Gallstone Disease

1. Gallstone Disease Tad Kim, M.D. Connie Lee, M.D.

2. Definitions • Cholelithiasis = gallstones • Acute calculous cholecystitis = 2/2 occlusion of the cystic duct by gallstone leading to gallbladder inflammation • Chronic calculous cholecystitis = recurrent episodes of cystic duct obstruction leading to scarring and a nonfunctional gallbladder • Chronic acalculous cholecystitis = symptoms of biliary colic, no gallstones, and an abnormal gallbladder ejection fraction • Acute cholangitis = bacterial infection of the biliary ducts • Choledocholithiasis = CBD stones • Mirizzi syndrome = when gallstones lodged in either the cystic duct or the Hartmann pouch of the gallbladder, externally compressed the common hepatic duct (CHD), causing symptoms of obstructive jaundice

3. Bile • Bile • Bile salts (primary: cholic, chenodeoxycholic acids; secondary: deoxycholic, lithocholic acids) • Phospholipids (90% lecithin) • Cholesterol • Cholesterol solubility depends on the relative concentration of cholesterol, bile salts, and phospholipid

4. Types of Gallstones • Mixed (80%) • Pure cholesterol (10%) • Pigmented (10%) • Black stones (contain Ca bilirubinate, a/w cirrhosis and hemolysis) • Brown stones (a/w biliary tract infection)

5. Gallstone Pathogenesis • Pathogenesis of cholesterol gallstones involves: (1) cholesterol supersaturation in bile, (2) crystal nucleation, (3) gallbladder dysmotility, (4) gallbladder absorption • Black pigment stones: contain Ca++ salts, a/w hemolytic conditions or cirrhosis, found in the gallbladder • Brown pigment stones: Asians, contain Ca++ palmitate, found in bile ducts, a/w biliary dysmotility and bacterial infection

6. Gallstone 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. Gallstone Complications • Gallstone ileus, gallstone pancreatitis • Acute cholecystitis: 10-20% of pts w/ symptomatic gallstones • GB gangrene • GB perforation • GB empyema (pus in the GB) • Emphysematous cholecystitis (a/w GB vascular compromise, stones, impaired immune system, infection w/gas-forming organisms - clostridium, E. coli, Klebsiella) • Cholecystoenteric fistula • Choledochohlithiasis: 8-15% of pts w/ symptomatic gallstones • Cirrhosis • Cholangitis • Pancreatitis

8. Symptomatic Gallstones • Provocation/Timing: meals (50%), nighttime • Quality: constant • Radiation: RUQ to the R scapula (Boas’ sign) • Severity: “severe” • PE: (+)Murphy’s sign

9. RUQ DDx • Gallbladder: cholecystitis, choledocholithiasis, cholangitis • Duodenal ulcer • Hepatitis • Appendicitis (atypical presentation) • PNA • Pancreatitis

10. Labs • Order: BMP, amylase/lipase, LFTs, CBC, coags • Acute cholecystitis: increased WBC, increased alk phos, slight increase in amylase and T bili

11. Imaging • KUB - only 15% of gallstones are radiopaque • U/S - gallstone identification false(-) rate is 5-15%. It identifies bile duct dilatation w/ 80% accuracy. • Look for: thickened GB wall (>3mm), pericholecystic fluid, distended GB, Murphy’s sign • HIDA scan - radionuclide IV, extracted from blood, excreted into bile • Uptake by liver, GB, CBD, duodenum w/in 1hr = normal • Slow uptake = hepatic parenchymal disease • Filling of GB/CBD w/delayed or absent filling of intestine = obstruction of ampulla • Non-visualization of GB w/ filling of the CBD and duodenum = cystic duct obstruction and acute cholecystitis (95% sensitivity & specificity) • CT scan - used to diagnose complications • MRI - can detect gallstones and common duct stones • ERCP - to look for CBD stones

12. Ultrasonographic Images of Three Gallbladders Strasberg S. N Engl J Med 2008;358:2804-2811

13. Hepatobiliary Scintigraphy Strasberg S. N Engl J Med 2008;358:2804-2811

14. CT Scan of the Abdomen Thomas L et al. N Engl J Med 1999;341:1134-1138

15. Diagnostic Criteria for Acute Cholecystitis, According to Tokyo Guidelines Strasberg S. N Engl J Med 2008;358:2804-2811

16. Cholecystitis: Management • NPO, IVF, IV antibiotics • Non-operative: dissolution therapy ursodeoxycholic acid, chenodeoxycholic acid • Operative: cholecystectomy • For unstable pts: percutaneous transhepatic cholecystostomy (CT or U/S guided)

17. Indications for Prophylactic Cholecystectomy • Pediatric gallstones • Congenital hemolytic anemia • Gallstones >2.5cm • Porcelain gallbladder • Bariatric surgery • Incidental gallstones found during intraabdominal surgery • Recommended prior to transplantation

18. Case 1 • HPI: 46y F p/w 4hr h/o nausea and RUQ pain radiating to the R scapula. Symptoms began 1 hr after a fatty meal. Pt currently has no pain. No prior episodes. • PMHx/PSHx None • PE: RUQ minimally TTP, (-)Murphy’s • Labs: WBC 8, LFT normal • Studies: RUQ U/S w/cholelithiasis without GB wall thickening or pericholecystic fluid • What is the diagnosis?

