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The function of the gallbladder as a lesser biliary circulation
MedicalHypotheses21:
165-170,
1986
THE FUNCTION OF THE GALLBLADDER AS A LESSER BILIARY CIRCULATION By: F. Al-Hilli. Department of Pathology, Salmaniya Medical Center, P.O.Box 12, Bahrain, Arabian Gulf. Address for correspondence:
P.O.Box 26569, Bahrain, Arabian Gulf. ABSTRACT
The function of the gallbladder is questioned in a hypothesis postulating that all bile which enters this reservoir is totally absorbed to the liver and none of it flows back to the cystic duct and duodenum. Cholecystokinesis is believed to increase and maintain a gradient of intravesical pressure which increases the filtration pressure necessary for the absorption of bile to the liver. The absorption is through the tributaries of the cystic veins, the ducts of Luschka and Rokitansky-Aschoff sinuses. Although the hypothesis lacks experimental support,it is based on a number of anatomical, histological, physiological, radiological and surgical observations. INTRODUCTION In the practice of medicine, many mechanisms in the various biological systems of man are regarded as facts. This is not only because the original discovery of these mechanisms was made long ago, but also because the scientific approach to investigate most biological problems has gradually deviated towards the peripheral details rather than the basic concepts. New approaches providing better understanding of the "established facts" must therefore be acknowledged. This paper puts forward a new challenge as to one of the physiological roles of the gallbladder (GB). It lacks experimental support but it is based on many clinical observations collected from the literature as well as from the practice of the author. THE HYPOTHESIS It is traditional to regard the GB as a reservoir of bile, the bile secreted from the liver is stored and concentrated until required for digestive purposes. The GB is believed then to
where
165
contract and discharge its contents through the cystic duct (CD) and common bile duct (cBD) into the duodenum. The hypothesis put forward is that all bile which enters the GB is totally absorbed and transferred back to the liver through the tributaries of the cystic vein (which terminates in the right branch of the portal vein with few small veins passing directly from the GB to the substance of the liver) and possibly through the ducts of Luschka (DL) and the Rokitansky-Aschoff sinuses (RAS). In this way, none of the bile contained in the GB flows into the CD, CBD or duodenum and the bile required for duodenal digestion must therefore come directly from the liver. The contractions of the GB are believed to increase and maintain a gradient of intravesical pressure which in turn increases the filtration pressure necessary for the absorption of bile from the GB. The GB may therefore act as a lesser biliary circulation (LBC), whereby all the GB bile is returned to the greater biliary circulation . . the liver. This hypothesis receives practical support from ia:y anatomical, histological, physiological, radiological and surgical observations. Anatomy Normally, the GB does not lie in line with the common hepatic and biliary ducts as it is usually illustrated. It rests on the transverse colon and curves on itself so that its body may reach as low as the level of the opening of the Sphincter of Oddi. This position does not help evacuation of bile into the tortuous CD but helps the retention of bile within the low-lying GB and then its absorption. The mucosal surface of the GB, which is designed for absorption, is divided into polygonal spaces by delicate mucosal folds. These folds are best appreciated if a fresh GB is examined under water using a dissecting microscope, when they are seen to float up like a water plant in a clear pool. Around the neck of GB the mucosa is thrown into series of ridges arranged around the neck which are known as the spiral valve (Valve of Heister). Being made of mucosal folds, this valve may only allow the flow of bile from the extrahepatic biliary ducts (EBD) to the GB but prevent bile flowing from the GB to these ducts. There is no known valve which would allow the flow of fluids in both directions unless it is controlled by automatic or manual mechanism. During routine postmortem examination, which is normally performed 24 hours after death, the pressure applied to the GB which causes the flow of bile into the extrahepatic biliary ducts is used to identify the choledochoduodenal opening. This does not contradict the present hypothesis of the GB as a LBC because of the rapid autolysis of the GB (and the gastroduodenal) mucosa, including the valve of Heister which occurs in less than 30 minutes after death.
