Nucpaedia
Nucpaedia
Mechanism 14 of 16

Hepatobiliary transport

The tracer is taken into the hepatocyte on the same transporter that handles bilirubin and pumped out into the bile canaliculus unchanged. Because it is a transit study, the diagnosis lives in the timing.

A normal sequence is hepatic uptake by five minutes and gallbladder plus duodenal activity by sixty. Non-visualisation of the gallbladder at sixty minutes — confirmed at four hours or after morphine, which raises intraluminal pressure by contracting the sphincter of Oddi — is cystic duct obstruction, and the study is close to 100% sensitive for acute cholecystitis.

The competition with bilirubin sets the failure mode. Mebrofenin, with about 98% hepatic extraction, works up to a bilirubin of roughly 20–30 mg/dL; disofenin is close behind, and it was the older lidofenin that gave up early. Hepatic uptake with no biliary excretion is hepatocellular dysfunction, not obstruction, and it is a different report.

SINUSOIDhepatocyteOATP1B1 / 1B3MRP2BILE CANALICULUS → COMMON DUCT → DUODENUMgallbladdernon-visualisation at 60 min= cystic duct obstructionunchanged andunconjugatedbilirubin competes at this doorHIDAHIDAHIDABiliBili
iminodiacetic acid tracerbilirubin — competes at the same doorOATP / MRP2
A borrowed pathway, end to end. OATP1B1/1B3 pulls the tracer out of the sinusoid — the same door bilirubin uses, which is why a high bilirubin degrades the study. MRP2 then pumps it into the canaliculus unchanged and unconjugated. Nothing is trapped anywhere, so what you are reading is transit time: uptake by 5 minutes, gallbladder and bowel by 60.

The agents

Tc-99m mebrofenin / disofeninHIDA · Choletec, Hepatolite

SPECT / planar

Tc-99m · t½ 6.01 h · iminodiacetic acid analogues

SINUSOIDhepatocyteOATP1B1 / 1B3MRP2gallbladdernon-visualisation at 60 min= cystic duct obstructionBILE CANALICULUS → DUODENUMbilirubin competes at this doorHIDAHIDAHIDABiliBili
Handle
OATP1B1/1B3 for uptake, MRP2 for canalicular excretion
Trapping
Taken into the hepatocyte and pumped into bile unchanged. Normal transit: liver by 5 min, gallbladder and duodenum by 60 min.
Use
Acute cholecystitis; biliary atresia versus neonatal hepatitis after five days of phenobarbital; bile leak; gallbladder ejection fraction with CCK for chronic acalculous cholecystitis (consensus lower limit of normal 38% with a 60-minute sincalide infusion); sphincter of Oddi dysfunction; post-surgical and biliary-enteric anatomy.
Pitfall
Bilirubin competes at the uptake step. Mebrofenin has the highest hepatic extraction (~98%) and stays diagnostic to a bilirubin of 20–30 mg/dL; disofenin (~89%) is close behind, while the older lidofenin failed above about 5 mg/dL. Fasting over 24 hours or TPN gives a viscous, full gallbladder that will not fill: pretreat with CCK. A recent meal gives a contracted gallbladder that also will not fill: fast 4 hours. The rim sign — increased pericholecystic hepatic activity — suggests gangrenous cholecystitis. Hepatic uptake without biliary excretion is hepatocellular dysfunction, not obstruction.