The V. jugularis are filled with blood and lie just medial to the sacs.

by Bardeen and Lewis, American J our. of Anat., Vol. I, 1901-1902, and by Dr. Mall, American J our. of Anat., Vol. IV, 1905; the outline and some of the details of the figure are taken from their reconstructions. As will be seen in Fig. 4, the sac lies external to the jugular vein and anterior to the primitive ulnar. In this embryo the question of a valve is an interesting one.

In studying through Dr. Mall’s collection it has proved that the finding of the valves depends wholly on the plane of the section. There is only one plane which is at all adequate for determining the FIG. 4. Reconstruction of the right jugular lymph sacs, shown in solid black, in a human 10.5 mm. long. Mall collection, No. 109. X about 14. G. N., gasserian ganglion; S. v., sinus venosus; V. c., V. cephalica: V. c. 1., vena cava inferior; V. 13., vena hepatica; V. 5. i., vena jugularls interna; V. p., vena porta; V. p. c., vena cardinalis posterior; V. s. c., vena subcardinalis;

V. u. (p.), Vena ulnaris (primitiva) ; V. u., vena umbilicalis; W. b, Wolflian body.

valves, namely the coronal. This will be readily seen in Fig. 10, which shows that the valve is made by along projection of the lymphatic duct into the angle of the internal jugular vein with the cephalic Vein. Imaginary cross sections through this figure will show that the place of the valve would be represented by a small duct in the angle between two veins and this is exactly what is seen in Fig. 5 for this embryo. A -study of Fig. 10 will also show that there could be nothing distinctive of the actual opening of the lymphatic to the vein in cross sections, for they would consist simply of a double layer of endothelium between the veins. In like manner sagittal sections are still more diflicult than transverse ones for locat ing the valves and indeed only in an occasional, fortunate section can it be accurately done.


FIG. 5. Transverse section through the jugular sacs of a human embryo, 10.5 mm. long. Mall collection, No. 109, to show the left valve. X 28. A., artery; N., nerve; Oe., oesophagus; P., pericardium; S. 1, j., vena jugularis; V. j. i., vena jugularis interna.

To return to the embryo 10.5 mm. long, I think that the valve is present, for, as is seen in Fig. 5, there is a small duct in the angle between two Veins and the duct connects with the sac as traced in serial sections. Secondly, the lateral vein in this section is the cephalic, see Fig. 4, and is therefore in the exact position of the undoubted valves seen later in Figs. 10 and 13. Whether this valve is open or not it is impossible to say. The sacs are both empty,’ and in the earlier stages where there are no valves they are often, though not always, full of blood. They measure .7 X .28 mm., showing a considerable increase over the two preceding specimens. This embryo shows. one further point of interest, namely a possible beginning of the thoracic duct in the shape of a duct running over toward the aorta as shown in Fig. 6. The entire question of a thoracic duct will be discussed later, on page 7 7 .l

The next embryo of the series (No. 353) is 11 mm. in length. This embryo is cut in coronal sections which proves to be the best plain not only for seeing the valves but for understanding all of the cervical lymphatics. This embryo is represented in a series of three figures, 7, 8 and 9, two of them sections and the third a diagram


FIG. 6. Transverse section through the left jugular sac to show the possible beginning of a vessel growing down to form the upper part of the thoracic duct. X 40. A., aorta; N. X., N. vagus; Oe., oesophagus; S. 1. j., saccus lymphaticus jugularis; V. j. i., vena jugularis interna.

from the same series. In Figs. 7 and 8 will be seen the extension of the lymphatic plexus along the external border of the jugular vein. These two figures show a number of important things, first in connection with the veins, they show the relations of the primitive ulnar and the cephalic to the jugular vein; for the lymphatics they show the relation of the lymphatics to the cephalic vein and in general to the arm bud. These relations are all brought together in the diagram of Fig. 9. Here it will be seen that this plexus which appears isolated in Fig. 7 is really continuous. The plexus is actually much more complex than is shown in Fig. 9. Measuring from the valve, which is in the angle between the cephalic and internal jugular veins, it extends 1.2 mm. along the jugular vein. By a comparison with the reconstruction of the preceding stage, Fig. 4, I think that the sections shown in Fig. 7 and 8 suggest that the sac is extending along the jugular vein by means of a plexus of veins.

