Biliary atresia pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Saud Khan M.D.
Overview
Biliary atresia is a progressive fibrosing obstructive cholangiopathy of the intrahepatic and extrahepatic biliary system, resulting in obstruction of bile flow and neonatal jaundice.
Pathophysiology
- As the biliary tract cannot transport bile to the intestine, bile is retained in the liver (known as stasis) and results in cirrhosis of the liver.
- At 20 days of gestation the extrahepatic bile ducts appear as an out-pouching of the foregut, while the intrahepatic bile ducts become visible at 45 days, which arise from the primitive hepatocytes. The porta-hepatis is where the extra and intrahepatic bile ducts combine, and any flaw in this joining results in an obstructed biliary system. The isolated type of biliary atresia may be due to flawed assembly at the hepatic hilum. Similarities in the cytokeratin staining of the bile ducts in patients with biliary atresia and first-trimester fetal bile ducts supports the possibility that biliary atresia could occur due to the failure of the bile duct remodeling at the hepatic hilum with the persistence of fetal bile ducts.[1]
- However, there have been extensive studies about the pathogenesis and proper management of progressive liver fibrosis, which is arguably one of the most important aspects of biliary atresia patients. As the biliary tract cannot transport bile to the intestine, bile is retained in the liver (known as stasis) and results in cirrhosis of the liver. Proliferation of the small bile ductules occur, and peribiliary fibroblasts become activated. These "reactive" biliary epithelial cells in cholestasis, unlike normal condition, produce and secrete various cytokines such as CCL-2 or MCP-1, Tumor necrosis factor (TNF), Interleukin-6 (IL-6), TGF-beta, Endothelin (ET), and nitric oxide (NO). Among these, TGF-beta is the most important profibrogenic cytokine that can be seen in liver fibrosis in chronic cholestasis. During the chronic activation of biliary epithelium and progressive fibrosis, afflicted patients eventually show signs and symptoms of portal hypertension (esophagogastric varix bleeding, hypersplenism, hepatorenal syndrome(HRS), hepatopulmonary syndrome(HPS)). The latter two syndromes are essentially caused by systemic mediators that maintain the body within the hyperdynamic states.[2]
Gross Pathology
Biliary atresia is a progressive fibrosing obstructive cholangiopathy of the intrahepatic and extrahepatic biliary system, resulting in obstruction of bile flow and neonatal jaundice.
Histopathological findings in liver biopsies include the expansion of the portal tracts, with edematous fibroplasia and bile ductular proliferation, with bile plugs in duct lumen. Lobular morphological features may include variable multinucleate giant cells, bilirubinostasis and hemopoiesis.
Associated Conditions
Associated anomalies include, in about 20% cases,
- Cardiac lesions
- Polysplenia
- Situs inversus
- Absent vena cava
- A preduodenal portal vein
References
- ↑ Tan CE, Driver M, Howard ER, Moscoso GJ (1994). "Extrahepatic biliary atresia: a first-trimester event? Clues from light microscopy and immunohistochemistry". J Pediatr Surg. 29 (6): 808–14. doi:10.1016/0022-3468(94)90377-8. PMID 7521396.
- ↑ Averbukh LD, Wu GY (2018). "Evidence for Viral Induction of Biliary Atresia: A Review". J Clin Transl Hepatol. 6 (4): 410–419. doi:10.14218/JCTH.2018.00046. PMC 6328731. PMID 30637219.