Placental barrier in anesthetic terms. Pharmacokinetics and pharmacodynamics of drugs used in obstetric anesthesiology. Transfer of antibiotics through the placental barrier
Today, the term "placenta" no longer surprise anyone. Modern girls are much better informed about pregnancy and childbirth than their grandmothers and mothers. However, most of this knowledge is superficial. Therefore, today we want to talk about what the placental barrier is in the womb. At first glance, what's incomprehensible here? Children's place has the ability to protect developing embryo from harmful effects and toxic substances. In fact, this organ is a real mystery and a miracle of nature.
under protection
The placental barrier is a kind of immune system. It serves as a boundary between two organisms. It is the placenta that ensures their normal coexistence and the absence of an immunological conflict. The first trimester of pregnancy is the most difficult. Partly because the placenta is not yet formed, which means that the body of the embryo is completely unprotected. From about 12 weeks, she is fully included in the work. From now on, she is ready to perform all her functions.
How is the placenta arranged?
This important point, without which we will not be able to continue our conversation. The very word "placenta" came to us from Latin. It translates as "cake". Its main part is special villi, which begin to form from the first days of pregnancy. Every day they branch out more and more. At the same time, inside them is the blood of the child. At the same time, maternal blood enriched with nutrients enters from the outside. That is, the placental barrier primarily has a separating function. This is very important, since this organ regulates the exchange of substances between two closed systems. According to this statement, the external and inner side placenta has different structure. Inside it is smooth. Outer side- uneven, lobed.
barrier function
What does the concept of "placental barrier" include? Let's deviate a little more towards the physiology of the ongoing processes. As already mentioned, it is the unique villi that provide the exchange of substances between the woman and the embryo. Maternal blood brings oxygen to the baby and the fetus gives carbon dioxide to the pregnant girl. while they have one for two. And therein lies the greatest mystery. The placental barrier separates maternal and fetal blood so well that they do not mix.
At first glance it seems unimaginable, but two vascular systems separated by a unique membrane partition. It selectively skips what is important for the development of the fetus. On the other hand, toxic, harmful and dangerous substances linger here. Therefore, doctors say that starting from 12 weeks expectant mother you can relax a little. The placenta is able to protect the body of the child from many adverse factors.
Only the most important
All necessary substances pass through the placental barrier. nutrients as well as oxygen. If the doctor observes the pathology of fetal development, he may prescribe special drugs that increase the blood supply to the placenta. This means that they increase the amount of oxygen that enters the baby. However, not all so simple. The membrane septum retains the bacteria and viruses contained in the mother's blood, as well as antibodies that are produced during the Rhesus conflict. That is, the unique structure of this membrane is tuned to preserve the fetus in a variety of situations.
It should be noted the high selectivity of the partition. The same substances that have got through the placental barrier overcome this boundary in different ways in the direction of the mother and fetus. For example, fluorine very easily and quickly penetrates from a woman to a baby, but does not pass back at all. The situation is similar with bromine.
What regulates metabolism?
We have already told the reader that the placental barrier separates the maternal and fetal lymph. How did nature manage to launch such a perfect mechanism of regulation, when what is needed penetrates the barrier, and what is harmful is delayed? In fact, we are talking about two mechanisms here at once. Next, let's take a closer look at each of them.
First of all, we are interested in how the supply of vital, nutrient elements is regulated. Everything is quite simple here. Lipids and carbohydrates, proteins and vitamins are constantly present in the mother's blood. This means that the body can develop a balanced scheme. It will initially imply that the concentration of certain substances in the blood of the mother and child is different.
placental permeability
It is much more difficult when we are talking about toxic substances that enter the body of a pregnant woman. The placental barrier separates lymph and blood. This means that those toxins that have passed through the mother's bloodstream will not get into pure form to the fetus. However, after passing through the natural filters (liver and kidneys) in a residual form, they can still harm the baby. The fact is that substances (chemicals, drugs) that accidentally enter the mother's body are much more difficult to stop. They often tend to overcome the placental barrier.
Limited barrier functions
Nature could not foresee the development of modern industry. Therefore, the products of chemical production relatively easily pass the natural barrier. They pose a threat to the growth and development of the fetus. The degree of penetration through the placenta depends on the properties and characteristics of a particular substance. We will only mention a few points, in fact there are many more. Thus, medicinal substances with a molecular weight (less than 600 g / mol) pass through the placental barrier much faster. At the same time, those that have a lower rate practically do not penetrate. For example, these are insulin and heparin, which can be prescribed without fear during pregnancy.
