The document discusses the pathogenesis of gallstones. It begins by describing the anatomy of the liver and its role in bile synthesis. Bile is composed of cholesterol, bile acids, phospholipids, and bilirubin. Cholesterol in bile can precipitate to form gallstones under certain conditions. Gallstones are usually either cholesterol stones or pigment stones, with different risk factors and pathophysiological mechanisms for each. Gallstones may be asymptomatic but can also lead to complications if they block bile ducts or the pancreas.

1. Presented by : H. Al-Buainain Supervised : Prof. Parashar PATHOGENESIS OF GALLSTONES

2. Introduction Anatomy “ liver lobules” . Bile synthesis . Role of bile acid . Clinical significance of bile . Gallstone

3. Liver is largest & most important metabolic Organ in the body . One of its importance function to the digestive system is synthesis & secretion of bile . ANATOMY

4. Liver Lobule

5. Bile acid Cholesterol Phospholipid Bilirubin Composition of Bile

6. Cholesterol Metabolism Cholesterol is an extremely important molecules in : - membrane structure - Precursor of Steroid Hormone and bile acids.

7. SYNTHESIS OF CHOLESTEROL Less than half of the cholesterol is derived from denovo . 10 % of cholesterol are synthesized in the liver while 15 % from SI.

8. Synthesis of Cholesterol

9. So End product of cholesterol utilization are bile acid Chenodeoxycholic acid cholic acid Glycine or Taurine Glycocholic Acid Taurocolic Acid

10. Bilirubin synthesis

11. Adult human produce 400 – 800 ml of bile daily . BILE SECRETION : Occur in two stages : 1- Active secretion from hepatocytes to the canaliculi , bile duct . 2- Modification in the bile duct through addition of H2O & HCO3 During fasting state , bile will be stored in the gallbladder .

12. Role of Bile In Fat Digestion Absorption Bile acids are Amphipathic

13. It is enable bile acid to carry out to important functions : - Emulsification of lipid aggregates - Solubilization & transport of lipid in aqueous enviroment .

14. Emulsification

15. Role Of Bile Acid In Cholesterol Homeostasis In human , 500 mg of cholesterol are converted to bile acids . This route will eliminate excess amount of cholesterol .

16. ENTEROHEPATIC CIRCULATION

17. CONTROL OF BILE SECRETION Bile secretion regulated by : Cholecystokinin Secretin - Bile salt

18. SIGNIFICANCE OF BILE ACID Bile acid play 4 physiological function: 1- Elimination of excess cholesterol. 2- Solubilize cholesterol which prevent PPT in the GB . 3- Facilitate digestion of TG through emulsification . 4- Facilitate absorption of fat soluble vitamines.

19. It is one of the digestive disorder . more common in females . Classified according to the chemical composition into : - Cholesterol . - Pigment . - Calcium . Each type has particular pathophysiology and special risk factors . GALLSTONES

20. It is the commonest type of G.stones mainly d/t : Abnormality in liver synthesis of bile : - Reduction in bile salt or phospholipid - Excessive amount of cholesterol. Genetic & dietary factors Cholesterol Stones

21. Cholesterol Gallstones Formation formation of gall stones pass through 3 processes :

22. Risk factors Gallstones Formation

23. Types of Cholesterol stones There are two types: 90-100% Solitary , Whitish > 2.5 cm 50 - 90% Multiple , Small ,# Variety of shape

24. PIGMENTED GALLSTONES - Calcium bilirubinate - Ca Soap - Bacteria has role in the synthesis - > in Asia - Mainly at bile duct -Periumpullary duodenal diverticula -Excess Bilirubin - > in : -Elderly Pt. - Chronic haemolysis - Alcoholic

25. Asymptomatic . Biliary cholic . Calcular cholecystitis . Cholangitis . Obstructive jaundice . Gallstone ileus Gallstone pancreatitis Complications

26. Conclusion The bile play a major role in the excretion of cholesterol & absorption of fat sol Vit. Alteration of bile composition lead to the formation of GS . Finally GB hypomotility & bile stasis promote GS formation .

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