The next point of interest is the location of the Valve. In Figs. 7 and 8, it will be seen that the beginning cephalic vein is easily recognized by its position opposite the upper curve of the arm bud. The lymphatic sac runs deep into the angle between the cephalic and the internal jugular veins, Fig. 7, but in no section is there any break in the endothelium of the sac, which leads one to think that the valve may not yet be open and that this fact may account for the complete filling of the lymphatic sacs with blood. The internal jugular vein is only partially filled with blood. The blood of the vein itself was omitted in the drawing.

In this embryo there is an extension of the jugular sac along the primitive ulnar and lateral thoracic veins. This extension forms the subclavian sac which gives rise to the lymphatics of the arm, Fig. 9. This is especially interesting in connection with F. T. Lewis’ s observations on the subclavian sac inrabbits where it begins as an isolated sac. I was able to confirm Lewis’ observations on his specimens of rabbit embryos, but feel sure that in human embryos the sac in the arm bud is an extension of the jugular sac. The sac along the ulnar veins measures .8 mm. beginning from the valve. This makes 2 mm. the total extent of the lymphatics in this embryo.

By putting together Figs. 7 and 8, relating them by the position of the cephalic veins, it will be noted that following along the ex— ternal border of the internal jugular vein there are a series of branches which we might call segmental, some of them, as for example above the lymphatics in Fig. 7 0-r between the lymphatics and the primitive ulnar vein in Fig. 8, are obviously small veins, others like the cephalic and primitive ulnar are large veins, while still others are being transformed into lymphatics. This suggests the process of transformation of the various branches of the internal jugular vein from the original simple segmental type into the adult system. In these transformations some of the branches become enlarged, others reduced and dropped out, while still others are changed into lymphatic sacs.

The next embryo of the series (No. 317 ), measuring 121/2 cm., has not been illustrated because it is exactly like the preceding except that the lymphatics have much less blood, and the plexus along the


FIG. 7. Coronal section through the arm bud of a human embryo, 11 mm. long. Mall collection, No. 353, to show the plexus of veins or lymphatic sacs along the internal vein. This section is to be related to Fig. 8 by means of the composite section, Fig. 9. X about 36. S. 1. j., saccus lymphaticus jugularis; V. c., vena cephalica; V. j. i., vena jugularis interna.

FIG. 8. Coronal section through the arm bud of the same embryo as Fig. 7, to show the relation of the lymphatic sac to the primitive ulnar vein. The larger lymphatic sac is the upper part of the extension along the primitive ulnar vein, shown in Fig. 18. X about 36. S. l. j., saccus lymphaticus jugularis; V. c., vena cephalica; V. j. i., vena jugularis interna; V. t. l.. vena thoracicus lateralis; V. u. (p.), vena ulnaris (primitiva).

jugular vein has been definitely transformed into a single sac. The extent of the lymphatics along the jugular vein is practically the same. The Valve is definite, showing the same type as seen in Fig. The Lymphatic System in Human Embryos. 71

FIG. 9. A composite diagram made by superimposing the sections showing the jugular sacs, as shown in Figs. 16 and 17, of human embryo, 11 mm. long, Mall collection. X about 36. D. 0., ductus Cuvier; V., position of valve; V. j. i., vena jugularis interna; V. t. 1., vena thoracicus lateralis; V. u. (p.) vena nlnaris (primitiva).

10, except that an opening cannot be made out. It is impossible to say whether the opening is not pre-sent or whether the shrinkage of preservative is sufiicient to conceal it.

The sixth embryo of the series (No. 144), 14 mm. long, shows only one new point in the formation of the jugular sac, namely the beginning of the process of bridging of the sac which is illustrated for a later stage in Fig. 14. This cutting of the sacs by slender connective tissue bridges, which has already been described in the development of the jugular lymph sacs in the pig, is, believe, the beginning of the transformation of the sac into a lymph node.” This’ will be considered later.

Two of the embryos of the series, one (No. 350) measuring 15 mm. and the other (No. 106) measuring 17 mm., have very abortive sacs near the junction of the primitive ulnar with the jugular vein. In both instances the preservative is not good enough to show the endothelium, so there is no way of telling these small sacs, which measure less than half a millimeter in their longest diameter, from mcscnchyme spaces except by their position in coniparisoan with other embryos. They certainly are an evidence that there are marked irregularities in the development of the lymphatic system. _

Another embryo of 15 mm. (No. 423) has also only a small sac, this one measuring .9 mm. In the collection there are some embryos in which the preservative is too poor to admit determining the lymphatics at all, but out of the series of 22 which have been studied there are four cases of abortive jugular sacs, or 18. per cent. These embryos measure 15, 17 and 20 mm.

