Modern antimicrobial drugs for the treatment of community-acquired pneumonia. Pneumonia. Treatment regimen for an adult, antibiotics, folk remedies, medicines. How to use drugs for severe cases in adults

Despite the fact that the biliary system (the system of bile ducts and sphincters that regulate the flow of bile) is trying to be considered separately from the main organ (liver), it is part of it and functions in accordance with this.

In the hepatocyte, 3 independent links are conditionally distinguished: sinusoidal, lateral and canalicular parts. The apical (canalicular) part of the cytoplasmic membrane of the hepatocyte differs in histological and biochemical properties and is involved in the formation of the lumen of the bile capillary. Each hepatic cell takes part in the formation of several bile ducts (BH). At the periphery, the lobules of the FA merge into the bile duct proper, passing at the exit into the interlobular connective tissue into the interlobular tubules, which, merging, form the interlobular ducts of the first order (the second - when they are already lined with prismatic epithelium). Tubular-acinous mucous glands, connective tissue membrane, elastic fibers appear in their walls. The interlobular ducts, merging, form large hepatic ducts - the lobar ducts, emerging from the liver and, in turn, forming the common hepatic duct, the continuation of which is the common bile duct, its beginning is the junction of the hepatic duct with the cystic duct. In the common bile duct, supraduodenal, retroduodenal, retropancreatic, intrapancreatic and intramural divisions are distinguished.

The distal part of the common bile duct passes through the thickness of the head of the pancreas, and the duct opens on the posterior wall of the descending duodenum, 2-10 cm below the pylorus. According to different authors, the width of the ducts can vary: common bile (OJ) - from 2 to 4 mm; hepatic - from 0.4 to 1.6 mm; cystic - from 1.5 to 3.2 mm. According to x-ray data, the width of the coolant duct is from 2 to 9 mm; according to ultrasound - in the presence of the gallbladder (GB) - from 2 to 6 mm, and without the gallbladder - from 4 to 10 mm. The capacity of the gallbladder ranges from 30 to 70 ml. At the site of transition of the gallbladder into the cystic duct, the muscle fibers take a circular direction, forming the sphincter of the duct of the gallbladder (Lütkens). Motor innervation is carried out by the sympathetic and parasympathetic nervous systems. Nerve plexuses are present in all layers of the biliary system. Sensitive fibers of the gallbladder are able to perceive only stretching.

The secretion of bile is continuous throughout the day, with some fluctuations. From 0.5 to 2.0 liters of bile is secreted per day. The direction of bile flow is determined by the interaction of hepatic secretion, the rhythmic activity of the sphincters of the terminal common bile duct, the sphincter of the gallbladder, the valve of the cystic duct, and the absorption function of the mucous membrane of the gallbladder and all ducts, which creates pressure gradients. From the hepatic ducts and the common bile duct, bile enters the gallbladder at the time of the closure of the sphincter of Oddi (it plays a decisive role in creating a pressure gradient). The sphincter of Oddi is closed intermittently outside of digestion, and small portions of bile systematically enter the duodenum. After the end of the digestive phase, bile enters the gallbladder for 3 or more hours. Most researchers believe that the extrahepatic bile ducts are never at rest, and their active peristalsis is considered from the point of view of the regulation of bile flow; duodenal tone (intraluminal pressure) also affects bile output. The motor reaction of the gallbladder and the sphincter of Oddi is directly dependent on the quantity and quality of food, as well as on the emotional state of a person.

The muscles of the sphincter of Oddi are independent of the muscles of the duodenum. The sphincter of Oddi consists of: the actual sphincter of the OBD (Westphal sphincter), which provides separation of the ducts from the duodenum; proper sphincter of the common bile duct; sphincter of the pancreatic duct.

The work of the entire biliary system is strictly coordinated, which is ensured by nervous and humoral regulation. Until now, the regulatory effect of endogenous peptides of the endorphin group is not entirely clear. The basic principle of the entire regulatory system is multi-level self-regulation (including locally produced hormones and biologically active substances).

The regulatory component is very complex under physiological conditions and is not completely clear in various pathologies of this system.

Classification, definition of clinical variants of dysfunction, diagnostic approaches

Functional diseases of the biliary tract are a complex of clinical symptoms that have developed as a result of motor-tonic dysfunction of the gallbladder, bile ducts and sphincters.

According to the latest International Classification, instead of the definition of "functional diseases of the biliary tract" (Rome Consensus, 1999), the term "dysfunctional disorders of the biliary tract" is adopted. At the same time, regardless of the etiology, they are usually divided into 2 types: gallbladder dysfunction and dysfunction of the sphincter of Oddi.

In the latest International Classification of Diseases (ICD-10), under heading K82.8, only "dyskinesia of the gallbladder and cystic duct" and under heading K83.4 - "spasm of the sphincter of Oddi" are allocated.

The regulation of the motor activity of the biliary system involves the parasympathetic and sympathetic divisions of the autonomic nervous system, as well as the endocrine system, which provide a synchronized sequence of contraction and relaxation of the gallbladder and sphincter apparatus.

It has been shown that moderate irritation of the vagus nerve causes coordinated activity of the gallbladder and sphincters, and strong irritation causes spastic contraction with a delay in bile evacuation. Irritation of the sympathetic nerve helps to relax the gallbladder. Of the gastrointestinal hormones, cholecystokinin - pancreazimin (CCK-PZ) has the maximum effect, which, along with the contraction of the gallbladder, helps to relax the sphincter of Oddi. The stimulating motive for the development of CCK-PZ is fatty food, and for nervous regulatory influences - the pressure gradient and its change.

The main cause of disorders of the rhythmic activity of the biliary system is inflammatory processes in the liver, leading to a violation of bile synthesis, a noticeable decrease in pressure in the ductal system and the gallbladder and, in connection with this, to a constant spastic contraction of the sphincter of Oddi.

Various surgical interventions (cholecystectomy, vagotomy, resection of the stomach) also lead to significant dysfunction of the biliary system. Unlike the processes occurring in other digestive organs, the formation of bile occurs continuously, however, the flow of bile into the intestine is noted only in certain phases of digestion. This is ensured by the reserve function of the gallbladder and its rhythmic contractions with consequent relaxation of the sphincters of Lutkens and Oddi. The relaxation of the gallbladder is accompanied by the closure of the sphincter of Oddi.

