1. DR. FIRAS OBEIDAT, MD GBS, pathogenesis and complications

2. Types of gallstones  Mixed (80%): cholesterol content 50-80%. various shape and colors, radiopaque. usually small multiple stones of faceted surface.  Pure cholesterol (10%): cholesterol content around 100%. pale yellow, radiolucent. usually large solitary.

3. Types of gallstones  Pigmented (10%)  cholesterol content less than 20%. Black stones :  Pts with cirrhosis and hemolysis.  Contain mainly Ca bilirubinate.  Homogenous, brittle, radiopaque (75%).  Usually small multiple stones. Brown stones:  After biliary tract infection.  Contain mainly Ca palmitate  Usually small multiple stones, radiolucent.

4. Types of gallstones

6. Risk factors  “Female, Fat, Forty, Fertile”  Oral contraceptives  Obesity  Rapid weight loss (gastric bypass pts)  Fatty diet  DM  Prolonged fasting  TPN  Ileal resection  Hemolytic states  Cirrhosis  Bile duct stasis (biliary stricture, congenital cysts, pancreatitis, sclerosing cholangitis)  IBD  Vagotomy  Hyperlipidemia

7. Pathogenesis of gallstones  Bilirubin, bile salts, phospholipids, and cholesterol are the major organic solutes in the bile.  Cholesterol is produced primarily by the liver with little contribution from dietary sources.  Cholesterol is insoluble in water, and thus in bile.  The way to keep cholesterol from precepitation is the complexes (micelles and visicles).

8. Pathogenesis of gallstones  Excessive cholesterol or decreased bile salts and phospholipids portion will lead to cholesterol precepitation.  Failure to maintain these solutes primarily cholesterol and calcium salts will lead to preceptation of crystals and stone formation.  GB dysmotility and disturbed acidification of GB bile by mucin, which inhance precipitation of Ca bilirubinate that acts as a nidus for GS formation.

9. Pathogenesis of gallstones  Pathogenesis of cholesterol GS: Cholesterol supersaturation:  Excessive secretion of cholesterol is the main cause.  Decreased portion of bile salts has less value.  Saturation of bile with cholesterol is not sufficient for stone formation, so additional factors are important to inhance or prevent nucleation).

10. Pathogenesis of gallstones Nucleation:  Formation of solid crystals from bile saturated with cholesterol.  Nidus (Ca bilirubinate) is another mechanism by which solid crystals form.  Promotors of nucleation like mucous glycoproteins are important for this step. Growth:  Indivisual growth of each crystal.  Aggregation of multiple crystals.  Promotors like Ca and mucous glycoproteins which acts as a framework for crystal deposition.

11. Pathogenesis of gallstones  Pathogenesis of pigment gallstones: Black stones:  Frequently occurs in patients with hemolysis and cirrhosis as load of unconjugated bilirubin is increased which then precipetate with calcium.  Usually are not associated with infected bile.  Located almost exclusively in the GB.

12. Pathogenesis of gallstones Brown stones:  Typically found in the bile duct as a primary stones.  Contain more cacium palmitate and cholesterol.  Usually secondary to bacterial infection which has enzyme glucorinidase causing hydrolysis of soluble conjugated bilirubin to form unconjugated bilirubin, which then precepitate with calcium.  Another bacterial enzyme is phospholipases, which hydrolyzes the lecithin to form palmitate...

13. Complications of GBS  Biliary pain.  Acute cholecystitis with it is complications.  Chronic cholecystitis.  Choledocholithiasis with and without cholangitis.  Biliary pancreatitis.  Gallstone ileus.  Gallblader carcinoma.

14. Acute cholecystitis  Definition: Clinicopathological entity characterized by acute inflammation of the gallbladder caused by the obstruction of the Hartmann's pouch or cystic duct comprising impacted gallstones(90-95%) of cases or biliary sludge. The inflammation of the gallbladder wall is chemical, at least during the early phase. Following this early phase, 20-50% of patients manifest a proliferation of aerobic enteric bacteria, and occasionally anaerobes, resulting in secondary bacterial infection of the organ. Progression of the disease into severe form (5-10%) of cases perforation ans sepsis (emphysematous cholecystitis,empyema, and perforation).

15. Acute cholecystitis  Types: Calculous (90%-95%). Acalculus (5%-10%):  Stasis and ischemia.  Critically ill patients.  High mortalitiy (40%).  Incidence: 70%-80% patients remain asymptomatic through life. Risk of symptoms is 1%-3%/yr. Acute cholecystitis usually occurs in symptomatic group.

16. Acute cholecystitis Xanthogranulomatous cholecystitis:  Leakage of bile into the wall  Inflammatory reaction with formation of xanthoma cells  More acute presentation and more complications  US diagnosis is rare, presence of intramural nodules overlap with GB Ca. Emphysematous cholecystitis:  Gas forming bacteria  Early complications  High morality 15%-25%  1% of all cases of acute cholecystitis  More in diabetic male pts

17. Acute cholecystitis  Clinical features:  Pathogenesis:  Complications: Empyema, perforation, Mirrizi syndrome.  Diagnosis: Plain X ray US CT scan ERCP,MRCP HIDA scan  Management:

18. Chronic cholecystitis  may arise from repeated attacks of symptomatic acute cholecystitis or it develops without any history of acute attacks.  almost always associated with gallstones.  Macroscopic findings: gallbladder may be contracted (from fibrosis).

19. biliary dyskinesia  Cholecystokinin-Tc-HIDA scan (ejection fraction of <35% at 20 min of cholecystokinin is diagnostic).  Most pts have evidence of chronic chole.  > 50% of pts have improvement after cholecystectomy.

20. Biliary pain  Biliary colic is a misnomer, because the pain is not usually as intermmitent and spasmodic as the term suggests.  Time of pain.  The duration of biliary pain is typically 1 to 5 hours. The episode rarely persists for less than one hour or more than 24 hours. Pain lasting beyond 24 hours suggests the presence of acute cholecystitis.  They are usually less frequent than one episode per week with nausea and vomiting often accompaning each episode in 60 to 70% of cases.

21. Choledocholithiasis  Incidence:  Types: Secondary: Primary:  Clinical picture and complications.  Diagnosis (clinical, biochemical, and radiological)  Management.

22. Biliary pancreatitis  Among patients with gallstones, 4-8% will present acute pancreatitis.  In patients with multiple calculi less than 3 mm in diameter (microlithiasis) the risk escalates to 30%.  Gallstones are responsible for 50% of all cases of pancreatitis.  90% have mild to moderate self limited pancreatitis.

23. Indications for Prophylactic Cholecystectomy  Pediatric gallstones.  Congenital hemolytic anemia.  Gallstones >2.5cm.  Porcelain gallbladder (25% risk of Ca).  Incidental gallstones found during intraabdominal surgery.  Recommended prior to transplantation.  in young women.  GB polyp > 1 cm ( risk of malgnancy)

28. Xanthogranulomatous cholecystitis