Biliary clearance

Bile is a concentrate of organic compounds (both exogenous and endogenous) with a high molecular weight (> 400) and a certain degree of hydrophilicity. It is produced by the liver in quantities of about 1 liter per day.

Bile is very similar to plasma, but it differs from the latter due to the reduced concentration of lipids and proteins.

The concentrated bile (given the considerable absorption of water) goes to pour into the hepatic duct, and then go to accumulate in a kind of bag called the gallbladder. Following a stimulus, the gallbladder contracts, pouring the bile into the choledochus duct that flows into the "intestine and more precisely into the duodenum. At the end of this duct there is the presence of a sphincter that regulates the excretion of bile fluid. This sphincter it is called sphincter of Oddi or hepatopancreatic sphincter (because there is also the presence of the pancreatic duct, in addition to the presence of the choledochus duct). The activity of the sphincter is regulated by the hormone cholecystokinin, which is mainly produced following a meal rich in lipids. As we know, bile plays a very important role, which is to emulsify the lipids introduced with food to aid digestion and absorption. Thanks to this emulsion, the lipids are in fact more digestible, therefore they can be attacked by specific enzymes called lipases.

At the level of the liver and intestine there is the so-called ENTEROEPATHIC CYCLE, which favors the elimination through the liver and the reabsorption through the intestine of many substances, including drugs. However, many of these can be reabsorbed in the intestine (mesenteric vein) and return to the liver thanks to the portal vein. Once the drugs or the various metabolites have reached the liver again, they can return to the circulation thus increasing their pharmacological action.

As mentioned above, the enteropathic circulation not only has the function of elimination, but also has the function of reabsorption of all those substances that our body cannot afford to lose, such as bile pigments, fat-soluble vitamins, hormones. steroids and folic acid.
Drugs that get to the liver can come from oral or parenteral administration. In the first case, therefore, the medicine is administered orally, is absorbed in the intestine, reaches the liver through the portal vein and finally undergoes changes thanks to the first hepatic passage. In the second case, however, the drugs administered parenterally , they reach the liver directly through the hepatic artery. In both cases, however, the substance taken reaches the hepatic sinusoids through the bloodstream. Once the drug reaches that level, it enters the liver cell, where it undergoes some metabolism. Only after metabolism is the drug eliminated by renal and / or biliary elimination pathways.
The excretion of drugs in the bile is influenced by 2 main physical characteristics:

• POLARITY (conjugation reactions increase);
• PESOMOLECULAR (only compounds with a MW> 300-500 are actively excreted in the bile by means of transporters).

There are four distinct conveyor systems:

• Transporters for organic anions (glucuronoconjugates);
• Transporters for organic cations (dextrotubocurarine);
• Transporters for bile acids;
• Conveyors for non-ionized substances (digitalis).

In a nutshell, summarizing the concepts seen, bile is useful for the elimination of substances that have a high degree of hydrophilicity, a high molecular weight, but above all metabolites that are formed by conjugation.

 

Other articles on "Clearance and biliary excretion"

1. Renal clearance
2. Area under the plasma (concentration) curve - time