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1 THE APPLIED ANATOMY OF THE GALL-BLADDER AND EXTRA-IEPATIC BILIARY PASSAGES, WITH SPECIAL REFERENCE TO THEIR DEVELOPMENT Lecture delivered at The Royal College of Surgeons of England on 1st July, 1947 by Professor J. Kirk, M.B., Ch.B., F.R.C.S.(Ed.) Courtauld Professor of Anatomy, University of London Embryology THE 4.5 MM. HUMAN EMBRYO (4th to 5th week) shows an entodermal bud growing from the distal end of the foregut into its ventral mesentery. This is the hepatic bud whose branching stem produces the liver with its intra- and extra-hepatic duct system, including the gall-bladder. Only that portion of the gut which is supplied by the celiac axis artery -the foregut-possesses a ventral mesentery. This is attached to the anterior abdominal wall as far as the umbilicus. Cranialwards it broadens out and thickens to become the septum transversum which at this stage partially separates the thoracic and abdominal cavities. Caudalwards it ends abruptly on the gut at a point which later will be recognized as the junction of the upper J with the lower I of the second part of the duodenum. Here the hepatic bud first forms and determines the site of the future duodenal papilla and ostium of the common bile duct and main pancreatic duct. Embedded in the ventral mesentery the hepatic bud as it grows extends upwards and penetrates the septum in the interior of which its terminal branches produce innumerable rods of cells (hepatic cylinders) which after canalisation become the intra-hepatic biliary ducts and canaliculi. The entodermal cells in the walls of these minute channels become the glandular cells of the liver, and the mesoderm of the mesentery and septum transversum forms the connective tissue of the whole hepatic system. From the base of the bud, close to the gut, two secondary buds arise in a lateral position, right and left-the ventral pancreatic buds. In man the left of these quickly degenerates and disappears, but the right one grows rapidly and produces the lower part of the head of the pancreas (uncinate lobe) and the terminal portion of the main pancreatic duct (Wirsung) whose opening into the duodenum, therefore, will inevitably be closely associated with the opening of the common duct on the duodenal papilla. The main hepatic stem continues to lengthen and on its 132

2 APPLIED ANATOMY OF GALL-BLADDER AND EXTRA-HEPATIC BILIARY PASSAGES right side produces a branch which, without further division, ends in a blind diverticulum-the gall-bladder-whose stalk becomes the cystic duct. More distally the parent stem again sprouts, this time dichotomously, to form the right and left hepatic ducts. These continue the branching process and eventually form the intra-hepatic biliary duct system and the liver itself. In the light of the foregoing elementary facts regarding the development of the biliary tree it will not be surprising to find that certain anomalies, due to exuberant or aberrant growth, are quite common, and that others of a rarer type occasionally present themselves to the surgeon. Anomalies of the Biliary Tree The gall-bladder may not remain as a blind cul-de-sac but may itself sprout like the other terminal parts of the tree and thus produce accessory ductules which communicate directly between it and the liver. Two gall-bladders may form on the biliary stem, each connected to the common bile duct by its own cystic duct (vesica duplex) or sharing the same cystic stalk (vesica divisa). A much commoner anomaly is the presence of an accessory hepatic duct usually coming from the right extremity of the porta hepatis and uniting with the common hepatic duct at a point more distal than the junction of the other two. Such a duct, when present, inevitably has a close relation to a normally situated cystic artery lying, as it does, in the angle between the cystic and common hepatic ducts. Commonest of all are the variations in the length of the ducts themselves. The two hepatic ducts are usually short and lie high up in the porta hepatis. They may, however, extend much lower before uniting, thus shortening the length of the common hepatic duct. The cystic duct may be only a few mm. in length or it may be absent altogether, leaving the gall-bladder as a sessile diverticulum on the common duct stem. The gall-bladder itself may be absent as is the case in many animals, e.g., the rat, the pigeon, and the horse. On the other hand, a normally formed gall-bladder may be enveloped and buried in the liver substance, just as the inferior vena cava and the umbilical vein are sometimes found to have been embedded by the exuberant growth of the surrounding hepatic tissue. The cystic duct may extend far down, running close and parallel to.the main duct for several inches, before opening into the latter close to the duodenal wall. In such circumstances the two ducts are often enclosed in a common fascial sheath. If an apparently normal junction of the cystic and common duct is slit open, an internal partition is frequently found separating them for a considerable distance beyond their point of meeting, the common duct here possessing a double lumen. The importance of this to the surgeon is obvious, e.g., in division of the common duct followed by cholecystenterostomy. 133

