Bile components and the effect of nutrition
The organic composition of bile is primarily based on bile acids and bile pigments.
The bulk of bile acids is in the form of conjugates (chemical compounds). Approximately 80% of them bind to the amino acid glycine, forming glycocholic acids. The remaining 20% are conjugated with taurine, turning into taurocholic acids.
Interestingly, diet is capable of directly modifying this composition:
- A diet high in carbohydrates leads to an increase in the proportion of glycocholic acids.
- A high-protein diet stimulates the production of taurocholic acids.
As for bile pigments, they are breakdown products of hemoglobin and other porphyrin derivatives. The liver captures these metabolites from the bloodstream and excretes them along with bile.
Differences between hepatic and gallbladder bile
Bile that has just been synthesized by liver cells differs significantly from that stored in the gallbladder. As it passes through the biliary tract and resides in the reservoir, the composition of the secretion changes:
- Concentration. Due to the active absorption of water and mineral salts by the gallbladder walls, the concentration of bile increases by 4–10 times.
- Addition of mucin. The mucous secretion makes the bile thicker, increasing its density.
- Change in pH. The medium becomes more acidic (pH drops to 6–7). This is due to the formation of new bile acids in the lumen and the absorption of bicarbonates.
Mechanisms of bile formation (choleresis)
The process of bile formation is continuous, but its intensity can vary. Choleresis is enhanced via conditioned reflexes as well as unconditioned reflexes: by the act of eating itself, various types of food, and the stimulation of receptors in the gastrointestinal tract and internal organs.
The following stimulants of bile formation are distinguished:
- Humoral factors: secretin, glucagon, gastrin, cholecystokinin-pancreozymin. Bile acids themselves, returning to the liver, also powerfully stimulate the production of new bile.
- Neural mechanisms: stimulation of the vagus nerves (nervus vagus).
- Alimentary (food) stimuli: a high content of high-quality proteins in the diet or exogenous administration of bile acids.
All these factors not only increase the volume of the liquid part, but also enhance the excretion of organic components with it.
Regulation of bile excretion (cholekinesis)
Outside of digestive processes (on an empty stomach), bile accumulates in the gallbladder and is released into the intestine only against the background of periodic motor activity of the GI tract. During digestion, the gallbladder contracts, the pressure inside it rises sharply, the sphincter of Oddi opens, and a portion of bile is poured into the duodenum. 3–6 hours after a meal, cholekinesis decreases, and the secretion begins to be stored again.
Strong stimulators of cholekinesis include fats, egg yolk, milk, and magnesium sulfate. The regulation of the process is divided into two pathways:
1. Reflex mechanisms Executed via the vagus nerve in response to the stimulation of oral cavity and gastric receptors (especially upon mechanical stretching and the intake of fatty food).
- Weak stimulation of n. vagus: relaxation of the sphincter of the common bile duct and contraction of the gallbladder $\rightarrow$ bile excretion.
- Strong stimulation of n. vagus: contraction of the sphincter and relaxation of the gallbladder $\rightarrow$ bile retention.
- Sympathetic nervous system: inhibits gallbladder contraction (via $\alpha_2$-adrenergic receptors).
2. Humoral mechanisms It has been proven that blood transfusion from a fed animal to a fasting one induces bile excretion.
- Stimulators: the leading factor is cholecystokinin-pancreozymin, which is produced in the cells of the duodenal mucosa under the action of hydrochloric and fatty acids. Gastrin, secretin, bombesin, and substance P also stimulate cholekinesis.
- Inhibitors: gallbladder contraction is inhibited by glucagon, calcitonin, vasoactive intestinal peptide (VIP), and pancreatic polypeptide.
Barrier function of the liver
In addition to producing bile, the liver acts as a crucial filter, inactivating toxic substances. The mechanism lies in the detoxification of a number of hydrophobic compounds.
Sources of such toxins can include:
- Substances ingested with food.
- Metabolites produced by the microflora in the intestine.
- Various medicinal drugs.
- Infectious agents and their waste products.
Briefly: answers to topical questions
What are the primary and secondary bile acids?
The following are the main primary and secondary bile acids synthesized in the liver and formed in the intestine:
- Cholic acid — a primary bile acid (3,7,12-trihydroxycholanoic).
- Chenodeoxycholic acid — a primary bile acid (3,7-dihydroxycholanoic).
- Deoxycholic acid — a secondary bile acid (formed from cholic, 3,12-dihydroxy).
- Lithocholic acid — a secondary bile acid (formed from chenodeoxycholic, 3-monohydroxy).
From which precursor and with the help of which enzyme are bile acids synthesized in hepatocytes?
In hepatocytes, bile acids are synthesized from cholesterol with the participation of the enzyme 12$\alpha$-monooxygenase. The initial compound undergoes modifications: under the action of 12$\alpha$-monooxygenase, the dihydroxylated precursor acquires a third hydroxyl group. Subsequently, oxidative shortening of the side chain occurs, leading to the formation of primary bile acids.
What is the enterohepatic circulation of bile acids?
The enterohepatic circulation of bile acids is their rotation between the liver, bile, intestine, and back to the liver. Primary bile acids are synthesized in the liver, then they are conjugated with glycine or taurine and secreted into the bile. In the intestine, they participate in the emulsification of fats; under the action of microflora, deconjugation and 7$\alpha$-dehydroxylation occur with the formation of secondary bile acids. About 95% of bile acids are reabsorbed in the ileum, returned to the liver via the portal vein, re-conjugated, and excreted into the bile. Each bile acid molecule completes this pathway 5–8 times per day.
Which specific toxic metabolites of the intestinal microflora are detoxified in the liver?
The liver detoxifies the following toxic products generated by microflora in the large intestine (products of protein putrefaction):
- Indole — formed from tryptophan, metabolized to animal indican.
- Skatole — methylindole, detoxified similarly to indole.
- Cresol — a product of tyrosine and phenylalanine putrefaction.
- Putrescine — accumulates in hepatic coma.
- Cadaverine — a marker of intoxication.
- Ammonia — a toxic metabolite whose inactivation occurs via the synthesis of low-toxicity urea.
Class and exam questions
What happens to bile secretion on an empty stomach?
On an empty stomach, the bulk of bile accumulates in the gallbladder. Its release into the duodenum occurs only episodically, during the periodic motor activity of the digestive tract.
What is the paradoxical effect of the vagus nerve on bile excretion?
The effect depends on the strength of the stimulus. Weak stimulation causes gallbladder contraction and sphincter relaxation (bile is released), whereas strong stimulation leads to sphincter spasm and gallbladder relaxation (bile is retained).
Which foods are considered the most potent stimulants of bile excretion?
The strongest food stimulants of bile excretion include fats, egg yolk, and milk. Magnesium sulfate is also a potent non-food stimulant.
What else to study on this topic
- Mechanisms of enterohepatic circulation of bile acids
- Biochemical stages of bile pigment formation from hemoglobin
- The role of cholecystokinin-pancreozymin in the coordination of gastrointestinal tract function
- Receptor apparatus of the gallbladder and the sphincter of Oddi
- Phases of detoxification of hydrophobic compounds in hepatocytes
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