The Common Vein

The function of every biological unit in the body is based on its ability to receive a product, process it, and deliver the new product efficiently and effectively to where it is used and needed.

The gallbladder receives bile produced by the liver, processes it by concentration and storage, and delivers it on demand to the duodenum via the bile duct, so that the digestion of fat can be optimized.

The process of bile production occurs in two stages;

primary production

concentration

The gallbladder has no part in the primary production but is essential for the concentration.  Bile is produced 24 hours a day, but seemingly is only needed for 3 short periods during mealtimes. On the other hand it is also provides a route for the excretion of end products of hemoglobin breakdown and to some degree excretion of cholesterol.

 With its simple design of a musculomembranous bag, and single duct it is able to receive and concentrate 24 hours a day and deliver the bile via seemingly complex contraction patterns.  Although it is not an essential organ, it does help optimize the function of the digestive process.  People who have had a cholecystectomy do and can live an otherwise normal life, and seemingly have no untoward effects without it.

Bile

Bile is a yellow or green bitter fluid that is smooth, sterile, relatively thick, and sticky, with “spinnbarkeit” character.  Spinnbarkeit is a German word that means ability to be spun and it infers that when bile is pulled apart it forms a continuous thin thread much like thin nasal mucus.  The specific gravity ranges between 1.010 to 1.040 but can be as high as 1.059. (Yeh)

Structurally it consists mainly of water, cholesterol, bile pigments, and bile salts.  It is continually produced by the hepatocytes.  It contains no enzymes and it is only the bile salts that are important in digestion.  The end products of cholesterol are the bile acids (aka bile salts) which are synthesized by oxidation of cholesterol in the liver, and then conjugated with taurine or glycine.   The major primary bile acids are chenodeoxycholic acid and cholic acid. When the bile acids mix with the alkaline milieu of the duodenum they become bile salts.  About 20-30gms of bile acids are produced per day, but 90% are reabsorbed via the enterohepatic circulation where they are reused and recycled 10-12 times per day.

Bile has two main functions: It aids the in the solubilization  and digestion of fats including cholesterol and fat soluble vitamins, and it eliminates certain waste products – mainly hemoglobin and excess cholesterol from the body. Within the bile itself, the bile acids and phospholipids solubilize the cholesterol, thus preventing its precipitation.

While bile acids are important in fat digestion, they do not actually digest it.  Rather, they help emulsify fat particles into smaller particles to facilitate the digestive process.  The net effect is to expose active receptors that enable the pancreatic lipases (enzymes) to act.  They also continue to facilitate polar-non-polar molecular interactions by aiding in the absorption of these digested fat products through the intestinal mucosa and into the into the lymphatics of the small bowel.

Bile salts are also an important vehicle for excretion.  Two important excreted solutes are bilirubin (which once conjugated is not water-soluble and thus can not be excreted through the kidneys) in appreciable amounts, as well as cholesterol.

Bile is a noxious substance when not confined to the tubes of the digestive tract.  Bile in the peritoneal cavity causes bile peritonitis which is a potentially fatal disease.  Jaundice is a clinical sign indicating excessive bilirubin in the serum.  This has many causes but in general is obstructive, hepatocellular or hemolytic in origin.

From a diagnostic point of view, excessive bilirubin in the body is diagnosed clinically by looking at the sclera and skin color, and by evaluation of serum bilirubin.  Ultrasound is helpful to exclude obstructive causes.

The treatment of jaundice depends on the cause, with surgical treatments usually indicated for obstructive causes, and medical treatments for hepatocellular or hemolytic causes.

Receiving

As the bile secretion flows from the hepatocytes to the bile ducts via the bile canaliculi,  a secondary secretion of water containing sodium and bicarbonate ions from the epithelial cells lining ductules occurs resulting a total volume for an average human adult of between 600-1000mL daily.  The bile ducts are gracile and of low volume with a maximum normal pressure of about 20cms of water when the sphincter is closed, and which falls to 10cms of water or less as the sphincter opens.  With the sphincter of Oddi closed and the cystic duct open overflow of bile into the cystic duct occurs as a result of the small rise in pressure.