There is another sign. Fat-soluble substances cross the placenta much better than water-soluble ones. Therefore, hydrophilic compounds are more desirable. In addition, physicians know that the probability of penetration of a substance through the placenta depends on the residence time of the drug in the blood. All long-acting drugs are more dangerous than those that are rapidly metabolized.
Transport medicines through the placenta is a complex and little-studied problem. The placental barrier is functionally similar to the hematoliquor barrier. However, the selective ability of the hematoliquor barrier is carried out in the direction of the blood-cerebrospinal fluid, and the placental barrier regulates the transfer of substances from the mother's blood to the fetus and in the opposite direction.
The placental barrier differs significantly from other histo-hematic barriers in that it is involved in the metabolism of two organisms that have significant independence. Therefore, the placental barrier does not belong to typical histo-hematic barriers, however, it performs important role in defense developing fetus.
The morphological structures of the placental barrier are the epithelial cover of the chorionic villi and the endothelium of the capillaries located in them. Syncytiotrophoblast and cytotrophoblast have high activity regarding absorption and enzymatic activity. Such properties of these layers of the placenta largely determine the possibility of penetration of substances. An essential role in this process is played by the activity of nuclei, mitochondria, endoplasmic reticulum and other ultrastructures of placental cells. The protective function of the placenta is limited to certain limits. Thus, the transition from mother to fetus of proteins, fats, carbohydrates, vitamins, electrolytes, constantly contained in the mother's blood, is regulated by mechanisms that have arisen in the placenta in the process of phylo- and ontogenesis.
Studies of transplacental transport of drugs were carried out mainly on the means used in obstetrics. There is evidence from chemical experiments illustrating the rapid transition from mother to fetus ethyl alcohol, chloral hydrate, gaseous anesthetics general action, barbiturates, sulfa drugs and antibiotics. There is also circumstantial evidence of morphine, heroin and other drugs passing through the placenta, as newborns from drug-addicted mothers show withdrawal symptoms.
More than 10,000 children with limb deformities (phocomelia) and other pathological signs, born of women who took thalidomide during pregnancy are another sad piece of evidence for transplacental drug transfer.
The transfer of drugs across the placental barrier occurs through all the mechanisms discussed above, of which highest value has passive diffusion. Non-dissociated and non-ionized substances pass through the placenta quickly, and ionized - with difficulty. Facilitated diffusion is possible in principle, but has not been proven for specific drugs.
The transfer rate also depends on the size of the molecules, since the placenta is impermeable to substances with a molecular weight of more than 1000. This is due to the fact that the pore diameter in the placenta does not exceed 10 nm and therefore only low molecular weight substances penetrate through them. This barrier is especially important for short-term use of certain substances, such as neuromuscular junction blockers. However, with prolonged use, many drugs can gradually penetrate into the body of the fetus.
Finally, proteins such as gamma globulin can enter through pinocytosis.
Chervertic ammonium bases, as well as muscle relaxants (decametonite, succinylcholine) penetrate the placenta with difficulty, due to high degree their ionization and low lipid solubility.
From the body of the fetus, drugs are excreted by reverse diffusion through the placenta and renal excretion into the amniotic fluid.
Therefore, the content of a foreign substance in the body of the fetus differs little from that of the mother. Considering the fact that the binding of drugs to blood proteins in the fetus is limited, their concentration is 10-30% lower than in the mother's blood. However, lipophilic compounds (thiopental) accumulate in the liver and adipose tissue of the fetus.
Unlike other barrier functions, placental permeability varies widely during pregnancy, which is associated with the increasing needs of the fetus. There is evidence of an increase in permeability towards the end of pregnancy. This is due to changes in the structure of the boundary membranes, including the disappearance of the cytotrophoblast and the gradual thinning of the syncytiotrophoblast of the placental villi. The permeability of the placenta in the second half of pregnancy does not increase to all substances introduced into the mother's body. So, the permeability of sodium bromide, thyroxin and oxacillin is higher not at the end, but at the beginning of pregnancy. Apparently, a uniform or limited supply to the fetus of a number of chemical substances depends not only on the permeability of the placental barrier, but also on the degree of development of the most important fetal systems that regulate its needs and homeostasis processes.
