The enterohepatic circulation describes the transport pathway of some substances, such as those of nutrients, drugs, or even toxins in the body. These substances circulate from the liver through the gallbladder to the intestine and back to the liver. Some substances may pass through this circuit multiple times.
What is the enterohepatic circulation?
The enterohepatic circulation is also known as the liver–gut circulation. The enterohepatic circulation is also referred to as the liver–gut circulation. It describes the circulation of substances in the body, which occurs from the liver through the gallbladder to the intestine and back to the liver. This pathway can be passed by the corresponding substance up to twelve times in one day. Substances that are no longer needed or could not be absorbed after passing through the enterohepatic circulation are excreted again in the stool. The enterohepatic circulation does not represent an endogenous mechanism, but results from the chemical and physical properties of the substances. From these properties, the behavior of the substances in the body is determined. Not all substances that enter the body are subject to hepatic-intestinal circulation. Primarily, orally ingested substances are subject to it.
Function and task
The enterohepatic circulation begins in the liver. Here, the respective substances (for example, cholesterol) are formed. After their production, the substances are stored in the next station of the cycle, the gallbladder. From the gallbladder, the substances are then released into the duodenum. After the substances have fulfilled their respective purpose from there, they are returned from the small intestine to the liver. The recirculation takes place through the so-called portal vein, which is the connection between the small intestine and the liver. The enterohepatic circulation is of great importance for a whole range of substances that the body absolutely needs to maintain its functions. These include bile acid and vitamin B12, among others. The hepatic-intestinal circulation enables the human body to more effectively absorb and utilize the supplied substances such as nutrients or even drugs. Accordingly, the enterohepatic circulation reduces the amount that the body has to absorb or produce itself from such substances. By chemically modifying a substance, it is possible to influence its chemical properties in such a way that it is subject to the enterohepatic circulation to a different degree. The extent to which the substances in question are subject to the enterohepatic circulation depends not only on their chemical and physical properties but also on their concentration in the blood and intestine. For bile acids, the hepatic-intestinal circulation has a particularly important function. About 90 percent of bile acids are subject to enterohepatic circulation. About four grams of the acid circulate between the liver and intestine several times a day. As a result, the demand for newly synthesized bile acid from the liver drops considerably. Normally, the level of all substances relevant to bile acid regulates itself. However, if bile acids are prevented from being absorbed, their synthesis in the liver is increased. Since cholesterol is a substance necessary for this purpose, the level of cholesterol in the blood decreases. This principle has been transferred to the mode of action of cholesterol-lowering drugs. In the case of drugs, the enterohepatic circulation is only relevant for substances that are absorbed via the intestine. This applies in particular to preparations taken orally. Conversely, the enterohepatic circulation can be bypassed with drugs that are not absorbed via the gastrointestinal tract. These include intravenous and intermuscular injections and drugs taken sublingually, as well as nasal sprays. It is also possible, for example after the accidental ingestion of toxins, to remove substances from the enterohepatic circulation by administering activated charcoal, thus preventing their full effect from developing. Activated charcoal binds the substances in the intestine and excretes them unprocessed.
Diseases and ailments
The enterohepatic circulation does not represent an endogenous mechanism, but results from the properties of supplied substances. Thus, it does not perform any specific function for the body, but it can alter the mode of action of substances such as drugs in a positive but also in a negative way.The enterohepatic circulation also plays an important role for the vitamin B12 balance. Vitamin B12 is stored in the liver. Since the body can reabsorb it, it only needs a very small amount per day. The body’s own stores usually last up to ten years even on vitamin B12-free diets such as veganism. However, if the circulation of vitamin B12 is disturbed, the supply can be depleted much more quickly. This can cause a vitamin B12 deficiency that has far-reaching implications for the body. Enterohepatic circulation can alter the strength and timing of a substance’s effect. Substances produced by the liver can be cleaved in the intestine, making them more soluble. As a result, their absorbability increases. If a substance circulates very frequently due to its chemical and physical properties, the effect of the substance may occur later, while its half-life and thus its residence time in the body are prolonged. If this is not taken into account when a drug is administered several times, an overdose may occur. Overdose can cause symptoms of poisoning and liver damage. The same principle is applicable to some poisons. Due to the circulation between the liver and the intestine, their effect is delayed and therefore more surprising, but at the same time stronger and more long-term. As a result, dangerous poisonings are often not registered at all in the beginning.
