Functional anatomy of Liver & Biliary System .
[1]. Liver is a dual organ having both secretory and excretory functions.
[2]. It is the largest gland in the body, weighing about 1.5 kg in man.
[3]. It is located in the upper and right side of the abdominal cavity, immediately beneath diaphragm.
Liver .
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| Posterior surface of liver . |
Hepatic Lobes .
[1]. Liver is made up of many lobes called hepatic lobes .
[2]. Each lobe consists of many lobules called hepatic lobules.
Hepatic Lobules .
[1]. Hepatic lobule is the structural and functional unit of liver.
[2]. There are about 50,000 to 100,000 lobules in the liver.
[3]. The lobule is a honeycomb-like structure and it is made up of liver cells called hepatocytes.
Hepatocytes and Hepatic Plates .
[1]. Hepatocytes are arranged in columns, which form the hepatic plates.
[2]. Each plate is made up of two columns of cells. In between the two columns of each plate lies a bile canaliculus .
[3]. In between the neighboring plates, a blood space called sinusoid is present.
[4]. Sinusoid is lined by the endothelial cells. In between the endothelial cells some special macrophages called Kupffer cells are present.
Portal Triads .
[1]. Each lobule is surrounded by many portal triads.
[2]. Each portal triad consists of three vessels:
1. A branch of hepatic artery .
2. A branch of portal vein .
3. A tributary of bile duct.
[3]. Branches of hepatic artery and portal vein open into the sinusoid.
[4]. Sinusoid opens into the central vein. Central vein empties into hepatic vein.
[5]. Bile is secreted by hepatic cells and emptied into bile canaliculus.
[6]. From canaliculus, the bile enters the tributary of bile duct.
[7]. Tributaries of bile duct from canaliculi of neighboring lobules unite to form small bile ducts.
[8]. These small bile ducts join together and finally form left and right hepatic ducts, which emerge out of liver.
Biliary System .
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| Biliary System . |
[1]. Biliary system or extrahepatic biliary apparatus is formed by gallbladder and extrahepatic bile ducts (bile ducts outside the liver).
[2]. Right and left hepatic bile ducts which come out of liver join to form common hepatic duct. It unites with the cystic duct from gallbladder to form common bile duct .
[3]. All these ducts have similar structures.
[4]. Common bile duct unites with pancreatic duct to form the common hepatopancreatic duct or ampulla of Vater, which opens into the duodenum.
[5]. There is a sphincter called sphincter of Oddi at the lower part of common bile duct, before it joins the pancreatic duct.
[6]. It is formed by smooth muscle fibers of common bile duct.
[7]. It is normally kept closed; so the bile secreted from liver enters gallbladder where it is stored.
[8]. Upon appropriate stimulation, the sphincter opens and allows flow of bile from gallbladder into the intestine.
Blood Supply to Liver .
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| Blood flow through liver . |
[1]. Liver receives maximum blood supply of about 1,500 mL/minute.
[2]. It receives blood from two sources, namely the hepatic artery and portal vein .
Hepatic artery .
[1]. Hepatic artery arises directly from aorta and supplies oxygenated blood to liver.
[2]. After entering the liver, the hepatic artery divides into many branches.
[3]. Each branch enters a portal triad.
Portal Vein .
[1]. Portal vein is formed by superior mesenteric vein and splenic vein.
[2]. It brings deoxygenated blood from stomach, intestine, spleen and pancreas.
[3]. Portal blood is rich in monosaccharides and amino acids.
[4]. It also contains bile salts, bilirubin, urobilinogen and GI hormones. However, the oxygen content is less in portal blood.
[5]. Flow of blood from intestine to liver through portal vein is known as enterohepatic circulation .
[6]. The blood from hepatic artery mixes with blood from portal vein in hepatic sinusoids.
[7]. Hepatic cells obtain oxygen and nutrients from the sinusoid.
Hepatic Vein .