The mature placenta contains a set of enzymes that catalyze drug metabolism (CYP) and transport proteins (OCTNl/2, OCN3, OAT4, ENTl/2, P-gp). Enzymes can be produced during pregnancy, therefore, the metabolic processes occurring in the placenta, as well as the duration of the use of drugs, should be taken into account when deciding whether the fetus may be exposed to a substance circulating in the blood of a pregnant woman.
Discussing the role of histo-hematic barriers in the selective distribution of drugs in the body, it is necessary to note at least three more factors influencing this process. First, it depends on whether the drug is in the blood in free or protein-bound form. For most histo-hematic barriers, the binding form of the substance is an obstacle to their entry into the corresponding organ or tissue. So, the content of sulfonamides in the cerebrospinal fluid correlates only with the part that is in the blood in a free state. A similar picture was noted for thiopental in the study of its transport through the blood-ophthalmic barrier.
Secondly, some biologically active substances contained in the blood and tissues or introduced from the outside (histamine, kinins, acetylcholine, hyaluronidase) in physiological concentrations reduce the protective functions of histo-hematic barriers. The opposite effect is exerted by catecholamines, calcium salts, vitamin P.
Thirdly, when pathological conditions organism, histo-hematic barriers are often rebuilt, with an increase or decrease in their permeability. Inflammatory process in the membranes of the eye leads to a sharp weakening of the blood-ophthalmic barrier. When studying the entry of penicillin into the cerebrospinal fluid of rabbits in control and experiment (experimental meningitis), its content was 10-20 times higher in the latter case.
Therefore, it is difficult to imagine that even substances that are similar in structure according to the distribution profile will behave in a similar way. This is explained by this process depends on many factors: chemical structure and physical and chemical properties drugs, their interaction with plasma proteins, metabolism, tropism to certain tissues, the state of histo-hematic barriers.
Table of contents of the subject "Structure of the Placenta. Main Functions of the Placenta. Umbilical cord and succession.":1. The structure of the placenta. surface of the placenta. Microscopic structure of the mature placental villus.
2. Utero-placental circulation.
3. Features of blood circulation in the system mother - placenta - fetus.
4. The main functions of the placenta.
5. Respiratory function of the placenta. Trophic function of the placenta.
6. Endocrine function of the placenta. Placental lactogen. Chorionic gonodotropin (hCG, hCG). Prolactin. Progesterone.
7. The immune system of the placenta. Barrier function of the placenta.
8. Amniotic fluid. Volume of amniotic fluid. The amount of amniotic fluid. Functions of amniotic fluid.
9. Umbilical cord and last. The umbilical cord (umbilical cord). Options for attaching the umbilical cord to the placenta. Umbilical cord sizes.
The immune system of the placenta. Barrier function of the placenta.
The immune system of the placenta.
The placenta is a kind immune barrier, separating two genetically alien organisms (mother and fetus), therefore, during a physiologically proceeding pregnancy, an immune conflict between the organisms of the mother and fetus does not occur. The absence of an immunological conflict between the organisms of the mother and the fetus is due to the following mechanisms:
Absence or immaturity of the antigenic properties of the fetus;
- Availability immune barrier between mother and fetus (placenta);
- Immunological characteristics of the mother's body during pregnancy.
Barrier function of the placenta.
Concept " placental barrier"includes the following histological formations: syncytiotrophoblast, cytotrophoblast, a layer of mesenchymal cells (stroma of the villi) and the endothelium of the fetal capillary. The placental barrier to some extent can be likened to the blood-brain barrier that regulates the penetration various substances from blood to cerebrospinal fluid. However, unlike the blood-brain barrier, the selective permeability of which is characterized by the passage of various substances in only one direction (blood - cerebrospinal fluid), placental barrier regulates the transition of substances in the opposite direction, i.e. from fetus to mother. The transplacental transition of substances that are constantly in the mother's blood and accidentally entered it obeys different laws. The transition from mother to fetus of chemical compounds that are constantly present in the mother's blood (oxygen, proteins, lipids, carbohydrates, vitamins, microelements, etc.) is regulated by fairly precise mechanisms, as a result of which some substances are contained in the mother's blood in higher concentrations than in fetal blood and vice versa. In relation to substances that accidentally entered the mother's body (agents of chemical production, drugs, etc.), the barrier functions of the placenta are much less pronounced.
Placental permeability is not constant. At physiological pregnancy the permeability of the placental barrier progressively increases up to the 32-35th week of pregnancy, and then decreases slightly. This is due to the structural features of the placenta at different stages of pregnancy, as well as the needs of the fetus in certain chemical compounds.