166
Histology The tall lining of the mucosal surface of the GB is designed for absorption rather than secretion and the various droplets commonly seen in the mucosa of sections of normal GB may indicate its absorptive role including lipids. These droplets must not be confused with those of cholesterolosis in which the droplets are not only confined to the epithelial cells but also seen in the phagocytic histiocytes in the lamina propria. On the other hand, the ultrastructure of the lining epithelium of the GB shows great absorptive similarity to that of the intestinal mucosa (1). The absence of submucosa from the GB indicates that the contractions of its muscles are not true peristalsis such as those of the stomach or intestine where the contractions of the well developed muscle coat permit the mucosal folds to move and slide over a large surface of the submucosa and thus aid in absorption. The contraction of the randomly orientated (i.e. weak) smooth muscle fibers of the GB may principally be aimed at maintaining a certain gradient of intravesical pressure necessary for the total absorption of bile. Another possible route for the absorption of bile from the GB is through the DL and the RAS. The DL are present on the hepatic side of the GB and communicate freely with each other in the serosal coat of the GB as well as with the intrahepatic biliary ducts (1,2) but they may possibly communicate in the serosal coat with the RAS which are themselves mucosal extensions into this coat. The presence of these sinuses in sections of GB submitted for histological examination is not an indication of a diseased GB because they are commonly encountered in sections of normal GB (3) . It follows that during cholecystokinesis the GB bile may flow directly through the RAS and DL to the liver. This route may account for the absorption of such bile components as cholesterol and bile salts and pigments which are believed not to be absorbed from the GB mucosa (4,5,6,7). Physiology During a fasting period, when there is no food in the duodenum, the tonic contractions of the sphincter of Oddi can raise the pressure in the biliary ducts to as much as 15-25 cm of water and at this pressure range bile can flow through the CD to the GB, but at pressure levels above 25 cm of water the secretion of bile by the liver ceases (7). The rhythmic contraction of the GB can however, raise the pressure in this viscus to 30-40 cm of water without affecting the secretion or the flow of bile from the liver (7). It seems very probable that this high intramural pressure is the essential factor in raising the filtration pressure required for the absorption of bile from the GB. Another 167
inference would be that the function of the GB is not only its role as a LBC but also its control of the pressure within the biliary ducts thus preventing its rise above the physiological limits of bile secretion. The bile which enters the GB is composed of water (98% ), and solids (2%) which include bile salts, bile pigment, cholesterol, mucin and inorganic salts (7). Given the capacity to hold about 30-40 ml the GB would soon be filled with bile beyond its storage capacity were it not for the gallbladder's remarkable ability rapidly to absorb water and inorganic salts (bicarbonates and chloride salts of sodium and potassium) (4,7,8). For example, the canine GB can absorb 10-16E' of its volume per hour and almost 90% of the GB bile is absorbed during this period (4,9,10,11). Thus the organic contents of the 50-60 ml GB bile represent the organic contents of 500-600 ml liver bile. This ability of the GB to absorb water and inorganic salts leaves the GB with concentrated bile consisting of bile salts, bile pigments and cholesterol which are reported as being non-absorbable (4,5,6,7). But this is debatable and there is much evidence that even these substances are normally entirely absorbed by the GB mucosa (12). For example, investigation into the absorption of bile salts reveals that the normal GB can absorb these salts by passive diffusion (6). Again it seems probable that the absorption of these substances can only take place when a certain level of "absorptive intraluminal pressure" is attained and when certain other bile components are absorbed into the intrahepatic (or biliary duct) circulation. Bilirubin is the chief bile pigment in the human bile and thus must be conjugated with glucuronic acid prior to its excretion by the liver (5,7). Again, there is evidence to indicate that unconjugated forms of bilirubin are readily absorbed by