3 JOHN KIRK It will be remembered that the- cystic duct itself possesses a permanent internal spiral fold of its mucous membrane (valve of Heister) which prevents kinking of the duct in spite of its S-shaped bends, and thus no doubt, facilitates the flow of bile up or down the tube according to need. The ridge extending distalwards from the junction of the cystic and common ducts, above described, has probably a similar functional value. On the inferior part of the neck of the gall-bladder there is frequently an accessory diverticulum (Hartmann's pouch) which is of special interest since in inflammatory conditions it is one of the first parts of the viscus to form adhesions to neighbouring structures, particularly the first part of the duodenum. The cystic duct instead of coming from the right side of the main tube may sprout from its anterior wall or from its left side, in which case it crosses the common duct to reach the gall-bladder-a circumstance again of great import to the surgeon. A Critical Point in the Duodenum The site of outgrowth of the primary hepatic bud is obviously a critical point in the anatomy, physiology and pathology of the duodenum. From about the 5th to the 6th week the rapid proliferation of the entodermal epithelium in the biliary stem as well as in the duodenum itself, causes, quite normally, a temporary occlusion of the gut (Keithl). After the 6th week the expansion of the tube and the absorption of the excess of its entodermal lining restores the lumen. Sometimes resolution fails to take place and atresia duodeni, partial or complete, is the result. Fig. 1 shows a case of this type in which, at birth, a stenosis of the duodenum existed exactly at the point where the common bile duct penetrated the gut wall. In severe cases the atresia may extend to the gall-bladder and the hepatic duct system. Blood Supply The blood supply of the biliary tract is notoriously variable but when it is remembered that the hepatic bud arises from the gut on the boundary line between the foregut (supplied by the coeliac axis) and the midgut (supplied by the superior mesenteric artery), it is not surprising that the main artery of the liver sometimes comes from the one and sometimes from the other of these vessels, and not infrequently there are two hepatic arteries, one coming from each source. Nor is it to be wondered at that the superior pancreatico-duodenal branch of the cceliac axis tree anastomoses with the inferior pancreatico-duodenal branch of the superior mesenteric artery in the region of the duodenal papilla. The pancreaticoduodenal arteries are often duplicated. It is the cystic artery itself, however, which is, perhaps, of greatest importance to the surgeon. You will remember that it is usually given 134

4 APPLIED ANATOMY OF GALL-BLADDER AND EXTRA-HEPATIC BILIARY PASSAGES off by the right branch of the hepatic artery just after the latter has crossed from left to right behind the common hepatic duct and in front of the portal vein. Not infrequently, however, the parent stem, or the cystic artery itself, crosses anterior to the duct, and in rare cases (9 per cent.) (Grant2) it may be found running deeply and crossing behind the portal vein. In all these cases, however, the cystic artery finally comes to lie above and to the left of the cystic duct in the cleft between it and the common hepatic duct, and running to the neck of the gall-bladder it divides into two branches, one taking a course beneath the peritoneum of its free surface and the other taking the side apposed to the liver. An accessory cystic artery is occasionally present. This may ascend from the main hepatic vessel or even from the superior mesenteric artery. An accessory hepatic artery arising from the left gastric artery is quite common. The cystic vein as a rule drains into the right branch of the portal vein in the porta hepatis, but one or more small veins may pass direct to the liver from the upper surface of the gall-bladder, thus accounting for the venous bleeding which sometimes occurs when the gall-bladder is separated from its hepatic bed. Peritoneal Folds At an early period the duodenum and its two mesenteries (with their contained structures) lie in the sagittal plane, but the " rotation of the gut," and all that this involves, profoundly alters the anatomy of the upper abdomen. This is not the occasion to describe these processes in detail. Suffice it to recall that the end-result, as far as the duodenum is concerned, is to lay it over on its right side and to plaster it down in this position so that it and its mesenteries adhere to the structures on the posterior abdominal wall, e.g., the right kidney, the renal vessels and the inferior vena cava. This rotation movement, combined with a differential growth of its wall which causes an unequal expansion of the duodenal tube brings the original anterior wall and the site of the duodenal papilla to a posterior position. The ventral mesentery containing the biliary stem likewise becomes folded over with the gut so that the common bile duct comes to occupy a position dorsal to the head of the pancreas and the first part of the duodenum. The latter portion of the gut, like the pylorus, retains a considerable amount of mobility because its ventral mesentery still has an unattached border-the free border of the lesser omentum. Above, this mesenteric fold encloses the porta hepatis and, extending to the right and forwards, enfolds the gall-bladder. Extending to the left and backwards it becomes continuous with the attachment of the gastro-hepatic ligament in the fissure which contains the ligamentum venosum. Between the liver and the duodenum it forms the anterior wall of the epiploic foramen (of Winslow) containing the common bile duct and the cystic duct, the hepatic artery and the portal vein. Remembering the relation of the hepatic bud and its derivatives to the ventral mesentery 135

