Biliary Secretion and Composition - Physiology - Lecture Notes | Study notes Physiology

Biliary Secretion And Composition

Bile represents the product of secretion and excretion of hepatic cells/hepatocytes. It is secreted

all the time, but its delivery into the intestin takes place during digestion period. Between meals, bile is

stored in the gallbladder (GB) . The capacity of gallbladder is only 50 – 70 ml. It can stored the amount

of bile released by liver in 12 hours, because the mucosa of gallbladder is permeable to water, which is

reabsorbed and by this bile is concentrated. Through the mucosa of GB , first Na is absorbed actively,

followed by passive absorption of Cl, HCO3 and water. Daily , liver secretes 500 ml of bile. Vesicular

bile is 5 –10 times more concentrated than hepatic bile.

Even if bile does not contain enzymes(except alkaline phosphatase) it intervenes in

emulsification and absorption of fats. Biliary secretion appears as a consequence of active transport of

different substances in biliary ducts, followed by passing of water, according to the osmotic gradient.

Bile is secreted in biliary ducts at a pressure of 14 – 20 mmHg. During passing of bile through the

biliary ducts , its composition is changed, because here NaHCO3 is actively secreted, followed by

passive movement of water in the some direction. That is why the volume and the conc. of bicarbonate

increase, while the conc. of biliary slats decreases. The secretion of bicarbonate in ducts is stimulated by

secretin.

Composition of bile

Hepatic bile contains 97% water and 2,5g% residuu, while vesicular(GB) bile contains 89%

water and 11-14 g% residuu.

Bile contains inorganic and organic substances.

Inorganic substances are : chlorides, bicarbonates, phosphates of Na, K, Ca. Vesicular bile

contains 5 times more calcium than plasma, that favorises calcification of some stones of GB. The conc.

Of bicarbonates and Cl from vesicular bile are lower than their values in hepatic bile. That is why the pH

of hepatic bile is 7.8 –8.6, and vesicular bile pH= 7.0 –7.4. The concentration of electrolytes in bile

varies according to the biliary flow. Increasing the biliary flow also increases the concentration of

bicarbonate ions(HCO3-).

Organic substances are: biliary acids/ salts, biliary pigments, cholesterol, lecithin.

Biliary acids/salts (BA)

They represents the main product of exocrine secretion of liver. Their synthesis starts from the

cholesterol produced in the liver (80%) from acetate. Cholesterol also comes from lipoproteins – LDL

and HDL. (20%) They are hydrosoluble.

Liver synthetises two primary biliary acids: cholic acid and chenodeoxycholic acid. They are

conjugated with glycine and taurine, resulting glycocholic acid and glycochodeoxycholic acid,

respectively taurocholic acid and taurochenodeoxycholic acid. By reaction with Na, K these biliary acids

become biliary salts (glycocholate or taurocholate of Na or K).

When the level of biliary acids increases above a certain value, the BA form micelles, which are

spherical or cylindrical agglomerations of molecules(20 – 40 molecules of biliary acids) = simple

micelles. In these micelles , the hydrophobic part of BA is oriented central and the hydrophilic one,

outside. The polar groups, hydrosoluble, are negative electrical charged, favorising the dissolving of

micelles in water of digestive juices and their stability in solution. BA decrease the surface tension of

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Biliary Secretion And Composition

Bile represents the product of secretion and excretion of hepatic cells/hepatocytes. It is secreted all the time, but its delivery into the intestin takes place during digestion period. Between meals, bile is stored in the gallbladder (GB). The capacity of gallbladder is only 50 – 70 ml. It can stored the amount of bile released by liver in 12 hours, because the mucosa of gallbladder is permeable to water, which is reabsorbed and by this bile is concentrated. Through the mucosa of GB , first Na is absorbed actively, followed by passive absorption of Cl, HCO 3 and water. Daily , liver secretes 500 ml of bile. Vesicular bile is 5 –10 times more concentrated than hepatic bile. Even if bile does not contain enzymes(except alkaline phosphatase) it intervenes in emulsification and absorption of fats. Biliary secretion appears as a consequence of active transport of different substances in biliary ducts, followed by passing of water, according to the osmotic gradient. Bile is secreted in biliary ducts at a pressure of 14 – 20 mmHg. During passing of bile through the biliary ducts , its composition is changed, because here NaHCO3 is actively secreted, followed by passive movement of water in the some direction. That is why the volume and the conc. of bicarbonate increase, while the conc. of biliary slats decreases. The secretion of bicarbonate in ducts is stimulated by secretin.

Composition of bile

Hepatic bile contains 97% water and 2,5g% residuu, while vesicular(GB) bile contains 89% water and 11-14 g% residuu. Bile contains inorganic and organic substances. Inorganic substances are : chlorides, bicarbonates, phosphates of Na, K, Ca. Vesicular bile contains 5 times more calcium than plasma, that favorises calcification of some stones of GB. The conc. Of bicarbonates and Cl from vesicular bile are lower than their values in hepatic bile. That is why the pH of hepatic bile is 7.8 –8.6, and vesicular bile pH= 7.0 –7.4. The concentration of electrolytes in bile varies according to the biliary flow. Increasing the biliary flow also increases the concentration of bicarbonate ions(HCO 3 - ). Organic substances are: biliary acids/ salts, biliary pigments, cholesterol, lecithin.

