BILE AND SUCCUS ENTERICUS Dr Aqsa Malik Biochemistry

BILE AND SUCCUS ENTERICUS Dr. Aqsa Malik Biochemistry

SYNTHESIS AND SECRETION OF BILE �Both a secretion and excretion of liver. �Secreted continously by hepatocytes. �Central blind end of canaliculi→portal triad→canals of Hering→biliary ductules →Intralobular bile ducts →Interlobular bile ducts →Left & Right Hepatic ducts →Common Hepatic duct +Cystic duct →Common Bile duct

BILE COMPOSITION �WATER – 97. 4% �SOLID COMPONENTS – 2. 6% �ORGANIC Bile salts Bile pigments Mucin Lipids(lecithin, fats, fatty acids, cholesterol) �INORGANIC Na⁺, Cl¯, HCO₃¯, K⁺.

�p. H – 7. 8 -8. 6 �Sp Gravity - 1. 010 �Volume – 500 – 1100 ml �Colour – Golden yellow

Changes in bile composition occuring during it’s storage in gall bladder �Capacity is only 50 ml �Water is reabsorbed and concentrate it 5 to 10 times. �Na. Cl is reabsorbed by Na ⁺K⁺ATPase �Bile pigments, bile salts, cholesterol are not reabsorbed. �Gall bladder exchange H for Na. H combine with HCO 3 to form H 2 O and CO 2 , bile in gall bladder is neutral or even acidic. �H⁺+HCO₃¯→CO 2 + H 2 O �Mucin is secreted into bile.

Factors affecting billiary secretion �Bile salts �Ingestion of food �Hepatocrinin, secretin, gastrin, CCK �Stimulation of vagus nerve

BILE ACIDS 24 C 2 or 3 hydroxyl groups Side chain that terminates in a carboxyl group Carboxyl group has a p. Ka 6 The molecules have both a polar and a non polar face and can act as emulsifying agents in the intestine, helping prepare dietary triacylglycerol and other complex lipids for degradation by pancreatic digestive enzymes.

SYNTHESIS OF BILE ACIDS �Multistep pathway �Hydroxyl groups are inserted at specific positions on steroid structure �Double bond of B ring is reduced �Hydrocarbon chain is shortened by 3 C �Carboxyl group is introduced at end of chain

�The most common resulting compounds cholic acid and chenodeoxycholic acid are called “primary” bile acids. � The rate-limiting step in bile acid synthesis is the introduction of a hydroxyl group at carbon 7 of the steroid nucleus by cholesterol 7α hydroxylase. �Expression of the enzyme is downregulated by bile acids.

CONJUGATION OF BILE SALTS �Bile acids are conjugated to a molecule of Glycine or Taurine. �Amide bond is formed between Carboxyl group of bile acid and amino group �These new structures include glycocholic and glycochenodeoxycholic acids and taurocholic and taurochenodeoxycholic acids � The ratio of glycine to taurine forms in the bile is approximately 3: 1

�The conjugated, ionized bile salts are more effective detergents than the unconjugated ones because of their enhanced amphipathic nature. �Therefore, only the conjugated forms are found in the bile. � Individuals with genetic deficiencies in the conversion of cholesterol to bile acids are treated with exogenously supplied chenodeoxycholic acid. �Only significant mechanism of cholesterol excretion.

Action of intestinal flora on bile salts �Bacteria in the intestine can deconjugate (remove glycine and taurine)bile salts. �They can also remove the hydroxyl group at carbon 7, producing “secondary” bile salts such as deoxycholic acid from cholic acid and lithocholic acid from chenodeoxycholic acid.

ENTEROHEPATIC CIRCULATION

FUNCTIONS OF BILE SALTS �↓ Surface tension→emulsification of fats �Strong choleretic effect �Activate pancreatic lipase �Formation of micelles �Stimulation of intestinal peristalsis �Antiseptic effect �Indirectly inhibit hepatic synthesis of cholesterol

Other constituents of bile �BILE PIGMENTS �Bilirubin and Biliverdin � 1 g haemoglobin→ 35 mg bilirubin �Daily 250 -350 mg �Formed in peripheral tissues is transported by plasma albumin �Unconjugated/Conjugated with glucoronic acid.

CHOLESTEROL �Excretory product �Daily excretion 1 -2 g in bile �Mostly in form of micelles which also contain bile salts and lecithin �Normal cholesterol to bile salt ratio 1: 20 1: 30 �If falls below 1: 13 cholesterol gets precipitated and associated with inflammation of gall bladder.

�Other constituents of bile �Immunoglobulins �Calcium palmitate �Alkaline phosphatase �Excretory products

Effects of billiary Fistula �When bile is drained out of body by a fistula and not allowed to enter the intestine, effects are �Steatorrhea �Feces become grey(clay coloured). �Deficiencies of fat soluble vitamins. �Obstructive jaundice.

CHOLELITHIASIS �The movement of cholesterol from the liver into the bile must be accompanied by the simultaneous secretion of phospholipid and bile salts. � If this dual process is disrupted and more cholesterol is present the cholesterol may precipitate in the gallbladder, leading to cholesterol gallstone disease, or cholelithiasis. �This disorder is typically caused by a decrease of bile acids in the bile. �Cholelithiasis also may result from increased secretion of cholesterol into bile, as seen with the use of fibrates to reduce cholesterol in the blood.

Treatment �Laparoscopic cholecystectomy (surgical removal of the gallbladder through a small incision) is currently the treatment of choice. �However, for patients who are unable to undergo surgery, ora l administration of chenodeoxycholic acid to supplement the body’s supply of bile acids results in a gradual dissolution of the gallstones.

SUCCUS ENTERICUS COMPOSITIONS �Thin, colorless secreted by two types of glands � 98 -99% water. �Organic and Inorganic. �p. H 8. 3

ENZYMES �Enteropeptidase. �Intestinal amylase. �Oligosaccharidases. 1. Lactase 2. Sucrase 3. Maltase 4. Trehalase 5. α-Dextrinase � Peptidases. � Phospholipases. � Polynucleotidases, nucleotidases and nucleosidases.

ACTIONS �Neutrilization of acidity. �Protection by mucus. �Intrinsic factor. �Dilutes chyme to isosmotic. �Ig. A. �Enzyme action.

REGULATION �Stimulation of vagus nerve increases secretion �Sympathetic stimulation inhibit secretion �Certain hormones as duocrinin and enterocrinin increases secretion