[1]. Substances synthesized by hepatic cells, waste products and carbon dioxide are discharged into sinusoids.
[2]. Sinusoids drain them into central vein of the lobule.
[3]. Central veins from many lobules unite to form bigger veins, which ultimately form hepatic veins (right and left) which open into inferior vena cava.
Properties & Composition of Bile .
Properties of Bile .
[1]. Volume Reaction : 800 to 1,200 mL/day :
[2]. Alkaline pH : 8 to 8.6
[3]. Specific gravity : 1.010 to 1.011
[4]. Color : Golden yellow or green.
Composition of Bile .
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| Composition of bile . |
[1]. Bile contains 97.6% of water and 2.4% of solids.
[2]. Solids include organic and inorganic substances.
Secretion of Bile .
[1]. Bile is secreted by hepatocytes.
[2]. The initial bile secreted by hepatocytes contains large quantity of bile acids, bile pigments, cholesterol, lecithin and fatty acids.
[3]. From hepatocytes, bile is released into canaliculi.
[4]. From here, it passes through small ducts and hepatic ducts and reaches the common hepatic duct .
[5]. From common hepatic duct, bile is diverted either directly into the intestine or into the gallbladder. [6]. Sodium, bicarbonate and water are added to bile when it passes through the ducts.
[7]. These substances are secreted by the epithelial cells of the ducts. Addition of sodium, bicarbonate and water increases the total quantity of bile.
Storage of Bile .
[1]. Most of the bile from liver enters the gallbladder, where it is stored.
[2]. It is released from gallbladder into the intestine whenever it is required.
[3]. When bile is stored in gallbladder, it undergoes many changes both in quality and quantity such as:
1. Volume is decreased because of absorption of a large amount of water and electrolytes (except calcium and potassium) .
2.Concentration of bile salts, bile pigments, cholesterol, fatty acids and lecithin is increased because of absorption of water and electrolytes .
3. The pH is decreased slightly .
4. Specific gravity is increased .
5.Mucin is added to bile .
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| Differences between liver bile and gallbladder bile . |
Bile Salts .
Bile salts are the sodium and potassium salts of bile acids, which are conjugated with glycine or taurine.
Formation of Bile Salts .
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| Formation of bile salts . |
[1]. Bile salts are formed from bile acids.
[2]. There are two primary bile acids in human, namely cholic acid and Chenodeoxycholic acid, which are formed in liver and enter the intestine through bile.
[3]. Due to the bacterial action in the intestine, the primary bile acids are converted into secondary bile acids:
Cholic acid → deoxycholic acid
Chenodeoxycholic acid → lithocholic acid
[4]. Secondary bile acids from intestine are transported back to liver through enterohepatic circulation. [5]. In liver, the secondary bile acids are conjugated with glycine (amino acid) or taurin (derivative of an amino acid) and form conjugated bile acids, namely glycocholic acid and taurocholic acids.
[6]. These bile acids combine with sodium or potassium ions to form the salts, sodium or potassium glycocholate and sodium or potassium taurocholate .
Enterohepatic Circulation of Bile salts .
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| Enterohepatic circulation . |
[1]. Enterohepatic circulation is the transport of substances from small intestine to liver through portal vein.
[2]. About 90% to 95% of bile salts from intestine are transported to liver through enterohepatic circulation.
[3]. Remaining 5% to 10% of the bile salts enter large intestine.
[4]. Here, the bile salts are converted into deoxycholate and lithocholate, which are excreted in feces.
Functions of Bile Salts .
Bile salts are required for digestion and absorption of fats in the intestine. The functions of bile salts are:
1. Emulsification of Fats .
[1]. Emulsification is the process by which the fat globules are broken down into minute droplets and made in the form of a milky fluid called emulsion in small intestine by the action of bile salts.
[2]. Lipolytic enzymes of GI tract cannot digest the fats directly because the fats are insoluble in water due to the surface tension.