19. Case 1 • → denotes gallstones • ► denotes the acoustic shadow due to absence of reflected sound waves behind the gallstone → → ►

20. Case 1: Continued • Dx: symptomatic cholethiasis • Plan: NPO, IVF, cholecystectomy

21. Case 2 • 46y F p/w 4hr h/o nausea and RUQ pain radiating to the R scapula. Symptoms began 1 hr after a fatty meal. Pt currently has no pain. Has had multiple similar episodes. • PMHx/PSHx None • PE: RUQ minimally TTP, (-)Murphy’s • Labs: WBC 6, LFT normal • Studies: RUQ U/S w/cholelithiasis without GB wall thickening or pericholecystic fluid • Diagnosis: ?

22. Case 2: Continued • Dx: chronic calculous cholecystitis • Recurrent inflammatory process due to recurrent cystic duct obstruction leading to scarring/wall thickening • Treatment: cholecystectomy

23. Case 3 • 46yF p/w h/o >24hr of RUQ pain radiating to the R scapula, started after fatty meal, a/w nausea, vomiting, fever • Exam: Febrile, RUQ TTP, (+)Murphy’s sign • Labs: WBC 13, Mild ↑LFT • U/S: gallstones, wall thickening, GB distension, pericholecystic fluid, sonographic Murphy’s sign • What is the diagnosis?

24. Case 3: Continued • Curved arrow • Two small stones at GB neck • Straight arrow • Thickened GB wall • ◄ • pericholecystic fluid = dark lining outside the wall ◄

25. Case 3: Continued → • → denotes the GB wall thickening • ► denotes the fluid around the GB • GB also appears distended ►

26. Case 3: Continued • Dx: acute calculous cholecystitis • Persistent cystic duct obstruction leads to GB distension, wall inflammation & edema • Risk of: empyema, gangrene, rupture • Treatment: • NPO • IVF • ABX: • Common organisms: E coli, Bacteroides fragilis, Klebsiella, Enterococcus, and Pseudomonas • Piperacillin/tazobactam (Zosyn), ampicillin/sulbactam (Unasyn), or meropenem • Cholecystectomy

27. Case 4 • 87y M critically ill, on long-term TPN c/o RUQ pain • PE: febrile, RUQ TTP • U/S: GB wall thickening, pericholecystic fluid, no gallstones • What is the diagnosis?

28. Case 4: Continued • Dx: acute acalculous cholecystitis • Caused by gallbladder stasis from lack of enteral stimulation by cholecystokinin • Risk of: gangrene, empyema, perforation due to ischemia • TX: cholecystectomy • If pt is too sick, percutaneous cholecystostomy tube followed by cholecystectomy

29. Case 5 • 46y F p/w RUQ pain, jaundice, acholic stools, dark tea-colored urine, w/o fever • PMHx: cholelithiasis • Exam: unremarkable • WBC 8, T.Bili 8, AST/ALT NL, Hep B/C neg • U/S: gallstones, CBD stone, dilated CBD > 1cm • What is the diagnosis?

30. Case 5: Continued • DX: choledocholithiasis • Similar presentation as cholelithiasis, except with the addition of jaundice • DDx: cholelithiasis, hepatitis, cholangitis, CA, choledochal cyst, bile duct stricture, UC, pancreatitis • Plan: • Endoscopic retrograde cholangiopancreatography (ERCP) w/ stone extraction and sphincterotomy • Interval cholecystectomy after recovery from ERCP

31. Case 6 • 46y F p/w fever, RUQ pain, jaundice • PE: tachycardic, hypotensive, RUQ pain • Immediate management: • ABC • Resuscitate • CBC, LFTs, blood cultures • Abdominal U/S • What is the diagnosis? • What is the plan?

32. Case 6: Continued • Dx: cholangitis • Infection of the bile ducts due to CBD obstruction secondary to stones/strictures • Common organisms: E. coli, Klebsiella, Pseudomonas, Enterobacter, Proteus, Serratia • 70% p/w Charcot’s • May lead to life-threatening sepsis and septic shock (Raynaud’s pentad) • Common lab findings: leukocytosis, hyperbili, elevated alk phos • Treatment: • NPO, IVF, IV ABX • Emergent decompression via ERCP or perc transhepatic cholangiogram (PTC)

33. Case 7 • 46y F p/w persistent epigastric & back pain • PMHx: symptomatic gallstones • SHx: no ETOH • PE: Tender epigastrum • Labs: Amylase 2000, ALT 150 • U/S: gallstones • What is the diagnosis? • What is the plan?

34. Case 7: Continued • Dx: gallstone pancreatitis • 35% of acute pancreatitis secondary to stones • Pathophysiology: reflux of bile into pancreatic duct and/or obstruction of ampulla by stone • ALT >150 (3-fold elevation) has 95% PPV for diagnosing gallstone pancreatitis • Treatment: • ABC, resuscitate, NPO/IVF, pain medication • ERCP once pancreatitis resolves • Cholecystectomy before d/c

35. Take Home Points • Start with ABCs • Cholelithiasis = “Female, Fat, Forty, Fertile” • Stone formation based on the relative concentration of cholesterol, bile salts, and phospholipid • Cholecystitis PE = Murphy’s sign • RUQ evaluation: U/S, HIDA, CT, MRI, ERCP • Acalculous cholecystitis a/w TPN, ICU setting • Cholangitis = Charcot’s triad, Reynold’s pentad