Transplantation of organs and tissues. Reference
The questions of the essence, status and functions of bioethics, its genesis and historical evolution are considered. Interdisciplinary strategies and priorities of bioethics are identified. Moral, ethical, organizational and ethical aspects of life and death, transplantology, psychiatric care, the use of new genetic engineering technologies, manipulation of stem cells, human cloning, biosafety regulation and biomedical research involving humans and animals are analyzed.
For students, undergraduates, graduate students, teachers of medical, biological and other specialties of higher educational institutions, as well as all those who are interested in the problems of bioethics and the ethics of modern scientific research.
Blood transfusion as a scientific method arose from "blood magic". Doctor I. T. Spassky in 1834, taking part in a discussion of the method of blood transfusion during childbirth, he wrote: “The blood introduced into a vein in these cases (blood loss during childbirth) probably acts not so much in its quantity as in its life-giving properties, stimulating the activity of the heart and blood vessels. vessels".
Blood transfusion in the history of transplantation, as ensuring the transfer of life, is the logical and concrete historical beginning of the theory and practice of organ and tissue transplantation. The development of the modern problem of organ transplantation was prompted by the original discovery of Russian surgeons - transfusion cadaveric blood. This became the impetus for the creation of the first Soviet legislation on the right to remove blood, bones, joints, blood vessels and corneas from corpses.” The world's first department for the procurement of cadaveric blood at the Research Institute named after. N.V. Sklifassovsky was the prototype of the “organ bank” later created in the USA.
Medical historians determine stage of scientific transplantation itself XIX century. The first studies are associated with an Italian doctor Baronio and a German doctor Raizinder. The activities of the Russian surgeon and anatomist were of particular importance during this period. N. I. Pirogova on the creation of osteoplastic surgery.
At the initial stage of scientific transplantation itself, according to researchers G. S. Azarenko and S. A. Pozdnyakova, transplantation involved surgical removal of pathological tissue changes And autotransplantation. The next step was related to homotransplantation itself, i.e., replacing an organ that had lost its functionality with a new one from another organism of the same species (be it a kidney, heart, lungs). Significant milestones of this period are experimental kidney transplants A. Carrel; first xenotransplantation (transplantation within different classes and species) of a kidney (from a pig) Ullman(1902); The world's first cadaver kidney transplant (from a corpse) - allotransplantation Yu. Voronym(1931); first artificial heart implantation V. P. Demikhov(1937); first successful kidney transplants from living donors in the clinic D. Huma(1952); development of a working artificial heart model for clinical purposes W. Kolff And T. Akutsu(1957); Russia's first successful kidney transplant in a clinic B. Petrovsky(1965); first pancreas transplant V. Kelly And R. Lillihey(1966); first successful liver transplant T. Starzi(1967); world's first human-to-human heart transplant K. Bernard(1967); publication of the “Harvard” criteria for “brain death” (1967); organization of Eurotransplant for organ exchange based on histological compatibility tests V. Road(1967); creation of a research institute for organ and tissue transplantation of the USSR Academy of Medical Sciences G. Soloviev(1967); heart-lung transplantation B. Reitsom(1981); first successful lung transplant D. Cooper(1983); Russia's first successful heart transplant in a clinic V. Shumakov(1986); award D. Thomas Nobel Prize for work (1957–1989) on bone marrow transplantation (1990); adoption by the Supreme Council of the Russian Federation of the Law “On Transplantation of Human Organs and (or) Tissues” (1992). For the development of transplantation in Belarus, milestones such as the first kidney transplantation in the Republic of Belarus (1974), the first bone marrow transplantation in the Republic of Belarus (1993), and the first human stem cell transplantation in the Republic of Belarus (1997) are important.
Each type of transplantation differs from the other not only in the means and methods of transplantation, but also in ethical problems.
When transplanting an organ from living donor We are talking about the removal of only those organs or tissues without which the donor is able to continue a full life. Most often, a kidney is borrowed; operations are also performed to transplant part of the liver, etc. Of course, the donor takes on a certain risk associated, firstly, with the operation itself to remove the organ and, secondly, with the possibility of such undesirable consequences that may be detected months and even years after surgery.
The main problems encountered in living donor transplantation relate to the extent to which and how truly voluntary donor consent can be guaranteed. Consent given under duress cannot be considered voluntary. Consent in which the donor receives a reward, or, more simply put, sells his organ, is considered controversial. The commercial use of organs is prohibited, but, nevertheless, it is known that in a number of countries around the world this practice exists.
A whole range of moral and legal problems arise in connection with the removal and transplantation of organs and tissues from a deceased donor. First of all, it is necessary to clarify the concept of “deceased donor”. According to traditional criteria, death is declared when the heart and lungs stop functioning irreversibly. But what is the point of transplanting non-viable organs? And if these organs are viable, is it possible to recognize a person as dead? These questions arose immediately after the first heart transplant by a South African physician.
