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LIVER AND BILE SECRETION DR. AMEL EASSAWI DR. SHAIKH MUJEEB AHMED 1 Slide 2 OBJECTIVES The student should be able to: Enlist the functions of Liver. Know the blood supply to Liver. Describe bile secretion. Discuss bile salts and their Entrohepatic Circulation. Know the role of bile Salt in lipid emulsification, fat digestion and absorption. Discuss control of bile secretion. Discuss Jaundice. 2 Slide 3 LIVER AND BILE SECRETION Bile is formed in the liver, emptied in the duodenum via bile duct. Biliary system includes: - Liver - Gallbladder - Ducts 3 Slide 4 LIVER FUNCTION Liver cell is called HEPATOCYTE HEPATO means liver, CYTE means cell. Metabolism of carbohydrate, protein, and fat, after their absorption from the digestive tract. Detoxification of drugs, hormones, body waste products. Plasma protein synthesis. Blood clotting factors synthesis. Excreting cholesterol and bilirubin [bilirubin is breakdown product of RBC]. 4 Slide 5 LIVER FUNCTION Store glycogen, fat, iron, copper. Store vitamin A, D, Vit B12. Activating vitamin D. Secreting hormones e.g. insulin like growth factor 1 [stimulates growth], thrombopietin [stimulates platelet production]. Removing bacteria and old red blood cell by macrophages. Hepatocyte does not do Phagocytosis. Phagocytosis is done by macrophages present in the liver called KUPFFER cells. 5 Slide 6 LIVER BLOOD FLOW Two sources: 1. Hepatic Artery supplies arterial blood. 2. Portal Vein from GIT. 3. Hepatic Vein carries blood away from the liver. NOTE Portal Vein breaks in sinusoids which exchange with hepatic cells before draining into hepatic vein which joins inferior venaceva. 6 Slide 7 LIVER BLOOD FLOW 7 Slide 8 Liver has functional units called lobules, they are hexagonal with central vein. Each lobule has three vessels: - Branch of Hepatic Artery - Branch of Portal Vein - Bile Duct From Hepatic artery and Portal vein blood goes to expended capillary space called SINUSOIDS which runs to central vein. The Kupffer cells line the sinusoids destroy old RBC and bacteria that pass through them. Central veins of all liver lobules converge to form hepatic vein, which carries blood away from the liver. 8 Slide 9 9 Slide 10 BILE SECRETION The bile is formed and continuously secreted by liver cells [Hepatocyte]. Bile goes to bile duct. Bile ducts from different lobules form right and left Hepatic duct, it combines with Cystic duct (from Gall bladder) to form Common bile duct. Common bile duct transports bile to the duodenum. 10 Slide 11 11 Slide 12 BILE SECRETION Bile is continuously secreted by liver and sent to the gallbladder between meals. Opening of the bile duct in the duodenum is guarded by the sphincter of Oddi. It allows the bile to pass in the duodenum during meals. When food is not taken sphincter of Oddi is closed, therefore bile secreted by the liver goes to the gallbladder. In the gallbladder bile is stored and concentrated between the meals. 12 Slide 13 BILE SECRETION Bile secreted 500 ml per day. Bile is alkaline fluid pH 8 (has NaHCO 3 from bile ducts). Bile contains: Bile salts, cholesterol, lecithin (phospholipid) and bilirubin (all derived from Hepatocyte activity). Bile does not contain any enzyme. Bile is important for emulsification and helping in digestion and absorption of fats. 13 Slide 14 BILE SECRETION BILE SALTS AND THEIR ENTROHEPATIC CIRCULATION Bile salts are derivates of cholesterol. They are actively secreted in bile. Most of the bile salts [95%] are reabsorbed from terminal ileum [small intestine] into the blood by active transport. Bile salt are returned to liver by hepatic portal system. Liver re-secretes bile salts into bile. This recycling of bile salt between small intestine and liver is called ENTROHEPATIC CIRCULATION [Entro means intestine, hepatic means liver]. 14 Slide 15 BILE SECRETION BILE SALTS AND THEIR ENTROHEPATIC CIRCULATION On average bile salts cycle between liver and small intestine twice during one meal. Only 5% of bile salt are lost in the feces per day. Lost bile salts are replaced by new bile salts synthesized by liver. Bile salts cause lipid emulsification [breaking fat into small molecules], therefore, increasing the surface area, so that pancreatic lipase can act. NOTE If no bile salt, it will take long time for lipase to digest fat. 15 Slide 16 16 Slide 17 17 Slide 18 BILE SALTS AND FAT DIGESTION AND ABSORPTION Micelle Formation Micelle is small lipid particle 3-10 nm [emulsified fat droplet is 1000 nm]. bile salt, cholesterol and lecithin help in Micelle formation. Micelle carry Monoglycerides and free fatty acids. Gall Stones - Cholesterol Gall Stone 75% - Bilirubin Gall Stone 25% 18 Slide 19 BILE SALTS AND FAT DIGESTION AND ABSORPTION Bilirubin It is bile pigment, derived from the breakdown of RBC. It does not play any role in digestion. Bilirubin is taken from the blood by Hepatocyte and actively excreted into the bile. Bilirubin is yellow pigment, therefore, gives yellow color to bile. In intestine, bilirubin is acted by enzyme and converted to biliverdin, which gives brown color to feces. If bile duct is obstructed by stone, color of feces turns to grey white. Small amount of bilirubin is reabsorbed in the intestine in the blood and excreted in the urine and gives yellow color to urine. 19 Slide 20 20 Slide 21 CONTROL OF BILE SECRETION Three Mechanism: 1. Chemical 2. Hormonal 3. Neural 1. Chemical Mechanism: By bile salt, they are most potent stimulus for increasing bile secretion. Any substance which increases bile secretion is called CHOLERETIC. 21 Slide 22 CONTROL OF BILE SECRETION 2. Hormonal Mechanism: Secretin hormone stimulates watery alkaline bile secretion from the bile ducts. Food in duodenum [fat] causes release of CCK. This hormone causes contraction of gallbladder and relaxation of sphincter of Oddi. 3. Neural Mechanism: Vagal stimulation plays minor role in bile secretion during cephalic phase of digestion. 22 Slide 23 GALL BLADDER It stores and concentrates bile between meals and empties bile into the duodenum during meals. As bile secretion occurs continuously in liver, therefore, bile secreted between the meals is send to the gall bladder, where it is stored and concentrated. In gall bladder, bile is concentrated 5-10 times due to absorption of bile salt and water. Gall bladder can hold 50 ml of bile. 23 Slide 24 CLINICAL APPLICATION Jaundice: When bilirubin increases more than 2mg/dL jaundice occurs. Causes of Jaundice Pre-hepatic [problem before liver] or Hemolytic Jaundice due to increased breakdown of RBC. Hepatic [problem in liver] e.g. Viral Hepatitis Post-hepatic [problem after the liver] or Obstructive Jaundice e.g. stone in the bile duct. 24 Slide 25 REFERENCES Human Physiology by Lauralee Sherwood, seventh edition. Text book Physiology by Guyton &Hall,11 th edition. Text book of Physiology by Linda S. Contanzo, third edition. 25