Pathophysiology
Summary
The hepatobiliary system consists of the liver, gallbladder, and network of bile ducts that contribute to the production and storage of bile, which facilitates the digestion and absorption of fats in the GI tract. Bile is synthesized in the liver and stored in the gallbladder, and is connected to the hepatic duct by the cystic duct, which together forms the common bile duct.
Bile is mainly composed of free cholesterol, bile salts, & phosphatidylcholines (lecithins). Gallstones precipitate when there is an imbalance in bile constituents, and occur as cholesterol stones or pigment stones. In cholesterol stones, excessive cholesterol can build up and increase the ratio of cholesterol to bile salts, resulting in supersaturated cholesterol that promotes the formation of the characteristic yellow cholesterol stones. Black-pigmented gallstones are composed of conjugated bilirubin, and typically seen in states of intravascular hemolysis like hemoglobinopathies and G6PD deficiency.
Gallstone formation can be influenced by several factors that can be remembered as: ’fat, fertile, forty, & female’. The high estrogen states that occur among these demographics increases cholesterol biosynthesis by upregulating HMG-CoA reductase activity. Decreased gallbladder motility—which occurs in conditions like pregnancy, somatostatin administration, TPN, and fasting, can also contribute to gallstone formation by causing bile stasis.
Clinical manifestations often include biliary colic, which can worsen at night after a fatty meal. Acute cholecystitis can occur when a gallstone persistently obstructs the gallbladder outlet, and typically presents with fever and leukocytosis, as well as Murphy's sign. Diagnostically, acute cholecystitis often shows a thickened gallbladder wall on ultrasound, and can be confirmed by a HIDA scan. Acalculous cholecystitis is seen in critically ill patients, and can occur in cases of gallbladder stasis, hypoperfusion, and infection.
Chronic cholecystitis is caused by repeated episodes of acute cholecystitis, and is diagnosed histologically by herniations of gallbladder mucosa into the muscular wall (Rokitansky-Aschoff sinuses). Choledocholithiasis occurs when a stone obstructs the common bile duct, resulting in cholestasis and elevations in alkaline phosphatase, GGT, and conjugated bilirubin.
Further complications include ascending cholangitis, an acute inflammation of the bile ducts usually caused by obstruction and bacterial migration. Ascending cholangitis typically presents with Charcot's Triad of jaundice, fever, and RUQ pain. Rarely, a biliary-enteric fistula can arise when the gallstone causes erosion through the biliary wall, known as gallstone ileus.
Chronic gallbladder inflammation, such as in gallstones, increases the risk of developing strong>gallbladder adenocarcinoma, which often forms a ‘cauliflower-like’ mass . Chronic inflammation can lead to dystrophic calcification, which can progress to carcinoma and appears as a ‘porcelain gallbladder’ on X-ray.
Lesson Outline
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FAQs
The gallbladder is a key site for gallstone formation, which are solidified deposits of bile components. An imbalance in bile constituents, such as an excess of cholesterol relative to bile salts, can lead to cholesterol supersaturation and the formation of cholesterol stones. Factors like pregnancy, the use of somatostatin, and fasting can also reduce gallbladder motility, leading to bile stasis and further contributing to gallstone development.
The enzyme 7-α-hydroxylase serves as the rate-limiting step in the conversion of cholesterol to bile salts. This process is critical for maintaining bile composition. An imbalance, specifically an elevated cholesterol-to-bile salt ratio, can result in cholesterol supersaturation and contribute to the formation of cholesterol stones in the gallbladder.
Acute cholecystitis is an inflammatory condition of the gallbladder, typically triggered by a gallstone persistently blocking the gallbladder outlet. This leads to mucus accumulation, increased inflammation, and elevated intraluminal pressure. Chronic cholecystitis, however, results from repeated episodes of acute cholecystitis and is usually diagnosed through histology, which reveals herniation of the gallbladder mucosa into the muscular wall.
Cholesterol stones are yellow in appearance and form due to an excess of cholesterol in bile. Pigmented stones can be black or brown; black stones contain conjugated bilirubin and are often linked to conditions causing intravascular hemolysis, while brown stones are associated with biliary infections and conditions like Crohn's disease that elevate bilirubin levels in bile.
Acute cholecystitis is typically diagnosed through a combination of clinical symptoms, physical examination, and imaging studies. Murphy's sign, which is pain upon palpation of the RUQ during deep inspiration, is a classic clinical indicator. Imaging studies like ultrasound may reveal a thickened gallbladder wall and sometimes visible gallstones. Radioscintigraphy, also known as a HIDA scan, can confirm an impacted stone causing the condition if the radiotracer does not enter the gallbladder.