There are primary and secondary dysfunctional disorders. Primary are rare and average 10-15%. At the same time, a decrease in the contractile function of the gallbladder can be associated both with a decrease in muscle mass (rarely) and with a decrease in the sensitivity of the receptor apparatus to neurohumoral stimulation. Moreover, a small number of receptors can be genetically determined and acquired due to inflammatory, degenerative and metabolic disorders. Secondary dysfunctional disorders of the biliary tract can be observed with hormonal disorders, treatment with somatostatin, premenstrual syndrome, pregnancy, systemic diseases, diabetes, hepatitis, liver cirrhosis, jejunostomy, as well as existing inflammation and gallstones. Moreover, the presence of these diseases does not imply a stable failure of the regulatory systems and the perceiving apparatus - we are talking about a different degree of disorders in different periods, phases of the course of diseases; in connection with this, there is an “undulation” of disorders, up to periods of rather long stability, but with an “easy” transition of this system from stability to motor disorders. At the same time, psycho-emotional overload, stressful situations, and general neuroses are of great importance. For the vast majority of patients who underwent cholecystectomy, insufficiency of the sphincter of Oddi with a continuous flow of bile is characteristic, its spasm is less often noted. Another most common cause of biliary disorders is distal resection of the stomach, leading to a weakening of hormonal regulation and hypotension of the gallbladder.

The classification of dysfunctional disorders of the biliary tract is presented in the table.

For ease of perception and more convenient application in practice, unidirectional disorders are presented in the classification, although in life they are more often complex, with a predominance of one of the components.

Clinical manifestations are quite well known: with hyperkinetic disorders, colicky pains of varying intensity occur without irradiation or with irradiation to the right, to the back, sometimes to the left half of the abdomen (with the involvement of the ductal system of the pancreas). With hypokinesia - dull pain in the right hypochondrium, a feeling of pressure, fullness, which increases with a change in body position and with an increase in intra-abdominal pressure, which changes the pressure gradient for bile flow. Common to various forms of dysfunction are bitterness in the mouth, bloating, and unstable stools.

So, the central symptom of gallbladder dysfunction is the biliary type of pain, and delayed emptying of the gallbladder can be considered the only objective characteristic. Available diagnostic methods do not explain the cause of this phenomenon. There may be several causative factors. It is impossible to exclude such moments as a violation of filling or a decrease in the sensitivity of the perceiving apparatus of the gallbladder.

Diagnostic criteria for gallbladder dysfunction are episodes of severe persistent pain localized in the epigastrium or in the right upper quadrant of the abdomen, with the following features:

• episodes lasting 30 minutes or more;
• symptoms occur 1 or more times in the previous 12 months;
• the constant nature of pain, a decrease in the daily activity of patients and the need to consult a doctor;
• lack of evidence of organic pathology causing symptoms;
• the presence of dysfunction of the emptying of the gallbladder.

A very important objective symptom of impaired motility of the gallbladder is the ultrasonic phenomenon of "sludge" (precipitation), which, according to our data, can be presented in 2 versions: a) diffusely; b) near the wall. The parietal variant, depending on the clinical situation, can be characterized as "inflammatory". If there is no inflammation, then the elements of the sediment that form it are quite large. The entire clinical symptom complex should also be analyzed: nausea and vomiting, irradiation, provoking factors (food, its quality, etc.).

With regard to dysfunction of the sphincter of Oddi, 4 clinical and laboratory types are distinguished (3 types of biliary dysfunction and 1 type of pancreatic dysfunction). The diagnostic criteria are based on an attack of biliary-type pain and 3 laboratory and instrumental signs: an increase in AST and/or alkaline phosphatase by 2 or more times with a double determination; slowing down the excretion of contrast agents during ERCP (more than 45 minutes); expansion of the common bile duct more than 12 mm (research is carried out during an attack).

The first type of dysfunction is characterized by pain and 3 signs.

The second type of dysfunction is characterized by pain and 1 or 2 signs.

The third type - only an attack of pain.

The fourth type - pancreatic - is characterized by "pancreatic" pain and an increase in the level of amylase or lipase (with mild pain); increase in enzymes (amylase, lipase) may be absent.

In cases where endoscopic retrograde pancreatocholangiography excludes the absence of stricture pathology, monometry of the biliary and pancreatic sphincters is shown.

The World Congress of Gastroenterologists (Bangkok, 2002) determined that evidence-based medicine does not require consensus, but evidence. The congress participants came to the conclusion that sphincter of Oddi dysfunction should not be classified as a well-defined disease, but as a condition with a variable dysfunction/symptom relationship. It has been specifically emphasized that impaired gallbladder emptying is well known as a consequence of inflammatory injury, mechanical obstruction, or autonomic denervation. In the absence of these conditions, it is unclear whether delayed gallbladder emptying can be considered a specific clinical problem (nosological form).

Some principles of treatment of dysfunctional biliary disorders

Given the above, it should be noted that the main goal of treating patients with dysfunctional disorders of the biliary tract is to restore the normal flow of bile and pancreatic secretion through the biliary and pancreatic ducts. In this regard, the tasks of treatment include:

• restoration, and if it is impossible, replenishment of bile production (with the development of chronic biliary insufficiency, which means a decrease in the amount of bile and bile acids entering the intestine 1 hour after the introduction of the stimulus. Patients after cholecystectomy almost always develop dysfunction of the sphincter of Oddi, since from normal functioning of the biliary system, the gallbladder is excluded, and in connection with this, an irreparable loss of bile acids is observed with the development of chronic biliary insufficiency, which causes both indigestion and dysfunctional disorders);
• increase in the contractile function of the gallbladder (with its insufficiency);
• decrease in the contractile function of the gallbladder (with its hyperfunction);
• restoration of the tone of the sphincter system;
• restoration of pressure in the duodenum (which determines an adequate pressure gradient in the biliary tract).