The next specimen (No. 424), measuring 17 mm., is valuable, for it has a double vascular injection. An extravasation along the jugular region interferes with a study of the jugular lymph sacs, but the vascular injection of the posterior part of the embryo gives conclusive evidence that the other sacs, namely the retroperitoneal, the posterior and the receptaculum chyli have not begun.

Embryo (No. 296) measuring 17 mm. is the earliest specimen in which I have found a valve undoubtedly open. This is shown in

"Sabin. Amer. Jour. Anat., Vol. IV, 1905.

10. It is in exactly the position found in the embryo 11 mm. long (Fig. 7) and in No. 317 which is 12.5 mm., which are cut in coronal sections, but in the two earlier embryos I could not make out the break in the endothelium. The extent of the lymph sac in the section is 1.5 mm. and there is a slight extension along the primitive ulnar vein.

The next embryo of the series (No. 7 4) measures 16 mm. In Dr. Mall’s catalogue it is placed after those measuring 17 mm., for


FIG. 10. Coronal section through the arm bud of a human embryo, 17 mm. long, Mall collection, No. 296, to show the open valve of the jugular lymph sac in relation to the veins. X about 26. S. 1. j., saccus lymphaticus jugularis; V. c., vena cephalica; V. j. i., vena jugularis interna; V. 11. (p.). vena ulnaris (primitiva).

it is undoubtedly further developed. This embryo, 'in which the sections are 50 microns thick, is a very satisfactory one for determining the sacs, for the veins are unusually distended with blood and the lymph sacs are filled with a serum which takes a definite stain. The sacs extend a distance of 1.8 mm. along the internal jugular vein. There is no sac on the primitive ulnar vein and there are 74 Florence R. Sabin.

no traces of the other sacs in the posterior part of the body. The veins are especially large in the posterior part of the body. The sections are too thick to show the valves well. The sacs appear as in Fig. 3 except that they are larger.

The next embryo of the series (No. 22) measures 20 mm. and shows several interesting points. The series is cut transversely and the sacs also appear much as they are shown in Fig. 3 for an embryo 10.5 long except that they are much wider. The sacs measure 1.6 x 7. The new point of interest is, that in this series the third nerve cuts through the sac; in a later stage, in an embryo measuring 30 mm., Fig. 12, three nerves cut through the sac, namely the third, fourth and fifth. For the first t.ime, in this stage, there are vessels extending from the sac toward the skin. It will be remembered that this is the point in.which the recent American workers on the lymphatic system differ.

A further point of interest in this series is a group of small vessels along the renal anastomosing vein. These vessels, I think, are forerunners of the mesenteric sacs. The indications of lymphatics for the posterior part of the body appear at this stage.

In another embryo (No. 128) measuring 20 mm. the jugular sacs are again abortive, measuring only .75 mm. The specimen is, however, very interesting in connection with the lymphatics for the posterior part of the body. In the neck, as we have seen, the early lymphatics are the two jugular sacs, with either an extension or a supplementary sac along the primitive ulnar vein, in the arm bud. In the posterior part of the body three sacs have been found, two of them median, the mesenteric sac and the cisterna chyli; and one paired, namely the posterior lymph sac. In this embryo, in the place of the future cisterna chyli, there is an extensive median vein connecting the two sciatic veins. Just ventral to this, compare with Fig. 12, is the renal anastomosis running through the great mass of the sympathetic system in the hilum of the two adrenal bodies. Around these two large median anastomosing veins there is as yet no evidence of the future median lymphatic sac. However, to the side of the two sciatic veins, just posterior to the median anastomosis, is an abundant plexus of veins on the one side and a possible beginning posterior lymph sac on the other, making a definite indication of the posterior lymphatic sacs. This stage is, I believe, just preliminary to the ’formation of the three abdominal sacs. In the next specimen these sacs become definite.

Thus in the first fourteen specimens of the series, measuring from 38 to 20 mm., simply the jugular sacs are present. From now on, that is in embryos above 20 mm., we shall have to follow no-t only the jugular sacs but the mesenteric sac, the cisterna chyli and the posterior lymph sacs as well.