Limited barrier functions placenta in relation to chemicals that accidentally enter the mother's body, are manifested in the fact that toxic products of chemical production relatively easily pass through the placenta, most medicines, nicotine, alcohol, pesticides, infectious agents, etc. It creates real danger for the adverse effects of these agents on the embryo and fetus.
Barrier functions of the placenta appear most fully in physiological conditions, i.e. with uncomplicated pregnancy. Under the influence of pathogenic factors (microorganisms and their toxins, sensitization of the mother's body, the effect of alcohol, nicotine, drugs), the barrier function of the placenta is disturbed, and it becomes permeable even to substances that, under normal physiological conditions, pass through it in limited quantities.
PLACENTAL BARRIER
placental barrier, a histohematic barrier that regulates the penetration of various substances from the mother's blood into the fetal blood and vice versa. Functions P. b. are aimed at protecting the internal environment of the fetus from the penetration of substances circulating in the mother's blood that do not have energetic and plastic significance for the fetus, as well as protecting the mother's internal environment from the penetration of substances that violate it from the fetal blood. P. b. consists of the epithelium of the trophoblast, syncytium covering the villi of the chorion of the placenta, the connective tissue of the villi and the endothelium of their capillaries. In the terminal villi, many capillaries are located just below the syncytium, and P. b. at the same time they consist of 2 unicellular membranes. It has been established that substances with a molecular weight below 350 can mainly enter the blood of the fetus from the mother's body. There are also data on the passage through P. b. macromolecular substances, antibodies, antigens, as well as viruses, bacteria, helminths. The penetration of macromolecular substances, antigens, bacteria is observed in the pathology of pregnancy, since the function P. b. is violated. P. b. is selectively permeable and in relation to substances with a molecular weight below 350. So, through P. b. acetylcholine, histamine, adrenaline cannot penetrate. Function P. b. in this case, it is carried out with the help of special enzymes that destroy these substances. In the pathology of pregnancy, many medicinal substances, as well as products of impaired metabolism, penetrate the blood of the fetus and have a damaging effect on it. See also .
Veterinary encyclopedic dictionary. - M.: "Soviet Encyclopedia". Chief editor V.P. Shishkov. 1981 .
See what the "PLACENTAL BARRIER" is in other dictionaries:
placental barrier- ANIMAL EMBRYOLOGY PLACENTAL BARRIER - a histohematological barrier that regulates the penetration of various substances from the mother's blood into the fetal blood and vice versa. It consists of the epithelium of the trophoblast, syncytium, covering the villi of the chorion of the placenta, ... ...
placental barrier- a set of morphological and functional features placenta, which determine its ability to selectively pass substances from the mother's blood to the fetus and vice versa ... Big Medical Dictionary
Placental barrier- - a set of morphological and functional features of the placenta, providing the ability to selectively pass certain substances from the mother's blood to the fetus, subject them to biological processing and retain them from the fetus to the mother ... Glossary of terms for the physiology of farm animals
place barrier- ANIMAL EMBRYOLOGY PLACED BARRIER - a barrier between the mother and the fetus, consisting of the trophoblast, the basal lamina underlying it, the connective tissue lying between the trophoblast and the fetal blood vessel, the basal lamina surrounding ... ... General Embryology: Terminological Dictionary
BARRIER PLACENTAL- a set of structural features of the placenta that prevent (or reduce) the ingress of toxic substances and infection from the mother's blood into the blood of the fetus. See also Placenta… Encyclopedic Dictionary of Psychology and Pedagogy
BARRIER FUNCTION- BARRIER FUNCTION. Barriers are devices that protect the body or its individual organs from environment and thus making it, to a certain extent, independent of the changes taking place in it. There are two kinds... ... Big Medical Encyclopedia
Pharmacotherapy- I Pharmacotherapy (Greek pharmakon medicine + therapeia treatment) treatment of a patient (diseases) with medicines. In the traditional sense of F. one of the main methods conservative treatment(Treatment). Modern F. is ... ... Medical Encyclopedia
Through the placenta, the fetus communicates with the mother's organisms. The human placenta is of the discoidal and hemochorial type. Distinguish the following types placenta:
Epitheliochorial- diffuse placenta, this type of placenta is in contact with the glands of the uterus, and these large molecules are broken down into amino acids (in the fetal liver). Found in camels, horses, pigs and cetaceans.
Desmochorionic or multiple placenta. This type of placenta splits the epithelium of the uterus, and the chorionic villi directly contact the connective tissue. It occurs in animals - sheep, cows, goats, etc. Children of such animals after birth are capable of independent nutrition and movement.