Until now, diet therapy plays a significant role in the system of therapeutic measures. The general principles of the diet are a diet with frequent meals of a small amount of food (5-6 meals a day), which contributes to the normalization of pressure in the duodenum and regulates the emptying of the gallbladder and ductal system. Alcoholic drinks, carbonated water, smoked, fatty and fried foods, seasonings are excluded from the diet - due to the fact that they can cause a spasm of the sphincter of Oddi. When choosing a diet, the influence of individual nutrients on the normalization of the motor function of the gallbladder and biliary tract is taken into account. So, with a hyperkinetic type of dysfunction, the consumption of products that stimulate the contraction of the gallbladder should be sharply limited - animal fats, vegetable oils, rich meat, fish and mushroom broths. With hypotension of the gallbladder, patients usually tolerate weak meat and fish broths, cream, sour cream, vegetable oils, soft-boiled eggs. Vegetable oil is prescribed in a teaspoon 2-3 times a day 30 minutes before meals for 2-3 weeks. To prevent constipation, dishes that promote bowel movement are recommended (carrots, pumpkin, zucchini, herbs, watermelons, melons, prunes, dried apricots, oranges, pears, honey). This is especially important, since a normally functioning intestine means normalization of intra-abdominal pressure and the presence of a normal passage of bile into the duodenum. The use of food bran (with enough water) is important not only for the functioning of the intestines, but also for the motility of the biliary tract, especially the gallbladder, which has sediment.

Of the drugs that affect the motor function of the gastrointestinal tract, the following are used: anticholinergic drugs, nitrates, myotropic antispasmodics, intestinal hormones (CCK, glucagon), choleretics, cholekinetics.

Anticholinergics, reducing the concentration of intracellular calcium ions, lead to muscle relaxation. The intensity of relaxation depends on the initial tone of the parasympathetic nervous system, but when using drugs of this group, a wide range of side effects are observed: dry mouth, difficulty urinating, visual impairment, which significantly limits their use.

Nitrates(nitroglycerin, nitromint, sustonite, nitro-time, nitrong forte, nitromac, nitrocor, nitrosorbide, cardonite) through the formation of free radicals of nitric oxide in smooth muscles, which activate the content of cGMP, lead to their relaxation. However, these drugs have significant cardiovascular and other side effects. The development of tolerance makes them unsuitable for long-term therapy.

Non-selective calcium channel blockers (nifedipine, verapamil, diltiazem, etc.) are able to relax smooth muscles, including the biliary tract, but this requires the highest possible doses, which practically excludes the use of these drugs due to pronounced cardiovascular effects.

Some antispasmodics selectively block calcium channels (dicetel, panaverium bromide, spasmomen) and act predominantly at the level of the colon, where they are metabolized. 5-10% of these drugs are absorbed and metabolized in the liver and can work at the level of the biliary tract. This side requires further research, and indirect effects associated with the restoration of the pressure gradient have been noted and can be used.

Currently, among the myotropic antispasmodics, attention is drawn to the drug gimecromon (odeston), which has a selective antispasmodic effect on the sphincter of Oddi and the sphincter of the gallbladder. Odeston is effective in patients with dysfunction of the biliary tract, has a choleretic effect, eliminates biliary insufficiency, as well as dysfunction of the sphincter of Oddi, its hypertonicity, including in patients after cholecystectomy.

Of the other myotropic antispasmodics, duspatalin should be noted, which selectively affects the tone of the sphincter of Oddi (directly and indirectly), it is devoid of a universal antispasmodic effect (and, therefore, side effects), but does not have a choleretic effect and is inferior to odeston in this.

With hypofunction of the gallbladder, the main approach to treatment should be considered pharmacotherapeutic.

The use of drugs that enhance the motility of the gallbladder.

Cholesterics:

• preparations containing bile or bile acids: allochol, dehydrocholic acid, lyobil, cholenzym;
• synthetic drugs: oxafenamide, nikodin, tsikvalon;
• herbal preparations: hofitol, flamin, cholagogum, corn stigmas, etc.

cholekinetics: magnesium sulfate, olive oil and other oils, sorbitol, xylitol, holosas, etc.

The choice of drug, which is a very important, if not the main issue, depends on how quickly you need to get the effect of therapy. If the most rapid effect on the patient's body is required, then it is better to use cholekinetics, and the effect also depends on the dose of the drug; if long-term course treatment is necessary, then bile-containing drugs are used; if an anti-inflammatory effect is required at the same time, then the choice should be made in favor of synthetic drugs, but their course treatment will be short; when a patient simultaneously has a liver pathology, then the choice should be made in favor of hofitol, which has a choleretic and protective effect.

Use of drugs with prokinetic effects

(motilium, debridat). Myotropic antispasmodics can also be included here: dicetel, spasmomen, duspatalin, halidor, no-shpa. It should be remembered that their effects are usually indirect (reduce either the tone of the sphincter of Oddi or the pressure in the duodenum). Their effectiveness is dose-dependent, so the selection of an effective dose is necessary.

The use of drugs that reduce inflammation and visceral hyperalgesia. Non-steroidal anti-inflammatory drugs: anopyrin, upsarin UPSA, dicloberl, naklofen, ketanov, solpaflex, brustan, ketonal, movalis, donalgin, ambene, celebrex and low doses of tricyclic antidepressants (amizol, saroten, elivel, melipramine, coaxil).

It is necessary to pay attention to other aspects of treatment. With dysfunction of the sphincter of Oddi: when establishing the first type, papillosphincterotomy is required; the second or third type - the possibility of prescribing drug therapy is allowed. It should be borne in mind that hormones (CCK, glucagon) can temporarily reduce the tone of the sphincter of Oddi; nitrates give a very short-term effect. Botulinum toxin is a strong inhibitor of acetylcholine release. Its use as an injection into the sphincter of Oddi reduces its pressure, improves the flow of bile and brings relief, but the effect of the treatment is transient. With pancreatic type of dysfunction of the sphincter of Oddi, the standard therapy is operative sphincteroplasty and pancreatic lithoplasty (medication is carried out only at the stage of absence of complications).