The use of organs from deceased donors became possible after a new criterion of death was legalized - brain death - after the onset of brain death, it is still possible to artificially maintain the autonomic functions of the body for several days, in particular, the functioning of the heart, lungs, and liver.
Transplantology confronts doctors with a morally difficult situation. On the one hand, they must do everything possible to save the patient’s life, on the other, the sooner manipulations to remove organs and tissues from his body begin, the greater the likelihood that their transplantation will be successful.
Be that as it may, special measures are taken to resolve the conflict between the need to fight for the life of a dying person and the need to quickly obtain organs for transplantation. According to the Law of the Republic of Belarus “On Transplantation of Human Organs and Tissues” (Article 10), removal of organs and tissues from a corpse for transplantation is possible only in the event of irreversible loss of brain function (brain death), recorded by a council of doctors.
Two legal models of organ retrieval from cadaveric donors: “presumption of consent” (unsolicited consent) and “requested (informed) consent” generate special discussions both among specialists and among everyone interested in the problems of transplantology.
The first legal model “presumption of consent” (unsolicited consent) assumes that the collection and use of organs from a corpse is carried out if the deceased during his lifetime did not express any objections to this, or if His relatives do not voice any objections. The absence of an expressed refusal is interpreted as consent, i.e., almost every person automatically becomes a donor after death, if he has not expressed his negative attitude towards organ transplantation. The “presumption of consent” is one of the two main legal models for regulating the procedure for obtaining consent for the removal of organs from deceased people.
The second legal model - “requested (informed) consent”, means that before his death the deceased clearly stated his consent to organ removal, or the family member clearly consents to the removal in that case when the deceased did not leave such a statement. The doctrine of “sought informed consent” presupposes some documented evidence of “consent.” An example of such a document are “donor cards” received in the United States by those who express their consent to donation. The doctrine of “sought (informed) consent” has been adopted in the health care legislation of the USA, Germany, Canada, France, and Italy.
Experts, as a rule, consider the principle of “presumption of consent” to be more effective, i.e., more consistent with the goals and interests of clinical transplantation, and the process of obtaining consent for organ removal is the main factor constraining the development (expansion) of donation.
Due to the cultural and historical characteristics of a number of countries, the direct appeal of doctors to the patient or his relatives (“requested consent”), as a rule, does not cause a response, but at the same time, the doctor’s decision on “unsolicited consent” in conditions of almost complete ignorance of the population on legal issues, organ donation may have further negative consequences for the official on the part of the relatives of the deceased.
In modern medicine, the process of expanding the indications for various types of transplants continues, which is a consequence of the “shortage of donor organs” (at any given time, approximately 8,000-10,000 people are waiting for a donor organ). This forces transplant specialists to look for additional sources of donor material (by determining the “moment of death”, “early recognition of brain death”, identifying “potential donors”, etc.).
Some guarantee of fairness in the distribution of donor organs is the inclusion of recipients in transplantation programs, which are formed on the basis of a “waiting list”, and where “equal rights” are implemented through the mechanism of selection based on medical indications, the severity of the recipient patient’s condition, and indicators of the immunological or genotypic characteristics of the donor. The programs also provide for the exchange of donor transplants between transplant associations. Well-known transplant centers include Eurotransplant, France-transplant, Scandiotransplant, Nord-Italy-transplant, etc. Assessing such a system of organ distribution as a guarantee against all sorts of abuses, recommendations for creating a “donor organ procurement system at the regional or national levels” are assessed as one of general ethical rules.
Liberal position bioethics in relation to transplantology comes down to the justification of transplantation as a new direction in medicine. The expansion of the practice of transplantation is associated with overcoming the “mythical attitude towards the heart as the seat of the soul” and a symbol of human identity, with overcoming the attitude towards death as a “transitional state”. The success of transplantology is possible only in the conditions of “a developed and prepared public opinion that recognizes the unconditionality of humanistic values on the entire range of issues in the practice of organ transplantation.” Among the unconditional humanistic values, voluntariness, altruism, and independence stand out.
The concept of “anatomical gifts” occupies a special place in liberal bioethics. By emphasizing donation, that is, the gratuitousness of anatomical gifts, liberal bioethics tries to overcome and eliminate possible economic motives for this act. The inclusion of any form of economic calculation means the loss of the value-significant, moral status of donation. However, liberal bioethics is also represented by attempts to combine economic benefit and humanity.
The humanity of the goals of transplantation is beyond doubt, but the means of its implementation, which involve economic relations of the “purchase and sale” type, including their forms, inevitably detract from its ethical meaning.
Conservative Christian position which was expressed by the professor of theology V. I. Nesmeloe, is based on the position that physical death is not so much a transition to a new life, but rather “the last moment of real life.” Understanding death as the last stage of life, as a personally significant event, the attitude towards which is the area of philanthropy, the area of the actual moral relationship between a deceased person and a living person, in particular, between a deceased patient and a doctor as a subject of moral relations. In Christianity, the dead body remains the space of the individual. Respect for the deceased is directly related to respect for the living. Loss of respect for the deceased, in particular, damage to the body, entails loss of respect for the living.
