Summary

This document provides an overview of disorders of the biliary tract, including objectives, anatomy, bile formation, metabolism of bilirubin, hyperbilirubinemia, primary biliary cholangitis, PSC pathology and sclerosing cholangitis. It is intended for healthcare professionals looking to learn or refresh their knowledge on these topics.

Full Transcript

DISORDERS OF THE BILIARY TRACT 2024 WE M AKE DOCTORS OBJECTIVES Definition of cholestasis Normal metabolism of bilirubin and bile formation Pathophysiology of jaundice Obstructive diseases of the biliary tract (Cholelithiasis, Choledocolitiasis, extra...

DISORDERS OF THE BILIARY TRACT 2024 WE M AKE DOCTORS OBJECTIVES Definition of cholestasis Normal metabolism of bilirubin and bile formation Pathophysiology of jaundice Obstructive diseases of the biliary tract (Cholelithiasis, Choledocolitiasis, extrabiliary) Autoimmune cholangiopathies Tumors of the biliary tract ANATOMY BILE FORMATION In blood it binds albumin, for transport, Uptake by hepatocytes at the sinusoidal membrane is conjugated in bilirubin with one or two molecules of glucuronic acid and excreted of the water-soluble, nontoxic bilirubin glucuronides into bile. Glucuronides deconjugate in the gut lumen by bacterial β-glucuronidases and degraded to colorless urobilinogen excreted in feces. 20% of urobilinogen is reabsorbed, back to the liver, and re-excreted into bile. A small amount in the urine. METABOLISM OF BILIRUBIN Bile eliminates bilirubin, excess cholesterol, xenobiotics, copper, arsenic, selenium, and zinc, Detergent action emulsifies dietary fat Components of bile are bilirubin, bile salts, cholesterol, and phospholipids (mainly phosphatidylcholine) Bilirubin toxic end-product of heme degradation Uptake from the circulation, intracellular storage, conjugation with glucuronic acid, and excretion into bile. Most bilirubin produced daily (0.2 to 0.3 g, 85%) breakdown of senescent red cells by macrophages in the spleen, liver, and bone marrow. Turnover of hepatic proteins containing heme groups (e.g., P-450 cytochromes). HYPERBILIRRUBINEMIA CRITERIA NORMAL VALUE RANGE DESCRIPTION DIRECT BILIRRUBIN 0.0 to 0.2 mg/dl Conjugated (water-soluble) Reacts rapidly with reagent NON-TOXIC INDIRECT BILIRRUBIN 0.2 to 0.8 mg/dl Unconjugated (water-insoluble) Slow reaction Diffuses into tissues TOXIC TOTAL BILIRRUBIN 0.2 to 1.0 mg/dl DB+IDB DEFINITION HYPERBILIRUBINEMIA: – Increase in blood levels of bilirubin whether conjugated (direct) unconjugated (indirect) or total (both) – Over 95%percentile for post-natal age in hours – Severe 20-24 mg/dl – Extreme or critical 25-30mg/dl in newborns over 35 wk gestation JAUNDICE: – Yellow coloration of skin, mucosa, and sclera due to hyperbilirubinemia – Clinically determined beyond doubt when total bilirubin reaches 2.5mg/dl CHOLESTASIS – Alteration of biliary flow – hepatocyte canaliculi → canals of Hering → bile ductules → interlobular bile ducts → larger bile ducts → duodenum PRIMARY BILIARY CHOLANGITIS Autoimmune disease. Nonsuppurative, inflammatory destruction intrahepatic bile ducts Diagnosed in the early stage Not all end-stage PBC is fully cirrhotic (misnomer) Antimitochondrial antibodies (AMA) most sensitive and specific immunologic hallmark of the disease Located on the inner mitochondrial membranes AMA do not appear to be cytotoxic (ANA) are present in nearly half of patients with PBC and in up to 85% of patients with AMA negative PBC PRIMARY BILIARY CHOLANGITIS Middle-aged women, female predominance of 9 : 1 Ages of 30 and 70 years, (peak 40/ 50 years of age) Prevalent in northern European countries (England and Scotland) and the Northern United States (Minnesota) Family members of PBC patients have an increased risk for the disease. PRIMARY BILIARY CHOLANGITIS Destruction of bile ductules within the triads of the liver. Intense mononuclear inflammatory infiltrates in portal tracts with loss of bile ductules. The inflammatory infiltrate can have granulomatous features as well. PSC PATHOLOGY LARGE DUCTS SMALL DUCTS UC like Little inflammation Epithelial injury Neutrophils Mild injury Chronic inflammatory Prominent ductular background reaction due to cholestasis Edema, fibrosis & Strictures Onion skin” fibrosis ”Tombstone ” scar SCLEROSING CHOLANGITIS PRIMARY Inflammation and obliterative fibrosis, dilation of healthy segments. Associated to intestinal inflammatory disease 3ª to 5ª decade, male 2;1 Biliary inmune lesion, lymphocytes T, lesion of biliary inmune. SCLEROSING CHOLANGITIS pANCA in 65% –T he pathogenic relationship of pANCA to PSC is unknown. Smooth muscle antibodies, typical and atypical antinuclear antibodies, reumathoid factor Lymphocytic infiltrate, progressive epithelial atrophy, closure of tubes Concentric periductal fibrosis, (onion ring) fibrous solid scarring Cholestatic liver up to billiary cirrhosis Increased serum alkaline phosphatase SCLEROSING CHOLANGITIS PATHOLOGY SCLEROSING CHOLANGITIS Increase level of GGT and AP Tiredness, pruritus, jaundice 5 to 17 years, weight loss, variceal hemorrhage, ascites, weight loss, encephalopathy 7% cholangiocarcinoma Chronic pancreatitis and hepatocellular carcinoma Obstructive Diseases of the Biliary tract The major components of bile are bilirubin, bile salts, cholesterol and phospholipids. Bilirubin