[3]. Bile salts emulsify the fats by reducing the surface tension due to their detergent action. Now the fats can be easily digested by lipolytic enzymes.
[4]. Unemulsified fat usually passes through the intestine and then it is eliminated in feces.
[5]. Emulsification of fats by bile salts needs the presence of lecithin from bile.
2. Absorption of Fats .
[1]. Bile salts help in the absorption of digested fats from intestine into blood.
[2]. Bile salts combine with fats and make complexes of fats called micelles.
[3]. The fats in the form of micelles can be absorbed easily.
3. Choleretic Action .
[1]. Bile salts stimulate the secretion of bile from liver.
[2]. This action is called choleretic action.
4. Cholagogue Action .
[1]. Cholagogue is an agent which causes contraction of gallbladder and release of bile into the intestine.
[2]. Bile salts act as cholagogues indirectly by stimulating the secretion of hormone cholecystokinin.
This hormone causes contraction of gallbladder, resulting in release of bile.
5. Laxative Action .
[1]. Laxative is an agent which induces defecation.
[2]. Bile salts act as laxatives by stimulating peristaltic movements of the intestine.
6. Prevention of Gallstone .
[1]. Formation Bile salts prevent the formation of gallstone by keeping the cholesterol and lecithin in solution.
[2]. In the absence of bile salts, cholesterol precipitates along with lecithin and forms gallstone.
Bile Pigments .
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| Formation and circulation of bile pigments . |
[1]. Bile pigments are the excretory products in bile.
[2]. Bilirubin and biliverdin are the two bile pigments and bilirubin is the major bile pigment in human beings.
[3]. Bile pigments are formed during the breakdown of hemoglobin, which is released from the destroyed RBCs in the reticuloendothelial system .
Formation & Excretion of Bile Pigments .
Stages of formation and circulation of bile pigments:
[1] . Senile erythrocytes are destroyed in reticuloendothelial system and hemoglobin is released from them
[2] . Hemoglobin is broken into globin and heme
[3] . Heme is split into iron and the pigment biliverdin
[4] . Iron goes to iron pool and is reused
[5] . First formed pigment biliverdin is reduced to bilirubin.
[6] . Bilirubin is released into blood from the reticuloendothelial cells
[7] . In blood, the bilirubin is transported by the plasma protein, albumin. Bilirubin circulating in the blood is called free bilirubin or unconjugated bilirubin
[8] . Within few hours after entering the circulation, the free bilirubin is taken up by the liver cells
[9] . In the liver, it is conjugated with glucuronic acid to form conjugated bilirubin
[10] .Conjugated bilirubin is then excreted into intestine through bile.
Fate of Conjugated Bilirubin .
Stages of excretion of conjugated bilirubin:
[1]. In intestine, 50% of the conjugated bilirubin is converted into urobilinogen by intestinal bacteria. First the conjugated bilirubin is deconjugated into free bilirubin, which is later reduced into urobilinogen.
[2]. Remaining 50% of conjugated bilirubin from intestine is absorbed into blood and enters the liver through portal vein (enterohepatic circulation). From liver, it is re-excreted in bile
[3]. Most of the urobilinogen from intestine enters liver via enterohepatic circulation. Later, it is re-excreted through bile .
[4]. About 5% of urobilinogen is excreted by kidney through urine. In urine, due to exposure to air, the urobilinogen is converted into urobilin by oxidation .
[5]. Some of the urobilinogen is excreted in feces as stercobilinogen. In feces, stercobilinogen is oxidized to stercobilin.
Normal Plasma Levels of Bilirubin .
[1]. Normal bilirubin (Total bilirubin) content in plasma is 0.5 to 1.5 mg/dL.
[2]. When it exceeds 1mg/dL, the condition is called hyperbilirubinemia. When it exceeds 2 mg/dL, jaundice occurs.
Function of Bile .
Most of the functions of bile are due to the bile salts.