The first embryo above 20 mm. in the series, is one (No. 382) measuring 23 mm. This series is cut in sagittal sections. It shows the jugular sac beautifully, which has now reached a size of 2 x1 'mm., and lies opposite the third, fourth and fifth cervical vertebrae. The series, however, is much more important in connection with the other. lymphatic sacs. I cannot find the posterior lymph sac, but both the mesenteric sac and the cisterna chyli are present. For these two median sacs the sagittal plane proves to be by far the best. In Fig. 11,. which was made by graphic reconstruction, is shown the retroperitoneal sac in its relation to the renal vein and the suprarenal body. It is designed to relate the mesenteric sac and cisterna chyli to the -surrounding structures. The point at which the vena cava turns ventralward, opposite the second lumbar vertebra, marks the position both of the renal veins and also the suprarenal branch which is a large vein running anteriorly along the ventral surface of the suprarenal body. The retroperitoneal sac extends along the renal and suprarenal veins, the latter being hidden in the diagram by the venacava. In following the suprarenal veins the lymphatic vessels approach the superior mesenteric artery, along which they subsequently grow out into the mesentery, as has been shown by Heuer.“ The line of mesentery is shown in the diagram. The diagram shows the mass of sympathetic ganglia closely related to the suprarenal body. In this early stage the lymphatic ducts are not likely to be confused with the sympathetic ganglia, but later when nodes begin to develop care must be exercised to distinguish them. The diagram also shows

”Heuer. Amer. Jour. Anat, Vol. IX, N0. 1. FIG. 11. A composite diagram made by superimposing the ections showing the relatlons of the mesenteric sac and cisterna chyli to the veins, in 9. human embryo measuring 23 mm., Mall collection, No. 382. X about 8. A. m. s., A. mesenterica su perior; C. c., cisterns. chyli; G. s., gangli sympathetica; S. 1. m., saccus Iymphaticus:

mesentericus; 8., suprarenal body; V. a., v. azygos; v. c. i.. vena cava inferior.


nteresting relations of the cisterna chyli. It arises opposite the second, third and fourth lumbar vertebrae, closely adjacent to the inferior vena cava where it anastomoses with the azygos veins. In studying through Dr. Mall’s collection I have become convinced that the cisterna chyli forms one of the primitive sacs and that the thoracic duct may grow forward, '5. e., anteriorly from it. Baetjer has shown that the mesenteric sac soon becomes connected with the cisterna chyli. In this series I cannot find any evidence of a thoracic duct. The cisterna chyli differs from the other sacs simply in not being completely transformed into lymph nodes, though its lower border develops into a large group of them, as will be shown in the last series.

The next embryo of the series (No. 6), measuring 24 mm., has a large jugular sac. The series is incomplete so that I cannot get the length of the sac, but its width is the same as the preceding, namely 1 mm. The valves are present and the sac shows much bridging. There is a well defined subclavian sac. This series is also more interesting in connection with the other sacs. It shows three things, the retroperitoneal sac, the cisterna chyli, the beginning thoracic duct and the anlage of the posterior lymph sacs. A point of especial interest in this series is in connection with the cisterna chyli. This sac is present as a few vessels dorsal to the aorta; and from the sac ducts extend anteriorly immediately adjacent to the azygos veins. On the left side, this duct extends into the thoracic cavity almost to the neck. I cannot trace it to the jugular sac nor is the series perfect enough to enable one to say whether it is present in every section or not, but there is sufficient evidence to indicate that the thoracic duct may be an outgrowth of the cisterna chyli.

The thoracic duct has proved to be the most difficult part of the lymphatic system to work out for this reason, we have not yet found a way to inject it in early stages and uninjected sections are not adequate. The evidence of sections is as follows, the jugular sac and the cisterna chyli, which the duct subsequently connects, develop before the duct. The question is, does the duct develop from multiple anlagen from the azygos veins for which there is no proof except that lymphatic vessels can be seen in sections adjacent to FIG. 12. Flat reconstruction of the primitive lymphatic system in a human embryo, 30 mm. long, Mall collection. No. 86. X about 5.4. C. c., cisterna chyli; L. g., lymphoglandula; N. III., N. IV., and N. V., Nn. cervicales; S. 1. jug., saccus lymphaticus jugularis; S. 1. 1119s., saccus lymphaticus mesentericus; S. 1. post, saccus lymphaticus posterior; S. 1. 5., saccus lymphaticus subclavius; V. c., vena cephalica; V. <3. i., vena cava inferior; V. f.. vena femoralis: V. j. i. vena jugularis inferior; V. 1. p., vasa lymphatica profunda; V. l. s., vasa lymphatica superficialis; V. 1-., vena renalis; v. s., vena sciatica; V. u. (1).), vena ulnai-is (primitiva).

