1. [Phy] Lecture 12 – Bile The objective of the lecture is to discuss the synthesis, secretion, flow and composition of bile, the regulation of bile secretion, functions of gall bladder, pathogenesis of gall stones, function of micelles in bile, and consequences of obstruction of the biliary tree. At the end of the lecture, students should be able to: – List primary bile acids and secondary bile acids – Describe neural and humoral influences on bile secretion and flow. – Describe the functions of the gall bladder. – Describe the functions of bile in digestion and absorption of fat. – Describe what is meant by enterohepatic circulation and the functional significance of enterohepatic circulation of bile salts and acids. – Predict the effect of deficiency of bile on digestion and absorption of fat and fat-soluble vitamins.

2. Bile Juice Bile is a bitter-tasting, dark green to yellowish brown fluid, produced by the liver, it is stored in the gallbladder and upon eating is discharged into the duodenum.. The principal function of the gallbladder is to serve as a storage reservoir for bile. The main components of bile are water, bile salts, bile pigments, and cholesterol Bile salts act as emulsifying agents in the digestion and absorption of fats. Cholesterol and bile pigments from the breakdown of hemoglobin are excreted from the body in the bile.

3. Physical properties; Hepatic bile: pH 7.4, colour is golden yellow, Hepatic bile: pH 7.4, colour is golden yellow, Bladder bile: pH 6.8, color is green dark to yellow (darker) Bladder bile: pH 6.8, color is green dark to yellow (darker) Volume of bile produced reaches to one liter of bile per day (depending on body size).

4. Bile Composition; Water (85%), bile salts (10%),(Cholic, chenodeoxycholic, deoxycholic, and lithocholic acid) mucus pigments (3%), bile pigments e.g bilirubin glucuronide fats (1%), such as Phospholipids (lecithin), cholesterol. 0.7% inorganic salts.

6. Bile secretion Bile is secreted in two stages ; Stage one; the liver hepatocytes will secret an initial secretion that is rich in bile salts, cholesterol, and other organic components, the initial secretion will drain through the many minute bile canaliculi that penetrate the liver. Stage Two ; The initial secretion will flow towards the bile ducts, during its flow in the ducts a secondary secretion is added to the initial bile which is a watery solution of sodium bicarbonate ions. The bile then will either empty into the duodenum when the sphincter of Oddi is open, Or( when the sphincter of Oddi is closed) it will be prevented from draining into the intestine and instead flows into the gallbladder, where it is stored and concentrated to up to 10-15 times its original potency. This concentration occurs through the absorption of water, sodium, chloride and other electrolytes, while retaining and concentrating all the original organic molecules.

7. Bile Secretion The components of bile are: 1.Bile acids (bile salts) 2.Cholesterol 3.Phospholipids 4.Bile pigments 5.Ions and water

8. Bile: Bile secreted by the hepatic cells. Bile contains bile salts, Bile pigments, cholesterol electrolytes

9. Bile secretion

10. Bile Secretion Bile secretion is primarily regulated by a feedback mechanism, with secondary hormonal and neural controls  CCK, secretin (hormonal control)  Parasympathetic and sympathetic innervations

11. Bile secretion stimulation 1-Under neural control mediated by e.g acetyl choline. 2- Under hormonal control ; When food is released by the stomach into the duodenum in the form of chyme, the duodenum releases cholecystokinin, which is the main stimulant causing the gallbladder to release the concentrated bile to complete digestion. - Gastrin and secretin also stimulate bile secretion. Lack of bile salts in the enterohepatic circulation stimulates bile synthesis and secretion.

12. COMPOSITION OF BILE Volume 700-1200 ml/day Inorganic constituents: Na, K, Cl, HCO3, Ca pH 8 Organic constituents: 1. Bile salts SYNTHESIZED IN THE LIVER BILE SALTS help in digestion and absorption of fat by forming:- emulsification of fat mixed micelles

13. Enterohepatic Circulation About 95% of the salts secreted in bile are reabsorbed actively in the terminal ileum and re-used. Blood from the ileum flows directly to the hepatic portal vein and returns to the liver where the hepatocytes reabsorb the salts and return them to the bile ducts to be re-used, sometimes two to three times with each meal. terminal ileumhepatic portal vein

15. Functions of Bile 1.Digestive function digestion and absorption of fat absorption of fat soluble vitamins neutralization of gastric acid 2.Excretory function bilirubin cholesterol many endogenous waste products

16. Functions of Bile salts: 1.Bile salts are important for fat digestion & absorption. 2.They activate pancreatic lipase. 3. With lecithin they reduce surface tension and break the large fat globules. 4.Choleretic action. 5.Exert mild laxative effect.

17. Function of bile juice 1- It is important in the digestion and absorption of lipids; Bile acts as a surfactant, helping to emulsify the fats in the food. Bile salt anions have a hydrophilic side and a hydrophobic side, and therefore tend to aggregate around droplets of fat ( triglycerides and phosphiolipids ) to form micelles, with the hydrophobic sides towards the fat and hydrophilic towards the outside.

