Influence of undifferentiated connective tissue dysplasia on the course of the diseases of biliary tract of young age persons

Reznichenko O.G.; Pylypenko N.O.; Gridnieva S.V.

Реферат

ЗДОРОВЬЕ ЧЕЛОВЕКА КАК ВЫСШАЯ СОЦИАЛЬНАЯ ЦЕННОСТЬ Орлюк О.П., Малюга Л.Ю., Синева Л.М., Зозуля Д.В.

Статья посвящена вопросу здоровья как высшей социальной ценности. Аргументировано, что с правовой точки зрения объектом права на здоровье является неимущественное благо - «здоровье физического лица», а собственное здоровье человека является объектом нематериального мира. Нормы различных отраслей права (конституционного,

административного, финансового, уголовного, гражданского права) так или иначе регулируют вопросы, связанные с реализацией, охраной и защитой права на здоровье. Тем самым еще раз подчеркивается конституционное положение о том, что здоровье является одной из самых высоких социальных ценностей в нашем государстве. Отмечается, что здоровье должно быть стратегическим направлением жизни человека, с помощью чего обеспечивается повышение жизнестойкости организма, естественной сопротивляемости организма стрессовым явлениям и депрессивным состояниям. И здесь следует учитывать, что состояние здоровья определяется количественными и качественными медицинскими показателями. Отсутствие таких показателей, нежелание лица знать их, не означает, что человек является здоровым. О здоровье надо думать, о нем следует заботиться. Но это уже вопрос субъективного отношения лица к самому себе. В то же время, лицо должно осознавать, что своим здоровьем можно не заниматься (в случае возникновения каких болезней - не лечиться), до тех пор, пока это не вредит интересам других.

Ключевые слова: здоровье человека, благополучие, идеал здоровья, социальная ценность.

Стаття надшшла 10.02.19 р.

HUMAN HEALTH AS THE HIGHEST SOCIAL VALUE Orlyuk OP, Malyuha LY, Sinyova LM, Zozulya DV.

The article deals with the issue of human health as the highest social value. It is argued that, from a legal point of view of health, more precisely, the object of the right to health is the non-material benefit of "health of an individual", given that health is the object of the intangible world. The rules of the various branches of law (constitutional, administrative, financial, criminal, civil law) in one way or another regulate issues related to the implementation, protection and protection of the right to health. This reaffirms the constitutional position that health is one of the highest social values in our country. It is emphasized that health should be a strategic direction of human life, which helps to increase the vitality of the body, the body's natural resistance to stress and depressive states. The health is determined by quantitative and qualitative medical indicators. The absence of such indicators, the reluctance or identification of a person as unnecessary to know them, does not mean that the person is healthy. Health needs to be thought of and should be taken care of. But this is a question of subjective attitude of the person to himself. At the same time, the person should be aware that one's own health can not be taken care of (in the event of any illness - not treated), as long as it does not harm the interests of others.

Keywords: human health, well-being, ideal of health, social value.

Рецензент Голованова 1.А.

DOI 10.26724/2079-8334-2019-3-69-136-141 UDC 616-018.2-007.17

O.G. Re/nichenko, N.O. Pylypenko, S.N . Gridnieva N.N. I\:ir;i/iii l\li;M'ki\ N;iti°ii;il I шмтч!^ Miiirlvix

INFLUENCE OF UNDIFFERENTIATED CONNECTIVE TISSUE DYSPLASIA ON THE COURSE OF THE DISEASES OF BILIARY TRACT OF YOUNG AGE PERSONS

e-mail: alex.p.24inches@gmail.com

Connective tissue, which makes 50-80% of the body weight, plays a special role in the human body. Due to the main component of the connective tissue - elastin - the vascular walls, the heart and the lungs tissues, the intestinal wall have elastic properties. Undifferentiated CTD (UCTD) is diagnosed if a set of phenotypic symptoms in a patient does not match any of the differentiated diseases. The frequency of UCTD detection among young people reaches 80%. The high prevalence of the UCTD syndrome (66.9%) is determined in patients with functional diseases of the biliary tract, affecting the clinical manifestations of these diseases. Patients with severe UCTD display the highest frequency of the biliary tract motor disorders, as well as asthenic syndrome and vegetative dysfunction. In addition, with the UCTD syndrome in patients with functional disorders of the cardiovascular system, functional disorders of the biliary tract are observed in 43% of cases. Thus, the high prevalence of the UCTD syndrome indicates the need for early detection of the connective tissue dysplasia signs in young people in order to timely perform a set of preventive and therapeutic measures.

