Pathology and Pathogenesis of Gallstones & Cholecystitis Dr. Mamlook Elmagraby

Objectives of the lecture: Upon completion of this lecture, students should be able to: Compare the various types of gallstones, how they are formed, what the risk factors for their development are, and what complications they can cause Describe the different types of cholecystitis Recognize the predisposing factors of cholecystitis Understand the pathogenesis of acute and chronic cholecystitis

Cholelithiasis (Gallstones)

Cholelithiasis (Gallstones) Gallstones affect 10% to 20% of adult populations in developed countries The majority of gallstones are silent, and most individuals remain free of biliary pain or other complications for decades There are two main types of gallstones: Cholesterol stones (90%) containing more than 50% of crystalline cholesterol monohydrate The rest are pigment stones composed predominantly of bilirubin calcium salts

Cholesterol Stones Pigment Stones Advancing age Female sex hormones Female gender Oral contraceptives Pregnancy Obesity and metabolic syndrome Rapid weight reduction Gallbladder stasis Inborn disorders of bile acid metabolism Hyperlipidemia syndromes    Pigment Stones Chronic hemolytic syndromes Biliary infection Risk Factors for Gallstones

Cholelithiasis (Gallstones) Pathogenesis Cholesterol Stones. Four conditions contribute to formation of cholesterol gallstones: Supersaturation of bile with cholesterol Hypomotility of the gallbladder Accelerated cholesterol crystal nucleation Hypersecretion of mucus in the gallbladder

Cholelithiasis (Gallstones) Pigment Stones They are complex mixtures of: Abnormal insoluble calcium salts of unconjugated bilirubin Inorganic calcium salts Factors increase the risk of developing pigment stones: ↑ Levels of unconjugated bilirubin in bile (hemolytic syndromes) Bacterial contamination of the biliary tree Severe ileal dysfunction or bypass

Cholelithiasis (Gallstones) Morphology Cholesterol stones Cholesterol stones arise in the gallbladder Pure cholesterol stones are pale yellow, round to ovoid ↑ proportions of calcium carbonate, phosphates, bilirubin → discoloration (gray-white to black) Most often, multiple stones are present The majority are radiolucent

Cholesterol stone and cholesterolosis of the gallbladder - Gross, mucosal surface This image shows a round, yellow, pure cholesterol gallstone next to an opened gallbladder, which shows a yellow mucosal surface caused by cholesterolosis (deposits of cholesterol in tissue) of the gallbladder.

Cholelithiasis (Gallstones) “Black” pigment stones. rarely >1.5 cm in diameter They are present in great number They crumble to the touch 50% to 75% are radiopaque “Brown” pigment stones. Soft and laminated & greasy consistency Stones, which contain calcium soaps, are radiolucent

Gallstones, pigment stones - Gross These minute black stones are pure pigment stones. Theyare present in large numbers

Cholelithiasis (Gallstones) Clinical Features Gallstones develop in 10% to 20% of Americans Between 50% and 60% of these individuals remain asymptomatic One third develop biliary colic or chronic cholecystitis 15% develop acute complications   Symptoms arise from: Contraction of the gallbladder during transient obstruction of the cystic duct by gallstones Persistent obstruction of the cystic duct leads to superimposed inflammation or infection of the gallbladder(acute cholecystitis)

Cholelithiasis (Gallstones) Obstruction by gallstones can occur at the level of the: Cystic duct Common hepatic duct Common bile duct Ampulla of Vater   Factors that may predict the presence of choledocholithiasis include jaundice, pancreatitis, abnormal liver test results, bile duct dilation Obstruction of the distal common bile duct may result in abdominal pain, cholangitis, or pancreatitis

Natural history of asymptomatic gallstones Natural history of asymptomatic gallstones. A, The clinical syndromes associated with gallstones are shown, and the numbers represent the approximate percentage of adults who develop one or more of these symptoms or complications over a 15- to 20-year period. Over this period, about 30% of individuals with gallstones undergo surgery. (The risk for developing complications of gallstones varies considerably among series. The figures shown represent those derived from more recent studies.) B, Clinical manifestations of symptomatic gallstones. Locations of blockages associated with various conditions are indicated

Cholelithiasis (Gallstones) Biliary colic refers to the group of symptoms experienced when the gallbladder contracts against outlet obstruction Gallstones are best demonstrated by transabdominal ultrasonography Laparoscopic cholecystectomy has replaced open cholecystectomy as the treatment of choice for recurrent biliary pain