A separate specific area of organ and tissue transplantation today is neurotransplantation. The term “neurotransplantation,” leaving aside the aspects of autotransplantation of nerve trunks in restorative neurosurgery as a separate clinical area, refers to the transplantation of adrenomedullary adrenal tissue or embryonic brain tissue into the central nervous system (brain or spinal cord).
In the clinical range, such a transplantation can help a number of pathological conditions: Parkinson's disease, cerebral palsy, Huntington's chorea, brain degeneration, consequences of traumatic brain injury, apallic syndrome, epilepsy, microcephaly, multiple sclerosis, torsion spasm, oligophrenia, Down syndrome, schizophrenia , Alzheimer's disease, syringomyelia, traumatic spinal cord disease, pain syndromes.
In March 1983, Cuban doctors transplanted fetal brain tissue from aborted human fetuses aged 9–13 weeks into four Parkinson's patients. Subsequently, homotransplantation of embryonic mesencephalon tissue was carried out by neurosurgeons in many countries around the world. Only until 1991, about 100 such operations were performed. However, the use of embryonic human tissue as a transplant has encountered certain moral and ethical problems, which have become the subject of discussion at numerous congresses and symposia on transplantation. And even in those countries where there is no law on transplants, doctors perform them, guided by the international provisions adopted by the World Medical Association, especially the “Declaration of Helsinki: Recommendations for physicians conducting biomedical research on humans,” adopted by the 18th World Medical Assembly.
An important ethical document regulating transplantation is the “Declaration on Human Organ Transplantation” adopted by the 39th World Medical Assembly (Madrid, 1987), and the “Regulations on Fetal Tissue Transplantation” adopted by the 41st World Medical Assembly (Hong Kong, 1989) , regulates transplantation, including neurotransplantation, using fetal (embryonic) tissues.
Human-to-human organ transplantation is one of the most outstanding achievements of modern medicine.
Transplantology, as a science, has only in the last three decades moved from the experimental to the clinical stage of its development, but today the old dream of humanity about replacing damaged or diseased organs with new ones has left the realm of science fiction and is being developed in many industrialized countries.
To date, there are more than one and a half thousand transplant centers in the world, which have performed about four hundred thousand kidney transplants, more than forty thousand heart transplants, over fifty thousand liver transplants, and more than seventy thousand bone marrow transplants. Heart-lung transplants and pancreas transplants are also performed.
Naturally, the development of clinical transplantology, aimed at providing medical care to previously incurable patients, increases the need for donor organs, and their number is limited. At the same time, the number of patients waiting for an organ transplant is constantly increasing.
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Transplantation is the transfer of tissue or an entire organ from one organism to another in order to cure a serious disease. Transplantation and replacement of tissues within one organism is possible.
Such an important medical field as transplantation of human organs and tissues has begun to actively develop thanks to the study and understanding of the ongoing immunological processes in the body and their mechanisms. It is carried out in cases where it is impossible to save the life of a sick or injured person in any other way.
The possibility of organ transplantation was influenced by the active development of vascular surgery, as well as the discovery of the histocompatibility antigen. Transplantation of organs and tissues became possible thanks to immunosuppressive therapy, namely, the process of inhibiting the body's production of antibodies and immune cells.
Types of transplantation
Currently, modern medicine practices several types of this technique, namely:
Autotransplantation. In which tissue transplantation is performed within one individual.
- Homotransplantation. Transplantation is carried out from one organism to another, but within individuals of the same species.
- Heterotransplantation. An organ or tissue is transplanted from a donor to a recipient when they belong to different species but the same genus.
- Xenotransplantation. A transplant operation where the donor and recipient are from different genera, families, and sometimes orders.
Transplanted tissues, organs
In clinical transplantology, autotransplantation is more often practiced. This is a type of transplantation in which there is no tissue incompatibility. The most common transplants are skin, fat tissue, and muscle connective tissue (fascia). Transplantation of cartilage, pericardium, as well as bone fragments and nerves is also often performed.
Speaking from reconstructive surgery, vein transplantation is often practiced here. For example, when transplanting the great saphenous vein of the thigh, resected arteries are used, namely the internal iliac and deep femoral artery.
With the development of microsurgical practice, with the advent of the possibility of using modern medical devices and technology, the importance of autotransplantation has become even greater. Transplantations are actively carried out on the vascular, and often nerve, connections of the skin. Skin and musculocutaneous flaps are transplanted. Musculoskeletal fragments and individual muscles are transplanted.
Modern clinical transplantology actively practices toe to hand transplants. Surgeons transplant the greater omentum to the lower leg area, transfer segments of the intestine, and perform esophageal plastic surgery.
If we talk about organ autotransplantation, the most common operation is kidney transplantation. Indications include extensive ureteral stenosis, as well as extracorporeal reconstruction of the renal hilum vessels.
Tissue allotransplantation operations are increasingly being carried out: transplantation of the cornea, bone marrow and bones.
