Bile physiology.pptx

Bile physiology

1. Bile Physiology Dr Mohd Shahimin Bin Soaid Postgraduate Student Year 1 Supervisor : Mr Abdul Malek Bin Mohamad

2. Outlines Overview Production Function Absorption and secretion Regulation Clinical correlation

3. Overview Bile is a physiological aqueous solution produced and secreted by the liver The hepatocyte produces bile continuously and excretes it into bile canaliculi Bile leaves the liver through the right and left hepatic ducts,into common hepatic duct and then the common bile duct With an intact sphincter of Oddi, tonic contraction diverts bile flow into the gallbladder for storage, while mealtime stimulation allows it passage into the duodenum About 500mL is secreted per day In the small intestines, bile acids facilitate lipid digestion and absorption 5%  excreted 95%  reabsorbed from the ileum, secreted into the portal venous system, and returned to the liver in a process known as enterohepatic recirculation

4. Bile salts Bile salts (including bile acids) constitute 50-65% of the organic component of bile The total bile salt pool is approximately 2.5 g Hepatocytes synthesize two primary bile acid ( cholic and chenodeoxycholic ) from cholesterol by the process of hydroxylation When these primary bile acids are secreted into the lumen of the intestine, a portion of each is dehydroxylated by intestinal bacteria to produce two secondary bile acids, deoxycholic acid and lithocholic acid The liver conjugates the bile acids with the amino acids glycine or taurine to form bile salts This conjugation step causes them to become much more water soluble

5. Bile salts concentration in gallbladder In the fasting state , approximately 80% of the bile secreted by the liver is stored in the gallbladder Gallbladder can hold up to 30-60mL of bile Concentration of bile occurred by: Active absorption of Na+, Cl-and HCo3 by the lining epithelium Associated passive water movement out of the lumen This process concentrating the remaining bile constituents that contain the bile salts, cholesterol, lecithin, and bilirubin up to 5 to 20 fold

6. The gallbladder absorbs water both actively via sodium-hydrogen (Na+/H+) pumps and passively through aquaporin channels. Both chloride (Cl−) and bicarbonate (HCO3−) are absorbed by the gallbladder epithelium via the cystic fibrosis transmembrane regulator (CFTR; Swartz-Basile et al, 2007). The secretion of hydrogen ions and the absorption of bicarbonate by the gall- bladder alter the acid-base balance from basic in hepatic bile to acidic in gallbladder bile.

7. FUNCTION OF BILE SALTS IN FAT DIGESTION AND ABSORPTION The function of bile salt is to solubilize dietary lipids Amphipathic properties ( Hydrophilic : water soluble ) ( hydrophobic : lipid soluble) 1. Hydrophilic side : negatively charged groups point outward from a hydrophobic steroid nucleus dissolves in the aqueous phase 2. Hydrophobic side: dissolves in the oil phase. Roles of bile salts: Emulsify dietary lipids Micelles formation

8. 1. Emulsify dietary lipids Through the process of emulsification, bile acids break down large lipid droplets into smaller ones The negatively charged bile salts surround the lipids, creating small lipid droplets in the intestinal lumen. The negative charges on the bile salts repel each other, so the droplets disperse, rather than coalesce, thereby increasing the surface area for digestive enzymes

9. 2. Micelles formation Bile salts also allow the products of lipid digestion to be transported as micelles. The core of the micelle contains monoglycerides, lysolecithin, fatty acids, and the hydrophobic portion of the bile salt. The hydrophilic portion of the bile salt surrounds the lipid core, increasing solubility. Without bile salts, the fat-soluble vitamins (A, D, E, K) cannot be absorbed.

10. Enterohepatic Circulation of Bile Salts most of the secreted bile salts are recirculated to the liver via an enterohepatic circulation In the ileum, the bile salts are transported from the intestinal lumen into the portal blood by Simple diffusion Na+-bile salt cotransporters , aka apical-sodium bile acid transporter (ASBT) The portal blood carries bile salts to the liver The liver extracts the bile salts from portal blood and adds them to the hepatic bile salt/bile acid pool the fecal loss is about 600 mg/day (out of the total bile salt pool of 2.5 g)