Key words: syndrome of undifferentiated connective tissue dysplasia, functional state of the biliary and cardiovascular system, diagnosis, young age.

The work is a fragment of the research project "Remodeling of elastic-tissue structures in early diagnosis of heart failure with undifferentiated dysplasia of connective tissue in young persons with metabolic disorders ", state registration No. 0116 U002934.

A special feature of a modern patient is polymorbidity, when one patient has several diseases simultaneously. Concomitant pathology affects the course, clinical picture and consequences of the disease as a whole. Connective tissue, which makes 50-80% of body weight, plays a special role in the human body [6, 7, 9]. Due to the main component of the connective tissue - elastin (consisting of protein glycans, glucoproteins and minerals) - vascular walls, heart and lungs tissue, intestinal wall have elastic properties. In UCTD an abnormal structure of this protein is detected.

Most authors distinguish differentiated and undifferentiated CTD. Differentiated CTDs are characterized by a definite type of inheritance, a clearly marked clinical picture (Marfan and Ehlers-Danlos syndromes, imperfect osteogenesis, and fragile skin syndrome, etc.). Undifferentiated CTDs (UCTD) are diagnosed if a set of phenotypic features in a patient does not fit into any of the differentiated diseases. It is a genetically and phenotypically heterogeneous group, which is the basis for the various chronic diseases formation. Multisystemacity of lesions in UCTD is due to the fact that the teratogenic germinal period for many organs and systems is roughly the same (the 7th-12th weeks). Due to the widespread presence of connective tissue and its generalized defect, signs of the connective tissue's "weakness" are detected in many organ systems. In this regard, the doctor who is not familiar with the variety of CTD clinical manifestations, with certain symptoms and / or syndromes, does not see a systemic CT defect that makes the patient apply to different specialists [1].

According to some data, the frequency of UCTD detection among young people reaches 80%. Despite the variety of UCTD clinical manifestations in various organs and systems, the most studied and clinically significant are its manifestations in the cardiovascular system. UCTD is known to be often accompanied by changes in the heart connective tissue carcase and heart valve apparatus - minor cardiac abnormalities (MCA). AS of today, several MCA variants are described, including both well-studied abnormalities - mitral valve prolapse (MVP), dilatation of the aorta root and the pulmonary artery, and abnormalities, the clinical and prognostic significance of which is not still completely understood, such as abnormal trabeculae of the left ventricle, the atrial septum aneurysm, asymmetric tricuspid aortic valve, etc. [2].

Over the past ten years, the functional pathology morbidity of the biliary system has grown by 35.3% in Ukraine. In this situation, the damage of the gallbladder (GB) and bile ducts (BD) develops mainly in young women. Among the typical visceral markers of the CTD, along with the MCA, include the GB abnormalities (folded and constricted gallbladder, S-shaped and spherical deformation) [4]. Diseases of the biliary tract, including those of functional nature, occupy a significant place among diseases of the gastrointestinal tract. The functional pathology of the gastrointestinal tract of any localization is characterized by the presence of chronic recurrent symptoms that can not be explained by structural or biochemical changes. The wide prevalence of both the biliary tract functional pathology and the UCTD syndrome, as well as a small number of publications devoted to UCTD with the biliary system's pathology, make this study relevant.

Modern literature does not contain complete reflection of simultaneous changes in these pathological conditions (diseases).

The purpose of the work was to diagnose functional state of the biliary and cardiovascular systems in young people with syndrome of undifferentiated connective tissue dysplasia (UCTD).

Materials and methods. Within the framework of the university-wide "Students' Health" program, which is being carried out at V.N. Karazin KhNU, on the basis of the General Practice-Family Medicine Department at the Faculty of Medicine, 488 students aged 16 to 27 years old (mean age 21.4 ± 5.3 years) were questioned, among them 351 women and 137 men (ratio 3: 1).

The analysis included 175 patients with functional diseases of the biliary tract, of which 122 cases were diagnosed with the biliary type sphincter of Oddi dysfunction, 40 patients with the pancreatic type sphincter of Oddi dysfunction, and 13 cases of isolated gallbladder dysfunction. The mean age of patients was 20.5 ± 4.7 years.