these veins, or does the duct grow from the two sacs, the cisterna chyli and the jugular one. For this second view the evidence is also weak, it consists in this, that other lymph ducts wherever we can study them grow from the sacs; and secondly in pig embryos and in human embryos one can trace a duct forward from the cisterna chyli and caudalward from the jugular sac, and in later stages these two ducts have joined. The weakness of this evidence lies in the fact that in the earlier stages the picture is always liable to be confused by Lewis’ multiple anlagen. In both pig and human embryos the stages to be studied for the thoracic duct lie between 20 and 30 mm. In an embryo pig the complete thoracic duct can be injected at 27 mm. It should be quite clearly noted that whichever method of formation of the thoracic duct proves ultimately to be correct, that is whether it arises from the azygos veins in situ or from an outgrowth of the lymphatic sacs, the most fundamental point remains the same, that its endothelium is vascular.

However, it should be stated here that wherever growing lymphatic capillaries have been absolutely tested, they grow by the sprouting of their own endothelium rather than by additions of new anlagen from the veins. This has already been noted for the living lymphatics; it is also shown by the work of Dr. H. M. Evans” on the growth of new lymphatic capillaries into a sarcoma of the intestine. His injections show that theinew lymphatic capillaries are derived from the mucosal plexus and that these new vessels are analogous with the central lacteals of the villi. In the tumor, however, they are developing beyond the normal limits of the terminal lacteals into a spreading plexus. This plexus shows all gradations as seen in Evans’ figure to the normal lacteal.

From the next specimen (No. 86), measuring 30 mm., a graphic reconstruction has been made of the entire primitive lymphatic system, Fig. 12. It does not show the extent of the peripheral lymphatics, but does show the relations of the primitive system. At this stage, as will be seen in the reconstruction, the lymphatic system consists of the large jugular sac, measuring 5 X 3.6 mm., with its large extension along the ulnar vein to the arm bud. Emptying into the jugular sac on one side is the thoracic duct which connects


"Evans. On the occurrence of newly-formed lymphatic vessels in malignant growths. Johns Hopkins Hospital Bulletin, 1908.


FIG. 13. Coronal section through the jugular lymph sacs in a human embryo of 30 mm., Mall collection, No. 86. X about 11. The level of the section is shown on the reconstruction of Fig. 21. The section shows the complete lymph sac on the right side and is cut to show the valve on the left. S. 1. j., saccus Iymphaticus jugularis; V. i., V. innominata; V. j. i., V. jugularis interna; V. I. s., vasa Iymphatica superficialis.

ond median sac, the retroperitoneal, which is adjacent to the renal veins. At this stage a connection between the cisterna chyli and the mesenteric sac, which has been so well shown by Baetjer for. the_ pig of the same size, could not be made out. The posterior sac has now become a long narrow sac, along the course of the primitive sciatic veins and inferior vena cava. It measures 4.6 X .5 x .96 (dorso—ventral), and runs almost to the cisterna chyli, with which a connection cannot be made out. The plane of the section, coronal, is not especially advantageous for determining whether the connection has been made or not-.


FIG. 14. Coronal section through the jugular lymph sac of the same embryo, at the level shown in Fig. 21, to show the simple bridging of the sac which is the anlage of the first lymph node. X about 19. S. I. j.,

saccus lymphaticus jugularis.

The jugular sacs show a number of points of interest. First their increase in size, this being the stage of the maximum size. The valve is very beautifully shown, as is seen in Fig. 13. The level of this section is shown on the diagram. A second point of interest is the extensive bridging of the sac. This occurs especially near the dorsal border, as is shown in Fig. 14. At this stage the bridges of connective tissue, which cut the sac, show more connective tissue cells than the surrounding mesenchyme. This thickening of the mesenchyme around a plexus of lymph ducts makes the anlage of a lymph node.

A third point of interest is the spreading of the ducts from the jugular sac to the skin. I want to call especial attention to the great size of these ducts, one especially which leaves the lateral surface of the sac. These ducts are the first lymphatics to reach the skin; as has been said, they first reach the skin in a human embryo of about 20 mm., and by this stage they have grown over the head and down over the shoulders. These peripheral vessels have not been reconstructed.

