The Biliary Tract 1 2 - Lecture.pdf

THE BILIARY TRACT 1 & 2 Dr Jason Harry Department of Anatomical Pathology Lecture outline 1. Introduction 2. Congenital abnormalities 3. Cholelithiasis 4. Cholecystitis Acute Chronic 5. Extrahepatic bile duct disorders 5....

THE BILIARY TRACT 1 & 2 Dr Jason Harry Department of Anatomical Pathology Lecture outline 1. Introduction 2. Congenital abnormalities 3. Cholelithiasis 4. Cholecystitis Acute Chronic 5. Extrahepatic bile duct disorders 5. Tumours Introduction 1L bile secreted by liver per day Between meals, bile stored in gallbladder – concentrated Adult gallbladder capacity approximately 50ml Not essential for biliary function Congenital Anomalies Congenitally absent Duplications – Conjoined – Independent cystic ducts Bilobed Abberant locations (5 – 10% of population) Phrygian cap – folded fundus (most common) Agenesis – All or portion of hepatic or common bile ducts Hypoplastic narrowing (Biliary Atresia) Choledochal cyst Phyrgian cap Gallbladder Disorders CHOLELITHIASIS Gallstones are common cause of morbidity worldwide 10-20% of population: developed countries >80% clinically “silent” (no symptoms) Approximately 70% of gallstone carriers have cholesterol stones (cholesterol content >50%) Rest have pigment stones Classification Gallstones are predominately composed of ▪Cholesterol ▪Bilirubin ▪Calcium salts Classification is based on amount of cholesterol within stones Two main categories: Cholesterol stones Pigment stones (Black & Brown) Types of Gallstones Cholesterol Black Pigment Brown Pigment Epidemiology Western countries > Africa & Asia > Asia > Africa > Western Africa > Asia Western countries countries > Appearance Small or large, yellow Small, black, firm, Large,brown,soft, single, single or Multiple multiple or multiple Composition Bile Salts Calcium bilirunate Calcium bilirunate Phospholipids Calcium Phosphate Palmitate Cholesterol Calcium Carbonate Cholesterol Low cholesterol Associated conditions Generally Absent Haemolysis Biliary Infection Alcoholism Cirrhosis Risk Factors CHOLESTEROL STONES CHOLESTEROL STONES PIGMENT STONES Demography: northern Obesity and metabolic Demography: Asians > Europeans, North and South syndrome Westerners, rural > urban Americans, Native Americans, Advancing age Rapid weight reduction Chronic hemolytic syndromes Female sex hormones Gallbladder stasis Biliary infection Inborn disorders of bile acid Gastrointestinal disorders: Female gender metabolism ileal disease (e.g., Crohn’s disease) Hyperlipidemia syndromes cystic fibrosis with pancreatic Oral contraceptives insufficiency Pregnancy Ileal resection or bypass Risk Factors : Cholesterol stones Age and Sex ▪ Middle to older age ▪ Females: higher risk in any region ▪ Prevalence in caucasian women - twice as high as in men Environmental Factors ▪ Oestrogen exposure: OCT and Pregnancy ▪Increased: expression of hepatic lipoprotein receptors and hepatic HMG-CoA reductase activity ▪Enhancing cholesterol uptake and biosynthesis leading to excess biliary secretion of cholesterol ▪ Obesity and rapid weight loss – increased biliary cholesterol secretion Risk Factors : Cholesterol stones Acquired Disorders ▪ Gallbladder stasis: neurogenic or hormonal Hereditary Factors Genes encoding hepatocyte proteins that transport biliary lipids are associated with gallstone formation ATP-binding cassette (ABC) transporters Pathogenesis of Cholesterol Stones Major components – Cholesterol > 50% ▪Up to 100% (pure; rare) Rest: Bilirubin Phosphates Calcium carbonate Pathogenesis of Cholesterol Stones Cholesterol is rendered soluble in bile Through aggregation with water-soluble bile salts and water-insoluble lecithins Both of which act as detergents (Combination of hydrophilic and hydrophobic agents in solution) Pathogenesis of Cholesterol Stones When cholesterol concentrations Exceed the solubilising capacity of bile (super saturation) Cholesterol can no longer remain dispersed and nucleates into solid cholesterol monohydrate crystals. Pathogenesis of Cholesterol Stones Cholesterol gallstone formation involves four simultaneous conditions ▪ The bile must be supersaturated with cholesterol ▪ Hypomotility of the gallbladder promotes nucleation ▪ Cholesterol nucleation in the bile is accelerated ▪ Hypersecretion of mucus in the gallbladder traps the nucleated crystals, leading to their aggregation into stones.  