Clinical and pathologic effects of cholelithiasis Ileus is a partial or complete non-mechanical blockage of the small and/or large intestine There are two types of intestinal obstruction, mechanical and non-mechanical. Mechanical obstructions occur because the bowel is physically blocked and its contents can not pass the point of the obstruction. This happens when the bowel twists on itself (volvulus) or as the result of hernias, impacted feces, abnormal tissue growth, or the presence of foreign bodies in the intestines. Non-mechanical obstruction, called ileus or paralytic ileus, occurs because peristalsis stops

Cholecystitis

Acute Cholecystitis Acute calculous cholecystitis Acute cholecystitis refers to distention, edema, ischemia, inflammation, and secondary infection of the gallbladder Acute calculous cholecystitis It is an acute inflammation of the gallbladder, triggered by obstruction of the neck or cystic duct It frequently develops in diabetic patients Acute acalculous cholecystitis Cholecystitis without gallstones It may occur in severely ill patients

Acute Cholecystitis Pathogenesis Acute calculous cholecystitis Chemical irritation of the obstructed gallbladder The protective glycoprotein mucus layer is disrupted Prostaglandins contribute to inflammation Gallbladder dysmotility Increased intraluminal pressure compromise blood flow to the mucosa Later in the course bacterial contamination may develop

Acute Cholecystitis Acute acalculous cholecystitis: It may result from ischemia Contributing factors: Inflammation and edema of the wall Gallbladder stasis Biliary sludge Primary bacterial infection

Acute Cholecystitis Risk factors in acute acalculous cholecystitis include (seriously ill patients): Sepsis with hypotension and multisystem organ failure Immunosuppression Major trauma and burns Diabetes mellitus Infections

Acute Cholecystitis Morphology The gallbladder is usually enlarged and having a bright red to green-black discoloration The serosal covering is coated by fibrin or suppurative exudate In calculous cholecystitis: An obstructing stone is present in the neck of the gallbladder or the cystic duct The lumen is filled with turbid bile that may contain large amounts of fibrin, pus, and hemorrhage

Acute Cholecystitis Clinical Features The characteristic feature of acute cholecystitis is the acute onset of upper abdominal pain that lasts for several hours   The pain gradually increases in severity and localizes to the epigastrium or right hypochondrium The pain radiate to the right lumbar, scapular, and shoulder area Nausea and vomiting, anorexia, and low-grade fever are common Unlike biliary pain, the pain of acute cholecystitis does not subside spontaneously

Acute Cholecystitis Complications of acute cholecystitis include emphysematous cholecystitis, empyema, gangrene, perforation of the gallbladder Ultrasound has emerged as the initial test of choice Because of the high risk for recurrent acute cholecystitis, most patients need to undergo cholecystectomy Antibiotics are used when fever or leukocytosis is present

Chronic Cholecystitis An evolving inflammatory process, caused by repeated episodes of low-grade gallbladder obstruction over a period of days to years resulting in recurrent mucosal trauma and inflammation   Chronic cholecystitis is a term used to describe chronic inflammatory cell infiltration of the gallbladder on histopathology Gallstones are the causative agent in most patients In 12% of patients with chronic cholecystitis, there are no demonstrable stones

Chronic Cholecystitis Morphology Gross changes Dense fibrous adhesions, subserosal fibrosis, thickened wall The lumen contains clear, green-yellow, mucoid bile & stones Histological changes: Mononuclear cell infiltration Subepithelial and subserosal fibrosis Extensive dystrophic calcification within the gallbladder wall (Porcelain gallbladder, with increased risk of cancer)

Gallbladder, cholelithiasis and acute and chronic cholecystitis - Gross This case of acute and chronic cholecystitis shows marked fibrous thickening of the wall of the gallbladder. The mucosal surface is erythematous and is also ulcerated in the regions of the neck and fundus of the gallbladder due to impaction of a large gallstone (cholelithiasis)

Chronic Cholecystitis Clinical Features The symptoms are those of biliary colic without clinical features of acute cholecystitis It is characterized by recurrent attacks of colicky abdominal pain Nausea, vomiting, intolerance for fatty foods are frequent Transabdominal ultrasound is the best initial test   The treatment is laparoscopic cholecystectomy