Conclusion

Recently, the attention of the medical community has been drawn to functional disorders of the gastrointestinal tract in general and the biliary system in particular. This is largely due to the fact that in relation to functional disorders there is still hope for their cure, as well as successful prevention or delay in the development of more prognostically more severe organic pathology (including cancer). Today, diagnostic approaches to the treatment of the diseases we have considered, presented in this article, are being developed. In addition, this work reflects a large arsenal of drugs at the disposal of a doctor who has the opportunity to choose a drug or complex depending on the pathogenetic features of a particular disorder.

Literature

O. N. Minushkin, doctor of medical sciences, professor
Medical Center of the Administration of the President of the Russian Federation, Moscow

Responsible for the removal of bile and some other organic substances from the body, the biliary tract is a rather weak point in the human body. Sooner or later, the pathological conditions of this area disturb almost any inhabitant of our planet. The likelihood of violations is determined by lifestyle and comorbidities, health nuances and other aspects. From medical statistics it is known that most often people are concerned about gallstone disease.

general information

Before considering what disorders of the biliary tract are, you should first pay attention to this element of the human body. The relevance of the issue is the prevalence of pathologies that significantly impair the quality of human life. The last decades have been marked for medicine by breakthroughs in the treatment of dysfunctional conditions, and the latest methods and tools are actively considered and discussed at world-class symposiums and conferences regularly organized by prominent universities and clinics.

The biliary tract is formed by the gallbladder and ducts designed to drain the fluid secreted by the glands from it. The lobar ducts vary on average in diameter of about 2 mm, and the common duct of the liver reaches 5 mm. The dimensions of the common bile duct are similar. The relatively small size makes the site quite vulnerable, which affects the statistical information: doctors note that the success of the pharmaceutical market and new treatment technologies do not lead to a decrease in the incidence of gastrointestinal disorders, including the biliary system. The frequency of pathological conditions of the considered element of the body varies, according to various estimates, from 12% to 58%. Specific indicators are determined by the characteristics of a person’s lifestyle and the nuances of his body. So, for women, the danger is higher, on average, three times, in comparison with the representatives of the strong half.

Question Features

Dysfunctional disorders of the biliary tract, disorders of the bladder, sphincter often first appear spontaneously. The cause may be various aspects of the body's work, and the clinical manifestations of failures differ from time to time. Cases vary in severity and duration, issues of clarification.

As can be seen from the statistics, most of the people who encounter such difficulties almost immediately go to the clinic. A bad condition is aggravated if a person does not immediately come to see a doctor, but at first tries to cope with the pathology on his own. If the case is among the problematic diagnosed, and the detection of a somatic, neurological disorder takes a long time, the risk of developing a hypochondriacal state increases. There is a risk of depression.

Experts urge to pay special attention to the patient if there is a suspicion of functional failures and working disorders of the biliary tract in children and adults. The more time it took to clarify the diagnosis, the later a suitable treatment program was selected, the worse the patient's quality of life will be.

Many are convinced that they have an extremely severe, deadly and untreatable disease. In addition, incorrectly diagnosed and incorrectly chosen treatment is usually accompanied by a recommendation to adhere to a strict diet, which also negatively affects the person, especially with prolonged observance of forced restrictions, which are actually inappropriate for the current illness.

Cholelithiasis

GSD is the most common disorder of the biliary tract in children and adults. The pathological condition is considered perhaps the most typical for people of any age, living in a variety of localities and countries. In developed countries, the number of patients is estimated at 10-40% of the total population. On average, this parameter doubles every 10 years. In our country, the frequency of cholelithiasis varies between 5-20%, specific indicators are determined by the region and the characteristics of the sample group.

The prevalence of the problem, a persistent trend towards an increase in cases lead to an increase in the frequency of surgical measures aimed at eliminating cholecystolithiasis. More often, surgery is performed only when necessary to treat appendicitis. GSD is recognized by the medical community as a social, medical and economic phenomenon that greatly affects the well-being of the population of all corners of the planet.

Digestive system and overweight

Recently, the attention of doctors has been attracted by the interconnection of dysfunctional disorders of the biliary tract in children and adults and extra pounds. As medical statistics show, excess weight negatively affects the state of the body in all its aspects. Various internal systems and organs suffer. The greater the weight of a person, the more often he is sick with diabetes, sleep apnea, vascular disease, heart disease. Being overweight is associated with an increased risk of PCOS. Almost 88% of overweight patients suffer from high blood pressure. At the same time, the risks of development and dyslipidemia increase. Hepatic steatosis worries all overweight people without exception.

The probability of developing cholelithiasis in the presence of extra pounds is estimated at 20%. And bile cholesterosis worries every tenth obese person. The likelihood of pathological disorders of the biliary tract is largely related to the characteristics of the diet. The more the diet is saturated with animal fats, the higher the risk of metabolic syndrome, which entails first overweight, and then the formation of gallstones.

Today, the most common cholelithiasis is observed in Americans. The number of operations on this occasion in our country is less than is typical for Western medicine, approximately seven times. True, some experts believe that this is due not only to the occurrence of cholelithiasis, but also to the typical behavior of an ordinary patient: among Americans, the practice of going to clinics for worrying ailments is more common.

Dangers and pathologies

It is more likely to learn from your own experience what a functional disorder of the biliary tract can be, what symptoms it manifests itself and what treatment it requires if a person suffers from excess weight. The risk group includes primarily women, in whom cholelithiasis occurs approximately three times more often than in men. This is due to hormonal disruptions, characteristic of many representatives of the fair half. All this corrects metabolism, affects the biliary system. With polycystic ovaries, studies have shown that a fatty liver is formed in 42% of patients, and this almost always causes the appearance of stones in the gallbladder.

Risk factors for functional disorders of the biliary tract include a person's age and the use of contraceptives that control the amount of estrogen in the body. More often, stones form during pregnancy and in individuals who are rapidly and actively losing weight on an aggressive weight loss program.

In metabolic syndrome, the risk of stone formation is 5.54 times higher than for other people. The risks are the more significant, the more pronounced all the symptoms of the syndrome. High blood pressure, high serum triglycerides, obesity and a low percentage of high-density lipoproteins indicate great dangers. Metabolic syndrome is observed in every second patient with gallstones.