The UCTD diagnosis was based on a combination of phenotypic manifestations and internal organs changes in combination with their morphofunctional features. For verification of the UCTD syndrome the presence of the following phenotypic characteristics was taken into account: deformation of the spine (kyphosis, scoliosis), winged scapula, arachnodactylia, hypermobility of joints, flat feet, hyperextensibility of skin, chest deformity, hypoplasia of the breast glands, blue sclera, Gothic palate, high palate and others [3, 8]. Visceral UCTD manifestations were detected by means of ultrasound examination of the heart and abdominal organs.

In the diagnosis of the biliary tract functional diseases, we focused on the International Recommendations (Rome III Diagnostic Criteria), according to which the main symptom of the biliary tract functional disorders is biliary pain in the absence of organic diseases in patients [5]. To evaluate the motor-evacuation function of GB, the method of dynamic echo-cholecystography, using Boyden's cholekinetic breakfast, was used. Ultrasound study of GB, biliary tract and liver was carried out by the method of continuous dynamic scanning using the SL-450 "Siemens" scanner in real time. This study permits to identify motor disturbances of GB by ultrasound control with dynamic observation of its contraction rhythm at standardized time intervals (on the 15th, 30th, 45th and 60th minutes of the study), as well as to determine variants of GB dyskinesia.

An echocardiographic study was performed using the "Sonos 1500" apparatus produced by "Hewlett Packard".

Statistical processing was performed using the SPSS 9.0 software package. Quantitative indices are presented in the form X ± o, where X is the mean value, o - standard deviation of the mean. For qualitative indices, the absolute number and / or relative value in percent was indicated. To check the coincidence of the quantitative indices distribution, the Kolmogorov-Smirnov criterion of agreement was used, for the paired inter-group comparison - Mann-Whitney U-test criterion, for the general intergroup comparison - Kruskal-Wallis H-test criterion was used. The correlation coefficients of Pearson and Spearman correlations were used to determine the relationship between the studied features. The critical significance level in checking statistical hypotheses (p) was assumed to be 0.05. The odds ratio (OR) at confidence intervals (95% CI) was calculated by conjugation tables. The confidence intervals (CIs) given in the work were constructed for the confidence probability with p = 95%.

Results of the study and their discussion. According to the results of the study, 66.9% of patients with functional diseases of the biliary tract were diagnosed with the UCTD syndrome, which are consistent with the previously determined frequency of the UCTD syndrome in persons with gastroenterological diseases - from 46.7% to 70.1% [9].

It should be noted that the critical period of undifferentiated connective tissue dysplasia (UCTD) manifestations is adolescence, when the volume of connective tissue increases in proportion to the growth and development of the body. According to our survey, in the vast majority of patients with UCTD (86.4%), phenotypic manifestations of UCTD were observed while studying at school.

When diagnosing UCTD, data indicating dysplastic-dependent morphofunctional changes in organs and systems were taken into account: the age of UCTD clinical manifestations onset; hereditary burden: the presence of UCTD clinical manifestations in first-line relatives, as well as hereditary burden by UCTD.

Among the risk factors for an unfavorable prognosis of UCTD clinical manifestations the following ones were recorded:

• the presence of associated anomalies and malformations (2.3%);

• severe manifestations of valve, arrhythmic, vascular syndromes (59.8%);

• hereditary burden in cases of early or sudden death (0.3%);

• history of intensive care or intensive care (0.09%);

• chronic inflammatory diseases (77.6%);

• smoking (61.2%);

• poor nutrition (89.2%);

• malnutrition (32.7%);

• low physical activity (60.8%).

Among phenotypic markers of UCTD patients with functional diseases of the biliary tract, more than half of the cases had the joints hypermobility syndrome (78.7%), arachnodactylia (52.5%), kyphoscoliotic posture (50.4%), asthenic type of constitution (55.2 %) Among visceral manifestations of UCTD the following pathologies were revealed: in 53.7% of cases - abnormalities of the chordal heart apparatus, 45,8% - cardiac valves prolapse, in 35,6% - gallbladder deformity. Intensive postprandial pain that occurs immediately after eating, was observed in 41.4% of patients with functional diseases of the biliary tract.