11. Bile involvement in bilirubin metabolism and secretion

12. Control of Bile Secretion Three mechanism Chemical - Hormonal – CCK/secretin Neural - Vagus

13. Chemical control Substances that stimulate hepatic secretion of bile( choleresis ) are choleretics Potent stimulus : bile salt

14. Neuronal and hormonal control

15. Clinical application

16. Gallstones formation Gallstones form as a result of solids settling out of solution Gallstones are classified by their cholesterol content as either 1. cholesterol stones (80-85 % ) 2. pigment stones/ calcium bilirubinate stones (15-20%) – black/brown Factors involved in stone formation 1. Supersaturation of the bile 2. Bile stasis 3. Nucleation factors that favors formation of stones from the supersaturated bile

17. Cholesterol stones Pure cholesterol stones are uncommon and account for <10% of all stones  They usually occur as a single large stone with a smooth surface The majority of cholesterol stones are mixed but are at least 70% cholesterol by weight in addition to variable amounts of bile pigments and calcium  multiple, of variable size, and may be hard and faceted or irregular, multilobed, and soft Colors range from whitish yellow to green or black Most cholesterol stones (>90%) are radiolucent, though some have a high calcium carbonate component and become radioopaque

18. Pathophysiology of cholesterol stones: The primary event in the formation of cholesterol stones is supersaturation of bile with cholesterol its solubility in water and bile depends on the relative concentration of cholesterol, bile salts , and lecithin When cholesterol hypersecretion is present, either through increased intake or dysfunctional processing  supersaturation occurs When cholesterol concentrations exceed the ability of the bile salts and phospholipid to maintain solubility, the cholesterol precipitates out of solution into a solid, forming a cholesterol stone Ratio of b ile acids : phospholipids (Lecithin) : cholesterol 10:3:1 ADMIRAND TRIANGLE

19. PIGMENTED STONES Pigmented stones contain <20% cholesterol and are dark because of the presence of calcium bilirubinate . Black and brown pigment stones have little in common and should be considered as separate entities. BLACK PIGMENT STONES: small, brittle, dark, and sometimes spiculated formed by supersaturation of unconjugated bilirubin within the bile Aetiology: excessive levels of conjugated bilirubin excretion ( hemolytic disorders like hereditary spherocytosis and sickle cell disease)  increased rate of production of unconjugated bilirubin. The insoluble unconjugated bilirubin will then precipitate with calcium as insoluble calcium bilirubinate , forming a pigment stone Due to their high calcium content, pigment stones are often radiopaque. Higher percentage of gallstones in Asian Countries than in the Western hemisphere.

20. BROWN PIGMENT STONES: usually <1 cm in diameter Brownish yellow, soft, and often mushy form either in the gallbladder or in the bile ducts secondary to bacterial infection and bile stasis Bacteria such as Escherichia coli secrete β- glucuronidase that enzymatically cleaves conjugated bilirubin to produce the insoluble unconjugated bilirubin This unconjugated bilirubin then precipitates with calcium, and along with dead bacterial cell bodies, forms soft brown stones in the biliary tree Brown stones are typically found in Asian population Also associated with stasis secondary to parasite infection with Ascaris lumbricoides (roundworm) or Clonorchis sinensis (liver fluke)

21. Resection of ileum most of the secreted bile acids are lost in feces , increasing the demand for synthesis of new bile acids. The liver is unable to keep pace with the demand, causing a decrease in the total bile acid pool emulsification of dietary lipids for digestion and micelle formation for absorption of lipids are compromised dietary lipids are excreted in feces , seen as oil droplets in the stool ( steatorrhea). high concentration of bile acid in colon lumen  stimulate cAMP-dependent Cl− secretion in colonic epithelial cells  Na+ and water follow Cl− into the lumen  secretory diarrhea absorption of vitamin B12 impaired

22. EFFECTS OF CHOLECYSTECTOMY The periodic discharge of bile from the gallbladder aids digestion but is not essential for it Cholecystectomized patients maintain good health and nutrition with a constant slow discharge of bile into the duodenum although eventually the bile duct becomes somewhat dilated, and more bile tends to enter the duodenum after meals than at other times.

23. references Ganong’s Review of Medical Physiology -25 th Edition Linda S. Contanzo – Physiology 6 th edition Schwartz’s Principle of Surgery 11 th edition Guyton and Hall Textbook of Medical Physiology 13 th edition