Case Features

If the biliary tract is compromised, symptoms include pain after eating in the epigastrium and/or spasms in the right hypochondrium. Manifestations of pathology indicate dyskinesia of the bile flow pathways. Studies have shown that about 90% of cases of the appearance of stones on the background of the metabolic syndrome are formations that appeared on the basis of cholesterol: the processes are closely related to the active generation of cholesterol and the excretion of this compound into bile. Paths secrete mucin, the ability of the bladder to contract decreases.

As observations have shown, vegetative failures are another significant factor in the formation of stones in the gallbladder. Parasympathetic, sympathetic NS work inadequately, the balance between them is lost, a condition known as hypersympathicotonia is formed. For this reason, hypomotor dyskinesia of the biliary tract appears, the sympathetic effect increases, and the parasympathetic pathologically decreases.

Weight and stones: are there options?

Doctors are actively working not only on the study of the features of biliary tract disorders, but also on methods for preventing such a condition. In particular, special attention is paid to overweight patients. Currently, ursodeoxycholic acid is used, which is presented in pharmacies under the trade name Ursosan. The active compound of this drug affects hepatocyte membranes, gastrointestinal epitheliocytes, cholangiocytes. Thanks to it, the structure of cellular elements is stabilized, the aggressive external influence of toxic substances is reduced, the concentration of cholesterol in bile is reduced, since its production by the liver structures is inhibited. In addition, under the influence of acid, cholesterol dissolves more efficiently. The drug stimulates the dissolution of solid structures and prevents the appearance of new ones. Clinical trials have shown that ursodeoxycholic acid gives a good effect in 80% of cases.

A prophylactic course with the use of this pharmaceutical product is also recommended in case of a high probability of biliary tract disorders due to biliary lithogenicity. The drugs are indicated if studies have revealed numerous cholesterol stones, the diameter of which is less than 5 mm. This acid protects liver cells, reduces the activity of the inflammatory focus by inhibiting the generation of cytokines. The drug has antiapoptotic, antifibrotic effects. The agent affects the active excretion of very low-density lipoproteins from the body.

Functional Disorders

Different variants of dysfunction of the biliary tract in the ICD are encoded with codes K80-K87. As doctors have established, before gallstones are detected in a patient, biliary sludge develops, and it is preceded by a state of functional disorder. If fairly accurate statistics are known regarding the incidence of gallstones, then for functional disorders such a clear picture does not exist.

Some experts who have dealt with this issue have found that phenomena and symptoms indicate functional disorders, on which an approximate statistical study can be carried out. Thus, pathological changes in the organ detected during ultrasound are 70% of various deformities, and it is safe to say that all these people have a functional disorder. In addition to biliary disorders, there are pancreatic disorders.

Diagnosis and phenomena

Conditions preceding ICD-coded dysfunctions of the biliary tract were considered within the framework of a medical congress organized in Rome by specialists dealing with the digestive system of the human body. The event held in 2006 was dedicated to the work of the biliary system.

Here it was decided to consider the patient's complaints of soreness, discomfort, sometimes manifested in the epigastric region, under the ribs from the top right or left, as the main diagnostic signs of pathology. Each of the phenomena can appear on its own, a complex symptom is possible. Attacks of pain, allowing us to talk about functional disorders, should last half an hour or more. When diagnosing, it is necessary to clarify exactly when the pain comes: the pathological condition under consideration is indicated by sensations that appear shortly after a meal (in the range from a quarter of an hour to three hours).

When diagnosing a functional disorder preceding the conditions indicated as K80-K87 in ICD 10 codes (biliary tract dysfunction), it is necessary to clarify what type of pain the patient has. Intensity indicating serious pathology - the level at which a person cannot function normally and needs to be hospitalized. At first, the pains come in episodes, gradually they turn into permanent ones. After defecation, sensations do not weaken. Neither changing posture nor taking antacids helps to alleviate the condition.

Features and phenomena

If functional disorders of the biliary tract are suspected, differential diagnosis comes first. It is known that the symptoms described earlier can appear with a wide range of pathological conditions affecting the gastrointestinal tract. Only a full range of tests and instrumental examinations will help to make the correct diagnosis.

In some patients, the pathology leads to nausea or provokes a gag reflex. Pain can be given under the shoulder blade on the right or in the back. There is a possibility of night attacks: as a rule, these occur no earlier than two in the morning. Dyspeptic, asthenoneurotic phenomena are distinguished as concomitant symptoms.

The nuances of the diagnosis

Officially, at the congress in 2006, they not only determined what a functional disorder could be, what nuances it manifests itself in the work of the biliary tract, but also considered how to correctly enter the conclusions into the patient's chart.

Possible options: FRZHP, FBRSO, FPRSO. Alternative encodings: E1, E2, E3. In the first case, we are talking about a functional disorder, in the second there is a clear indication of biliary disorders in the work of the sphincters of Oddi, in the third - pancreatic.

Pain: causes and consequences

If a person develops dysfunction of the biliary tract according to the hypotonic scenario, the patient is likely to regularly notice pronounced discomfort and discomfort. Systematic suffering leads to depressive disorders, which reduces the ability to endure pain and intensifies it, and also initiates the transition of the process into a chronicity. Functional diseases affecting the area under consideration are often neurotic manifestations, although there is a possibility of a viscero-visceral reflex of a pathological nature. The same is possible with violations of the gastrointestinal tract and other systems, organs.

Clinical studies of work disorders are particularly interesting because they provide insight into the development and progress of many organic pathological conditions. Often, dysfunction is accompanied by an inflammatory process localized in the flow of bile. The colloidal qualities of the secreted substance are lost, which sooner or later forces an urgent surgical intervention.

Dysfunction of the biliary tract according to the hypotonic type, as well as developing according to other flow scenarios, is a classic obligatory factor in lithogenesis, especially pronounced at the beginning of the process. The most prompt diagnosis and a successful choice of a program for correcting the condition is the most important clinical task, according to all modern doctors.

It was decided to consider functional disorders as permanent or temporarily manifested complexes of clinical symptoms expressed in different parts of the digestive system. These include problems that cannot be explained by the nuances of biochemistry or the structural features of internal organs. Regarding the biliary tract, functional pathological conditions are said to be a symptomatic complex caused by malfunctions of the motor-tonic function of the bladder, the sphincter present in it, and the bile flow pathways.

