What are the mechanisms by which small gallstones cause acute pancreatitis?

Mechanisms of Small Gallstones in Acute Pancreatitis

Small gallstones cause acute pancreatitis primarily through obstruction leading to ductal hypertension, with additional mechanisms including the common channel hypothesis and incompetent sphincter of Oddi. 1, 2

Primary Mechanisms

Obstruction Leading to Ductal Hypertension

• Small gallstones can transiently impact at the ampulla of Vater, causing obstruction of the pancreatic duct 1
• This obstruction leads to increased pancreatic duct pressure (ductal hypertension) 2
• The increased pressure results in reflux of activated trypsin and subsequent activation of other pancreatic enzymes within acinar cells 1
• Intra-acinar activation of trypsinogen plays a central role in the pathogenesis of acute pancreatitis 1
• This mechanism is particularly important in gallstone-induced pancreatitis, which represents approximately 50% of all acute pancreatitis cases 3, 4

Common Channel Hypothesis

• When a small gallstone impacts at the ampulla, it can create a "common channel" between the pancreatic and bile ducts 5
• This allows reflux of bile into the pancreatic duct 5
• Studies have shown that reflux of contrast into the pancreatic duct during cholangiography is more common in patients with gallstone pancreatitis (50%) compared to those with uncomplicated gallstones (25%) 5
• The refluxed bile can activate pancreatic enzymes, leading to autodigestion of the pancreas 2
• Small stones (<4mm) are more likely to cause this phenomenon than larger stones 5

Incompetent Sphincter of Oddi

• Small gallstones can cause transient dysfunction or incompetence of the sphincter of Oddi 3
• This dysfunction allows duodenal contents to reflux into the pancreatic duct 6
• The refluxed duodenal contents, which contain activated digestive enzymes, can initiate pancreatic inflammation 6
• Sphincter of Oddi dysfunction is identified through biliary manometry, which carries a significant risk of precipitating acute pancreatitis itself 3

Clinical Implications

• Small gallstones (<4mm) are more likely to cause acute pancreatitis than larger stones 5
• Multiple small stones increase the risk further, with 78% of patients with gallstone pancreatitis having four or more stones 5
• Faceted stones are more common in patients with gallstone pancreatitis (29%) compared to those without (20%) 5
• Early identification of gallstones is crucial, with at least two good quality ultrasound examinations recommended 3
• For severe gallstone pancreatitis, urgent ERCP and sphincterotomy may reduce morbidity, particularly in cases with biliary obstruction or cholangitis 3
• Cholecystectomy should be performed within 2-4 weeks for mild cases to prevent recurrent attacks 3, 4

Diagnostic Considerations

• Microlithiasis (tiny stones not visible on conventional imaging) may account for two-thirds of "idiopathic" acute pancreatitis cases 1
• Endoscopic ultrasound is highly sensitive for detecting small gallstones and microlithiasis in the gallbladder or common bile duct 3
• Bile sampling may be the only way to identify patients with recurrent acute pancreatitis due to microlithiasis 3
• MRCP can demonstrate most duct stones and ductal anomalies such as pancreas divisum 3

Pathophysiological Subtypes

• Severe gallstone pancreatitis may present as either a biliary type (acute cholangitis with mild pancreatitis) or pancreatic type (necrotizing pancreatitis without biliary tract disease) 6
• The severity of hepatobiliary versus pancreatic lesions is inversely related to the presence or absence of impacted ampullary stones 6
• Understanding the status of stones and presence of ampullary impaction helps predict the clinical course and outcome 6