the GB, and that conjugated bilirubin is also absorbed, but at a slower rate (13). It is interesting to note that the conjugated forms are water-soluble and thus may diffuse easily, possibly alongside the bile salts. The unconjugated forms, on the other hand, are lipid-soluble and may possibly be absorbed alongside the cholesterol which the GB can absorb (12). The absorption from the GB of bile and possibly the secretion of other substances including salts, mucin (from the mucus secreting glands which are normally present in the neck of the GB) and cholesterol is kept under constant equilibrium so that a disturbance of either mechanism may result in the appearance of various pathological conditions of the GB including gallstones. Radiology In cholecystography, the dye salts of phenolphthalein are given either orally or intravenously but the first radiograph which normally shows the shadow of the GB is taken 2-14 hours 168
later depending on the route of administration of the salt. A second radiograph showing the "emptying" (i.e. contraction) of the GB is taken l-5 hours after the ingestion of a fatty meal. If these x-rays are meant to show the evacuation of the gallbladder's content to the CD and the CBD, then they should be taken immediately after the administration of the dye or the fatty meal. It appears that these contractions are like those of the splenic capsule in response to shock conditions. Thus, just as the splenic capsule may take several hours to undergo gradual contractions to evacuate its contents into the general circulation and alter the peripheral hematological indices, the GB may also take several hours to raise its intraluminal filtration pressure for the absorption of its bile. Surgery It is interesting to note that after cholecystectomy the biliary ducts become dilated not only to accommodate the bile which is continuously secreted by the liver, but also to "reestablish" to some extent the lost role of the GB as a LCB. similarly, the tributaries of the retroduodenal vein (which drains the EBD to the gastroduodenal vein and then to the portal vein) become dilated and tortuous. Likewise, this is to compensate for the role of the tributaries of the cystic vein. There is some evidence to indicate that cholecystectomy is followed by increased biliary duct pressure and this may cause the liver to secrete less bile than normal (7,141. It should also be noted that patients with biliary dyskinesia who are advised to avoid fatty meals continue to complain of fatty dyspepsia even after cholecystectomy. This is not only due to the cholecystokinetic effects of these fatty meals but also to their choleretic effect on the liver which induces the secretion of more bile than the EBD can accommodate.
CONCLUSION The hypothesis requires experimental support including the study of pressure gradients between the GB and the intrahepatic ducts; chemical composition of bile in the liver, GB and the EBD and the use of radioactive markers to label each of the components of the GB bile. REFERENCES 1.
Bloom W , Fawcett DW. A Textbook of Histology. 10th ed. WB Saunders , Philadelphia, London, Toronto, 1975.
169
2.
Misson AJB. Abberrations of the biliary passages on the surface of the liver and in the gallbladder. Br J Surg 56: 427, 1969.
3.
Hoffbaur FW. Needle biopsy of the liver. JAMA 134: 666, 1947.
4.
Dietschy JM. Recent developments transport across the gallbladder 50: 692, 1966.
5.
Lester R Troxler F. Recent advances in bile pigment metabolisk. Gastroentrol 56: 143, 1969.
6,
O&row JD. Absorption of the gallbladder of bile salts, sulphobromophthalein and iodopamide. J Lab Clin Med 74: 482, 1969.
7.
Brobeck JR (ed). Best & Taylor's Physiological Medical Practice. Williams & Wilkins, 1979.
8.
Banfield WJ. Physiology 770, 1975.
9.
Rous P , McMaster PD. The concentrating gallbladder. J exp Med 34: 47, 1921.
10.
Ravdin IS , Johnston CG , Riegel C , Wright SL. Studies of gallbladder function. Am J Physiol 100: 317, 1931.
II.
Grim E , Smith GA. Water flux rates across dog gallbladder wall. Am J Physiol 191: 550, 1957.
12.
Wheeler HO. Concentrating Med 51: 588, 1971.
13.
Ostrow JD. Absorption Clin Invest 46: 2035,
14.
in solute and water epithelium. Gastroentrol
of the gallbladder.
Basis of
Gastroentrol
69:
activity of the
function of the gallbladder.
Am J
of bile pigments by the gallbladder. 1967.
Menguy RB , Hallenbeck GA , Bollman JL , Grindley H. Intraductal pressure and sphincteric resistance in canine pancreatic and biliary ducts after various stimuli. Surg Gynec Obstet 106: 306, 1958.