Problems and solutions

When determining the characteristics of biliary tract dysfunction in children and adults, although it is important to determine the etiology of the process, it is practically not taken into account in further correction. The doctor's task is to normalize the bile duct, regardless of what became the root cause of the problem. As a rule, patients receive outpatient treatment. With polymorphism of disorders, conflict at work, in everyday situations, with difficulties in clarifying the condition and the presence of an associated pathological process that requires a thorough approach to therapy, the patient may be referred to a hospital. As a rule, he is hospitalized for one and a half or two weeks - usually this period is enough.

Sometimes dysfunction of the biliary tract in children and adults is associated with neurotic disorders. This requires the use of sedative, tonic medicinal formulations and sleep stabilization agents.

An important aspect of the therapeutic program is the trusting and close communication between the doctor and the patient - the doctor must explain to the client what caused the discomfort and serious consequences, how to correct the violations. It is not uncommon for a patient to need a consultation or program supervision of a psychotherapist.

Eat right

With dysfunction of the biliary tract, one of the most important aspects is a correct, balanced menu that is sufficient in its caloric content and nutritional value. The diet is formed taking into account what kind of disturbances in the work of the gastrointestinal tract are disturbing. A person who adheres to the program developed by a nutritionist is rehabilitated much faster, and the quality of life improves in the first few days after the start of a new food intake regimen. The best option is considered frequent, fractional meals - up to six servings per day. This stimulates the gallbladder to empty regularly, normalizes internal pressure in the ducts and intestines. The last meal is recommended to be consumed shortly before going to bed.

With dysfunction of the biliary tract, alcohol and carbonated drinks are strictly prohibited. The ban is imposed on smoked meats, fried foods, as well as those with a high content of animal fat. You can not use spicy. You will have to exclude all seasonings from the diet, since such products are highly likely to provoke sphincter spasms.

Too active and too weak

When compiling a diet, it is supposed to take into account how the substances contained in food products can correct the motility of the digestive tract. In particular, hyperkinetic dysfunction requires limiting the entry into the body of compounds that can activate contractions. This obliges to exclude vegetable fats, rich broths on mushrooms, fish and meat, as well as oils squeezed from plants from the menu. The patients will benefit from magnesium-rich foods that lower muscle tone - buckwheat, millet, cabbage. You should either completely abandon or significantly reduce the consumption of egg yolks. Of the drinks, coffee, tea, especially in a strong form, are subject to restrictions. Patients are advised to stop eating creams, nuts, muffins.

If dysfunction develops according to a hypokinetic scenario, it is reasonable to revise the diet in such a way that the body receives a sufficient amount of useful products that positively affect tissue contractility.

Patients are shown not too strong broths on meat, rich fish soup. Sour cream and cream are considered useful. To activate the contraction of the sphincter, you should eat salads seasoned with vegetable oil, boil soft-boiled eggs. You can use vegetable oil as food as an independent product - 30 minutes before a meal, a teaspoon, daily, three times. The duration of the program is up to three weeks.

In order to eliminate constipation, you should eat foods that activate the intestinal tract. Carrots and beets, watermelons and various greens are distinguished by a pronounced effect. Patients are recommended to eat melons, zucchini, cook pumpkin dishes. Among dried fruits, dried apricots and plums are the most useful, and from fresh ones, you should pay attention to pears and oranges. When compiling a diet, the doctor will definitely recommend including honey in the diet. Activation of motility is possible with the use of bran.

General state

Often, dysfunction of the biliary system adversely affects the psycho-emotional status, provoking various kinds of disorders. Clinical appearances become the basis for identifying endogenous depression. To correct it, the means are selected by assessing the state of the nervous system, including the autonomic, as well as psycho-emotional manifestations.

Patients are shown drugs that simplify adaptation to external conditions, tranquilizers and antidepressants. In severe cases, antipsychotics may be used. In some cases, it is recommended to use sedatives, ganglionic blockers. Special gymnastic complexes and physiotherapy will benefit.

Recently, antidepressants have been considered the most effective option for combating visceral hyperalgesia. Among antipsychotics, preference is given to medicines containing sulpiride. The drug program helps block dopamine D2 prescriptions, eliminates vomiting and stabilizes gastrointestinal motility. This course should be prescribed to adults, but in old age it is permissible only if it is possible to regularly monitor the progress of the patient's condition. It is known that over the years the risks of hypersensitivity become greater, which means that taking sulpiride can provoke undesirable consequences.

Biliary tract diseases are one of the common causes of abdominal syndrome in children. As a rule, functional disorders of the biliary tract are more common, less often - diseases of an inflammatory nature (cholecystitis, cholangitis). However, functional disorders of the passage of bile can contribute to the development of organic pathology from the biliary system, liver, pancreas, duodenum. At the same time, it is not always possible to establish the primacy of the disease of any of the organs of the gastrointestinal tract, since there are very complex functional relationships between them.

Bile is produced by hepatocytes and then secreted into the bile ducts. It consists of water (82%) and organic and inorganic substances dissolved in it (bile acids (12%), phospholipids (4%), cholesterol (0.07%), proteins, bilirubin, electrolytes, etc.).

The physiological significance of bile:

• neutralization of hydrochloric acid, pepsin;
• activation of intestinal and pancreatic enzymes;
• fixation of enzymes on the villi;
• emulsification of fats;
• increased absorption of vitamins A, D, E, K;
• increased intestinal motility, increased intestinal tone;
• reduction in the growth of putrefactive bacteria;
• stimulation of choleresis in the liver;
• excretion of medicinal, toxic substances, poisons, etc.

Disorders of the functions of the biliary system are based on disorders characterized by inconsistent, untimely, insufficient or excessive contraction of the gallbladder, bile ducts and / or sphincters of the extrahepatic bile ducts. The bile ducts have a complex sphincter apparatus, which is a bundle of longitudinal and circular muscles:

• sphincter of Lutkens (located at the confluence of the cystic duct into the neck of the gallbladder);
• sphincter Mirizzi (located at the confluence of the cystic and common bile ducts);
• sphincter of Oddi (located at the end of the common bile duct and not only regulates the flow of bile, pancreatic juice into the duodenum, but also protects the ducts from reflux of intestinal contents).

