Since extrahepatic biliary obstruction is frequently amenable to surgical treatment, correct and prompt diagnosis is imperative. In contrast, cholestasis due to diseases of the intrahepatic biliary tree or hepatocellular secretory failure (collectively termed intrahepatic cholestasis) is not benefited by surgery (short of transplantation), and the patient’s condition may be worsened by an operative procedure. It is thus important to establish the underlying basis for jaundice and cholestasis.
MORPHOLOGYAcutebiliaryobstruction,eitherintrahepaticorextrahepatic,causesdistentionofupstreambileducts,whichoftenbecomedilated.Inaddition,ductular reactions appearattheportalparenchymalinterfacealongwithstromaledemaandneutrophils.Thehallmarkofsuperimposedinfection(ascending cholangitis) istheinfluxofperiductularneutrophilsintothebileductepitheliumandlumen(
Fig.16.24
Leftuncorrected,theinflammationandductularreactionsresultingfrom chronic biliary obstruction initiateperiportalfibrosis,eventuallygeneratingsecondary or obstructive biliary cirrhosis (
Fig.16.25 ).Cholestaticfeaturesintheparenchymamaybeprominent.Thesetaketheformofextensivefeathery degeneration of periportal hepatocytes,atypeofcytoplasmicswellingoftenassociatedwithMallory-Denk bodies andbile infarcts causedbythedetergenteffectsofextravasatedbile.
Prolonged conjugated hyperbilirubinemia in the neonate, termed neonatal cholestasis (as opposed to the already discussed neonatal jaundice) affects approximately 1 in 2500 live births. The major conditions causing it are (1) cholangiopathies, primarily biliary atresia (discussed later), and (2) a variety of disorders causing conjugated hyperbilirubinemia in the neonate, collectively referred to as neonatal hepatitis.
Fig. 16.24 Acutelarge-ductobstructionwithascendingcholangitis.Super-imposedonfeaturesofductobstruction(edema,ductularreaction)isaninfiltrateofneutrophilsinvolvingthebileduct,thehallmarkofascendingcholangitis.
Neonatal hepatitis is not a specific entity, nor does it necessarily have an inflammatory basis. Rather it is an indication to conduct a diligent search for recognizable toxic, metabolic, and infectious liver diseases, as greater than 85% of cases have identifiable causes.
Differentiation of biliary atresia from nonobstructive neonatal cholestasis is very important, since definitive treatment of biliary atresia requires surgical intervention (Kasai procedure), whereas surgery may adversely affect a child with other disorders. Fortunately, discrimination can be made on the basis of clinical data in about 90% of cases. In 10% of cases, liver biopsy may be necessary to distinguish neonatal hepatitis from an identifiable cholangiopathy. Affected infants have jaundice, dark urine, light or acholic stools, and hepatomegaly. Variable degrees of hepatic synthetic dysfunction may be identified, such as hypoprothrombinemia.
Fig. 16.25 Cirrhosissecondarytoprimarybiliarycholangitis.
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Fig. 16.26 Neonatalhepatitis.Notethemultinucleatedgianthepatocytes.
Fig.16.26 )includestrikinggiant-celltransformationofhepatocytes,associatedwithlobulardisarray,focallivercellapoptosisandprominenthepatocellularandcanalicularcholestasis.Insomecases,thisparenchymalpatternofinjuryalsoisaccompaniedbyductularreactionandfibrosisofportaltracts.