Fig. 12 shows that the sac has now been cut through by three of the cervical nerves, the third, fourth and fifth. This is interesting in connection with the shifting of the structures in the neck and in the placing of the sacs. Just at the edge of the subclavian sac is a second small beginning lymph node.— This lymph node is like the jugular one, consisting of bridges of thickened connective tissue between a rich plexus of lymphatic capillaries. The beginning of the deep lymphatics for the arm is also shown. I could not trace them farther in the sections.

The thoracic duct shows beautifully in the sections. It begins at the cisterna chyli as a double duct, but the right one soon crosses obliquely in the plane of the coronal section to the left side and joins its fellow. The duct lies adjacent to the azygos veins and has many irregularities. At this stage, the duct reaches the jugular sac, an advance from embryo No. 6, of 24 mm., in which it only extended into the thoracic cavity.

In the angle of the bifurcation of the trachea in this embryo is a clump of lymphatic vessels which possibly connect with the thoracic duct, though the connection could not be made out in the sections. These vessels extend a short distance along the bronchi and are the first visceral lymphatics I have found in the series.

The retroperitoneal sac is shown in Fig. 15, which corresponds with the line on Fig. 12. The section shows the relation of the sac to the renal vein and brings out the especially large masses of the sympathetic ganglia in this region.

The posterior lymph sac shows on one side in Fig. 15, but much better in Fig. 16. The posterior lymph sac is a double sac extending


FIG. 15. Coronal section through the retroperitoneai sac of the human embryo, at a level indicated on Fig. 21. X about 39. A., aorta; K., kidney; S. I. m., saccus lymphaticus mesenterica; S. 1. p., saccus lymphatica posterior; V. c. i., vena cava inferior; V. r., vena renalis.

along the primitive sciatic veins. The reconstruction is made of the left side, but shows where the left primitive sciatic vein joins the 84 Florence R. Sabin.

right to form the inferior vena cava, and shows that the sacs now extend forward almost to the cisterna chyli. The cisterna chyli being median and the posterior sacs being lateral, the plane of the section made it impossible to trace whether the connection has been made or no-t. The two sacs, however, run to the same level and probably do connect. The posterior sac measures 4.6x.2 (lateral X .9 (dorso-ventral). In the angle where the femoral vein branches


FIG. 16. Coronal section through the posterior lymph sacs as they lie along the primitive sciatic veins, of the same embryo, at a level shown i! Fig. 21. X about 49. S. 1. p., saccus lymphaticus posterior; V. c., vena candalis; V. s., vena sciatica primitiva.

oil from the primitive sciatic is a lymph node and it will be seen that deep lymphatic vessels follow both the sciatic and femoral veins. There is also a group of superficial lymphatics covering the skin of the hip in the groove between the body wall and the leg. These superficial lymphatics could be traced to a connection with the sac on the opposite side, but not on the side reconstructed. This gap is probably due to the accidental plane of the section; it comes where the vessels turn directly outward and are so cut in cross section. These gaps to be found in serial sections have already been discussed, they occur in thin sections, but much more often in thick ones like these, this embryo being cut at 50 microns, where the slender lymphatics must often be missed. The extent of these superficial lymphatics has not been shown in the reconstruction, they are readily made out in the skin over the back and hip. There is no difliculty in telling them, they are so sharply lined by endothelium, are empty and about three times the size of the blood capillary. This specimen then shows all the primitive sacs; and their relations to the thoracic duct. It marks also the beginning of the peripheral lymphatic system, both visceral, to the lungs, and superficial to the skin.

The next specimens consist of a group of four embryos of about the same stage, No. 95 measuring 46 mm. and three others (No. 96, No. 84 and No. 224;) all measuring 50 mm. They all prove to be especially interesting in connection with the development of the posterior lymph sac. In connection with the jugular sac the measurements are given in the table. These sacs show certain differences. In No. 95 the transformation into lymph nodes is not extensive and is chiefly at the upper end. No. 224.», on the other hand, shows a fine bridging throughout the sac. The other two specimens show an important stage in the evolution of lymph nodes. By referring back to Fig. 14 it will be seen that when the nodes first begin in an embryo, 30 mm. long, they consist simply of a thickened connective tissue between a plexus of ducts. But at this stage, 50 mm., there appear round clumps of lymphocytes in the connective tissue bridges. These clumps of lymphocytes are the primary lymph follicles and they occur around the blood vessels of the connective tissue bridges. These primary follicles are well illustrated in Fig. 17, in the femoral lymph node, or in Fig." 18. The evolution of the lymph node depends on the balance between the two elements; the lymph ducts which multiply until they are sinuses and the vascular part with its attendant lymphocytes which make the follicles and cords. It will be seen in the figures of these embryos, that in early stages the lymphatic element by far predominates.