The sphincter of Oddi is a fibromuscular formation consisting of:

• sphincter of the major duodenal papilla (Westphal's sphincter), which provides separation of the ducts from the duodenum;
• sphincter of the common bile duct;
• sphincter of the pancreatic duct.

For the normal functioning of the biliary tract, the synchronous, consistent activity of the entire sphincter apparatus is extremely important. The term "dysfunctional disorders of the biliary tract" is currently accepted to refer to disorders of the functioning of the biliary system (Rome Consensus, 1999). Dysfunction of the biliary tract, according to this classification, is divided into two types: dysfunction of the gallbladder and dysfunction of the sphincter of Oddi ( ).

The following classification of dysfunctional disorders of the biliary tract has been adopted.

By localization:

gallbladder dysfunction;

Dysfunction of the sphincter of Oddi.

By etiology:

Primary;

Secondary.

By functional state:

hyperfunction;

Hypofunction.

With a lack of bile in the intestinal lumen:

• the motor function of the intestine is inhibited;
• the absorption of calcium and vitamins decreases;
• increases the risk of developing osteoporosis;
• the level of fibrinogen decreases;
• the level of hemoglobin decreases;
• possible development of ulcers, dysfunction of the sex glands, cirrhosis of the liver.

Diagnostic criteria for dysfunction of the sphincter of Oddi in adults, according to the Rome consensus, are defined as a complex of functional disorders observed for more than 3 months, the main clinical symptoms of which are recurrent attacks of severe or moderate pain lasting 20 minutes or more, localized in the epigastrium or right hypochondrium (biliary type); in the left hypochondrium, decreasing when leaning forward (pancreatic type); encircling (combined type). Pain may be associated with eating, appear at night, be accompanied by nausea and / or vomiting.

There are primary and secondary dysfunctions of the biliary tract.

Primary biliary dysfunctions include diseases based on functional disorders of the biliary system, arising from disorders of neurohumoral regulatory mechanisms and leading to impaired outflow of bile and / or pancreatic secretion into the duodenum in the absence of organic obstructions. Secondary dysfunctions of the biliary tract are combined with organic changes in the gallbladder, sphincter of Oddi, or occur with various diseases of the abdominal organs.

There are several variants of violations of the motor activity of the gallbladder and the sphincter apparatus of the biliary tract: hypotonic, hypokinetic, hypertonic and hyperkinetic. Hypotonic dyskinesia is caused by a weak contraction of the gallbladder in a normal or spastic state of the sphincter apparatus. Hypokinetic dyskinesia is characterized by weak contraction of the gallbladder combined with weakness of the sphincters. Hypertonic (hyperkinetic) dyskinesia is characterized by a strong contraction of the gallbladder with an insufficient or normal state of the sphincter apparatus. In children with a predominance of the tone of the sympathetic nervous system, hypomotor dysfunctions are more often observed with a predominance of the parasympathetic - hypermotor.

According to our data, chronic gastroduodenitis in children in 100% of cases is combined with dysfunctional disorders of the biliary tract. In every third patient with this pathology, heredity is burdened along the line of gastric ulcer and duodenal ulcer. For the most part, the children were on early artificial feeding (76%), 52% of them had a history of allergies. Every fourth child had previously had an acute intestinal infection, had chronic foci of infection, and every third child often had ARVI and received antibiotic therapy. Neurological disorders were detected in 24% of patients with dysfunction of the biliary tract.

When interviewing a patient with suspected pathology of the biliary system, attention should be paid to the following signs: abdominal pain is localized mainly in the right hypochondrium, less often in the umbilical or epigastric region, they can be short-term (paroxysmal) or prolonged (aching), occur after an error in diet (when eating fatty, fried foods). Dyspeptic symptoms are possible - nausea (occasionally there may be vomiting), anorexia (decreased or selective), a change in the nature of the stool (more often - constipation, less often - unstable). As a rule, there are symptoms of autonomic dysfunction in the form of headaches, dizziness, increased fatigue, sleep disturbances, and a decrease in mental and physical performance. In patients with dysfunctional disorders of the biliary tract, psychoemotional disorders can often be observed.

When examining a patient, pallor is often noted, less often - dryness of the skin. The tongue may be coated with a yellow-brownish coating. There may be bloating, liver enlargement, positive liver or bladder symptoms. In the presence of transient cholestasis - subicteric staining of the skin and visible mucous membranes, an increase in the liver up to 2-3 cm from under the edge of the costal arch, periodically - acholia of the stool.

With dysfunction of the biliary tract, changes are usually not detected in a clinical blood test. In inflammatory diseases (cholangitis, cholecystitis), leukocytosis with neutrophilia and stab shift, accelerated ESR are observed in the blood.

In a biochemical study of blood in patients with dysfunctional disorders of the biliary tract, no significant changes are detected, and in the presence of cholestasis syndrome, an increase in the level of total and direct bilirubin, cholesterol, alkaline phosphatase, lactate dehydrogenase is most often noted, sometimes a moderate increase in transaminase activity.

With duodenal sounding, first of all, a visual assessment of the duodenal contents is carried out (color, consistency (presence of turbidity, flakes, mucus, sediment) with its subsequent microscopic examination). It should be borne in mind that the diagnostic value of the detected cellular elements under microscopy is limited, since bile destroys them within a few minutes. With dysfunctions of the biliary tract, small amounts of mucus, cholesterol crystals, microbes are determined in the bile. In the biochemical analysis of bile, a study of portions B and C is carried out with the determination of the concentration of phospholipids, phospholipases, alkaline phosphatase, C-reactive protein, the total content of bile acids, and the cholate-cholesterol coefficient. It is also advisable to determine in bile the products of lipid peroxidation (malondialdehyde) and the antioxidant system (tocopherol, retinol, etc.).

Ultrasound examination (ultrasound) occupies a leading position among other methods used to diagnose pathology of the biliary tract, it can be used in a child of any age and has practically no contraindications. Sonography allows you to determine the location and shape of the gallbladder, its external contours, the condition of the wall, intravesical pathological structures, as well as the condition of the liver, pancreas, and spleen. To clarify the functional state of the biliary tract, ultrasound is used to assess the function of the gallbladder and the sphincter of Oddi.

