See also: bile acids; biliary excretion of drugs
Bile is an isotonic aqueous solution produced by the liver and consisting mainly of water (95%), electrolytes, lipids (bile acids, cholesterol and phospholipids), proteins and pigments (bilirubin); its pH is slightly basic.
The liver produces an average of 600 ml of bile each day; the quantity secreted is influenced by the type of diet (it increases following the ingestion of foods rich in fat), by the frequency and consistency of meals, by some drugs and by the circadian rhythm (it is greater at night than during the day).
Towards the end of its path, the choledochus flows into the greater pancreatic duct and finally flows, through the left side of the duodenum, into the papilla of Vater.
The speed with which the bile flows into the intestine is regulated by the contractile fibers that make up the sphincter of Oddi. This muscular ring, contracted during fasting and relaxed during the intestinal phase of digestion, prevents the reflux of the enteric contents into the bile ducts. , in fasting conditions, opposes resistance to the passage of bile which, not being able to pour into the duodenum, runs through the cystic duct and flows into the gallbladder. Inside this vesicle, the bile is accumulated and progressively concentrated (up to 10%). ; this reabsorption involves water, sodium chloride and bicarbonates, while bile salts, pigments and lipids are not reabsorbed and become more and more concentrated.
Cholesterol, being insoluble in bile, would tend to precipitate in microcrystals (stones); this occurrence is prevented by the presence of bile salts and phospholipids (lecithins) which, by incorporating it into micelles, prevent its crystallization. However, it can happen that the bile is supersaturated with cholesterol and that this is deposited in solid aggregates called stones; for this reason, since the biliary elimination of cholesterol is directly proportional to the endogenous synthesis and the quantity introduced with the diet, a balanced diet reduces the risk that this lipid precipitates in its crystalline form.
The emptying of the gallbladder occurs in connection with meals and is favored by the "cholecystokinin hormone (CCK), produced by the mucosa of the duodenum in response to the passage of the gastric contents (called chyme), especially if rich in fat. This" hormone performs a triple action: induces an increase in biliary secretion (choleretic action); stimulates the contraction of the gallbladder (cholagogue action); promotes the relaxation of the sphincter of Oddi, thus allowing the outflow of bile into the duodenum. Another hormone, called secretin, has the ability to increase bile flow (choleretic properties); other hormones, such as intestinal vasoactive peptide (VIP), glucagon and somatostatin, promote the relaxation of the gallbladder and inhibit its contraction.
Bile salts and bile function
The secretion of bile is essential for the digestion and absorption of lipids, thanks to the presence of bile salts. These molecules, polar derivatives of cholesterol, are amphipathic, as they are formed by a fat-soluble "face" and a water-soluble "back". complete with negative charges facing outwards (it is defined amphipathic or amphiphilic, a molecule containing a hydrophilic and a hydrophobic group; the most classic example is given by the phospholipids that make up the cell membrane).
After being introduced into the intestine, the bile salts enter the lipid drops with their fat-soluble portion. In this way they reduce the cohesion between the various triglycerides, emulsifying the fat globules into small micelles and increasing the area accessible to specific pancreatic enzymes, called lipases, responsible for lipid digestion. The continuous mixing of the intestinal contents, favored by the peristaltic contractions, also contributes to the splitting of the lipid globules into much smaller molecules.
The whole process, which takes the name of emulsion, is irreversible since lipid re-aggregation is prevented by the negative electric charge associated with the water-soluble component of the bile salts, which stabilizes the emulsion by rejecting the various micelles.
In addition to facilitating digestion and the absorption of fats and fat-soluble vitamins, bile neutralizes the acidity of gastric secretions (HCl), stimulates intestinal peristalsis and exerts an antiseptic action against the bacterial flora, inhibiting putrefactive phenomena.
Through the bile the products deriving from the degradation of hemoglobin (bilirubin), substances with a toxic or pharmacological action and others of an endogenous nature (thyroid hormones, estrogens, etc.) are also removed from the organism.
Bile, bile salts and cholesterol
There are no biochemical mechanisms of cholesterol degradation in humans; therefore the only way of elimination of this lipid is its secretion in the bile and its conversion to bile salts. Every day the liver converts 200-400 mg of cholesterol into "primary" bile acids, represented by "cholic acid and chenodeoxycholic acid, in a 2: 1 ratio. These primary bile acids are released by the liver in conjugated form with the amino group of glycine. or taurine; bile acids conjugated with glycine (glycolic and chenodeoxycholic acids) are present in quantities three times higher than the acids deriving from conjugation with taurine (taurocholic and chenodeoxycholic acids).
Most of these salts (about 90%) are reabsorbed and return to the liver through the portal circulation, to then be secreted again in the bile juices. At the colic level, some bacteria metabolize non-absorbed "primary" bile acids by converting them into "secondary" bile acids (deoxycholic and lithocholic acids), of which about 20% is absorbed and re-conveyed to the liver through the enterohepatic circulation.
An adult subject who follows a "balanced diet produces on average 7-20 grams of bile acids per day, of which only 200-500 mg are eliminated in the faeces (this amount increases if the diet is rich in fiber). Free cholesterol present. in the bile, on the other hand, it is reabsorbed by 50%.
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