Where bile is produced_

Bile is an important substance that aids digestion, but where is bile produced_what produces bile? Bile is of course produced by the liver. After it is produced, part of the bile flows into the gallbladder for storage, and part of it enters the duodenum to better help digestion. Excessive or insufficient bile secretion will have an impact on the body, which requires the liver to maintain a healthy state, otherwise the balance will be broken.

An adult secretes about 800-1000 ml of bile per day. Bile is a thick, bitter, clear colored liquid. The composition of bile is very complex, and its composition is mainly composed of inorganic and organic components. Its inorganic components mainly include water, sodium, potassium, calcium, bicarbonate and a small amount of heavy metal ions such as copper and aluminum; organic components include bile acid, bile pigments, cholesterol, lecithin and albumen, etc. There are no digestive enzymes in bile.

Hepatic bile consists of capillary bile and biliary bile. Canaliculus bile accounts for about 2/3 of the hepatic bile, which is the bile secreted directly into the canaliculus by hepatocytes and the bile entering the canaliculus through the paracellular space or paracellular pathway. Bile duct bile accounts for about 1/3 and is produced by the bile duct epithelium. Liver bile is golden yellow or barrel brown, with a pH of 7.4. Hepatic bile can be discharged directly into the duodenum or stored in the gallbladder. The bile concentrated in the gallbladder is called gallbladder bile, which has the same osmotic pressure as plasma and a pH of 6.8. The formation of bile can be divided into the capillary bile duct part and the bile duct part. In the bile ductules, water and solutes in plasma enter the bile ductules from the perisinusoidal space through three pathways to form bile ductules:

① Transcellular pathway, that is, entering the hepatocyte from the liver sinusoidal membrane, and then passing through the bile capillary membrane to enter the bile capillary;

② Paracellular pathway, that is, through the paracellular space between two hepatocytes, through the tight junctions and into the bile capillaries;

③ The mixed pathway is to enter the hepatocytes through the sinusoidal membrane, then enter the paracellular space through the basolateral membrane, and then enter the bile capillary through the tight junction. In the bile duct part, water and solutes in the plasma directly enter the bile duct through the bile duct epithelial cells to form bile duct bile. These two types of bile combine to form hepatic bile.

The formation of bile can also be divided into two parts according to whether it depends on bile acid, namely bile acid-dependent bile and bile acid-independent bile. The formation of capillary bile includes these two parts, each accounting for half; bile duct bile is non-bile acid dependent bile, which is mainly completed through the secretion and reabsorption of water and electrolytes.

Bile acid-dependent bile formation: During the process of bile formation, solutes are actively secreted into the bile capillaries, forming an osmotic pressure gradient, causing water to passively transfer into the bile capillaries. Na+-K+-ATPase located on the cytoplasmic membrane at the base of hepatic sinusoids plays a very important role in the formation of bile acid-dependent bile. Na+-K+-ATPase pumps out 3 Na+ from the hepatocytes to exchange them with 2 K+ outside the cells, keeping the intracellular Na+ concentration at a low level and maintaining the transmembrane concentration gradient of Na+, which under certain conditions is conducive to Na+ entering the hepatocytes against the concentration gradient. Since organic anionic bile acids are coupled to Na+, bile acids from the hepatic sinusoids enter the hepatocytes in the form of Na+-bile acid conjugates, and the Na+ is pumped out of the cells again. As bile acids accumulate in hepatocytes, a certain chemical concentration gradient is formed between hepatocytes and the lumen of bile canaliculi, causing bile acids to quickly cross the concentration gradient and enter the lumen of bile canaliculi. In addition to bile acids, other organic anions can also enter the bile capillaries through this binding transport mechanism. In addition, bile acids can also be transported through another pathway, namely, through the vesicular transport system of the Golgi complex and microvesicles, transporting bile acids from hepatocytes to the bile capillaries. Since bile acids account for more than half of the solid components in bile, the entry of bile acids into the bile capillaries is a very important factor in promoting bile flow. Bile acids and other organic acid ions exist in the form of micelles in the bile canaliculi, forming a certain osmotic pressure, causing water to passively enter the bile canaliculi, increasing the bile flow and constituting bile acid-dependent bile flow.

Formation of bile acid-independent bile: In the bile in the bile ductules, the formation of some bile is not related to the secretion of bile acids, which is called bile acid-independent bile. In the formation of non-bile acid-dependent bile, Na+-K+-ATPase plays an important role, so it is also called Na+-dependent bile flow. There is no Na+-K+-ATPase in the hepatic bile capillary membrane. Therefore, the Na+ in the hepatocytes can be pumped to the paracellular space through the Na+-K+-ATPase on the basolateral membrane of the hepatocytes, and then passively diffused into the bile capillaries through tight junctions, while Cl- and HCO3- can be secreted into the bile with the help of the potential gradient of Na+, and water is also brought into the bile capillaries.