is a toxic end product of heme degradation that is processed by the liver and excreted on the bile. Hepatic handling of bilirubin involves uptake from the circulation intracellular storage, conjugation with glucoronic acid and excretion into bile. The majority of the bilirubin is derived from breakdown of senescent red cells by macrophages in the spleen, liver and bone marrow. Heme is converted to bilirubin by the action of several phagocyte enzymes and released into the blood, where it binds albumin, a necessary step for transport, as bilirubin is insoluble at physiologic pH. Large Bile Duct Obstruction Obstruction of the large bile ducts has diverse causes. In adults, the common causes are stone (choledocholithiasis), malignant neoplasm of the biliary tree or head of pancreas (usually adenocarcinoma), and strictures resulting from previous surgical procedures or ischemic injury. The resulting cholestatic changes are reversible if the obstruction is corrected early in the disease course, but persistent obstruction can lead to fibrosis and so-called biliary cirrhosis. Cholestasis Many hepatobiliary disorders that lead to hyperbilirubinemia are characterized by cholestasis, which refers to the retention of bilirubin and other solutes eliminated in bile due to impaired bile formation or obstruction of flow. The hallmark of cholestasis is accumulation of green-brown plugs of bile pigment in hepatocytes and dilated canaliculi. Rupture of canaliculi can lead to extravasation of bile, which is phagocytosed by Kupffer cells. Accumulation of bile salts in hepatocytes results in swollen, foamy appearance of the cytoplasm “feathery degeneration” Cholelithiasis (Gallstones) More than 95% of biliary tract disease is attribuible to gallstones. More than 20 million persons in the US have gallstones. There are two general classes of gallstones: cholesterol stones, containing more that 50% of crystalline cholesterol monohydrate and pigment stones composed predominantly of bilirubin calcium salts, each with different risk factors. Cholesterol stones They arise exclusively in the gallbladder. 90% of all cases Pure cholesterol stones are pale yellow, Four conditions appear to contribute round to void and have finely granular, has to formation of cholesterol gallstones 1.- Supersaturation of bile with external surface. cholesterol Stones composed largely of cholesterol are 2.- Gallbladder hypomotility radiolucent, sufficient calcium carbonate is 3.- Accelerated cholesterol crystal found in 10% to 20% of cholesterol stones to nucleation 4.- Hypersecretion of mucus in the render them radiopaque. gallbladder. Pigment Stones Brown to black. Disorders that are associated with Black stones: found in sterile elevated levels of unconjugated gallbladder bile bilirubin in bile. Brown: found in infected large bile ducts. These include Chronic hemolytic anemia and bacterial Approximately 50 to 75% of black contamination of the biliary tree. stones are radiopaque due to calcium salts, while brown stones, which contains calcium soaps, are radiolucent. Cholecystitis Inflammation of the gallbladder may be acute or chronic. It almost occurs in association with gallstones. Acute cholecystitis is precipitate in 90% of cases by obstruction of the neck of the gallbladder or the cystic duct by a stone. Acute calculous cholecystitis is the primary complication of gallstones and the most common reason for emergency cholecystectomy. Acute Cholecystitis Results from chemical irritation and inflammation of a gallbladder obstructed by stones. Prostaglandins released within the wall of the distended gallbladder contribute to mucosal and mural inflammation: distention and increased intraluminal pressure compromise blood flow to the mucosa. An attack begins with progressive right upper quadrant or epigastric pain that lasts for more than 6 hours and is associated with sweating, nausea and vomiting. More patients are free of jaundice, the presence of hyperbilirubinemia suggests obstruction of the common bile duct. Leukocytosis is often present. Choledocholithiasis Presence of gallstones in common bile duct, often leading to elevated ALP, GGT, direct bilirubin and/or AST/ALT. Cholangitis Infection of biliary tree usually due to obstruction that leads to stasis/bacterial overgrowth. Charcot Triad Reynolds Pentad -Jaundice Charcot triad + -Fever altered mental status -RUQ pain and hypotension. NEOPLASIA OF THE BILIARY TRACT Gallbladder Carcinoma Carcinoma of the gallbladder is the most common malignancy of the extrahepatic biliary tract. Gallbladder cancer is at least twice as common in women as in men. The common thread that ties The most important risk factor for gallbladder cancer is gallstones or chronic infections together with gallbladder cancer gallstones, which are present in 95% of cases. is chronic inflammation. However, only 1% to 2% of patients with gallstones develop gallbladder cancer. CHOLANGIOCARCINOMA 2nd primary malignant 7.6 deaths per cancer (3% in USA) In Asia is the most frequent cancer Inflammation and cholestasis – Opistorchis y Clonorchis – Sclerosing cholangitis – Hepatolithiasis or fibropolicystic disease – HBV and HCV Bibliography Robbins & Cotran, Pathologic Basics of the Disease, 10th edition

Use Quizgecko on...
Browser
Browser