The next type of placenta (the second type of placenta) receives sweat amino acids from the mother's body, as a result, the fetus receives sweat nutrient material. The first type of such a placenta is called endotheliochorial and its villi in the uterine mucosa form a female girdle. Chorionic villi splits the epithelium, connective tissue, and such a wall blood vessels uterus and directly in contact with blood (hedgehog, mole, little mouse, rats, rabbits, monkeys and humans). The cubs of these animals are born very tender and unable to feed on their own. The walls of the villi of the placenta have a very complex structure, and the blood of the mother and fetus never mixes, because a hematoplacental barrier forms between them. The barrier consists of the blood vessel endothelium and its basement membrane. Loose fibrous connective tissue surrounding the vessel, trophoblasts and its basement membrane, as well as syncytiotrophoblast.
The placenta performs trophic and excretory (for the fetus) endocrine (choral gonadotropin, progesterone and estrogen), protective (immunological protection) functions. However, alcohol, drugs, drugs, nicotine and hormones freely penetrate the hematoplacental barrier through the blood of the uterus to the fetus.
In the structure of the placenta, the fetal and maternal parts differ. The fetal part is represented by branches of the chorion, and the amniotic membrane associated with it. The maternal part is represented by the transformed basal layer of the endometrium. The development of the placenta begins on the 3rd week, vessels begin to grow into the secondary epitheliomesenchymal villi and tertiary vessels form. The permeability of the placenta depends on the content of hyaluronic acid and hyaluronidase enzymes in it. In addition, for a strong connection of the placenta with the mother's body, vitamins C and A are needed, which are involved in differentiation, fibroblasts and collagen synthesis. The surface of the chorion villi is covered with cytotroblast and syncytiotrophoblast. Syncytiotrophoblast is formed later and is a derivative of cytotrophoblast, as a result of which the fetus feeds on hematotrophy.
By the end of the 3rd month of development, the fetal part of the placenta forms stem or anchor plates. Initially, choral villi are covered with single-layer epithelium, later these cells divide mitotically and form a multinuclear structure - syncytiotrophoblast. Syncytiotrophoblast contains a lot of proteolytic and oxidative enzymes (ATPase, alkaline and acid phosphatase, 5-nucleotidase, SDHase (succinate dehydroginase), cytochrome oxidase, monoamine oxidase, etc.). By the end of the 2nd month, the cytotrophoblast disappears on the villi and only the syncetiotrophoblast remains.
In the second half of pregnancy, the syncytiotrophoblast becomes thinner, the chorion villi are covered with Langerhans fibrinoid, an oxyphilic mass in the formation of which, along with the trophoblast, plasma coagulation products are involved. The structural and functional unit formed by the placenta is the cotyledon formed by the stem villi and its secondary and tertiary branches. The overall quality of the cotyledons is about 200, the weight of the placenta is 500.0, the thickness is 3 cm, the diameter is 20 cm.
The maternal part of the placenta is represented by the basal plate, connective tissue septa and lacunae. In the cavity, large lacunae are covered with villi. In the basal part of the endometrium, decidual cells are formed, these cells are large, their cytoplasms are rich in glycogen and the cells are arranged in groups. In places where the villi are attached to the maternal part of the placenta, namely on the surface of the basal layer, an amorphous substance (Rohr's fibrinoid) is found, which plays an important role in ensuring immunological homeostasis in the mother-fetus system.
Around the placenta is the endplate, which prevents the outflow of blood from the lacunae of the placenta.
The connection between mother and fetus is provided by neurohumoral mechanisms. Chemo-, mechano-, thermoreceptors are located in the endometrium, baroreceptors are contained in the wall of blood vessels. If you act on the receptors of the mucous membrane of the uterus, the mother's breathing, heartbeat and blood pressure change, and this is reflected in the component of the fetus. An important regulatory function is performed by thyroxine, corticosteroids, insulin and sex hormones. During pregnancy, adrenal hormones are intensively produced. At the very ………, the hormone chorionic gonadotropin is produced, and it enhances the work of adenocorticotropin hormones in the pituitary gland. In general, neurohumoral mechanisms begin to function at 2-3 months, during this period it performs the first motor reactions of the fetus. In the fetus, the synthesis of insulin is somewhat increased, this is necessary for its growth and development. If the mother suffers from diabetes, then the fetus has a compensatory increase in insulin production.
