Talk:Paper - On the development of the biliary system in animals lacking a gall-bladder in post-natal life (1916)

From Embryology

On The Development Of The Biliary System In Animals Lacking A Gall-Bladder In Postnatal Life

Richard E. Scammon Institute Of Anatomy, University of Minnesota

Ten Figures

It is well known that the gall-bladder is always absent in some species of vertebrates. There seems to be no general rule governing the distribution of this peculiarity. Thus in the cyclostomes a gall-bladder is found in the myxinoids but is absent in the fully developed Petromyzon. It is present as a rule in fishes although absent in a few species of sharks. A gallbladder is said to be present always in amphibians and reptiles; it is wanting in a number of birds including the pigeons. Among mamnaals no gall-bladder is found in a number of rodents and in noany ruminants, pachyderms and some other ungulates. It is absent in the Cetacea. In other forms the gall-bladder may or ntiay not be present. This is the case in several species of birds and in a few mammals. With the latter may be included man where congenital absence of the gall-bladder is an unusual anonaaly. In man the gall-bladder alone ntiay be lacking, or more rarely both the gall-bladder and the larger biliary ducts.^

Only three of the forms consistently lacking a gall-bladder are commonly available for embryological study. These are the

This work was done with the aid of a grant from the Research Fund of the University of Minnesota.

The comparative list given above is by no means a complete one. A much more detailed statement is to be found in the Milne Edwards, Lecons sur la physiologie et I'anatomie comparce, T. 6, p. 454, ct seq. Later papers upon the partial or complete absence of the biliary system in man are: Hochst3tter, Arch. f. Anat., 1886; Latham, Journ. of Anat., 1838; Bubenhofer, Anat. Hefte, 1905; and Beneke, Marburger Universititsprogramm, 1905.



lamprey (Petromyzon), the pigeon and the rat. The development of the biliary system in these species will be taken up in the order given above.


I have made no study of Petromyzon material but include here a brief summary of the findings reported in the literature.

The early history of the liver in Petromyzon has been studied by Gotte C90), v. Kupflfer ('93), Brachet ('97) and others. A complete biliary system is developed including a large gallbladder and a common bile-duct of considerable diameter. These structures are lined with a high colunmar epithelium which later becomes somewhat flattened and they are surrounded by definite mesenchymal sheaths. The biliary apparatus takes part in the general rotation of the gut which occurs in this form and it persists during the Ammocoetes or larval period.

The later history of the common bile-duct and gall-bladder has been followed out in some detail by Nestler ('90). He found that in an Ammocoetes 13 cm. in length the bile-duct still opened into the anterior end of the mid-gut and was connected distally with the gall-bladder. Near its posterior or intestinal end there was a short segment in which the lumen was almost completely obliterated by the increased height of the lining epithelium. In a specimen a centimeter longer the common bile-duct was still connected with the gall-bladder but its connection with the intestine was lost and its caudal end obliterated. In this region was found a collection of 'Zellballen' or follicles which were connected with the part of the duct still intact. In still later stages the duct proper was found to have entirely disappeared but the follicles persisted. Nestler apparently regarded these follicles as cystic remains of the common bile-ducts or of outpouchings from it. The gall-bladder first became much reduced in size and the epithelium fining it increased in height. The surrounding sheath of mesenchymal tissue also was thickened. Later the structure was completely obfiterated.

These observations were confirmed in the main by Bujor ('91) who, however, accepted the earfier view of Langerhans ('73)


that the follicles observed near the cranial end of the common bile-duct were pancreatic. This view has been confirmed by the recent careful researches of Picqu6 ('13).^


In the pigeon, as in birds generally, there are two ducts leading from the liver to the intestine. Of these the anterior or cranial one is commonly termed the ductus hepato-entericus. The posterior one is divided into two parts by the point of attachment of the gall-bladder. The portion between the hepatic trabeculae and minor ducts and the gall-bladder is called the ductus hepato-cysticus, and the part between the gall-bladder and intestine the ductus cysticus or ductus cystico-entericus. Since the pigeon, as a rule at least, loses its gall-bladder in the course of development, the terminology above is not always an appropriate one. For simplicity the two main ducts will be designated in the following description as the anterior and posterior hepatic ducts.