In embryo No. 84, the size of the lymph ducts coming from the jugular sac is particularly striking. In one section, one of these ducts measures 2.7 5 X .5 mm. VVhen it is considered that these vessels are really capillaries, being lined by a single layer of endothelium, one sees that they are really enormous in size, almost as


FIG. 17. Sagittal section of a human embryo measuring 50 mm., Mall collection, No. 96, showing the posterior lymph sac within the pelvis and its extension along the femoral vein. )( about 8. F., femur; Lg., lymphoglandula (femoralis) ; O. s., os sacrum; S. 1. p., saccus lymphaticus posterior with lymph node in the border; V. s., vena sciatica; V. l. v., vertebra lumbalis v.

big as the inferior vena cava itself. In general, the lymphatic vessels are considerably larger than the blood capillaries.

The cisterna chyli could not be found in No. 95, but there is a small lymph node near its usual location and there is a thoracic duct. The second embryo (No. 96) was damaged at the area; the other two show the cisterna chyli well with large connections with the mesenteric sac. This is especially true in No. 84, when the series is transverse, the sections looking like Fig. 9 of Mr. Baetjer’s series. Both the cisterna chyli and the retroperitoneal sac are easily located from Fig. 11. They are bridged from the very beginning.

These four series, however, are much more interesting in connection with the posterior lymph sacs. As we have seen, these sacs begin in an embryo about 24: mm. long as sacs along the primitive sciatic veins. In an embryo of 30 mm. they are long, narrow sacs. In Fig. 17 it will be seen that in an embryo 50 mm. long they have become large sacs lying in the side of the pelvis opposite the first three sacral vertebrae. The entire dorsal wall of the sac is occupied by a lymph node. In one of the other series it is plain that the sac is opposite the bifurcation of the vein into the sciatic and femoral veins, and that there is a large lymph node in the angle of these two veins. From the sacs extend vessels, both along the femoral vein, as shown in the figure and along the sciatic; both of these groups of vessels have developing lymph nodes. These are secondary nodes in contrast with the primary nodes which come from the sacs. The primary groups of nodes are the jugular, subclavian, retroperitoneal and posterior. The early secondary nodes are near the sacs, a point also in support of the outgrowth of lymphatics from centre to periphery.

The last embryo of the series (No. 172), measuring 80 mm., is especially valuable in connection with the fate of the jugular lymph sacs, the development of lymph nodes and the spread of the peripheral lymphatics. The jugular sac is fast becoming transformed into a large group of lymph nodes. In a few sections there are remnants of the sac measuring 1.75 x .5 or even 1.75 x 1 mm., but most of the sac has disappeared. There are also secondary lymph nodes along the other veins of the neck, for example along the external jugular vein next the parotid gland, and along the facial vein ,at the angle of the aw.

In connection with the arm there is an extensive group of nodes over the shoulder.. In the axilla there are four groups—one posterior to the vessels and nerves, one along the subclavian vein, and two groups anterior to the pectoralis minor muscle.

Along the trachea is a group of nodes, of which the mass at the bifurcation is especially large. Nodes are also seen along the bronchi within the hilum of the lung, and large lymph vessels extend into the pleura while smaller ones are to be seen in the septa of the lung itself. No nodes are to be made out within the lung.

The thoracic duct is easy to follow as a plexus of vessels along the aorta. Along the vertebral column there are three chains of lymph no-des—o«ne on either side of the bodies of the vertebra not far from the mid-line and closely associated with the thoracic duct. The other two sets are farther to the side, against the body of the vertebrae near the base of the transverseiprocesses. These drain the body walls. So abundant are these vertebral lymph nodes that scarcely a section lacks them, the sections being 100 microns thick.

In passing into the abdominal cavity the cisterna chyli is readily located. Along its lateral borders is a complete chain of nodes, and at the lower end is a large clump of similar nodes.

