Bile is a fluid produced by liver cells, and around 97% of it is water. Other important constituents include bile acids / bile salts, bilirubin, fats and other salts.
Bile acids are produced from cholesterol. Bile acids combine with amino acids like taurine and glycine to form bile salts. Bile salts help breakdown and subsequent absorption of fats in our food across intestines.
Bilirubin is a breakdown product of the well known protein 'haemoglobin', which in turn is contained in the red blood cells (RBCs). RBCs have a typical lifespan of 120 days after which they are destroyed with resultant production of bilirubin. However, bilirubin thus produced (unconjugated) is insoluble in water. Liver cells combine (conjugate) this bilirubin with glucuronic acid to form 'conjugated bilirubin' that is water soluble and can be eliminated in the stools. Bilirubin and its subsequent breakdown products impart yellow-brown colour to the stool. Excess bilirubin in the blood manifests as yellowing of skin and eyes ('jaundice').
Bile is carried from liver cells ('hepatocytes') through very thin tubules called 'canaliculi', which converge to form 'bile ducts'. Each of the 2 lobes of liver contains a 'hepatic duct', which join together to form a single 'common hepatic duct' (CHD) that exits the liver through its undersurface. A balloon like structure called 'gallbladder' (GB) under the surface of liver joins the CHD through a thin tube called the 'cystic duct', beyond which the former is called the 'common bile duct' (CBD). Duodenum is the first part of intestine coming out from the stomach. CBD joins and empties bile into the duodenum.
The term 'hepatobiliary' stands for the system responsible for formation, transport and elimination of bile into the intestine.
Bile flows as follows: hepatocytes → canaliculi → hepatic duct → CHD → GB → cystic duct → CBD → duodenum. However, almost two-third of bile in the CHD flows directly into the CBD and further into the duodenum without ever entering the GB.
Obstruction at any point in the biliary tract (especially between the CHD and the duodenum) in its initial phases causes increased pressure. As the bile production continues, this pressure keeps on increasing further. Initially, conjugated bilirubin starts entering blood in abnormal quantities (which results in abnormally high level of 'direct' bilirubin in the blood test). If the obstruction is not relieved, hepatocyte function gets impaired. Apart from production of bile, hepatocytes have 2 other major class of functions: protein synthesis and conversion of harmful substances in the blood into less harmful forms. Hepatocytes are very resilient and regenerate readily. Hence, most of the manifestations of hepatocyte function impairment ('liver failure') are seen in advanced / long-standing cases of obstruction, but once they set in, they tend to be irreversible.
HIDA stands for 'hepatobiliary iminodiacetic acid', and is a class of compounds. Mebrofenin is a type of HIDA. Once injected into the blood, mebrofenin is avidly taken up by hepatocytes. From there it enters the canaliculi through the same transporter proteins as bilirubin. Thus, once into the hepatocytes, mebrofenin follows the same path as bile.
As part of nuclear medicine imaging, mebrofenin is tagged with the radioactive 99mTc.
Biliary atresia is a childhood condition involving absence or blockage of bile canaliculi and ducts. It results in biliary obstruction and its complications (described above).
Neonatal jaundice is a condition of the newborn with increased bilirubin level in the blood. It is either because of increased breakdown of RBCs or inability of the hepatocytes to conjugate bilirubin at sufficiently fast rate.
In the initial phases neonatal jaundice and biliary atresia can be difficult to distinguish. However, former tends to be self-limited and/or less severe with relatively normal or only modestly raised direct (conjugated) bilirubin. Biliary atresia results in progressive jaundice with markedly elevated direct bilirubin in the blood.
In neonatal jaundice, there is no obstruction, so bile produced by the liver reaches up to the intestines. In contrast, biliary atresia results in absent or near-absent flow of bile from the liver; hence, injected mebrofenin is taken up less avidly by the liver and enters the urinary system in concentration greater than expected (both because of impaired hepatocyte function), and it does not reach up to the intestines (because of blockage in the biliary tract).
There are no remarkable expected risks or side effects.
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