The cystic duct has an upward course to reach the neck of the gallbladder since in the upright position, the neck of the gallbladder is more cranial than the cystic duct/bile duct junction.  During the day we are upright, whether we are walking, standing, or sitting, it is an uphill climb for bile to reach the cystic duct.

In the body there is no handle to turn the valves (screws ) of Heister.  There are hydrostatic forces from below caused by the continued 24hour production of bile by the liver at about the rate of 1/2ccs per minute.  (approximately 800ccs in 24 hours, = approximately 1/2ccs per minute)

The maximum secreting pressures of bile from the hepatocystes is approximately 30cms of water.  The resting pressure of the sphincter of Oddi is 12-15cms of water, the opening pressure of the cystic duct is 8cms of water and the opening pressure of the gallbladder is 10cms of water.  Thus when the sphincter is closed the lowest pressure is in the cystic duct and hence filling of the cystic duct occurs.  (Clavien)

As the new drop of bile spills into the bile ducts it will cause a minute rise in pressure against the closed sphincter of Oddi.  Flow in the system is directed toward the cystic duct offers the least resistance as described above.  Bile will therefore fill the first valve which will push the bile upward to the second valve and so on.    With this repeated many times, each valve is filled until the bile reaches the top of the ladder after which it will spill over like a waterfall into the neck, and then body, and finally into the fundus.

The sphincter of Oddi is composed of a ring of circular and longitudinal muscle at the distal end of the common bile duct which has a phasic resting pressure of about 13mmHg.  It has a cyclical pattern during fasting that works in concordance with the intermittant myoelectric migratory complex of the intestinal tract (IMMC), as well as a pattern specific  to the presence of CCK and the parasympathetic nerve supply.

The common bile duct unites with  with the pancreatic duct to form a common channel  called the ampulla of Vater which empties into the duodenum at the papilla which is seen as a small nipple in the middle of the descending duodenum.

Mechanisms of Control

In between meals the sympathetic nervous system governing the gallbladder is relatively active and the parasympathetic system and CCK hormone are inactive.  Hence the sphincter of Oddi under the sympathetic control of the greater splanchnic nerves is contracted, and the gallbladder smooth muscle is relaxed.  With a fatty meal  release of CCK is instituted and it acts as the primary mechanism of smooth muscle and sphincter control. The  parasympathetic system provides accessory control with the right (posterior) vagus causing the sphincter to relax and the left vagus causing the gallbladder wall to relax.

It is becoming more apparent that the the neural and hormonal control of bile release into the duodenum is not as is not as tightly regulated by meals and that the sphincter of Oddi has periods between meals when it is relaxed and the gallbladder has phases when it contracts and partly empties between meals as well. (Kusano, Rodes, Toouli )  It is also well known that only half the bile produced by the liver enters the gallbladder and so it infers that the ampulla opens intermittantly between meals to allow unconcentrated bile into the duodenum.  We alluded to the intermittant myoelectric migratory complex of the intestinal tract (IMMC) which is a cyclical contraction pattern that coordinates muscular activity of the bowel and has emptying effects on the biliary system.

Processing

Concentration of bile

The shape and positon of the  gallbladder are well designed to enable bile concentration.  The bile in the fundus and body is mostly “old bile” and represents about 90% of the gallbladder volume since they are the most capacious parts of the gallbladder, most dependant in position, and contain the heavier, already concentrated bile.

The new bile which is delivered to the  gallbladder is small in volume, relatively dilute, has a  relatively low specific gravity, and consists of  water (97% ), bile acids (1-2%), and other metabolites and electrolytes that make up the remaining 1-2%.  The “other” components include cholesterol, phospholipids, bile pigments, sodium and chloride. The major cation is sodium and the dominant anion is chloride.  Small amounts of potassium, calcium, and approximately 20–50 mM bicarbonate are present.  Bile acid concentration is approximately 30-50mM.   Hepatic bile  is isotonic with plasma.