5 JOHN KIRK and the amount of rotation and enfolding to which this mass of plastic mesoderm has been subjected, it is not surprising that the definite attachments of the duodeno-hepatic fold are liable to some variation. This is the explanation of those frequent extensions of the lesser omentum to the right, attaching the inferior surface of the gall-bladder to the second part of the duodenum and transverse colon, or even reaching far enough completely to enfold the fundus of the gall-bladder and attach it to the right colic flexure (cystico-colic ligament). Some such outlying part of the lesser omentum, in greater or less degree, is very common. It is a bloodless fold because the biliary ducts and their accompanying vessels remain in their normal position. The clinical importance of such a ligament, however, lies in the fact that it forms a focus for adhesions binding gall-bladder to duodenum or transverse colon, thus permitting gallstones to ulcerate through into one or other of these viscera. The green discoloration of the pyloric canal sometimes seen at autopsy is due to the fact that the gall-bladder not infrequently lies in close relation with it. Adhesions may develop between the gall-bladder and the pyloric canal, and gallstones may ulcerate through into the stomach and be vomited (Wingate Todd3). In this connection it is well to remember, too, the close relationship of the fundus of the gall-bladder to the anterior abdominal wall. Treves and others have reported cases where gallstones have suppurated out through the anterior abdominal wall, and have been removed from abscesses in the parietes4. It will be obvious that in the operation of mobilizing the duodenum to gain access to the lower part of the common bile duct, the surgeon is actually restoring the duodenum to its original embryonic pgsition. Microscopic Anatomy A striking feature of the structure of the biliary tract, as a whole, is the relative absence of muscle as compared with the intestinal tube. Our investigations confirm the observations of Boyden5 and others that the biliary ducts are, for the most part, fibro-elastic tubes capable of great distension but non-contractile, except in the case of the gall-bladder and the lower one inch of the common bile duct in which smooth muscle is plentiful. This is nothing new, however, for some 90 years ago Ktllicker6 described the wall of the ductus choledochus and cystic duct as " distinctly divided into a mucous membrane and a fibrous layer, which latter contains a few muscular fibre-cells, though, upon the whole, so sparingly, that these ducts cannot be said to possess a special muscular coat." The muscle of the gall-bladder is not arranged in layers as in the intestine, but is composed of interwoven fibre bundles. Its mucous membrane is lined with high columnar epithelium and though there are no villi in the accepted sense of the term, the membrane is thrown up into a series of irregular ridges which give the inner surface of the mucosa a flattened 136

6 Stomach -. Duodenum (proxinal) Common Bile Duct Site of Stenosis _uuoaenum (distal) Fig. 1. Congenital atresia of duodenum, showing site of stenosis where common bile duct penetrates the gut wall.!-51 Fig. 2. Duodenum, human embryo, Fig. 3. Duodenum, human embryo. 27 mm. Transverse section x 62. Note 27 mm. Transverse section x 62. Note common bile duct embedded in developing common bile duct entering muscle coat of pancreatic tissue external to the gut wall. gut. By kind permission ol The Editor, Journal of Anatomy. Fig. 4. Duodenum, human embryo, 27 mm. Transverse section x 50. Note common bile and pancreatic ducts in submucosa surrounded by differentiating muscle continuous with muscle of duodenal wall. Facing page 136

7 Fig. 5. Duodenum, human embryo, 27 mm. Transverse section x62. Common bile and pancreatic ducts have now ioined. Note the surrounding muscle. Fig. 6. Duodenal papilla and ostium of human adult. Longitudinal section x 14. Fig. 7. Duodenal papilla of human adult. Transverse section x 15. Common and pancreatic ducts lying in submucous coat of bowel approaching ostium. Fig. 8. Duodenal papilla of human adult, x 2. Note typical arrangement of plicx of mucous membrane, also presence of the valvular plug in the orifice.

