Pathophysiology and Diseases of the Proximal Pathways of the Biliary System

Abstract

Care of the patient with cholestasis hinges on identifying the etiology. Diagnostic steps in cholestatic conditions comprise a thorough patient history, abdominal imaging, distinct serological studies, and liver biopsy. Primary biliary cirrhosis is characterized by distinctive serological and histological findings. The small-duct variant of primary sclerosing cholangitis is very rare and difficult to diagnose; imaging of the bile ducts is not helpful. Graft-versus-host disease is characterized by damage and loss of intrahepatic bile ducts. Drugs can cause injury variably at the level of bile canaliculus or the interlobular bile duct. Loss of bile ducts may be seen with primary biliary cirrhosis, primary sclerosing cholangitis, graft-versus-host disease, and drug-induced liver injury. Progressive familial intrahepatic cholestasis and progressive familial intrahepatic cholestasis represent 2 extreme ends of the spectrum of abnormalities in transporters responsible for bile formation. Intrahepatic cholestasis of pregnancy has a variable incidence in different parts of the world and may be due to abnormalities in transporter molecules.

A 10-year-old child presenting with syndromic paucity of bile ducts (Alagille syndrome): a case report

“…Congenital hepatic fibrosis can present with upper gastrointestinal hemorrhage or recurrent cholangitis and can be associated with medullary sponge kidneys; these features were not present in our case. Diagnoses of childhood autoimmune hepatitis and childhood primary biliary cirrhosis can be confirmed based on typical liver histology findings and the presence of typical autoantibodies [14], which were absent in our case. Patients with alpha-1-antitrypsin deficiency can present with panacinar emphysema and can be diagnosed by typical liver histology finding such as the presence of periodic acid Schiff-positive diastase-resistant globules in the periportal hepatocytes, which were absent in our case.…”

“…Patients with PFIC can present with deafness, pancreatic insufficiency, cholelithiasis, and diarrhea, and it usually runs in families, which was not so in our case, ruling out the possibility of PFIC. Patients with PSC usually present with recurrent cholangitis and diarrhea because most patients usually have inflammatory bowel disease, especially ulcerative colitis [14, 15]. Our patient did not have such a presentation.…”

“…PFIC is a clinical syndrome of intrahepatic cholestasis which presents in infancy or early childhood, and usually progresses rapidly to fibrosis and end-stage liver disease, whose confirmatory diagnosis can be made only following genetic analysis [14, 15]. Patients with PFIC can present with deafness, pancreatic insufficiency, cholelithiasis, and diarrhea, and it usually runs in families, which was not so in our case, ruling out the possibility of PFIC.…”

Pathological patterns of biliary disease

“…Because the microscopic changes are not autoimmune mediated, but are instead the sequelae of downstream pathology, they are classified under the heading of secondary sclerosing cholangitis. Possible causative factors include obstruction from a cholelith or external compression by a neoplasm (e.g., pancreatic carcinoma), trauma, ischemic injury, portal vein abnormality, and infection . As mentioned earlier, acute large‐duct obstruction is characteristically associated with portal edema.…”

How to apply clinical cases and medical literature in the framework of a modified “failure mode and effects analysis” as a clinical reasoning tool – an illustration using the human biliary system

“…Others have reported RUQ abdominal pain, jaundice, and recurrent cholangitis [51]Abdominal CT, MRI, MRCP, histopathologic findings on resected liver specimen [50]Obliterative cholangiopathy – biliary atresia [52]Neonatal biliary obstruction and cholestasis [52]Jaundice [52]Urinary urobilinogen combined with GGT; liver biopsy; diagnosis of biliary atresia was confirmed by operative cholangiography and/or laparotomy findings [52]Immune-mediated destruction of the intrahepatic bile ducts [53]Primary biliary cirrhosis leads to decreased bile secretion and the retention of toxic substances within the liver, resulting in further hepatic damage, fibrosis, cirrhosis, and eventually, liver failure [53]Fatigue and pruritus; unexplained discomfort in the RUQ of the abdomen; hepatomegaly; jaundice, portal hypertension and steatorrhea may occur in advanced disease; splenomegaly (uncommon); rarely ascites, hepatic encephalopathy, or hemorrhage from esophageal varices [53]Antimitochondrial antibodies, which are present in 90–95 % of patients and are often detectable years before clinical signs appear; liver enzymes; liver biopsy [53]Intense inflammatory fibrosis of the intrahepatic and extrahepatic biliary ducts [54]Primary sclerosing cholangitis (PSC): fibrosis involving the common bile duct, hepatic ducts, and sometimes the gallbladder; may progress to secondary biliary cirrhosis [54]Progressive obstructive jaundice, pruritus, weight loss, pain (RUQ or epigastric pain) [54]Elevation of total and direct (conjugated) serum bilirubin, serum alkaline phosphatase were 3 to 5 times normal; operative cholangiograms [54]PSC can be associated with inflammatory bowel disease. Primary biliary cirrhosis and sclerosing cholangiocarcinoma should be ruled out prior to diagnosing PSC [54]Extensive IgG4-positive plasma cells and T-lymphocyte infiltration of various organs including bile duct and gallbladder [55]Systemic fibroinflammatory causing sclerosing cholangitis [55]Painless jaundice and weight loss [55]CT abdomen, liver function test, serum IgG4; “ERCP with intraductal ultrasonography (IDUS), brush cytology and endobiliary biopsy would be helpful” [55]Another recent case reported that IgG4-related cholangitis is a rather uncommon cause of biliary obstruction, which can be easily mistaken for a cholangiocarcinoma [56]Abnormality in the genes encoding for canalicular bile formation [57]Defective bile canaliculi leading to intrahepatic cholestasis which may progress to fibrosis and endstage liver disease (progressive familial intrahepatic cholestasis) [57]…”