Once the bile comes into contact with the mucosal surface, about 90% of the water is reabsorbed, allowing the large volume of biliary secretions to be stored and concentrated in a space that can accomodate only 60-80ccs.  The concentration is achieved by the active absorbtion of electrolytes and  passive absorbtion of water.   Typically the gallbladder can concentrate the bile from 5-6  fold, but this can incrase to 10-12 fold.  Thus for every 100ccs of dilute bile received, between 10 and  20ccs of concentrated bile is produced. It is now becoming apparent that only half of the bile production goes through the gallbladder so the gallbladder may only “see” and concentrate between 250-500ccs per 24 hour period.  The concentration of bile acids increases by 10 fold, and the sodium and and chloride concentrations are reduced significantly.  The concentration of divalent calcium although low, is relatively high when compared to monovalent anions because phenomenon called the Gibbs-Donnan effect which favors the relative accumulation of divalent anions in the proteinaceous mileu that exists.

Applied Biology

From a practical perspective, it is routine to have a patient fast (usually overnight) for 8-12 hours before an ultrasound exam when the gallbladder is optimally distended without being dilated .  The wall is better evaluated in full distension, and stones that may hide in the neck or infundibulum are seen to better advantage as they are surrounded by the anechoic bile.

Storage

 The storage of bile is not as static as one would imagine.  During fasting, there is continued cyclical myoelectric activity in synchrony with duodenal activity called intermittant myoelectric migratory complex of the intestinal tract (IMMC) which we have discussed above.  This results in  gallbladder contraction between meals, with an  an open sphincter, and with 15-20% emptying.  Motilin is a polypeptide secreted by the small intestine probably as a result of an alkaline PH in the duodenum and is associated with the IMMC.  Despite the cyclical contractions, there are still prolonged periods of “down time” of muscular activity where storage of the bile occurs  enabling the process of bile concentration to occur.

Applied Biology

Static bile accumulates in the fundus and spends the majority of time in the fundus since we are in the upright position most the time.  Sediments of bile salts, stones and inflammation are therefore dominant in the fundus and it is not surprising therefore to find that 60% of gallbladder cancers occur in the fundus, 30% in the body, and the least (10%) originating in the neck.

Export Function

While we have stressed the apparent simplicity of gallbladder function the muscular function of the gallbladder brings this notion to a screeching halt.  Even during the fasting state bile is delivered through the ampulla at about the rate of about .5-1ml/minute.  At peak flow post prandially, this may increase to  2-3mls per minute.

The engines of delivery start to rev up even as we think of the meal we are about to partake in. This is called the cephalic phase of digestion and it affects the gallbladder as well.  The mere thought, sight, or smell of food stimulates the parasympathetic neural axis to the gallbladder resulting in stimulation of the vagus nerve and its effects on the smooth muscle.

When the fat-rich or protein rich foods reach the duodenum (typically 30 minutes post-prandially), CCK, the primary regulator of gallbladder contraction and Oddi function is released by the duodenum into the blood stream resulting in a serum CCK that rises over 15-30 minutes and then slowly plateaus.  The response is not all contraction by gallbladder muscle nor all relaxation by the sphincter.  Instead there is a  contraction and relaxation  pattern designed to provide a sustained, slow and steady stream of bile. (Howard) (Rodes),  with emptying occuring over two hours.

The contraction pattern is even more complex it seems.  During the post prandial phase  a tripahsic pattern; early emptying, early refilling, and late emptying seems to be an overall pattern.  duration of eachof the triphasic pghases includes emptying (40 minutes) refilling (10minutes) and emptying again (100minutes)  and it tales over two hours to occur during following a meal.

In addition to the triphasic pattern  there also appear to be contraction and relaxation phases, that occur minute to minute and are of a rhythmic nature.

The spiral valves of Heister prevent the rapid overdistension of the bile duct during the phases of contraction and also play a part of providing the staed  slow and steady stream of bile into the bile duct and therefpre into the duodenum.

CCK also affects the acinar cells of the pancreas and stimulates the productoion and transport of pancreatic juices to the duodenum at the same time.  these juices among many enzymes also contain lipases.

 Applied Biology

The gallbladder in the fasting state is distended amd its ability to deliver bile and contract can be evaluated by ultrasound or by nuclear medicine techniques.  Pre (fasting)  and post prandial volumes can be assessed.