Brouha ('98) has pubUshed the only information which we have concerning the later development of the liver in the pigeon. He modelled and described two stages, embryos of 59 and 100 hours incubation respectively, in coimection with his extensive study of the development of the liver in the chick. The liver forms from the floor of the foregut and the anterior intestinal portal, but the anlage, which is hollow in the chick, is solid at first in the pigeon. In Brouha's younger specimen the anlage was already partially divided into anterior and posterior diverticula as in other birds. In the older specimen this division was quite distinct and the anlage of the gall-bladder was represented by a distinct expansion of the left side of the extreme posterior end of the hepatic gutter at the point of origin of the posterior hepatic diverticulum or duct (Brouha, '98, pi. VIII, fig. II, V. B.). Brouha did not follow its later history.

' Although Nestler does not describe a pancreas in Petromyzon, he figures and labels as pancreas a group of tubules in the wall of the mid-gut on the side opposite to the follicles associated with the ductus choledochus.


The youngest pigeon embryo I have examined is 7 mm. in length, of 72 hours incubation (Minn. E. C. 588). In development it stands between the two stages described by Brouha. The anterior and posterior divisions of the hepatic diverticulum are differentiated into short wide ducts which connect with a considerable network of hepatic trabeculae surroimding, in part, the large right omphalo-mesenteric vein. All three pancreatic anlagen are present. The dorsal one forms a pouch which is

Fig. 1 A reconstruction of a portion of the mid-gut, liver and pancreas of a pigeon embryo 7 mm. long (Minn. E. C. 588). Right lateral view, X 50. A./i., anterior hepatic duct; D.p.j dorsal pancreas; G.b.j gall-bladder; L.v.p.y left ventral pancreas; PJi., posterior hepatic duct; R.v.p., right ventral pancreas.

almost as large in cross section as is the gut at this level. The ventral diverticula are smaller pouches which arise from the gut just above the posterior end of the hepatic gutter. A right lateral view of a reconstruction of this region is shown in figure 1. In the reconstruction the hepatic trabeculae are cut away near their origin from the hepatic diverticula. The posterior hepatic diverticulmn is very short and ends by dividing into two parts. The right division becomes continuous with the hepatic trabeculae and represents the ductus hepato-cysticus of other


birds. The left division is the anlage of the gall-bladder and at this time is simply a short rounded swelling. This swelling is due almost entirely to the thickening of the epithelium, there being no true lumen in the cystic anlage (fig. 3).

The posterior hepatic diverticulum lengthens rapidly, extending forward and to the right. The cystic anlage is carried along

Fig. 2 A reconstruction of a portion of the mid-gut, liver and pancreas of a pigeon embryo 8 mm. long (Minn. E. C. 590). Right lateral view X 50. Abbreviations as for figure 1.

with it and is soon located some distance from the gut in the margin of the hepatic parenchyma. The right branch of the bifurcation which connects with the hepatic trabeculae straightens out so that its axis falls in line with that of the main duct and the two form a single tube. The thickening representing the gall-bladder is strongly evaginated forming a small pouch which


joins with the posterior hepatic duct by a short broad neck. Its walls become thinner and its lumen is thereby widened, but as a whole it increases very little in size. An embryo (Minn. E. C. 590), 8 mm. in length and distinctly older than the one first described, shows these changes in progress. Figure 2 is a


Fig. 3 Transverse section of the liver and the duodenal region of a pigeon embryo 7 mm. long (Minn. E. C. 588). X 400. G.b., gall-bladder; H.t., hepatic trabeculae; P.h., posterior hepatic duct; R.v.p.f right ventral pancreas.

right lateral view of a model of this specimen, and figure 4 a section through the long axis of the gall-bladder.

