Enterohepatic cycle
The enterohepatic circulation or intestinal-liver circulation is the term used to describe the circulation of certain substances in the body of mammals between the intestines , liver and gall bladder . In addition to the body's own substances such as bile acids, this also applies to a number of drugs and toxins . The enterohepatic circulation is not an independent anatomical structure of the body with a specific task, such as the flow system of the blood circulation , but describes the behavior of certain substances in the body resulting from their chemical and physical properties.
A phenomenon with the opposite effect on bioavailability is the first pass effect .
principle
About the food absorbed substances enter after passage through the stomach from the intestine by absorption into the bloodstream and through the portal vein into the liver. There they are partly subject to a biochemical conversion, that is, they are split by enzymes and given certain chemical groups . The latter reactions produce so-called conjugates. The whole is used for detoxification and to increase the water solubility ( hydrophilicity ) and thus the excretion of these substances. This process is also known as biotransformation . They are then released from the liver with the bile via the gall bladder and bile duct into the intestine, from where, depending on their chemical and physical properties, they can be reabsorbed into the bloodstream and thus into the liver.
Since the enterohepatic circulation is not a specific anatomical structure with a special task, but a property of some substances, it has no specific function for the body with regard to substances that are foreign to the body. It can have both positive and negative effects on the effects of drugs and other foreign substances.
Physiological importance
A number of the body's own substances and substances that the body needs to maintain its functions are characterized by an enterohepatic cycle. It reduces the amount of these substances that must be newly formed or newly absorbed.
The enterohepatic cycle of bile acids was first described by Moritz Schiff in the second half of the 19th century . 85 to 95 percent of bile acids are subject to enterohepatic circulation and are mainly absorbed in the back of the small intestine . In this context, one also speaks of the bile acid pool . This contains an amount of three to four grams and circulates between the liver and intestine about four to twelve times per day, whereby the need for new synthesis of bile acids in the liver with 200 to 600 milligrams per day is only a fraction of the amount that without one such a circulating pool would have to be newly formed. The enterohepatic circulation with a reabsorption rate of 15 to 20 percent is also important for the bile pigment bilirubin , as is for cholesterol .
Another physiologically relevant substance with a pronounced enterohepatic circulation is vitamin B 12 (cobalamin). Because of this, vitamin B 12 is mainly stored in the liver with a total amount of two to five milligrams. The daily excretion and thus the need for new intake is in the range of only one to three micrograms due to the circulation. Corresponding deficiency symptoms therefore only appear after several years of a vitamin B 12 -free diet.
Pharmacological relevance
The extent to which medicinal substances and their breakdown products ( metabolites ) are subject to such a cycle depends, among other factors, primarily on their concentration in the intestine and blood . In addition, the conjugates formed in the liver to increase the hydrophilicity can be cleaved by intestinal bacteria , as a result of which their solubility in fat ( lipophilicity ) and thus their resorbability increases again. A pronounced circulation of a medicinal substance in the enterohepatic circulation leads to a later onset of action as well as an extension of the half-life and thus the duration of the substance in the body. This must be taken into account when a drug is administered repeatedly in order to avoid overdosing and overloading the detoxification capacity of the liver and damage to the liver.
The enterohepatic cycle is relevant for medicinal substances only in medicinal forms that are absorbed in the intestine, for example tablets , capsules , dragees and solutions taken orally . It can therefore be avoided with some drugs by choosing a drug form without gastrointestinal passage if possible, such as a sublingual tablet , a nasal spray or an intravenous or intramuscular injection . By changing the properties of an active substance chemically, it is possible to specifically influence the extent to which it enters an enterohepatic cycle.
In the case of some drugs, the enterohepatic circulation is also a reason why the accidental or mistaken swallowing of a sublingual tablet can lead to changes in the action profile, in addition to the already mentioned effects on the onset of action and the duration of action, among other things, side effects on the liver. A loss of effectiveness is also possible in this case if the medicinal substance only reaches its intended site of action in insufficient concentrations due to the circulation in the enterohepatic circuit.
Medicinal substances with an enterohepatic circuit relevant for therapy are, for example, digitoxin , tamoxifen , rifampicin , carbamazepine , barbiturates and many tricyclic antidepressants .
Toxicological Aspects
Some toxins such as colchicine , the poison of the autumn crocus , also show an enterohepatic cycle. The same applies to the amatoxins , the main toxins of the green cap mushroom . In particular, the extension of the half-life through the circulation between the liver and the intestine has negative effects on poisons. Analogous to the enterohepatic cycle with medicinal substances, there is a delay in the onset of action, an intensification of their effect and an increase in the duration of the intoxication. For example, poisoning with death cap mushrooms is characterized by a symptom-free phase lasting eight to twelve hours and often lasting several days.
The administration of activated charcoal can accelerate the excretion of toxins with enterohepatic circulation or of corresponding medicinal substances in the event of an overdose . This binds the relevant substances, removes them from the circulation between the liver and intestines and excretes them with the charcoal.
literature
- Ernst Mutschler, Gerd Geisslinger, Heyo K. Kroemer, Monika Schäfer-Korting: drug effects. Textbook of pharmacology and toxicology. Eighth edition. Wissenschaftliche Verlagsgesellschaft mbH, Stuttgart 2001, ISBN 3-80-471763-2
- Gerhard Thews , Ernst Mutschler, Peter Vaupel: Human anatomy, physiology, pathophysiology. Fifth edition. Wissenschaftliche Verlagsgesellschaft mbH, Stuttgart 1999, ISBN 3-80-471616-4
Individual evidence
- ↑ Alexandra Scheck: Nutrition compact. Third edition. UZV, Sulzbach im Taunus 2009, ISBN 978-3-930007-22-6 , p. 138
- ↑ Florian Horn: Biochemistry of humans. Thieme, Stuttgart 2005, ISBN 3-13-130883-4 , p. 482