Transplantation of b-cells located in the pancreas is performed less frequently. This operation may be indicated for diabetes mellitus. Also, hepatocyte transplantation is not very often performed when treating acute liver failure.
Transplant problems
This very important, necessary medical area, which saves the lives of almost hopeless patients, has a number of important problems. These include:
Immunological donor selection. The wrong choice can cause future rejection by the body and immune system of the recipient of the transplanted organ. To prevent this, the patient must take immunosuppressive drugs for the rest of his life. However, these drugs always have contraindications and side effects, which sometimes lead to the death of the patient.
Ethical and legal problems. There is much debate about the ethics of transplanting any vital organ. The issue of removing any organs from living people or corpses is very hotly discussed.
Transplantation still poses a great risk to life. Therefore, until now, many types of very important, necessary operations belong to the category of medical experiments and cannot enter clinical practice.
Risk groups, contraindications
The main contraindication to organ transplantation is the serious genetic differences between the donor and the recipient. There are contraindications for kidney transplantation. For example, it cannot be performed on patients with acute infectious or inflammatory diseases. It should not be done during exacerbation of chronic diseases.
The risk group includes patients with cancer who have malignant neoplasms within a short period of time after radical treatment. For the vast majority of malignant tumors, after treatment, at least two years must pass before transplant surgery.
Those patients who have undergone transplant surgery must strictly adhere to a certain regimen and follow medical instructions throughout their lives.
1. Transplantation of human organs and tissues from a living donor or a corpse can be used only if other treatment methods cannot ensure the preservation of the life of the patient (recipient) or the restoration of his health.
2. Removal of organs and tissues for transplantation (transplantation) from a living donor is permissible only if, according to the conclusion of the medical commission of a medical organization with the involvement of relevant medical specialists, drawn up in the form of a protocol, significant harm will not be caused to his health.
3. Removal of organs and tissues for transplantation (transplantation) is not permitted from a living person who has not reached the age of eighteen (except for cases of bone marrow transplantation) or who has been recognized as legally incompetent.
4. Removal of organs and tissues for transplantation (transplantation) is permitted from a living donor with his informed voluntary consent.
5. Transplantation (transplantation) of human organs and tissues is permitted with the informed voluntary consent of an adult capable recipient, and in relation to a minor recipient, as well as in relation to a recipient recognized as incompetent in accordance with the procedure established by law, if due to his condition he is not able to give informed voluntary consent , - in the presence of informed voluntary consent of one of the parents or other legal representative, given in the manner established by the authorized federal executive body.
6. An adult capable citizen may orally, in the presence of witnesses or in writing, certified by the head of a medical organization or notarized, express his will of consent or disagreement to the removal of organs and tissues from his body after death for transplantation (transplantation) in the manner, established by the legislation of the Russian Federation.
7. In the absence of an expression of will of an adult legally capable deceased, the right to declare his or her disagreement with the removal of organs and tissues from the body of the deceased for transplantation (transplantation) has the spouse, and in his (her) absence - one of the close relatives (children, parents, adopted children, adoptive parents, siblings, grandchildren, grandparents).
8. In the event of the death of a minor or a person recognized as legally incompetent in accordance with the established procedure, the removal of organs and tissues from the body of the deceased for transplantation is permitted on the basis of the requested consent of one of the parents.
9. Information about the existence of the will of the citizen specified in part 6 of this article, other persons in cases provided for in parts 7 and this article, expressed orally or in writing, certified in the manner provided for in part 6 of this article, is entered into the citizen’s medical documentation.
10. Removal of organs and tissues for transplantation (transplantation) from a corpse is not allowed if the medical organization at the time of removal in the manner established by the legislation of the Russian Federation is notified that this person is alive or other persons in the cases specified in parts 7 and of this article, declared their disagreement with the removal of his organs and tissues after death for transplantation.
11. Organs and tissues for transplantation (transplantation) may be removed from a corpse after death is declared in accordance with Article 66 of this Federal Law.
12. If it is necessary to conduct a forensic medical examination, permission to remove organs and tissues from a corpse for transplantation (transplantation) must be given by a forensic medical expert with notification of the prosecutor.
13. Forced removal of human organs and tissues for transplantation (transplantation) is not permitted.
Organ and tissue transplantation (synonymous with organ and tissue transplantation). Transplantation of organs and tissues within one organism is called autotransplantation, from one organism to another within the same species - homotransplantation, from an organism of one species to an organism of another species - heterotransplantation.
Transplantation of organs and tissues with subsequent engraftment of the graft is possible only with biological compatibility - similarity of antigens (see) that make up the tissue proteins of the donor and recipient. In its absence, the donor's tissue antigens cause the production of antibodies in the recipient's body (see). A special protective process occurs - a rejection reaction, followed by the death of the transplanted organ. Biological compatibility can only occur with autotransplantation. It is not present in homo- and heterotransplantation. Therefore, the main task when performing organ and tissue transplantation is to overcome the barrier. If in the embryonic period the body is exposed to some antigen, then after birth this body no longer produces antibodies in response to repeated administration of the same antigen. Active tolerance (tolerance) to the foreign tissue protein occurs.