1. Digestive Function .
2. Absorptive Functions .
3. Excretory Functions .
Bile pigments are the major excretory products of the bile. Other substances excreted in bile are:
[1]. Heavy metals like copper and iron
[2]. Some bacteria like typhoid bacteria
[3]. Some toxins
[4]. Cholesterol
[5]. Lecithin
[6]. Alkaline phosphatase.
4. Laxative Function .
Bile salts act as laxatives .
5. Antiseptic action .
Bile inhibits the growth of certain bacteria in the lumen of intestine by its natural detergent action.
6. Choleretic action .
Bile salts have the choleretic action .
7. Maintenance of pH in Gastrointestinal Tract .
[1]. As bile is highly alkaline, it neutralizes the acid chyme which enters the intestine from stomach.
[2]. Thus, an optimum pH is maintained for the action of digestive enzymes.
8. Prevention of Gall Stone Formation .
9. Lubrication Function .
The mucin in bile acts as a lubricant for the chyme in intestine.
10. Cholagogue action .
Bile salts act as cholagogues .
Function of Liver .
[1]. Liver is the largest gland and one of the vital organs of the body.
[2]. It performs many vital metabolic and homeostatic functions .
1. Metabolic Function .
Liver is the organ where maximum metabolic reactions such as metabolism of carbohydrates, proteins, fats, vitamins and many hormones are carried out.
2. Storage Function .
Many substances like glycogen, amino acids, iron, folic acid and vitamins A, B12 and D are stored in liver.
3. Synthetic Function .
[1]. Liver produces glucose by gluconeogenesis.
[2]. It synthesizes all the plasma proteins and other proteins (except immunoglobulins) such as clotting factors, complement factors and hormone binding proteins.
[3]. It also synthesizes steroids, somatomedin and heparin.
4. Secretion of Bile .
[1]. Liver secretes bile which contains bile salts, bile pigments, cholesterol, fatty acids and lecithin.
[2]. The functions of bile are mainly due to bile salts.
[3]. Bile salts are required for digestion and absorption of fats in the intestine.
[4]. Bile helps to carry away waste products and breakdown fats, which are excreted through feces or urine.
5. Excretory Function .
Liver excretes cholesterol, bile pigments, heavy metals (like lead, arsenic and bismuth), toxins, bacteria and virus (like that of yellow fever) through bile.
6. Heat Production .
[1]. Enormous amount of heat is produced in the liver because of metabolic reactions.
[2]. Liver is the organ where maximum heat is produced.
7. Hemopoietic Function .
[1]. In fetus (hepatic stage), liver produces the blood cells .
[2]. It stores vitamin B12 necessary for erythropoiesis and iron necessary for synthesis of hemoglobin .
[3]. Liver produces thrombopoietin that promotes production of thrombocytes.
8. Hemolytic Function .
The senile RBCs after a lifespan of 120 days are destroyed by reticuloendothelial cells (Kupffer cells) of liver.
9. Inactivation of Hormones & Drugs .
[1]. Liver catabolizes the hormones such as growth hormone, parathormone, cortisol, insulin, glucagon and estrogen.
[2]. It also inactivates the drugs, particularly the fat soluble drugs.
[3]. The fat soluble drugs are converted into water soluble substances, which are excreted through bile or urine.
10. Defensive & Detoxification Functions .
[1]. Reticuloendothelial cells (Kupffer cells) of the liver play an important role in the defense of the body.
[2]. Liver is also involved in the detoxification of the foreign bodies.
1. Foreign bodies such as bacteria or antigens are swallowed and digested by reticuloendothelial cells of liver by means of phagocytosis.
2 . Reticuloendothelial cells of liver also produce substances like interleukins and tumor necrosis factors, which activate the immune system of the body .
3 . Liver cells are involved in the removal of toxic property of various harmful substances. Removal of toxic property of the harmful agent is known as detoxification.
Detoxification in liver occurs in two ways:
1. Total destruction of the substances by means of metabolic degradation.
2. Conversion of toxic substances into non toxic materials by means of conjugation with gluconic acid or sulfates.
Gall Bladder .
