Liver and gallbladder congenital conditions Notes

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This Osmosis High-Yield Note provides an overview of Liver and gallbladder congenital conditions essentials. All Osmosis Notes are clearly laid-out and contain striking images, tables, and diagrams to help visual learners understand complex topics quickly and efficiently. Find more information about Liver and gallbladder congenital conditions:

Biliary atresia

Crigler-Najjar syndrome

Dubin-Johnson syndrome

Gilbert's syndrome

Rotor syndrome

NOTES NOTES LIVER & GALLBLADDER CONGENITAL CONDITIONS GENERALLY, WHAT ARE THEY? PATHOLOGY & CAUSES DIAGNOSIS ▪ Inherited metabolic/congenital structural anomalies, affect hepatobiliary system → hyperbilirubinemia DIAGNOSTIC IMAGING COMPLICATIONS LAB RESULTS ▪ ▪ ▪ ▪ Kernicterus Recurrent cholangitis, cirrhosis Portal hypertension Metabolic problems, impaired growth SIGNS & SYMPTOMS ▪ Jaundice, dark urine, light stools ▪ Impaired liver function ▪ Neurologic alterations ▪ Ultrasound ▪ Oral cholecystogram ▪ Conjugated vs. unconjugated bilirubin, liver function tests ▪ Biopsy TREATMENT ▪ See individual disorders BILIARY ATRESIA osms.it/biliary-atresia PATHOLOGY & CAUSES ▪ Congenital anomaly of extrahepatic duct fibrosis, obstruction of bile flow ▪ Infections, environmental toxins, immune dysregulation, genetic mutations → perinatal injury to biliary system ▪ Bile prevented from entering duodenum → impaired fat digestion, absorption + cholestasis, distension of gallbladder, ducts TYPES ▪ Biliary atresia only; not accompanied by other anomalies (most common) ▪ Biliary atresia + laterality malformations (left-right axis patterning/malpositioning of organs) ▫ Dextrocardia, situs inversus, asplenia/ polysplenia, interrupted inferior vena cava ▫ Related CFC1 gene mutation ▪ Biliary atresia + intestinal atresia, imperforate anus, kidney anomalies OSMOSIS.ORG 283
COMPLICATIONS ▪ Liver cirrhosis, portal hypertension, hepatic encephalopathy ▪ Recurrent cholangitis, cirrhosis ▪ Metabolic problems, impaired growth (associated with malabsorption) SIGNS & SYMPTOMS ▪ Neonates asymptomatic at birth; stools gradually become acholic, clay-colored ▪ Persistent jaundice ▫ Skin gradually turns yellow, greenishbronze ▪ Dark urine ▫ Increased bilirubin concentration ▪ Portal hypertension ▫ Splenomegaly, ascites, enlarged abdominal veins ▪ Impaired liver function → decreased coagulation factors, bleeding tendencies ▫ Impaired coagulation also related to decreased vitamin K absorption DIAGNOSIS DIAGNOSTIC IMAGING Ultrasound ▪ Abnormal gallbladder size, shape, contractility; absent common bile duct; “triangular cord” sign (triangle-shaped echogenic density above porta hepatis) Hepatobiliary scintigraphy ▪ Decreased/absent patency of extrahepatic biliary tree LAB RESULTS ▪ Increased conjugated serum bilirubin, aminotransferases Liver biopsy ▪ Identifies obstruction-related histological changes 284 OSMOSIS.ORG Figure 35.1 Intraoperative photography of extra-hepatic biliary atresia. The underside of the liver displays only connective tissue in the gallbladder fossa. TREATMENT MEDICATIONS ▪ Ursodeoxycholic acid (hydrophilic bile acid) SURGERY ▪ Type indicated by blood chemistry, imaging, biopsy Intraoperative cholangiogram ▪ Gold standard for confirming obstruction, diagnosis Hepatoportoenterostomy (Kasai HPE) ▪ Restores bile flow from liver; may need subsequent revision Liver transplant ▪ If Kasai procedure unsuccessful OTHER INTERVENTIONS Diet ▪ Fat-soluble vitamin supplements; high protein diet, medium-chain triglyceride supplements