The rejection reaction can be reduced by various influences that suppress the functions of the systems that develop immunity against the foreign organ. For this purpose, so-called immunosuppressive substances are used - imuran, cortisone, antilymphocyte serum, as well as general x-ray irradiation. However, this suppresses the body’s defenses and the function of the hematopoietic system, which can lead to serious complications.
Currently, autotransplantation of skin is widely used to close post-burn defects; bones, cartilage, etc. are successfully transplanted. Homotransplantation is used in transplantation of the cornea and cartilage. Kidney transplantation from one person to another is becoming increasingly common. The greatest chances for engraftment occur in cases where the tissues of the donor and recipient are similar in their antigenic composition. The most ideal conditions exist for identical twins. However, they are transplanted not only from living persons, but also from corpses. The selection of a donor is important, carried out by determining compatibility with erythrocyte and leukocyte blood antigens. There are a number of other tests that allow you to determine the degree of similarity between the organs and tissues of the donor and recipient.
Indications for a kidney transplant arise when there is a sharp impairment of their function due to a serious illness (polycystic disease, etc.). Many kidney transplants have already been performed, and some patients live after the operation for more than three years and are fully able to work.
In 1967, Barnard and his colleagues performed the world's first successful homotransplantation of the human heart. Further success in organ transplantation is associated with finding ways to overcome the barrier of tissue incompatibility.
ORGAN TRANSPLANT
removal of a viable organ from one individual (donor) and transfer it to another (recipient). If the donor and recipient belong to the same species, they speak of allotransplantation; if to different ones - about xenotransplantation. In cases where the donor and patient are identical twins or representatives of the same inbred line of animals, we are talking about isotransplantation. Xenografts and allografts, unlike isografts, are subject to rejection. The mechanism of rejection is undoubtedly immunological, similar to the body’s reaction to the introduction of foreign substances. Isografts taken from genetically related individuals are usually not rejected. In experiments on animals, almost all vital organs were transplanted, but not always with success. Vital organs are those without which preserving life is almost impossible. Examples of such organs are the heart and kidneys. However, a number of organs, such as the pancreas and adrenal glands, are usually not considered vital, since the loss of their function can be compensated for by replacement therapy, in particular the administration of insulin or steroid hormones. The person was transplanted kidneys, liver, heart, lungs, pancreas, thyroid and parathyroid glands, cornea and spleen. Some organs and tissues, such as blood vessels, skin, cartilage or bone, are transplanted to create a scaffold on which new recipient tissues can form; these are special cases that are not considered here. Bone marrow transplantation is also not considered here. In this article, transplantation refers to the replacement of an organ if it itself or its function is irreversibly lost as a result of injury or illness.
REJECTION REACTION
According to modern concepts, the set of immunological reactions involved in the rejection process occurs under conditions when some substances on the surface or inside the cells of the transplanted organ are perceived by immune surveillance as foreign, i.e. different from those present on the surface or inside the body's own cells. These substances are called histocompatibility antigens. An antigen in the broad sense of the word is a “non-self”, foreign, substance that can stimulate the body to produce antibodies. Antibody is a protein molecule produced by the body during the immune (protective) reaction, designed to neutralize a foreign substance that has entered the body.
(see also IMMUNITY). The structural features of histocompatibility antigens are determined by genes in much the same way as an individual's hair color. Each organism inherits from both parents different sets of these genes and, accordingly, different antigens. Both paternal and maternal histocompatibility genes work in the offspring, i.e. he exhibits histocompatibility antigens of both parents. Thus, the parental histocompatibility genes behave as codominant, i.e. equally active alleles (gene variants). Donor tissue that carries its own histocompatibility antigens is recognized by the recipient's body as foreign. The characteristic histocompatibility antigens inherent in each person are easy to detect on the surface of lymphocytes, so they are usually called human lymphocyte antigens (HLA, from the English human lymphocyte antigens). A number of conditions are required for a rejection reaction to occur. Firstly, the transplanted organ must be antigenic for the recipient, i.e. have foreign HLA antigens that stimulate the immune response. Secondly, the recipient's immune system must be able to recognize the transplanted organ as foreign and provide an appropriate immune response. Finally, thirdly, the immune response must be effective, i.e. reach the transplanted organ and in any way disrupt its structure or function.
WAYS TO COMBAT REJECTION
There are several ways to overcome the difficulties that arise on the way to organ transplantation: 1) depriving the graft of antigenicity by reducing the number (or completely eliminating) foreign histocompatibility antigens (HLA), which determine the differences between the tissues of the donor and recipient; 2) limiting the availability of transplant HLA antigens for recipient recognition cells; 3) suppression of the recipient’s body’s ability to recognize the transplanted tissue as foreign; 4) weakening or blocking the recipient’s immune response to the HLA antigens of the transplant; 5) reducing the activity of those immune response factors that cause damage to the graft tissue. Below we will consider those possible approaches that are most widespread.