170
J
165-170,
1986
THE FUNCTION OF THE GALLBLADDER AS A LESSER BILIARY CIRCULATION By: F. Al-Hilli. Department of Pathology, Salmaniya Medical Center, P.O.Box 12, Bahrain, Arabian Gulf. Address for correspondence:
P.O.Box 26569, Bahrain, Arabian Gulf. ABSTRACT
The function of the gallbladder is questioned in a hypothesis postulating that all bile which enters this reservoir is totally absorbed to the liver and none of it flows back to the cystic duct and duodenum. Cholecystokinesis is believed to increase and maintain a gradient of intravesical pressure which increases the filtration pressure necessary for the absorption of bile to the liver. The absorption is through the tributaries of the cystic veins, the ducts of Luschka and Rokitansky-Aschoff sinuses. Although the hypothesis lacks experimental support,it is based on a number of anatomical, histological, physiological, radiological and surgical observations. INTRODUCTION In the practice of medicine, many mechanisms in the various biological systems of man are regarded as facts. This is not only because the original discovery of these mechanisms was made long ago, but also because the scientific approach to investigate most biological problems has gradually deviated towards the peripheral details rather than the basic concepts. New approaches providing better understanding of the "established facts" must therefore be acknowledged. This paper puts forward a new challenge as to one of the physiological roles of the gallbladder (GB). It lacks experimental support but it is based on many clinical observations collected from the literature as well as from the practice of the author. THE HYPOTHESIS It is traditional to regard the GB as a reservoir of bile, the bile secreted from the liver is stored and concentrated until required for digestive purposes. The GB is believed then to
where
165
contract and discharge its contents through the cystic duct (CD) and common bile duct (cBD) into the duodenum. The hypothesis put forward is that all bile which enters the GB is totally absorbed and transferred back to the liver through the tributaries of the cystic vein (which terminates in the right branch of the portal vein with few small veins passing directly from the GB to the substance of the liver) and possibly through the ducts of Luschka (DL) and the Rokitansky-Aschoff sinuses (RAS). In this way, none of the bile contained in the GB flows into the CD, CBD or duodenum and the bile required for duodenal digestion must therefore come directly from the liver. The contractions of the GB are believed to increase and maintain a gradient of intravesical pressure which in turn increases the filtration pressure necessary for the absorption of bile from the GB. The GB may therefore act as a lesser biliary circulation (LBC), whereby all the GB bile is returned to the greater biliary circulation . . the liver. This hypothesis receives practical support from ia:y anatomical, histological, physiological, radiological and surgical observations. Anatomy Normally, the GB does not lie in line with the common hepatic and biliary ducts as it is usually illustrated. It rests on the transverse colon and curves on itself so that its body may reach as low as the level of the opening of the Sphincter of Oddi. This position does not help evacuation of bile into the tortuous CD but helps the retention of bile within the low-lying GB and then its absorption. The mucosal surface of the GB, which is designed for absorption, is divided into polygonal spaces by delicate mucosal folds. These folds are best appreciated if a fresh GB is examined under water using a dissecting microscope, when they are seen to float up like a water plant in a clear pool. Around the neck of GB the mucosa is thrown into series of ridges arranged around the neck which are known as the spiral valve (Valve of Heister). Being made of mucosal folds, this valve may only allow the flow of bile from the extrahepatic biliary ducts (EBD) to the GB but prevent bile flowing from the GB to these ducts. There is no known valve which would allow the flow of fluids in both directions unless it is controlled by automatic or manual mechanism. During routine postmortem examination, which is normally performed 24 hours after death, the pressure applied to the GB which causes the flow of bile into the extrahepatic biliary ducts is used to identify the choledochoduodenal opening. This does not contradict the present hypothesis of the GB as a LBC because of the rapid autolysis of the GB (and the gastroduodenal) mucosa, including the valve of Heister which occurs in less than 30 minutes after death.