Four contributing factors for cholelithiasis - Supersaturation - Gallbladder hypomotility - Crystal nucleation - Accretion within gallbladder mucous layer  Pathogenesis: Black Pigment Stones Unconjugated bilirubin: ▪Haemolysis ▪Chronic alcoholism followed by nonbacterial enzymatic or nonenzymatic hydrolysis ▪Cirrhosis Biliary epithelium functions to acidify bile – increase the solubility of Calcium Carbonate ▪Mucosal inflammation -> loss of protective function ▪ ↑ PH → precipitation of calcium carbonate  Pathogenesis: Brown Pigment Stones Formed in the bile ducts Associated with biliary infection e.g Ascaris lumbricoides, E. coli Bacteria in the bile ducts produce ▪b-glucuronidase: → unconjugated bilirubin ▪phospholipase A : → lysolecithin & FFA( Palminate) ▪bile acid hydrolase: → unconjugated bile acids COMPLEX WITH CALCIUM  Morphology: Cholesterol stones Arise exclusively in the gallbladder Pure cholesterol stones pale yellow round to ovoid Finely granular, hard external surface On transection reveals a glistening radiating crystalline palisade  Series of pure spherical or oval shaped cholesterol stones with smooth surface(A) , morular (B) surface, On the cut surface: tiny (C), medium (D) or large (E) dark pigment nucleus A very large (F), almost pure cholesterol stone is shown, which discloses a conglomeration of stones Morphology: Cholesterol stones Increasing proportions of calcium carbonate, phosphates, and bilirubin Discolouration lamellated and gray-white to black. Often - multiple stones present (up to centimetres in diameter) Rarely, there is a single much larger stone that may virtually fill the fundus. Multiple stones - rounded or faceted surfaces - because of tight apposition Stones composed largely of cholesterol are radiolucent Sufficient calcium carbonate -> radiopaque. Morphology: Black pigment stones Rarely > 1.5 cm in diameter Mostly present in great number Crumble to the touch. Contours spiculated and molded Because of calcium carbonates and phosphates, 50% to 75% of black stones are radiopaque Morphology: Brown pigment stones Tend to be laminated and soft May have a soaplike or greasy consistency Are radiolucent Clinical Symptoms 70-80% asymptomatic 1-4%/year convert to symptomatic Biliary pain RUQ / Epigastrium Radiate to right shoulder and back May be severe Usually constant vs colicky Exacerbated by fatty meal Gallbladder sometimes palpable (very large stone) Gallstones - Complications Local Chronic cholecystitis Empyaema Perforation Fistula formation Increased risk for carcinoma Cholangitis Pancreatitis Gallstone ileus or Bouveret's syndrome (large stone may erode directly into an adjacent loop of small bowel, generating intestinal obstruction ) CHOLECYSTITIS Inflammation of the gallbladder Acute Chronic Acute superimposed on chronic Acute Cholecystitis Acute calculous cholecystitis - acute inflammation - Precipitated 90% of the time by obstruction of the neck or cystic duct Acute Acalculous cholecystitis - Absent gallstones - Occur in severely ill patients - 10% of patients with cholecystitis Pathogenesis - Acute calculous cholecystitis Chemical irritation and inflammation of the obstructed gallbladder. Mucosal phospholipases -> hydrolyzes luminal lecithins to toxic lysolecithins. Protective glycoprotein mucus layer is disrupted - exposing epithelium to direct detergent action of bile salts Prostaglandins released within the wall - contribute to mucosal and mural inflammation. Gallbladder dysmotility develops Distention and increased intraluminal pressure compromise blood flow to the mucosa = ischemia Occur in the absence of bacterial infection bacterial contamination – secondary event Pathogenesis - Acute Acalculous cholecystitis ▪ Result from ischaemia ▪ The cystic artery is an end artery with no collateral circulation. ▪ Risk factors: Sepsis with hypotension and multisystem organ failure Immunosuppression Major trauma and burns Diabetes mellitus Infections Inflammation and oedema - compromising blood flow -> gallbladder stasis Accumulation of microcrystals of cholesterol (biliary sludge),viscous bile, and gallbladder mucus = cystic duct obstruction in absence of stone formation  Morphology Gallbladder enlarged and tense Bright red or blotchy, violaceous to green-black discoloration Serosal covering frequently layered by fibrin Severe cases - suppurative exudate Calculous cholecystitis - obstructing stone may be present in neck of gallbladder or cystic duct Lumen contain stones (variable amount) Filled with a cloudy or turbid bile May contain large amounts of fibrin, pus, and haemorrhage Empyema Empyema of the gallbladder Lumen contains pure pus Mild cases Wall is thickened, oedematous and hyperaemic Gangrenous cholecystitis Severe cases Transformed into a green-black necrotic organ May have small-to-large perforations “Emphysematous” cholecystitis The invasion of gas-forming organisms Notably clostridia and coliforms  Chronic Cholecystitis Associated cholelithiasis in 90%+ cases Pathogenesis: Repeated bouts of acute cholecystitis Morphology Changes extremely variable, sometimes minimal Serosa - Usually smooth and glistening - Dulled by variable subserosal fibrosis Wall - variably thickened - Opaque gray-white appearance Cholesterolosis - Multiple yellow spots on mucosal surface - Accumulation of lipid in lamina propria Content - Fairly clear, green-yellow, mucoid bile - Stones variable size and number Chronic Cholecystitis Chronic Cholecystitis The degree of inflammation is variable. Mild: Scattered lymphocytes, plasma cells, and macrophages In the mucosa and submucosal stroma May be ulcerated Reactive