In later stages the entire mass of the liver is much enlarged. Both the anterior and posterior hepatic ducts increase rapidly in length and in caliber, but the anterior one grows more rapidly


than the posterior. Although the liver and its ducts continue to increase in size, the gall-bladder renotains about constant until the embryo reaches a length of 12 to 15 nam. Thereafter the gall-bladder becomes somewhat smaller both absolutely and relatively than in earher stages. Both the lumen and the walls of the sac tend to dinMnish, and folds or sacculations naay appear in its fundic end. The surroimding mesenchyma begins to take the form of a definite sheath with concentrically placed

Fig» 4 Section through the long axis of the gall-bladder of a pigeon embryo 8 mm. long (Minn. E. C. 590). X 400. C.d., cystic duct; G.6., gall-bladder.

nuclei. The neck or true cystic duct becomes elongated and slender. Figure 5, an oblique section of the gall-bladder of an embryo 15.5 mm. long (Minn. E. C. 586), shows these changes in progress.

With the growth of the liver the gall-bladder changes its position, being carried away from the margin of the Uver parenchyma where it was formerly located. In later stages it comes to Ue more and more in the posterior part of the dorsal ligament.



The cystic duct is reduced in caliber and the lumen becomes very small or is occluded. From the specimens which I have examined it appears that the bladder generally becomes separated from the duct and renoains for a period as an isolated thick

Fig. 5 Section through the long axis of the gall-bladder of a pigeon embryo 15.5 mm. long (Minn. E. C. 586). X 400.

Fig. 6 Section through the gall-bladder and posterior hepatic duct of a pigeon embryo 26.8 mm. long (Minn. E. C. 596). X 400. The gall-bladder is the larger of the two epithelial tubes.

walled cyst lying in the dorsal hepatic mesentery close to the posterior hepatic duct. This condition is shown in figure 6 of a section of the gall-bladder in an embryo 26.8 mm. long (Minn. E. C. 596).


Later the gall-bladder degenerates in most cases. In an embryo 46 mm.* in length there was no definite cyst but in the region formerly occupied by the gall-bladder there was found a snaall cluster of deeply staining and degenerating cells which probably represented its ren^iains. There was no trace of this

Fig. 7 Section through the posterior hepatic duct and gall-bladder of^ajpigebn embryo 62 mm. long. X 400.

structure in an embryo 55 mm. in length. A specimen 62 mm. in length, however, showed a small persistent gall-bladder. It was of about the same diameter as the duct to which it was attached and a common musculo-fibrous tunic surrounded the

These measurements are crown-rump length taken with the neck straightened out until in line with the body.


two structures. A slender and abruptly curved cystic duct connected the gall-bladder with the posterior hepatic duct.

Fig. 8 Three sections showing the size of the gall-bladder in the pigeon embryo. A, embryo 6.8 mm. long (Minn. E. C. 591); B, embryo 8 mm. long (Minn. E. C. 554); C, embryo 62 mm. long. All X 50.

The lining epithelium of the bladder was of a low columnar type sinailar to that of the duct proper, and the lumen contained a small amount of granular precipitate (fig. 7). It is evident


from this specimen that the cystic anlage may persist in some cases mitil about the time of hatching and perhaps later. The structure is so small that it could hardly be detected by dissection. Attention has ah-eady been called to the great increase in the diameter of both hepatic ducts and the lack of corresponding growth of the gall-bladder. This is shown graphically in figures 8A, B and C which show longitudinal sections of the gall-bladder in embryos 6.7, 8 and 62 mm. in length respectively. These sections are all drawn at the same magnificatioL.


Helly ('01) while studying the development of the pancreas in the rat examined the hepatic anlagen in an extensive series of elnbryos ranging from 2.2 mm. to 10 mm. in length. He states that in no specimen could he find an indubitable trace of a gallbladder. He noted that in an embryo 2.8 mm. long the primitive ductus choledochus was of considerable caliber and that the ventral portion of its wall appeared somewhat thickened. But, as this thickening passed over directly into the sprouts of the hepatic trabeculae, he did not regard it as a clear anlage of a gall-bladder. Debeyre ('04), also working on the pancreas of the rat, studied a very complete series of embryos from 11 to 21 days old. He states definitely that he foimd no gall-bladder in an embryo 12 days old, and naakes no mention of the structure in his description of later stages.