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| Formation of bile from liver and changes taking place in the composition of gallbladder bile . |
[1]. Bile secreted from liver is stored in gallbladder.
[2]. The capacity of gallbladder is approximately 50 mL.
[3]. Gallbladder is not essential for life and it is removed (cholecystectomy) in patients suffering from gallbladder dysfunction.
[4]. After cholecystectomy, patients do not suffer from any major disadvantage. In some species, gallbladder is absent.
Functions of Gall Bladder .
Major functions of gallbladder are the storage and concentration of bile.
1. Storage of Bile .
Bile is continuously secreted from liver. But it is released into intestine only intermittently and most of the bile is stored in gallbladder till it is required.
2. Concentration of Bile .
[1]. Bile is concentrated while it is stored in gallbladder.
[2]. The mucosa of gallbladder rapidly reabsorbs water and electrolytes, except calcium and potassium. [3]. But the bile salts, bile pigments, cholesterol and lecithin are not reabsorbed. So, the concentration of these substances in bile increases 5 to 10 times .
3. Alteration of pH of Bile .
The pH of bile decreases from 8 – 8.6 to 7 – 7.6 and it becomes less alkaline when it is stored in gallbladder.
4. Secretion of Mucin
[1]. Gallbladder secretes mucin and adds it to bile.
[2]. When bile is released into the intestine, mucin acts as a lubricant for movement of chyme in the intestine.
5. Maintenance of Pressure in Biliary System .
[1]. Due to the concentrating capacity, gallbladder maintains a pressure of about 7 cm H2 O in biliary system.
[2]. This pressure in the biliary system is essential for the release of bile into the intestine.
Filling & Emptying of Gall Bladder .
[1]. Usually, the sphincter of Oddi is closed during fasting and the pressure in the biliary system is only 7 cm H2 O. Because of this pressure, the bile from liver enters the gallbladder.
[2]. While taking food or when chyme enters the intestine, gallbladder contracts along with relaxation of sphincter of Oddi.
[3]. Now, the pressure increases to about 20 cm H2 O. Because of the increase in pressure, the bile from gallbladder enters the intestine.
[4]. Contraction of gallbladder is influenced by neural and hormonal factors.
1. Neural Factor .
[1]. Stimulation of parasympathetic nerve (vagus) causes contraction of gallbladder by releasing acetylcholine.
[2]. The vagal stimulation occurs during the cephalic phase and gastric phase of gastric secretion.
2. Hormonal Factor .
When a fatty chyme enters the intestine from stomach, the intestine secretes the cholecystokinin, which causes contraction of the gallbladder.
Regulation of Bile Secretion .
[1]. Bile secretion is a continuous process though the amount is less during fasting.
[2]. It starts increasing after meals and continues for three hours.
[3]. Secretion of bile from liver and release of bile from the gallbladder are influenced by some chemical factors, which are categorized into three groups:
1. Choleretics .
2. Cholagogue .
3. Hydrocholeretic agents.
1. Choleretics .
[1]. Substances which increase the secretion of bile from liver are known as choleretics.
[2]. Effective choleretic agents are:
1. Acetylcholine .
2. Secretin
3. Cholecystokinin
4. Acid chyme in intestine
5. Bile salts.
2. Cholagogues .
[1]. Cholagogue is an agent which increases the release of bile into the intestine by contracting gallbladder.
[2]. Common cholagogues are:
1. Bile salts
2. Calcium
3. Fatty acids
4. Amino acids
5. Inorganic acids
[3]. All these substances stimulate the secretion of cholecystokinin, which in turn causes contraction of gallbladder and flow of bile into intestine.
3. Hydrocholeretic Agents .
[1]. Hydrocholeretic agent is a substance which causes the secretion of bile from liver, with large amount of water and less amount of solids.
[2]. Hydrochloric acid is a hydrocholeretic agent.
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