166
Histology The tall lining of the mucosal surface of the GB is designed for absorption rather than secretion and the various droplets commonly seen in the mucosa of sections of normal GB may indicate its absorptive role including lipids. These droplets must not be confused with those of cholesterolosis in which the droplets are not only confined to the epithelial cells but also seen in the phagocytic histiocytes in the lamina propria. On the other hand, the ultrastructure of the lining epithelium of the GB shows great absorptive similarity to that of the intestinal mucosa (1). The absence of submucosa from the GB indicates that the contractions of its muscles are not true peristalsis such as those of the stomach or intestine where the contractions of the well developed muscle coat permit the mucosal folds to move and slide over a large surface of the submucosa and thus aid in absorption. The contraction of the randomly orientated (i.e. weak) smooth muscle fibers of the GB may principally be aimed at maintaining a certain gradient of intravesical pressure necessary for the total absorption of bile. Another possible route for the absorption of bile from the GB is through the DL and the RAS. The DL are present on the hepatic side of the GB and communicate freely with each other in the serosal coat of the GB as well as with the intrahepatic biliary ducts (1,2) but they may possibly communicate in the serosal coat with the RAS which are themselves mucosal extensions into this coat. The presence of these sinuses in sections of GB submitted for histological examination is not an indication of a diseased GB because they are commonly encountered in sections of normal GB (3) . It follows that during cholecystokinesis the GB bile may flow directly through the RAS and DL to the liver. This route may account for the absorption of such bile components as cholesterol and bile salts and pigments which are believed not to be absorbed from the GB mucosa (4,5,6,7). Physiology During a fasting period, when there is no food in the duodenum, the tonic contractions of the sphincter of Oddi can raise the pressure in the biliary ducts to as much as 15-25 cm of water and at this pressure range bile can flow through the CD to the GB, but at pressure levels above 25 cm of water the secretion of bile by the liver ceases (7). The rhythmic contraction of the GB can however, raise the pressure in this viscus to 30-40 cm of water without affecting the secretion or the flow of bile from the liver (7). It seems very probable that this high intramural pressure is the essential factor in raising the filtration pressure required for the absorption of bile from the GB. Another 167
inference would be that the function of the GB is not only its role as a LBC but also its control of the pressure within the biliary ducts thus preventing its rise above the physiological limits of bile secretion. The bile which enters the GB is composed of water (98% ), and solids (2%) which include bile salts, bile pigment, cholesterol, mucin and inorganic salts (7). Given the capacity to hold about 30-40 ml the GB would soon be filled with bile beyond its storage capacity were it not for the gallbladder's remarkable ability rapidly to absorb water and inorganic salts (bicarbonates and chloride salts of sodium and potassium) (4,7,8). For example, the canine GB can absorb 10-16E' of its volume per hour and almost 90% of the GB bile is absorbed during this period (4,9,10,11). Thus the organic contents of the 50-60 ml GB bile represent the organic contents of 500-600 ml liver bile. This ability of the GB to absorb water and inorganic salts leaves the GB with concentrated bile consisting of bile salts, bile pigments and cholesterol which are reported as being non-absorbable (4,5,6,7). But this is debatable and there is much evidence that even these substances are normally entirely absorbed by the GB mucosa (12). For example, investigation into the absorption of bile salts reveals that the normal GB can absorb these salts by passive diffusion (6). Again it seems probable that the absorption of these substances can only take place when a certain level of "absorptive intraluminal pressure" is attained and when certain other bile components are absorbed into the intrahepatic (or biliary duct) circulation. Bilirubin is the chief bile pigment in the human bile and thus must be conjugated with glucuronic acid prior to its excretion by the liver (5,7). Again, there is evidence to indicate that unconjugated forms of bilirubin are readily absorbed by the