Biliary acids/salts (BA)

They represents the main product of exocrine secretion of liver. Their synthesis starts from the cholesterol produced in the liver (80%) from acetate. Cholesterol also comes from lipoproteins – LDL and HDL. (20%) They are hydrosoluble. Liver synthetises two primary biliary acids: cholic acid and chenodeoxycholic acid. They are conjugated with glycine and taurine, resulting glycocholic acid and glycochodeoxycholic acid, respectively taurocholic acid and taurochenodeoxycholic acid. By reaction with Na, K these biliary acids become biliary salts (glycocholate or taurocholate of Na or K). When the level of biliary acids increases above a certain value, the BA form micelles, which are spherical or cylindrical agglomerations of molecules(20 – 40 molecules of biliary acids) = simple micelles. In these micelles , the hydrophobic part of BA is oriented central and the hydrophilic one, outside. The polar groups, hydrosoluble, are negative electrical charged, favorising the dissolving of micelles in water of digestive juices and their stability in solution. BA decrease the surface tension of

lipids, that can form an emulsion. Emulsification of fats, namely their breaking down in smaller particles, suspended in a watery solution, it is a property of BA similary to that of detergents. In the intestin, the products of digestion of lipids- monoglycerides (TG), fatty acids (FA) cholesterol are uptaken in the middle of micelles. Phospholipides (PL), especially lecithin from bile, are oriented with the hydrophilic end towards the exterior. The complex made up of BA and lipids is name mixed micelles. By this mechanism, the lipids which are not watersoluble, are emulsified and transported in the mucosa of intestin , where they are absorbed. In the intestin the BA are deconjugated under the action of bacterial enzymes, being transformed in secondary BA. Cholic acid is transformed in deoxycholic acid and chenodeoxycholic in litocholic acid. Primary and secondary are reabsorbed in the terminal portion of small intestin (in the proportion of 90 –95%), by an active transport mechanism together with Na(cotransport). From the portal blood, the BA are uptaken by the hepatocytes from the portal blood and excreted again in bile. Inside of hepatic cells , BA are bound by the protein Y, which prevents the destructive effect of BA on the organelles. This is entero-hepatic circuit. The passing of BA in biliary ducts is made by an active transport, independent of Na transport. Hepatic cells excrete the secondary type BA without changing them (without transforming them in primary BA). Bile contains a mixture of primary and secondary BA. It is thought that every molecule of BA participates to entero-hepatic circuit of 10 –15 times, before being excreted. Daily loss through stool is 200- 400 mg, especially litocholic acid, which is insoluble. When the absorption of BA from Small intestin is not corresponding, BA accumulate in large intestin , impeding absorption of water and electrolytes through intestinal mucosa, that leads to diarrhoea. By a mechanism of negative feedback, BA inhibit their own production (they inhibit cholesterol 7 dehydroxilase) and also the synthesis of cholesterol in liver. In biliary ducts , they stimulate the biliary secretion and perform a very important role in maintaining cholesterol in solution. Daily production of BA represents the main metabolic pathway for degradation of cholesterol.

Biliary pigments (BP)

They represent 15 –25% of the residuu of bile. They derive from degradation of hemoglobin(80%) and myoglobin and cytochroms (20%). By lysis of RBC (red blood cells) it is releases 8 g of hemoglobin, from where 300 mg of BP are synthetized. In macrophages, hemoglobin is broken down in iron, globin which are reused and porphirin, from whose degradation biliverdin results. Biliverdin is reduced to bilirubin. Bilirubin is not soluble in water , that is why it circulates in blood bound to albumin. 1 mole of albumin can bind 2 moles of bilirubin. Bilirubin bound to albumin is called indirect bilirubin, because in reaction with the reagent van der Bergh it can be identified only by adding to the plasma alcohol. Bilirubin from the blood is taken up by the hepatocytes by an active mechanism and after that bilirubin is conjugated with glicuronic acid under the action of enzyme glicuroniltransferase, resulting in diglicurobid of bilirubin (soluble in water) that passes in blood. About 10% of bilirubin is conjugated with sulphate and 10% with other substances. Conjugated bilirubin is also called direct/hepatic bilirubin .Glicuroniltransferase can also be found in testis, ovary, suprarenal glands, skin, joints. Extrahepatic enzymes catalyse the formation of monoglicuronid of bilirubin , which is transformed in liver in diglicuronid. Bilirubin has an important antioxidant action , by which it inhibits the peroxidation of lipids and damage of hepatocytes membrane. In small intestin bilirubin is not absorbed (only to a very low extent). It passes into the large intestin where is deconjugated under the action of intestinal flora.Bilirubin is transformed into mezobilirubin, than in mezobilirubinogen/urobilinogen (by adding of 4 H) and finally in stercobilinogen( by adding more 4H ). Strecobilinogen in contact with the air is transformed in

Role of the bile

Bile has a very important role in absorption of lipids, favorising their emulsification and absorption of fatty acids. It also has importance in absorption of liposoluble vitamins. In the absence of bile, 50% of ingested lipids are lost through the stool. The food from digestive tract are covered with a layer of fats, that impedes their digestion under the intestinal enzymes. In these conditions the putrefaction flora developes more , producing a huge amount of gases. Bile is the pathway of excretion of some substances like : Zn, Mg, cholesterol. It has a laxative effect , due to its stimulatory action on intestinal motricity.

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