LIVER & BILE SECRETION

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

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

3. 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.

4. 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].

5. 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.

6. 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.

7. LIVER BLOOD FLOW

8. 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.

11. 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.

12. 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.

14. 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

15. 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 )

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

17. 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].

19. 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.

20. 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.

22. 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.

23. GALL STONES • Gall Stones - Cholesterol Gall Stone – 75% - Bilirubin Gall Stone – 25%

24. 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.

26. BILIRUBIN • In intestine, bilirubin is acted by bacteriaand 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.

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

28. 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’.

29. 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.

30. 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.

31. 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.

32. 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

33. Thank you