The retroperitoneal sac has been transformed into a group of nodes except at the upper end, just below the superior mesenteric artery where the sac still persists. Fig. 18 is taken just below the more open part of the sac and shows the bridging and some extension of the sac to the right. The retroperitoneal sac then becomes the group of nodes ventral to the aorta. It will be remembered that at the beginning, the sac extended along the veins of the adrenal bodies. At this stage there is an extensive mass of lymphatic tissue continuous with the mesenteric sac, extending along the hilum of the suprarenal bodies. The same mass of lymphatic tissue lies at the base of the mesentery at the portal of the liver. In no section, however, are there any nodes within the hilnm of the liver.

The most extraordinary development has taken place in the mesentery. A group of nodes follows the pancreas and there is a small node at the hilum of the spleen. A similar node lies against the stomach. , In the center of the mesentery is an exceedingly large node, measuring 2 mm. on a side, see Fig. 18. This large central lymphatic mass in the mesentery is connected with the mesenteric sac by a chain of nodes running along the superior mesenteric artery. From this central mass vessels run out in the mesentery toward the intestine.

The only structures with which the developing lymph nodes could be confused are the sympathetic ganglia. On this account care must be exercised, especially around the retroperitoneal sac, where both structures are very abundant. The sections of these stages are thick (50 to 100 microns) and the low powers of the microscope are inadequate to distinguish them, especially when the connective tissue around the ganglia is broken. With cane and serial sections the lymph nodes can be absolutely determined.


FIG. 18. Transverse section through the abdominal cavity of a human embryo, 80 mm. long, Mall collection, No. 172. It shows the kidneys, a little of the liver, and many loops of the intestine. X about 8. A. in. s., arteria mesenterica superior; C. c., cisterna chyli at its lower border; Lg. m., lymphoglandulae mesentericae; S. l. m., saccus Iymphaticus mesenterica.


The significance of this retroperitoneal sac is brought out in the injected specimens in Dr. Heuer’s paper. It will be noted that in the injected pig embryos the sac seems much larger than in the sections of human embryos. Its importance is that it is the anlage of the visceral lymphatics; it is transformed into the preaortic nodes of which the most anterior group is around the coeliao axis.


FIG. 19. Transverse section through the pelvis of a human embryo, 80 mm. long. Mall collection, No. 172, to show the posterior lymph sacs. X about 9. B., bladder; Lg., 1ymph0g1andu1a;‘R., rectum; S. 1. post, saccus Iymphaticus posterior.


In Fig. 18 is shown the lower part of the cisterna chyli; here the sac is being transformed into lymph nodes while farther anLymphatics in Small Intestine of the Pig. 91

terior the sac itself persists. In tracing the series caudalward, the central mass of lymph nodes corresponding with the cisterna chyli, can be traced to the pelvis, where the mass turns a little to the side and joins the posterior lymph sacs. The posterior lymph sacs are really enormous in size, measuring 2.8 x 2 x 3.5 mm. (dorscrirentral). These measurements include the glandular masses in the edge of the sac. The sacs are Well shown in Fig. 19, which illustrates that the posterior sacs are being transformed into lymph nodes. In some sections of the pelvis these masses of lymphatic tissue seem to take up almost two thirds of the area of the cross section. From the posterior sac two sets of vessels extend, one along the sciatic vein and the other along the femoral. There is one lymph no-de along the sciatic vessels and a chain of nodes along the femoral. In Fig. 19 is a tiny lymph node, labeled Lg., which illustrates well the simplest form of a lymph node, a central mass of lymphocytes with a plexus of lymph ducts around. This plexus of ducts is so close that it may already be termed a sinus, so the node consists ‘ of a single follicle with its peripheral sinus. It is the structural unit of the lymph node. '

From the description of this specimen it will be seen that. the foundations of the lymphatic system as it is found in the adult have been laid down in an embryo of 80 mm. ‘

The primitive system is complete, and the sacs are forming the primary nodes. The peripheral vessels have extended to the skin and to the viscera, and secondary nodes are forming along these vessels. I think that we have the key for working out the peripheral spread of the lymphatics and carrying them to their capillary bed. Injections of the retroperitoneal sac give us the material for tracing this development.



Cite this page: Hill, M.A. (2020, April 8) Embryology Paper - The lymphatic system in human embryos, with a consideration of the morphology of the system as a whole. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Paper_-_The_lymphatic_system_in_human_embryos,_with_a_consideration_of_the_morphology_of_the_system_as_a_whole

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