Gall Bladder Disease Cara Campbell

Anatomy Pear-shaped sac Fundus, body and neck 8cm by 4cm, capable of considerable distention Lined with mucus membrane, thrown into numerous folds (rugae) As gallbladder fills with bile the folds flatten out Sphincter of Oddi https://gi.jhsps.org/GDL_Disease.aspx?CurrentUDV=31&GDL_Cat_ID=BB532D8A-43CB-416C-9FD2-A07AC6426961&GDL_Disease_ID=214436D0-94CC-4B90-A1B6-8EC7C752A99D

Histology

Function Store and concentrate bile Bile emulsifies fats Cholecystokinin (CCK)  gallbladder contract rhythmically  bile enters CBD  duodenum Bile is concentrated by: Reabsorption of water and electrolytes Active transport of Na+ osmotic pressure  causing water and other electrolytes e.g. Cl- to be reabsorbed Store and concentrate bile, deliver it to small intestine during a meal Bile emulsifies fats When food containing fat enters the digestive tract, it stimulates the secretion of cholecystokinin (CCK). In response to cholecystokinin, the gallbladder rhythmically contracts and releases its contents into the common bile duct, eventually draining into the duodenum In the gallbladder bile is concentrated by removal of some water and electrolytes by active transport of Na+ ions across the epithelia of the gallbladder, which creates an osmotic pressure causing water and other electrolytes such as Cl- ions to be reabsorbed

Constituents of Bile Primary bile acids: cholic and chenodeoxycholic acid Secondary bile acids: deoxycholic and lithocolic acids Lipids (Phospholipids and cholesterol) Bilirubin Waste products Electrolytes Proteins

Gallbladder diseases Gallstones Common bile duct stones Biliary colic Acute cholecystitis Common bile duct stones Ascending cholecystitis Miscellaneous Conditions of the Biliary tract Non- calculous conditions of gall bladder Extra-hepatic biliary tract Tumours of biliary tract Gall bladder polyps Primary cancer of gall bladder Cholangiocarcinoma Carcinoma of pancreas – bile duct obstruction

Gallbladder diseases Gallstones Common bile duct stones Biliary colic Acute cholecystitis Common bile duct stones Ascending cholecystitis Miscellaneous Conditions of the Biliary tract Non- calculous conditions of gall bladder Extra-hepatic biliary tract Tumours of biliary tract Gall bladder polyps Primary cancer of gall bladder Cholangiocarcinoma Carcinoma of pancreas – bile duct obstruction

Gallstones Increasing age Prevalence F>M Types: Cholesterol gallstones (80%) Cholesterol crystallisation from gallbladder bile Cholesterol supersaturation of bile Crystallisation-promoting factors within bile Motility of the gallbladder Bile pigment stones

Risk Factors Gallstones 5 F’s: Fat, forty, female, fertile, fair FH Diet (high animal fat/low fibre) Drugs (e.g. OCP) Ileal disease or resection

Clinical Presentation of Gallstones Majority are asymptomatic, found incidentally Once symptomatic, recurrent complications Biliary colic Acute cholecystitis

Biliary colic Biliary colic - pain associated with temporary obstruction of cystic or common bile duct Severe pain, constant, crescendo Epigastric/RUQ Radiation over right shoulder and subclavicular region Nausea and vomiting After large meal, high fat Mid-evening lasting early hours morning

Acute Cholecystitis Initial event: obstruction gall bladder emptying (95% gallstones)  increase in gall bladder glandular secretion  progressive distention compromise vascular supply Inflammatory response Infection Clinical features Similar to biliary colic + fever After a few hours localised R UQP Distended by pus (empyema) Acute gangrenous cholecystitis  can perforate  generalised peritonitis Initial event in acute cholecystitis is obstruction to gallbladder emptying (95% gallstones) Results in increase in gall bladder glandular secretion, leading to progressive distention, may compromise vascular supply Inflammatory response secondary to retained bile Infection secondary to the above Clinical features Similar to biliary colic + fever After a few hours localised upper right quadrant pain (parietal peritoneal involvement) Distended by pus (empyema) Acute gangrenous cholecystitis – can perforate – generalised peritonitis

Investigations Biliary colic due to stone in neck of gallbladder or cystic duct Unlikely to have significantly abnormal tests Acute cholecystitis Moderate leucocytosis Raised inflammatory markers (ESR and CRP) Serum bilirubin, alkaline phosphatase and aminotransferase levels Marginally elevated in cholecystitis More significant elevation in bile duct obstruction Abnormal ultrasound scan PPV 92%, NPP 95%