Tissue typing. As with a blood transfusion (which can also be considered an organ transplant), the more “compatible” the donor and recipient are, the higher the likelihood of success, since the transplant will be less “foreign” to the recipient. Great strides have been made in assessing this compatibility, and it is now possible to identify different groups of HLA antigens. Thus, by classifying, or “typing,” the antigenic set of lymphocytes of the donor and recipient, it is possible to obtain information about the compatibility of their tissues. There are seven different histocompatibility genes known. All of them are located close to each other on the same DNA section and form the so-called. major histocompatibility complex (MHC, from English - major histocompatibility complex) of one (6th) chromosome. The location, or locus, of each of these genes is designated by a letter (A, B, C, and D, respectively; locus D carries 4 genes). Although in an individual each gene can be represented by only two different alleles, there are many such alleles (and, accordingly, HLA antigens) in the population. Thus, 23 alleles were identified in locus A, 47 in locus B, 8 in locus C, etc. HLA antigens encoded by the genes of the A, B and C loci are called class I antigens, and those encoded by the genes of the D locus are called class II antigens (see diagram). Class I antigens are chemically similar but differ significantly from class II antigens. All HLA antigens are present on the surface of different cells in different concentrations. Tissue typing focuses on identifying antigens encoded by the A, B, and DR loci.
Because histocompatibility genes are located close to each other on the same chromosome, each person's MHC region is almost always inherited in its entirety. The chromosomal material of each parent (half of the total material inherited by the offspring) is called a haplotype. According to Mendel's laws, 25% of descendants must be identical in both haplotypes, 50% must be identical in one of them, and 25% must not have the same haplotype. Siblings (brothers and sisters), identical in both haplotypes, have no differences in the histocompatibility system, therefore organ transplantation from one of them to another should not cause any complications. Conversely, since the likelihood of unrelated individuals possessing both identical haplotypes is extremely low, a rejection reaction should almost always be expected when organs are transplanted from one such individual to another. In addition to HLA antigens, typing also determines antibodies in the recipient’s blood serum to these donor antigens. Such antibodies may appear as a result of a previous pregnancy (under the influence of the husband’s HLA antigens), previous blood transfusions or previous transplantations. Detection of these antibodies is of great importance, since some of them can cause immediate transplant rejection. Immunosuppression consists of reducing or suppressing (depression) the recipient's immunological response to foreign antigens. This can be achieved, for example, by preventing the action of the so-called. interleukin-2 - a substance secreted by T-helper cells (helper cells) when they are activated during an encounter with foreign antigens. Interleukin-2 acts as a signal for the multiplication (proliferation) of T helper cells themselves, and they, in turn, stimulate the production of antibodies by B cells of the immune system. Among the many chemical compounds that have potent immunosuppressive effects, azathioprine, cyclosporine, and glucocorticoids are especially widely used in organ transplantation. Azathioprine appears to block metabolism in cells involved in the rejection reaction, as well as in many other dividing cells (including bone marrow cells), acting, in all likelihood, on the cell nucleus and the DNA it contains. As a result, the ability of T-helper and other lymphoid cells to proliferate is reduced. Glucocorticoids - steroid hormones of the adrenal glands or similar synthetic substances - have a powerful, but nonspecific anti-inflammatory effect and also inhibit cell-mediated (T-cell) immune reactions. A strong immunosuppressive drug is cyclosporine, which acts rather selectively on T helper cells, interfering with their response to interleukin-2. Unlike azathioprine, it does not have a toxic effect on the bone marrow, i.e. does not interfere with hematopoiesis, but damages the kidneys. Biological factors affecting T cells also suppress the rejection process; these include antilymphocyte globulin and anti-T-cell monoclonal antibodies. Due to the pronounced toxic side effects of immunosuppressants, they are usually used in one or another combination, which makes it possible to reduce the dose of each drug, and thereby its undesirable effect. Unfortunately, the direct effect of many immunosuppressive drugs is not specific enough: they not only inhibit the rejection reaction, but also disrupt the body’s defenses against other foreign antigens, bacterial and viral. Therefore, a person receiving such drugs is defenseless against various infections. Other methods of suppressing the rejection reaction are x-rays of the recipient's entire body, his blood, or the organ transplant site; removal of the spleen or thymus; flushing of lymphocytes from the main lymphatic duct. Due to ineffectiveness or complications caused, these methods are practically not used. However, selective X-ray irradiation of lymphoid organs has proven effective in laboratory animals and is in some cases used in human organ transplants. Blood transfusions also reduce the likelihood of allograft rejection, especially when using whole blood from the same donor from whom the organ is taken. Since identical twins are an exact likeness of each other, they have natural (genetic) tolerance, and there is no rejection when organs from one of them are transplanted to the other. Therefore, one of the approaches to suppressing the rejection reaction is to create acquired tolerance in the recipient, i.e. a long-term state of unresponsiveness to the transplanted organ. It is known that artificial tolerance can be created in animals by implanting foreign tissue in the early stages of their embryonic development. When the same tissue is later transplanted into such an animal, it is no longer perceived as foreign and rejection does not occur. Artificial tolerance appears to be specific to the donor tissue that was used to reproduce the condition. It has now also become clear that acquired tolerance can be created even in adult animals. It is possible that such approaches can be applied to humans.