18. * Control of bile secretion & gallbladder emptying Nervous regulation Nervous regulation Vagus nerve: ACh, gastrin Vagus nerve: ACh, gastrin Hepatic bile secretion  (small amounts) Hepatic bile secretion  (small amounts) Gallbladder contraction  (slightly) Gallbladder contraction  (slightly) Humoral regulation Humoral regulation Gastrin: direct to hepatic cells & gallbladder; Gastrin: direct to hepatic cells & gallbladder; Secretin: act to bile duct & not to hepatic cells, Secretin: act to bile duct & not to hepatic cells, so: H 2 O & HCO 3  , so: H 2 O & HCO 3  , Cholecystokinin (CCK): gallbladder Cholecystokinin (CCK): gallbladder contraction & Oddi’s sphincter dialation contraction & Oddi’s sphincter dialation Bile salt: enterohepatic circulation of bile salt Bile salt: enterohepatic circulation of bile salt

19. Regulation of Bile secretion Bile is formed continuously in the liver During interdigestive period, hepatic bile does not enter the duodenum, it enters gall bladder. Tone of sphincter of Oddi is closed during interdigestive period That is why hepatic bile enters gall bladder via cystic duct Bile gets concentrated in gall baldder 6-folds

20. Liver secretion and gallbladder emptying.

21. Functions of gall bladder 1.Storage of bile: bile is secreted continuously. But bile enters the duodenum intermittently during digestion. It is stored in the gall bladder during inter- digestive period. 2.Concentration of bile: In the gall bladder the bile becomes concentrated by 10-15 time. This brought about by the absorption of water and electrolytes. Bile salts, bile pigments and cholesterol, Ca ++ and K + are not absorbed. Water is absorbed passively secondary to absorption of electrolytes.

22. 3.Converts alkaline into neutral bile: The pH of hepatic bile is alkaline. But the pH of cystic bile is neutral. This is due to absorption of HCO 3 - from the bile. 4.Secretes mucin-like material.it acts as lubricant in the ducts and in the intestine for the chyme.

23. III. Gallbladder Diseases A. Cholelithiasis & Cholecystitis 1. Cholecystitis = inflammation of GB 2. Cholelithiasis = Stone(s) in GB

24. Anatomy of biliary system

25. Abnormalities associated with bile Gall stone ; The majority of gall stones are made up of cholesterol, (cholesterol tends to accrete into lumps in the gallbladder) Causes of gall stones; - Too much absorbtion of water from the bile. - Too much cholesterol in bile. - Inflammation of the epithelium.

26. Formation of gall stones

27. Gallstones are also associated with certain medical conditions including: 1-Diabetes 2-Liver disease 3-Crohn's disease 4-Blood disorders like sickle-cell anaemia 5-Stomach surgery - gallstones are more common if you have had surgery to remove part of your stomach Gall bladder Stone Risk Factors

28. Obstruction of common bile duct leading to pain & jaundice May Complicate to Charcot’s Triad: 1-Pain 2-Jaundice 3-Fever Reynold’s Pentad: 1-Pain 2-Jaundice 3-Fever 4-Altered Mental State 5-Shock Abdominal Ex: 1-Gall Bladder: in 80%Not Distended When gall bladder be distended?? Murphy’s sign +ve 2-Liver:Enlarged?????

29. Gall bladder Stone The majority of cases (approximately 80%)are asymptomatic (silent) gall stones, discovered accidentally by abdominal sonar. Other symptoms are related to site of movement of stone A gall stone may impact in the neck of gall bladder or in the cystic duct giving biliary pain or cholecystitis Biliary pain usually occurs in the epigastrium and right hypochondrium Obstruction of common bile duct leading to pain & jaundice Pancreatitis. Gall stones increase risk of carcinoma of the gall bladder

32. Normal serum bilirubin is 0.3-1.2mg Normal serum bilirubin is 0.3-1.2mg 2.0-2.5mg causes Jaundice 2.0-2.5mg causes Jaundice Main causes of Jaundice: 1.Excessive production of bilirubin 2. hepatocyte uptake 3.Impaired conjugation 4. hepatocyte excretion of bilirubin glucuronides 5.Impaired bile flow (obstruction of bile duct) Bilirubin

34. Jaundice

35. Yellow discoloration of the skin and mucous membranes due to elevated bilirubin level in the plasma. Normal plasma bilirubin level:0.2-1 mg % Types of jaundice pre-hepatic hepatic post-hepatic

36. E V Pathway for RBC Scavanging Liver, Spleen & Bone marrow Hemoglobin Globin Amino acids Amino acid pool HemeBilirubin Fe 2+ Excreted Phagocytosis & Lysis Through Liver 36

37. Bilirubin Production & Metabolism: F o r m a t i o n o f B i l i r u b i n M a i n l y i n R E S ( S p l e e n ) C o n j u g a t i o n o f b i l i r u b i n i n H e p a t o c y t e About 70 to 80% of the 250 to 300 mg of bilirubin produced each day is derived from the breakdown of hemoglobin in senescent red blood cells The remainder comes from prematurely destroyed erythroid cells in bone marrow and from the turnover of hemoproteins such as myoglobin and cytochromes found in tissues throughout the body. Excretion

38. Etiology Of Jaundice: Increase of production Impaired of Clearance