8 APPLIED ANATOMY OF GALL-BLADDER AND EXTRA-HEPATIC BILIARY PASSAGES honeycomb appearance. This greatly increases the surface area which is so much concerned with the absorption of bile. fluid. While in the gallbladder the concentration of the bile is such that it takes approximately 500 c.c. of bile from the liver to produce 50 c.c. of bile in the common duct. About 1,000 c.c. are secreted by the liver every 24 hours, and the normal capacity of the gall-bladder is 50 c.c. (approximately 14 ounces). Bile begins to be secreted by the liver at the end of the twelfth week (Lucas Keene and Hewer7). Large numbers of elastic fibres are mixed with the collagen fibres of its outer coat and, under certain pathological conditions, the distensibility of the gall-bladder is quite remarkable, e.g., mucocele and empyema. The biliary ducts themselves are lined by columnar epithelium of a similar type and the lamina propria of fibroelastic tissue is studded with many mucos-secreting tubulo-alveolar glands. These are typical of the whole biliary tract with the exception of the gall bladder in which, however, they are sometimes to be found near its neck. The terminal end of the common bile duct penetrates the wall of the duodenum and united with, or in close proximity to, the main pancreatic duct, opens on a papilla 31 to 4 inches from the pylorus. As the duct pierces the muscle coats of the duodenum it splits the two layers of muscle in grid-iron fashion, and, as it does so, first the longitudinal coat and then the circular coat contribute to form a muscular collar which surrounds both the extra-mural and intra-mural portions of the duct. The duct pierces the wall ofthe gut obliquely and comes to lie with the pancreatic duct in the sub-mucous coat of the bowel where they are now both surrounded by the muscular collar (sphincter of Oddi). As they lie in juxtaposition muscle bundles not only surround but pass between the two ducts. The extra-mural part of the sphincter is derived from the longitudinal coat and the intra-mural portion is continuous with the circular fibres of the gut. In the region of the muscular " window " the circular coat of the duodenum is markedly thickened and the amount of nerve tissue in Auerbach's plexus is noticeably increased. This development of a sphincter muscle around the ducts as they lie in the sub-mucous coat can be plainly seen in the human embryo of 27 mm. (8 weeks) as also can its derivation from the muscle of the duodenal wall even at this early stage. (Vide Figs. 2, 3, 4, and 5.) The so-called ampulla of Vater, i.e., a dilated channel common to the bile and pancreatic ducts, seems to be a misnomer, for it is not to be found in most human subjects. Figs. 6 and 7 show the usual mode of termination in the adult. As the united ducts pass to their opening on the duodenal papilla, the channel is packed with valvular folds of its mucous membrane and muscle fibres extend into the connective tissue core of these folds. Such an arrangement suggests that contraction of the sphincter muscle has the additional effect of retracting and bunching these folds together, thus preventing reflux of duodenal contents as well as controlling the exit of bile into the bowel

9 JOHN KIRK No muscle is found surrounding the actual orifice itself and often even with the naked eye the tip of the valvular plug can be seen occupying the aperture (Fig. 8). Large nerve bundles (nervus choledochus) accompany the common bile duct throughout its length and nerve fibre endings can be traced in the smooth muscle of the sphincter as well as in the muscle fibres of the valvular folds. REFERENCES I KEITH, A. (1933) Human embryology and morphology. 5th edition. 2 GRANT, J. C. B. (1944) A method of anatomy. 3rd edition. 3 WINGATE TODD, T. (1915) The clinical anatomy of the gastro-intestinal tract. 4 TREVES, F. (1897) Surgical applied anatomy. 5 BOYDEN, E. A. (1936) The pars intestinalis of the common bile buct. Anat.Rec. 66, 217. SCHWEGLER, R. A. and BOYDEN, E. A. (1937) The development of the pars intestinalis of the common bile duct in the human f(etus. Anat. Rec. 67, 431 ; 68, 17 and 193. KREILKAMP, B. L. and BOYDEN, E. A. (1940) Variability in the composition of the sphincter of Oddi. Anat. Rec. 76, K6LLIKER, A. (1860) A manual of human microscopic anatomy. 7 LUCAS KEENE, M. F. and HEWER, E. E. (1924) Glandular activity in the human ftetus. Lancet 2, (1929) Digestive enzymes of the human fcetus, Lancet 1,

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