Differential diagnosis Biliary colic Irritable bowel syndrome (spasm of hepatic flexure) Carcinoma of right side of colon Atypical peptic ulcer disease Renal colic Pancreatitis Acute cholecystitis (severe RUQ pain and fever) Acute episodes of pancreatitis Perforated peptic ulcer Intrahepatic abscess Basal pneumonia Myocardial infarction

Management of Gallstones Biliary colic Cholecystectomy (laparoscopic approach) Acute cholecystitis Initial management is conservative Nil by mouth IV fluids Opiate analgesia IV antibiotics (local policy – broad-spec cephalosporins, fluroquinolones or piperacillin/tazobactam) Cholecystectomy

Complications of cholecystectomy Biliary leak (from cystic duct or gallbladder bed) Injury to bile duct Bile duct stricture Secondary biliary liver injury Overall mortality 0.2% Post-cholecystectomy syndrome

Non-surgical techniques Rarely used Pure cholesterol stones can be solubilized by increasing bile salt content oral chenodeoxycholic acid and ursodeoxycholic acid, long term therapy, recurrence rates high Statins Extracorporeal shock wave lithotripsy

Gallbladder diseases Gallstones Common bile duct stones Biliary colic Acute cholecystitis Common bile duct stones Ascending cholecystitis Miscellaneous Conditions of the Biliary tract Non- calculous conditions of gall bladder Exrta-hepatic biliary tract Tumours of biliary tract Gall bladder polyps Primary cancer of gall bladder Cholangiocarcinoma Carcinoma of pancreas – bile duct obstruction

Common bile duct stones Can lead to ascending cholangitis Triad Biliary colic Fever Jaundice Investigations FBC – normal Elevated neutrophil count raised inflammatory markers (ESR and CRP) Raised serum bilirubin – mild (high = complete bile duct obstruction) Serum alkaline phosphatase and ɣ-glutamyl transpeptidase – raised Aminotransferase – mildly raised (marked rises in complete bile duct obstruction) Serum amylase – raised Pro-thombin time prolonged (decreased absorption of vitamin K) Imaging – ultrasound ERCP Endoscopic retrograde cholangiopancreatography

Management Ascending cholangitis High morbidity and mortality IV antibiotics Urgent bile duct drainage (endoscopic retrograde approach) CBD stones and gall bladder stones Laparoscopic cholecystectomy + exploration of CBD Endoscopic approach (immediately before/after cholecystectomy)

Complications of gallstones Acute cholecystitis Ascending cholangitis Gallstone-related pancreatitis Biliary enteric fistula (gallstone eroded through gall bladder wall, stone in small intestine – ileus/true obstruction) http://www.mayoclinic.org/diseases-conditions/pancreatitis/multimedia/pancreatitis-caused-by-gallstones/img-20007560

Gallbladder diseases Gallstones Common bile duct stones Biliary colic Acute cholecystitis Common bile duct stones Ascending cholecystitis Miscellaneous Conditions of the Biliary tract Non- calculous conditions of gall bladder Extra-hepatic biliary tract Tumours of biliary tract Gall bladder polyps Primary cancer of gall bladder Cholangiocarcinoma Carcinoma of pancreas – bile duct obstruction

Miscellaneous Conditions of the Biliary tract Non-calculous cholecystitis (chronic inflammation) Cholesterolosis of gall bladder (cholesterol deposited in macrophages in lamina propria) Adenomyomatosis of gall bladder (hyperplasia of mucosa, thickening of muscle wall and multiple intramural diverticular) Chronic cholecystitis

Miscellaneous Conditions of the Biliary tract Extra-hepatic biliary tract Primary sclerosing cholangitis Autoimmune cholangitis Congenital malformation of bile duct Benign bile duct strictures Haemobilia

Gallbladder diseases Gallstones Common bile duct stones Biliary colic Acute cholecystitis Common bile duct stones Ascending cholecystitis Miscellaneous Conditions of the Biliary tract Non- calculous conditions of gall bladder Extra-hepatic biliary tract Tumours of biliary tract Gall bladder polyps Primary cancer of gall bladder Cholangiocarcinoma Carcinoma of pancreas – bile duct obstruction

Tumours of biliary tract Gall bladder polyps Majority non-neoplastic Adenomas – benign neoplastic Cholecystectomy – any polyp >1cm Primary cancer of gall bladder Adenocarcinoma Cholangiocarcinoma Carcinoma of pancreas – bile duct obstruction

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