HISTORICAL ASPECTS AND PERSPECTIVES
Organ transplantation was one of the most outstanding and promising scientific achievements of the 20th century. Extending life by replacing damaged organs, which previously seemed like a dream, has become a reality. Let us briefly consider the main advances in this area and the current state of the problem.
Kidney transplant. It is not surprising that special attention is paid to the kidney in the problem of organ transplantation. The kidneys are a paired organ, and one of them can be removed from a living donor without causing chronic renal impairment. In addition, usually one artery approaches the kidney, and blood flows from it through one vein, which greatly simplifies the method of restoring its blood supply to the recipient. The ureter, through which urine produced in the kidney flows, can be connected in one way or another to the recipient’s bladder. The first kidney transplant in animals was carried out in 1902 by the Austrian researcher E. Ullmann. A significant contribution to the problem of kidney transplantation and suturing of blood vessels was then made by A. Carrel, who worked at the Rockefeller Institute for Medical Research (currently Rockefeller University) in New York. In 1905, Carrel, together with his collaborator K.K. Guthrie, published the most important work concerning heterotopic and orthotopic (i.e., in an unusual and ordinary place) kidney transplantation in a dog. Scientists in the USA and Europe continued to experiment on animals, but serious attempts to transplant a kidney into humans began only in 1950. At this time, a group of doctors in Boston at the P.B. Brigham Hospital performed a number of kidney transplants, which aroused considerable interest throughout the world and marked the real beginning organ transplantation in humans. Almost simultaneously, a group of Parisian doctors and a little later surgeons in other countries also began transplanting a kidney to a person. Although the recipients were not receiving anti-rejection drugs at the time, one of them survived the transplant for almost 6 months. In these first operations, the kidney was transplanted onto the thigh (heterotopic transplantation), but then methods were developed to transplant it to a more natural place for it - into the pelvic cavity. This technique is still generally accepted today. In 1954, the first kidney transplant from an identical twin was performed at Brigham Hospital. In 1959, they also performed a kidney transplant from a fraternal twin and for the first time successfully treated the rejection reaction with drugs, showing that the onset of the reaction is not irreversible. Also in 1959, a new approach was applied. It was discovered that a number of drugs that block cellular metabolism, called antimetabolites (in particular, azathioprine), have a powerful effect that suppresses the immune response. Specialists in the field of tissue transplantation, especially kidneys, quickly took advantage of these data, which marked the beginning of the era of immunosuppressive drugs in transplantation. Using immunosuppressive drugs, many clinics have achieved significant success in prolonging the function of human kidney transplants, and in 1987, for example, almost 9,000 such transplants were performed in the United States alone, and many more in the world. In approximately a quarter of currently performed kidney transplants, the donors are living close relatives of the patient who voluntarily donate one of their kidneys. In other cases, kidneys are used from recently deceased people, although occasionally from those for whom, for some reason, removal is indicated, or from volunteers who are not relatives of the recipient. Short-term positive results from kidney transplantation are usually observed in more than 75% of patients who undergo this operation due to irreversible loss of renal function. Such a high result is achieved through tissue typing and the use of combinations of immunosuppressive agents, especially cyclosporine and glucocorticoids. Success is now assessed by the duration (one or several years) of recipient survival or graft function. Although many patients live and remain healthy for more than 10 years after a kidney transplant, the exact period of survival of the graft is unknown. More than 90% of patients currently survive for at least a year after transplantation. The viability of the transplant depends on who the kidney was taken from: if it is from a relative identical in HLA antigens, the probability of engraftment and functioning of the transplant is 95%; if a living relative has a semi-identical (one haplotype matches) set of HLA antigens, then the probability of engraftment is 80-90%; if a cadaveric kidney is used, this probability is reduced to 75-85%. Currently, repeated kidney transplants are performed, but the likelihood of preserving graft function in these cases is lower than during the first operation.
Liver transplant. Although experiments on liver transplantation have been carried out since the mid-1960s, transplantation of this organ into humans began to be carried out relatively recently. Since the liver is an unpaired organ, the only source of transplant can be only the corpses of recently healthy people; the exception is children: there is experience in transplanting part of the liver from a living donor (one of the parents). The technical problems associated with anastomoses (i.e. connections between vessels and ducts) are also more complex than with kidney transplantation; In this case, the use of immunosuppressive drugs may also be less safe. There are no technical means yet, similar to an artificial kidney, that could support the life of the recipient before a liver transplant or in the immediate postoperative period, while the transplant has not yet begun to function normally. Nevertheless, the use of new immunosuppressive drugs, in particular cyclosporine, has made it possible to achieve significant progress in liver transplantation: within 1 year, grafts function successfully in 70-80% of cases. In a number of patients, liver allografts have been functioning for 10 years.