proliferation of the mucosa Fusion of the mucosal folds may give rise to buried crypts of epithelium within the gallbladder wall. - Rokitansky-Aschoff sinuses  Porcelain gallbladder In rare instances Extensive dystrophic calcification within the gallbladder wall Porcelain gallbladder Pearly white appearance Hydrops of the gallbladder Atrophic Chronically obstructed gallbladder Containing only clear secretions Extrahepatic Bile Duct Disorders  Choledocholithiasis Choledocholithiasis Stones within the bile ducts of biliary tree May be asymptomatic or cause symptoms Obstruction Pancreatitis Cholangitis Hepatic abscess Secondary biliary cirrhosis Acute calculous cholecystitis  Cholangitis and ascending Cholangitis Cholangitis = Bacterial infection of the bile ducts – Can result from any lesion that creates obstruction of bile flow – Cholecholithiasis, biliary strictures – Bacteria enter through Sphincter of Oddi (duodenum) – Infection of intrahepatic biliary radicles termed ascending cholangitis – Organisms: usually enteric gram negative aerobes –E. coli, Klebsiella, Enterococcus or Enterobacter – Presents with: Fever, chills, abdominal pain and jaundice Micro: Acute inflammation of the wall of ducts Entry of neutrophils into the luminal space Clinical features Charcot's cholangitis triad Jaundice, fever (with rigors) and RUQ tenderness (Murphey’s sign) With low BP and altered mental state = Reynold’s pentad Absence of palpable gallbladder Murphey’s sign – Tenderness in RUQ (in midclavicular line) on deep inspiration Biliary Atresia Complete or partial obstruction extrahepatic biliary tree within the first 3 months of life Characterised by progressive inflammation and fibrosis of intrahepatic and extrahepatic bile ducts Major contributor to neonatal cholestasis Congenital biliary atresia. This child died from hepatic failure and the thin, stenosed extrahepatic biliary system was dissected. The right and left hepatic ducts and the common bile duct with the gallbladder attached on the left, are displayed. Sections showed the presence of only a microscopic lumen. Pathogenesis Two major forms based on presumed timing of luminal obliteration Foetal and perinatal Foetal form - Associated with other anomalies - Resulting from ineffective establishment of laterality of thoracic and abdominal organ development Malrotation of the abdominal viscera, interrupted inferior vena cava, polysplenia, congenital heart disease Presumed cause is aberrant intrauterine development of the extrahepatic biliary tree Pathogenesis Perinatal form -Presumed normally developed biliary tree is destroyed following birth -Viral infection and autoimmunity play critical role in the pathogenesis -Reovirus, rotavirus, and cytomegalovirus implicated Morphology Salient features include - Inflammation and fibrosing stricture - hepatic / common bile ducts - Periductular inflammation of intrahepatic biliary tree - Features of extrahepatic biliary obstruction (evident in 2/3 of cases) ✓Portal tract oedema and fibrosis ✓Marked bile ductular proliferation ✓Parenchymal cholestasis - Remainder of cases Inflammatory destruction of intrahepatic ducts Leads to paucity of bile ducts and absence of oedema or bile ductular proliferation on liver biopsy B – Expanded PT C – Cholestasis D – Fibrosis E – Giant cell T Morphology Type 1 – disease limited to common duct Type 2 – hepatic bile ducts with patent proximal branches Type 3 – obstruction of bile ducts at or above porta hepatis (+/- extrahepatic duct involvement) Choledochal Cysts Congenital dilations of common bile ducts Often children < 10y age Non-specific symptoms Jaundice +/- recurrent abdominal pain typical of biliary colic Predispose to stone formation, stenosis and stricture , pancreatitis and obstructive biliary complications within the liver  Choledochal Cysts Choledochal cyst. The patient had been jaundiced since birth. At laparotomy this large cyst was found in the middle of the common bile duct and excised. The structure to the left is the attached gallbladder. Tumours Carcinoma of the Gallbladder Slightly more commmon in women Most common risk factor – gallstones Most are adenocarcinoma Two patterns of growth: Infiltrating Poorly defined area of diffuse thickening and induration of gallbladder wall Deep ulceration -> direct penetration of gallbladder wall or fistula formation to adjacent viscera into which neoplasm has grown Very firm consistency Exophytic Grows into the lumen of gallbladder Irregular cauliflower-like mass Luminal portion may be necrotic, haemorrhagic and ulcerated Most common sites of involvement – fundus and neck Carcinoma of the Gallbladder Other types of carcinoma Squamous cell carcinoma Adenosquamous carcinoma Neuroendocrine tumours (carcinoid) Carcinosarcoma  Carcinoma of the Gallbladder Carcinoma of the gallbladder. A large calculus is present in the gallbladder. Tumour has extended Carcinoma of the gallbladder. The tumour is present in the Into the adjacent liver. lumen of the gallbladder. Thank you