In the presence the UCTD syndrome, there are higher chances of intense postprandial pain (OR 2.2; 95% CI 1.2-4.4; p = 0.01). In patients with moderate manifestations of UCTD, the chances for this symptom are higher by 1.9 times (OR 1.9; 95% CI 1.04-4.3; p = 0.043), and with the expressed UCTD -by 2.5 times ((OR 2.5, 95% CI 1.20 - 5.40; p = 0.02) The effect of the UCTD syndrome on the frequency and severity of gastrointestinal symptoms was revealed: in the presence of UCTD in patients with functional diseases of the biliary tract, the chances of nausea (OR 2, 1. 95% CI 1.1 - 3.98; p = 0.02), flatulence ((OR 2.01; 95% CI 1.2-3.9; p = 0.024) and "intolerance to fatty food" (i.e., intake of fatty foods causes or exacerbates various gastrointestinal symptoms) (OR 3.6; 95% CI 1.9 - 6.9; p <0.01); gastrointestinal transit disorders (OR 2.2; 95% CI 1.1 - 4.1; p = 0.02) are higher. The frequency of symptoms grows as the number of UCTD signs increases. Thus, the frequency of complaints for diarrhea is higher in the presence of UCTD: 16.7% - in people without UCTD and 48.7% - in the presence of UCTD (p <0.01). The frequency of diarrhea grows with an increase of the UCTD syndrome severity: 36.8% - in moderate and 60% - in the expressed UCTD (p <0.01). The main pathogenetic mechanisms - disorders of motor activity and sensitivity in functional pathology - are generalized, therefore different parts of the gastrointestinal tract are involved in this process.

The term "cross-syndrome" means a combination of functional disorders in various parts of the gastrointestinal tract. Such "overlap" of the biliary tract and intestinal functional disorders (irritable bowel syndrome) was found in 37.2% of cases, with most of the patients (85.1%) having the UCTD syndrome (p <0.0001).

In 51.8% of patients with functional diseases of the biliary tract, an ultrasound study with a "fat breakfast" revealed the gallbladder motor function disorder of the hypokinetic type. Thus, in patients without UCTD, the frequency of hypokinetic type gallbladder motility disorder was 15.2%, and in the presence of UCTD - 86% (p <0.01). With pronounced UCTD, the incidence of gallbladder motility disorder by hypokinetic type is higher than that with moderate manifestations.

In the presence of UCTD, the chances of isolated bile dysfunction (OR 1.5; 95% CI 1.1 - 1.9; p = 0.01) grow by 1.5 times, and by 6.3 times - of combined functional disorders of bile ducts (hypertonic Oddi sphincter and gallbladder dysfunction) (OR 6.3; 95% CI 2.7-14.8; p <0.01). As the severity of the UCTD syndrome grows, the frequency of combined biliary tract disorders increases. Thus, with the pronounced UCTD, the chances of the sphincter of Oddi hypertonicity combination with the gallbladder dysfunction are by 3.5 times higher than with its moderate manifestations (OR 3.5; 95% CI 1.7-7.3; p <0.01).

In the examined patients, asthenic syndrome was detected at preschool (22.1%) and especially brightly at school, adolescence and young age. A direct correlation dependence of the severity of clinical manifestations of asthenia on the age of patients was noted: the older the patients, the more subjective complaints.

Asthenia syndrome was found in 61.1% of patients with functional diseases of the biliary tract, among them patients with the UCTD syndrome (72.9%, p = 0.02) prevailed. In pronounced manifestations of UCTD in patients with functional disorders of the biliary tract, the complaints incidence of weakness was higher (68.3% vs. 42% in patients without UCTD, p = 0.02), that of irritability (76.7% vs. 28.7%, respectively, p = 0.01), frequent headaches (53.3%, vs. 35%, respectively, p = 0.04), which were considered as vegetative dysfunction manifestations.

At the same time, such patients experienced dizziness (68.1%), increased fatigue (87.4%), decreased performance (48.9%), poor mood (66.7%), loss of interest in life (27.3%), anxiety (76.5%). Most often, these are patients with reduced body weight (61.1%), decreased tolerance for exercise (48.4%).

The UCTD syndrome is observed in 85% of patients with functional disorders of the cardiovascular

system.

