LECTURE 6 Dr. Zahoor Ali Shaikh LIVER & BILE SECRETION LECTURE 6 Dr. Zahoor Ali Shaikh

LIVER & BILE SECRETION Bile is formed in the liver, emptied in the duodenum via bile duct. Biliary system includes the liver, gallbladder, and ducts.

LIVER FUNCTION 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. Storing Glycogen, fat, iron, copper.

LIVER FUNCTION Storing vitamin A,D, Vit B12. Activating vitamin D. Removing bacteria and old red blood cell by macrophages. Secreting hormones e.g. insulin like growth factor 1 [stimulates growth], thrombopietin [stimulates platelet production]. Excreting cholesterol and bilirubin [bilirubin is breakdown product of RBC].

LIVER FUNCTION Liver cell is called HEPATOCYTE. ‘HEPATO’ means liver, ‘CYTE’ means cell. HEPATOCYTE performs metabolic and secretary functions. HEPATOCYTE does not do Phagocytosis. Phagocytosis is done by macrophages present in the liver called KUPFFER cells.

LIVER BLOOD FLOW Two sources 1. Hepatic Artery – supplies arterial blood 2. Portal Vein – from GIT Blood leaves the liver via hepatic vein. NOTE – Portal Vein breaks in sinusoids which exchange with hepatic cells before draining into hepatic vein which joins inferior venaceva.

LIVER BLOOD FLOW

LIVER BLOOD FLOW 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.

LIVER BLOOD FLOW The Kupffer cells line the sinusoids and 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.

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, then common hepatic duct is formed which combines with Cystic duct (from Gall bladder) to form Common bile duct. Common bile duct transports bile to the duodenum.

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

BILE SECRETION In the gallbladder bile is stored and concentrated between the meals. BILE Bile secreted per day --- 500 ml Bile is alkaline fluid PH 8 (it has NaHco3- from bile ducts) Bile contains Bile salts, cholesterol, lecithin (phospholipid) and Bilirubin (all derived from Hepatocyte activity )

BILE SALTS AND THEIR ENTROHEPATIC CIRCULATION BILE SECRETION Bile does not contain any enzyme Bile is important for Emulsification [breaking fat into small molecules] therefore helping in digestion and absorption if Fats BILE SALTS AND THEIR ENTROHEPATIC CIRCULATION Bile salts are derivates of cholesterol. They are actively secreted in bile.

BILE SALTS AND THEIR ENTROHEPATIC CIRCULATION 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 them into the bile. This recycling of bile salt between small intestine and liver is called ‘ENTROHEPATIC CIRCULATION’ [‘Entro’ means intestine, ‘hepatic’ means liver].

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. Last bile salts are replaced by new bile salts synthesized by liver.

BILE SALTS & FAT DIGESTION & ABSORPTION Bile salts cause lipid emulsification [breaking fat into small molecules], therefore, increasing the surface area, so that pancreatic lipase can act. These fat globules are triglyceride molecules. To digest fat globules, lipase must act on them. NOTE – If no bile salt, it will take long time for lipase to do fat digestion.

BILE SALTS & FAT DIGESTION & ABSORPTION MICELLAR 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 Gall Stones - Cholesterol Gall Stone – 75% - Bilirubin Gall Stone – 25%

BILIRUBIN Bilirubin is waste product excreted in bile. 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.

BILIRUBIN In intestine, bilirubin is acted by bacteria and converted to urobilinogen and stercobilinogen. Stercobilinogen is excreted in feces and gives brown color to feces. If bile duct is obstructed by stone, color of feces turns to grey white. Small amount of urobilinogen is reabsorbed in the intestine in the blood and excreted in the urine and gives yellow color to urine.

BILIRUBIN If increased amount of bilirubin in the blood, it causes Jaundice [yellow coloration of eyes]. Normal bilirubin is less than 2mg /dl.

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’.

CONTROL OF BILE SECRETION 2. Hormonal Mechanism Secretin hormone stimulates watery alkaline bile secretion from the bile ducts. 3. Neural Mechanism Vagal stimulation plays minor role in bile secretion during cephalic phase of digestion. IMPORTANT – Food in duodenum [fat] causes release of CCK. This hormone causes contraction of gallbladder and relaxation of sphincter of ODDI.

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 50ml of bile.

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.

What You Should Know From This Lecture Functions of Liver Blood supply to Liver Bile Secretion Bile Salts and their Entrohepatic Circulation Role of Bile Salt in Lipid Emulsification, Fat Digestion and Absorption Bilirubin – Source & Excretion Control of Bile Secretion Jaundice

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