Heart transplant. The first successful heart transplant was performed by Dr. K. Barnard in Cape Town (South Africa) in 1967. Since then, this operation has been performed many times in a number of countries. In general, it is associated with the same problems as with transplantation of other unpaired organs (in particular the liver). But there are also additional ones. Among them is the high sensitivity of the heart to a lack of oxygen, which limits the shelf life of a donor heart to only a few hours. In addition, due to a lack of material for transplantation, many patients in need of it die before a suitable donor can be found. However, there are good prospects for solving these problems. Devices have been created that temporarily support the functioning of the heart and increase the life expectancy of a patient awaiting a heart transplant. Modern methods of immunosuppression ensure one-year graft survival in 70-85% of cases. More than 70% of patients who have undergone a heart transplant regain their ability to work.
Transplantation of other organs. Lung transplantation is particularly difficult because the organ is exposed to air and is therefore easily infected; In addition, transplantation of both lungs is hampered by poor tracheal engraftment. However, in recent years, methods have been developed to transplant a single lung or a heart/lung unit. The latter method is used most often, as it provides the best engraftment and complete removal of the affected lung tissue. Successful transplant functioning within a year is observed in 70% of recipients. A pancreas transplant is performed to stop the development of severe complications of diabetes. In cases where kidney failure is one of the complications, pancreas and kidney transplantation are sometimes performed simultaneously. In recent years, the number of successful pancreas transplants has increased significantly and reaches 70-80% of cases. A method of transplanting not the entire gland, but only its islet cells (which produce insulin) is also being tested. The method involves introducing these cells into the umbilical vein, i.e., apparently, it will avoid abdominal surgery. Brain transplantation currently faces insurmountable difficulties, but transplantation of individual brain segments in animals has already been carried out.
Artificial substitutes. An important factor in the ongoing progress in the field of kidney transplantation is the improvement of methods for artificial replacement of renal function, i.e. development of an artificial kidney (see also KIDNEYS). The ability to long-term maintain the life and health of the future recipient (suffering from severe renal failure, which would lead to death) greatly determined the success of kidney transplantation. These two methods, dialysis and transplantation, complement each other in the treatment of kidney failure. Likewise, the development of permanent or temporary implantable artificial heart devices that can assist or replace the recipient's own heart should alleviate many of the problems associated with heart transplantation (see also HEART). However, replacing such a complex organ as the liver with an artificial device will
apparently unrealistic.
Use of animal organs. The difficulties associated with preserving cadaveric organs have led to consideration of the possible use of xenografts, such as organs from baboons and other primates. However, this creates a more powerful genetic barrier than with a human organ transplant, which requires much higher doses of immunosuppressive drugs to suppress the rejection reaction and, in turn, can lead to the death of the recipient from infection. There is still a lot of work to be done before such operations can begin.
Organ preservation. In any vital organ intended for transplantation, if it is deprived of blood and oxygen for a long time, irreversible changes occur that prevent its use. For the heart this period is measured in minutes, for the kidney - in hours. A huge amount of effort goes into developing ways to preserve these organs after they are removed from the donor's body. Limited but encouraging success has been achieved by cooling the organs, supplying them with pressurized oxygen, or perfusing them with cooled tissue-preserving buffer solutions. A kidney, for example, can be preserved in such conditions outside the body for several days. Organ preservation increases the time available for selecting a recipient through compatibility testing and ensures the suitability of the organ. Currently existing regional, national and even international programs are procuring and distributing cadaveric organs to ensure their optimal use. However, there are not enough organs for transplantation. It is hoped that as society becomes more aware of the need for such organs, the shortage will decrease and transplants can be performed more quickly and efficiently.
Collier's Encyclopedia. - Open Society. 2000 .
See what “ORGAN TRANSPLANT” is in other dictionaries:
Transplantology is a branch of medicine that studies the problems of organ transplantation, such as kidneys, liver, heart, bone marrow, etc. Transplantology has several areas: xenotransplantation, allotransplantation, artificial organs... ... Wikipedia
organ transplant- ▲ organ replacement (animal) transplantation. heterotransplantation. homotransplantation. heteroplasty. homoplasty. keratoplasty. organ replacement surgeries... Ideographic Dictionary of the Russian Language
KIDNEY TRANSPLANT, see ORGAN TRANSPLANT...
HEART TRANSPLANT, see ORGAN TRANSPLANT... Scientific and technical encyclopedic dictionary
See Transplantation... Big Encyclopedic Dictionary
See Transplantation. * * * TISSUE AND ORGAN TRANSPLANTATION TISSUE AND ORGAN TRANSPLANTATION, see Transplantation (see TRANSPLANTATION) ... Encyclopedic Dictionary