The mean age of detecting clinically significant, life-threatening heart rhythm disorders in UCTD is 25 years. According to our data, these rhythm disturbances were observed in 9.8% of those surveyed, with an average age of 19 ± 0.3 years. Complaints were dominated by heart failure and heart attacks (57.2%), cardialgia and heart failure (78.2%), "irregular" heartbeat, accompanied by severe weakness (33.1%). In this case, the most striking subj ective complaint in patients with ND ST are interruptions, j olts, "fading" in the heart. Often, these complaints were accompanied by weakness (48.9%), lack of air (49.5%), dizziness (68.1%), and fear of death (66.7%). These complaints arose after the provocative factors: anxiety (97.6%), exercise (54.2%), food (49,4%), coffee (73.7%). In this case, arrhythmias were closely associated with psycho-autonomic manifestations and were well stopped by sedatives.

The following pathologies were often observed with this syndrome in our study: mitral valve prolapse (63.3%), abnormal location of left ventricular chords (45%), decreased contractile function of the myocardium (18.0%), rhythm and conduction disorders (47%). The MVP grade I was found in 57.6% of patients; that of grade II - in 36.4%, and that of grade III - in 6%. Most frequently the anterior mitral leaflet prolapse was observed (88.4%). Erroneous chords were observed in 45% of cases, thickening and prolongation of the mitral leaflets - in 25.4%, the tricuspid valve leaflets prolapse - in 3.2%.

These values are somewhat higher than the general indices and indicate the need for studies of the heart and / or the biliary tract in the presence of the UCTD syndrome [4, 6]. This need is due, firstly, to the young age of patients (high mental load, unhealthy diet, sports or physical culture, etc.). Secondly, the majority of such patients are women of childbearing age, who are ahead of pregnancy, childbirth and child breeding.

Summarizing the results of the study, we noted that any of the listed signs of NDCT can be either an isolated defect in the development of connective tissue, which is diagnosed today (locus minoris resistencia), or act as a manifestation of systemic pathology. When characterizing the involvement of organ and tissue systems with NDCT, the following frequency of associated syndromes was identified:

• 1 system - 5.3 %; • 5 systems - 6.76 %;

• 2 systems - 32.17 %; • 6 systems - 0.91 %;

• 3 systems - 35.83 %; • 7 systems - 0.18 %.

• 4 systems - 18.83 %;

Our data reflect uncertainty both in the diagnosis of NDCT itself and in the interpretation of its clinical manifestations. From the point of view of a practical doctor, the allocation of individual nosological forms of NDCT as a manifestation of connective tissue inferiority on the part of any organ or system disorientates it in further practical activities. There is a need for early detection of signs of connective tissue dysplasia, since some of them subsequently determine an unfavorable prognosis for a deterioration in the quality of life and the onset of disability. And to exclude a hereditary monogenic disease of the connective tissue in children with external phenotypic signs of dysplasia, further observation and thorough examination are necessary.

Thus, if according to the literature, the combination of several syndromes in patients with UCTD manifestations occurred, we did not find a direct, practically 100% connection between the pathology of the cardiovascular and biliary systems. [8, 9]

Thus, the data obtained suggest that the UCTD syndrome may be manifested by dysplastic changes not only in a single organ, but also in several organs or systems. Morphological changes in tissues and organs are nonspecific and are manifested similarly in various dysplasia, with varying degrees of severity. [3, 5]

Congenital connective tissue failure can be diagnosed already at the stage of the patient's physical examination with a comprehensive assessing the phenotypic markers of the connective tissue' s dysplasia. Taken together, these signs indicate dysplasia of the connective tissue and, the more phenotypic symptoms are detected during the examination, the more reasons exist to expect pathological changes in the internal organs. [2, 7]

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1. The UCTD syndrome is found in 66.9% of patients with functional diseases of the biliary tract and affects clinical manifestations towards greater intensity of biliary pain, higher frequency of postprandial pain and other gastrointestinal symptoms: nausea, flatulence, "intolerance to fatty food", intestinal transit disorders.

2. In the presence of the UCTD syndrome the frequency of bile ducts motility combined disorders, isolated dysfunction, gallbladder hypomotor dyskinesia is higher. In persons with pronounced UCTD, the frequency of the biliary tract motility disorders is the highest.

3. In the presence of the UCTD syndrome in patients with functional diseases of the biliary tract, asthenic syndrome and vegetative dysfunction are more common, their frequency and pronouncement grow as the UCTD severity increases, the level of anxiety increasing, too.

4. The UCTD syndrome is found in 85% of patients with functional disorders of the cardiovascular system and affects the clinical manifestations of the disease.

Prospective fields are further studies on the possibilities of early detecting the signs of connective tissue dysplasia in young people in order to timely carry out a set ofpreventive and therapeutic measures.

References

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