GB, and that conjugated bilirubin is also absorbed, but at a slower rate (13). It is interesting to note that the conjugated forms are water-soluble and thus may diffuse easily, possibly alongside the bile salts. The unconjugated forms, on the other hand, are lipid-soluble and may possibly be absorbed alongside the cholesterol which the GB can absorb (12). The absorption from the GB of bile and possibly the secretion of other substances including salts, mucin (from the mucus secreting glands which are normally present in the neck of the GB) and cholesterol is kept under constant equilibrium so that a disturbance of either mechanism may result in the appearance of various pathological conditions of the GB including gallstones. Radiology In cholecystography, the dye salts of phenolphthalein are given either orally or intravenously but the first radiograph which normally shows the shadow of the GB is taken 2-14 hours 168
later depending on the route of administration of the salt. A second radiograph showing the "emptying" (i.e. contraction) of the GB is taken l-5 hours after the ingestion of a fatty meal. If these x-rays are meant to show the evacuation of the gallbladder's content to the CD and the CBD, then they should be taken immediately after the administration of the dye or the fatty meal. It appears that these contractions are like those of the splenic capsule in response to shock conditions. Thus, just as the splenic capsule may take several hours to undergo gradual contractions to evacuate its contents into the general circulation and alter the peripheral hematological indices, the GB may also take several hours to raise its intraluminal filtration pressure for the absorption of its bile. Surgery It is interesting to note that after cholecystectomy the biliary ducts become dilated not only to accommodate the bile which is continuously secreted by the liver, but also to "reestablish" to some extent the lost role of the GB as a LCB. similarly, the tributaries of the retroduodenal vein (which drains the EBD to the gastroduodenal vein and then to the portal vein) become dilated and tortuous. Likewise, this is to compensate for the role of the tributaries of the cystic vein. There is some evidence to indicate that cholecystectomy is followed by increased biliary duct pressure and this may cause the liver to secrete less bile than normal (7,141. It should also be noted that patients with biliary dyskinesia who are advised to avoid fatty meals continue to complain of fatty dyspepsia even after cholecystectomy. This is not only due to the cholecystokinetic effects of these fatty meals but also to their choleretic effect on the liver which induces the secretion of more bile than the EBD can accommodate.
CONCLUSION The hypothesis requires experimental support including the study of pressure gradients between the GB and the intrahepatic ducts; chemical composition of bile in the liver, GB and the EBD and the use of radioactive markers to label each of the components of the GB bile. REFERENCES 1.
Bloom W , Fawcett DW. A Textbook of Histology. 10th ed. WB Saunders , Philadelphia, London, Toronto, 1975.
169
2.
Misson AJB. Abberrations of the biliary passages on the surface of the liver and in the gallbladder. Br J Surg 56: 427, 1969.
3.
Hoffbaur FW. Needle biopsy of the liver. JAMA 134: 666, 1947.
4.
Dietschy JM. Recent developments transport across the gallbladder 50: 692, 1966.
5.
Lester R Troxler F. Recent advances in bile pigment metabolisk. Gastroentrol 56: 143, 1969.
6,
O&row JD. Absorption of the gallbladder of bile salts, sulphobromophthalein and iodopamide. J Lab Clin Med 74: 482, 1969.
7.
Brobeck JR (ed). Best & Taylor's Physiological Medical Practice. Williams & Wilkins, 1979.
8.
Banfield WJ. Physiology 770, 1975.
9.
Rous P , McMaster PD. The concentrating gallbladder. J exp Med 34: 47, 1921.
10.
Ravdin IS , Johnston CG , Riegel C , Wright SL. Studies of gallbladder function. Am J Physiol 100: 317, 1931.
II.
Grim E , Smith GA. Water flux rates across dog gallbladder wall. Am J Physiol 191: 550, 1957.
12.
Wheeler HO. Concentrating Med 51: 588, 1971.
13.
Ostrow JD. Absorption Clin Invest 46: 2035,
14.
in solute and water epithelium. Gastroentrol
of the gallbladder.
Basis of
Gastroentrol
69:
activity of the
function of the gallbladder.
Am J
of bile pigments by the gallbladder. 1967.
Menguy RB , Hallenbeck GA , Bollman JL , Grindley H. Intraductal pressure and sphincteric resistance in canine pancreatic and biliary ducts after various stimuli. Surg Gynec Obstet 106: 306, 1958.
170
J