The youngest rat embryos which I have examined were 1.75 mm. in length and 11 days old (Wistar Inst. Coll. Nos. 15346 and 15347) .* In these specimens the liver is already differentiated as a thickening of the ventral part of the foregut and anterior intestinal portal. The foregut is expanded a Uttle ventrally forming a shallow hepatic pouch. From this pouch extend the earUest hepatic trabeculae which appear as solid sprouts of epithelial cells. Sagittal sections show that the Uver is composed of two parts, an anterior, the true hepatic, from which the

My thanks are due to Dr. M. J. Greemnan, Director of The Wistar Institute, and to Dr. C. A. Heuser, for their kindness in loaning me these preparations for a considerable period.


trabeculae are arising, and a posterior which gives rise to no trabeculae and which becomes continuous with the wall of the anterior intestinal portal. There is no evident cellular differentiation between these two parts aside from that associated with the formation of the hepatic trabeculae and the presence of a larger number of mitotic figures in the pars hepatica. A median section of the hepatic anlage at this stage is shown in figure 9.

A specimen one day older and 3.36 mm. long (Wistar Inst. Coll. No. 15363) shows the liver anlage in the form of a distinct

Fig. 9 Sagittal section of the hepatic pouch of an Albino rat embryo 1.75 mm. long, II days, (Wistar Inst. Coll. No. 15346). X 400.

pouch sharply marked off from the gut anteriorly and posteriorly with the forward end somewhat recessed. A large number of looping and anastomosing trabeculae arise from the anterior part of the pouch and extend some distance into the surrounding mesenchyma (fig. 10). The posterior part of the pouch gives rise to no trabeculae. In the ventral wall of this portion just in front of the posterior end of the anlagen is a sUght swelling which is marked on the internal surface by a shallow pit (X, fig. 10). It extends but a little way on either side of the mid-line.


The arrangement of the cells in this swelling suggests that seen in taste-buds but the cell boundaries are not distinct. The nuclei are elongated and peripherally placed while those of the remainder of the hepatic pouch are rounded and more generally scattered. The cytoplasm is a little lighter than that of the remainder of the pouch. This structure may be the trace of a gall-bladder anlage. Its position corresponds to that of the gall-bladder in other manmials and to the thickening previously

Fig. 10 Sagittal section of the hepatic pouch of an albino rat embryo 3.36 mm. long, 12 days (Wistar Inst. Coll. No. 15363). X 400. X, possible cystic anlage.

described by Helly. The arrangement of the cells is distinct but not striking. The structure seems to be present in another embryo of the same age (Wistar Inst. Coll. No. 15362) which is cut in an oblique plane but only in sagittal sections would it be possible to be sure of it. Lewis and Thyng ('08) have observed well-defined pockets resembling those of intestinal diverticula in the hepatic anlagen of pig embryos, but none were found in specimens under 7.8 mm. in length. . This specimen just de 556 KICHARD E. SCAMMON

scribed is of so much earlier a stage that I do not think the two structures can be regarded as identical. I have found no diverticula, such as are described by Lewis and Thyng in other mammals, in the bile-ducts of later rat embryos. Debeyre ('04) has described numerous pancreatic tubules arising directly from the ductus choledochus in rat embryos, but these do not appear until the fifteenth day, and their position differs from that of the swelling described aboveOlder embryos examined show no trace of a gall-bladder. In embryos 5.4 mm. long the posterior part of the hepatic pouch has the form of a short wide duct bifurcated at its distal extremity. The lumen is large, particularly distally, and the cells of the ventral wall have peripherally placed nuclei but there is no cystic anlage. Other embryos (11, 13 and 18 mm. in length respectively) also show no trace of a gall-bladder. In all of these specimens the lumina of the hepatic and common bileducts are of unusual size.