Chapter 35 Liver & Gallbladder Congenital Conditions CRIGLER–NAJJAR SYNDROME osms.it/crigler-najjar-syndrome PATHOLOGY & CAUSES ▪ Rare inherited metabolic disorder; nonhemolytic hyperbilirubinemia ▪ Autosomal recessive inheritance pattern ▪ AKA congenital nonhemolytic jaundice with glucuronosyltransferase deficiency TYPES COMPLICATIONS ▪ Kernicterus (Type I), if not promptly addressed SIGNS & SYMPTOMS ▪ Persistent jaundice in first few days of life ▪ Neurological symptoms as kernicterus develops Type I ▪ Severe jaundice, bilirubin encephalopathy, possible kernicterus-associated neurologic impairment LAB RESULTS Type II ▪ Lower serum bilirubin concentration; no neurologic impairment Unconjugated hyperbilirubinemia ▪ Type I: 20–50 mg/dL ▪ Type II: < 20 mg/dL CAUSES ▪ Mutation in coding area of UGT gene, encodes for bilirubin-conjugating enzyme UGT1A1 (bilirubin-uridine diphosphate glucuronosyltransferase) → structurally abnormal enzyme → decreased/absent conjugation of bilirubin DIAGNOSIS Stool color ▪ Type I: pale yellow, low fecal urobilinogen (significantly decreased bilirubin conjugation) ▪ Type II: normal Normal liver histology, liver function tests RISK FACTORS ▪ Consanguinity OSMOSIS.ORG 285
TREATMENT MEDICATIONS Phenobarbital ▪ Useful in Type II, induces residual UGT activity SURGERY OTHER INTERVENTIONS Phototherapy ▪ In first years of life; effectiveness decreases over time Exchange transfusion Plasmapheresis + albumin infusions ▪ Removes bilirubin tightly bound to serum albumin Liver transplant ▪ Definitive treatment for Crigler-Najjar syndrome Type I DUBIN–JOHNSON SYNDROME osms.it/dubin-johnson-syndrome PATHOLOGY & CAUSES ▪ Inherited metabolic disorder; mild, fluctuating elevations in conjugated (predominantly), unconjugated bilirubin, no evidence of hemolysis ▪ Autosomal inheritance pattern ▪ MRP2 (ABCC) gene mutation → impaired hepatic excretion of non-bilesalt organic anions, bilirubin into bile via canalicular membrane → cholestasis → hyperbilirubinemia SIGNS & SYMPTOMS ▪ Mild jaundice; evident during physiological stress (e.g. illness)/hormonal fluctuations (e.g. pregnancy, oral contraceptives) ▪ Constitutional ▫ Vague abdominal pains, weakness ▪ Occasional hepatosplenomegaly 286 OSMOSIS.ORG DIAGNOSIS DIAGNOSTIC IMAGING Oral cholecystogram ▪ Gallbladder may not be visualized LAB RESULTS ▪ Hyperbilirubinemia, normal liver function tests ▪ Total urinary coproporphyrin normal; majority, coproporphyrin I Liver biopsy, histological exam ▪ Brown, black discoloration ▫ Pigment accumulates in lysosomes TREATMENT ▪ None required
Chapter 35 Liver & Gallbladder Congenital Conditions GILBERT'S SYNDROME osms.it/gilberts-syndrome PATHOLOGY & CAUSES SIGNS & SYMPTOMS ▪ Benign, inherited metabolic disorder; recurring unconjugated hyperbilirubinemia, jaundice ▪ Autosomal recessive inheritance pattern ▪ AKA Meulengracht disease, familial nonhemolytic jaundice ▪ Serum bilirubin increases during physiologic stress (e.g. illness, dehydration, fasting, overexertion, menses) ▪ Differs from other forms of non-hemolytic hyperbilirubinemia ▫ Genetic mutation in promoter region of UGT gene → structurally normal enzyme → impaired genetic expression of hepatic UGT with decreased activity → decreased conjugation of bilirubin ▪ Asymptomatic between episodes, jaundice evident during physiological stress ▪ Clinical manifestations ▫ During adolescence, with effects of sex steroids on bilirubin metabolism DIAGNOSIS ▪ Exclude other causes of unconjugated hyperbilirubinemia TREATMENT ▪ None required ROTOR SYNDROME osms.it/rotor-syndrome PATHOLOGY & CAUSES SIGNS & SYMPTOMS ▪ Rare benign inherited disorder; chronic conjugated, unconjugated hyperbilirubinemia; no hemolysis ▪ SLCO1B1, SLCO1B3 gene mutations (code for transporter proteins 1B1, 1B3 responsible for bilirubin re-uptake by hepatocytes) → alters bilirubin re-uptake → increases bilirubin in plasma ▪ Mild jaundice; during physiological hormonal fluctuations (e.g. pregnancy, oral contraceptive use) DIAGNOSTIC IMAGING COMPLICATIONS Oral cholecystogram ▪ Normal gallbladder opacification ▪ Impaired 1B1 activity → significant drug toxicities (e.g. statin-associated myopathy) DIAGNOSIS LAB RESULTS ▪ Hyperbilirubinemia, normal liver function tests OSMOSIS.ORG 287
▪ Total urinary coproporphyrin markedly increased; majority coproporphyrin I Liver biopsy, histological exam ▪ Normal TREATMENT ▪ None required 288 OSMOSIS.ORG

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