The history of the gall-bladder is quite different in each of the three forms under discussion. In Petromyzon a complete biliary apparatus is formed and persists throughout the larval or Ammocoetes stage. At the time of the transformation of the larval to the adult form there is a total degeneration of both gallbladder and ducts. In the pigeon the gall-bladder is developed apparently in a perfectly normal way, and later, in the majority of cases at least, is completely lost. The duct to which it is attached, persists and grows to some size. This case is complicated, however, by the presence of a larger anterior hepatic duct which opens independently into the duodenum and is never associated with the gall-bladder. In the rat there is at most but a trace of a cystic anlage in very early stages and this soon disappears. I have observed no common factors which would account for the absence of the gall-bladder in all of these examples. In the rat it is possible that the rapid and early reduction in size of the yolk-stalk which leaves the foregut wall


quite short antero-posteriorly may be a factor in inhibiting the development of the gall-bladder. In mammals generally, as compared with most lower forms, we find a distinct shortening of the liver anlage and a tendency towards consolidation of the cystic and hepatic portions. This condition is well exemplified in Bos tamiis as shown by Pensa's ('13) recent work. The rat may be but an extreme example of this consolidation due to the conditions above mentioned.

The occasional absence of the gall-bladder in man is not explained by these observations. Barring the cases of secondary obliteration of the bile-ducts, it is possible that there are in man two types of inhibition of the development of the biliary apparatus. In one the entire pars cystica of the liver anlage is suppressed. This type would be represented by the rare cases in which both gall-bladder and bile-ducts are absent. In the second only the gall-bladder fundament is lost either early or late in development and this type would be represented by the more common anomaly of absence of the bladder only.

The large size of the bile-ducts is noticeable in both pigeon and rat embryos. This seems to be a compensation for the absence of the usual bile reservoir in the form of a definite sac. A general dilation of the bile-ducts or their local expansion into chambers capable of containing a considerable amount of bile is often but not always found in animals regularly lacking a gall-bladder. This is frequently true in cases of congenital absence of the gallbladder in the human subject. Dilation of the bile ducts after cholecystectomy is also a common observation.



Brachbt, a. 1897 Sur le d^veloppement du foie et sur le pancreas de PAmmo coetes. Anat. Anz., Bd. 13. Brouha, M. 1898 Recherches sur le d^veloppement du foie, du pancreas, de

la cloison m^nt^rique et des cavit^s h^pato-ent^riques chez lea

oiseaux. Journ. de TAnat., T. 34. BujORi P. 1891 Contribution a I'^tude de la metamorphose de TAmmocoetes

branohialis^n Petromyzon planeri. Revue Biol, du Nord de la France,

T. 3. Debetre, a. p. p. 1904 Les bourgeons pancr^atiques tardifs. Thtee, Lille. Q5TTE, A. 1890 Abhandlungen zur Entwicklungsgeschichte der Tiere. Heft

V. Entwicklimgsgeschichte des Flussneimauges. Hellt, K. 1901 Zur Pankreasentwicklung der Saugethiere. Arch. f. mikr.

Anat., Bd. 57. y. KuPFFER 1893 Ueber das Pankreas bei Ammocoetes. Mtlnchener med. Abh.,

Reihe VII, Heft 5. Lanqerhans 1873 Untersuchungen ueber Petromyzon Planeri. Diss. Freiburg. Lewis, F. T., and Thtng, F. W. 1908 The regular occurrence of intestinal

diverticula in embryos of the pig, rabbit and man. Am. Jour. Anat.,

vol. 7. Nbstler, K. 1890 Beitrage zur Anatomie imd Entwicklungsgeschichte von

Petromyzon Planeri. Arch. f. Naturgeschichte, Jahrg. 52, Bd. 1.

Also: Diss. Leipzig. Pensa, a. 1914 Lo sviluppo del pancreas e delle vie biliari-extra epatiche in

Bos taurus.' Arch. Ital. Anat. Embriol., vol. 13. PiCQui, R. 1913 Recherches sur la structure et le d^veloppement du pancreas

chez Petromyzon. M^m. Soc. de la Zool. de France, T. 26.