Dynamic hepatoscintigraphy is the most accurate method in terms of differential diagnosis of various forms of biliary dysfunction. Using this method, it is possible to diagnose initial functional changes in the biliary tract, refluxes into the bile ducts, and determine a non-functioning gallbladder. However, in children, the use of this method is possible only from the age of 12. Indications for liver testing with Tc-99m-IDA in children are abdominal pain and hepatomegaly if ultrasound fails to establish the diagnosis. A relative contraindication to hepatocholescintigraphy is an increased level of direct serum bilirubin, since some IDA derivatives (HIDA, MESIDA) compete with bilirubin for binding to blood proteins, thereby reducing the information content of the method in children with hyperbilirubinemia.

In adults, in recent years, it has been possible to measure the amount of bile secreted from various parts of the biliary system, manometric studies, which suggests a violation of the sphincter of Oddi in the form of muscular dyskinesia or in combination with its structural disorders. Manometry can serve as the "gold standard" in the diagnosis of dysfunctional disorders of the sphincter of Oddi.

Thus, using modern diagnostic studies, it is possible to establish the nature of functional or organic diseases of the biliary system, determine the nature of the course of the disease and develop an optimal treatment complex.

With dysfunctional disorders of the biliary tract, treatment cannot be standard, it must be complex, depending on the form and nature of the underlying disease of the gastrointestinal tract. If dysfunctional disorders are identified, it is necessary to draw up an individual treatment plan during the period of exacerbation and rehabilitation therapy.

Sanitation of chronic foci of infection, elimination of functional disorders of the intestines, restoration of metabolic and energy disorders are necessary. Reception of multivitamin-mineral complexes is shown (such as "Multi-tabs baby" (from 1 year old), "Jungle" (from 4 years old), "Alphabet for children" (from 7 years old), oxyvital, extreme multivit, St. John's wort with vitamin C).

Given the high role of disorders of the autonomic and central nervous systems, stressful situations in the implementation of movement disorders of the biliary system in children, it is important to use means aimed at restoring sleep, behavioral reactions, neurotic disorders, autonomic disorders. A good effect on vegetative dysfunctions is provided by herbal preparations based on valerian, peppermint and lemon mint (Persen type). In case of sleep disturbances, difficulties in falling asleep, you can use the drug sanason in the form of tablets containing hop cones (it is prescribed one hour before bedtime).

Rehabilitation therapy provides for the rational use of physical therapy, depending on the type of nervous activity (at an accelerated pace - for choleric people, at a slow pace - for phlegmatic people). It is necessary to carry out a back massage 1-2 times a year - to restore impaired posture. Showing water treatments (baths, showers, underwater massage), massage of the hands and feet.

With dysfunctional disorders of the biliary tract, diet number 5 is recommended. It is known that the very fact of eating is a good stimulant for the flow of bile into the duodenum. Therefore, meals should be regular, not plentiful, up to 5-6 times a day, it is advisable to eat at the same time. The diet should be physiological, age-appropriate, easily digestible, with the optimal introduction of protein and carbohydrates, vitamins and microelements. In the treatment of gallbladder dysfunction caused by an increase in the tone of the sphincters of the biliary system, the diet should be characterized by a reduced fat content (0.5-0.6 g/kg/day). Fats of predominantly vegetable origin are recommended. Also shown: the use of dry heat at the site of the projection of the gallbladder; limiting the intake of choleretic drugs; taking antispasmodic drugs (no-shpa) in a short course, since they do not have a selective effect on sphincters, but affect the intestines. Among myotropic antispasmodics, attention is drawn to the drug Odeston, which has a selective antispasmodic effect on the sphincter of Oddi and the sphincter of the gallbladder, and also has a choleretic effect. The advantage of Odeston over other antispasmodics is that it has practically no effect on other smooth muscles, in particular the cardiovascular system and intestines. After removing the spasm and pain, it is recommended to use procedures and drugs that cause mechanical emptying of the gallbladder for 3-6 months according to an individual plan (tubage according to Demyanov).

With dysfunction of the gallbladder due to hypomotor dyskinesia, a diet with a sufficient content of vegetable fats (up to 1.0-1.2 g / kg / day) is recommended. To restore the motility of the digestive tract, prokinetics are prescribed - domperidone (motilium), cholecystokinetics (sorbide, xylitol, magnesium sulfate).

In the presence of not only hypomotor dysfunction of the gallbladder, but also an increase in the tone of the sphincters, the appointment of odeston is recommended, which ensures harmonious emptying of the intra- and extrahepatic biliary tract, timely and unhindered flow of bile into the duodenum.

Among the wide range of drugs used in diseases of the hepatobiliary system, the drug hepabene deserves attention. The advantage of hepabene is its plant origin, one capsule of the drug contains: fume extract 275 mg and milk thistle fruit dry extract 70-100 mg. Gepabene can be used to treat biliary dysfunction in children as a choleretic, antispasmodic and hepatoprotective agent.

You can use the drug hofitol, which is an aqueous solution of fresh artichoke leaves, which has a hepatoprotective effect. The active components included in this tool determine the systemic action of hofitol:

• cinnarine with caffeolichinic acids has a choleretic and hepatoprotective effect;
• flavonoids, selenium, manganese improve redox processes in cells;
• inulin, ascorbic acid, carotene, B vitamins contribute to the normalization of metabolic processes in cells. Children over 6 years of age are recommended to take 1-2 tablets 3 times a day 30 minutes before meals.

Liv.52 K is a hepatoprotector. The preparation contains a complex of biologically active substances of plant origin that normalize the protein-synthetic function of the liver, have a choleretic effect, and increase appetite. Children over 2 years old are prescribed 10-20 drops 2 times a day.

In dysfunctional disorders of the biliary tract, mineral waters are widely used. Water intake is usually carried out 3 times a day at the rate of 3-4 ml per kilogram of body weight per reception. In the first 5-6 days, in order to avoid a sharp choleretic effect, the dose of water is reduced by 2 times. With normal acidity, water is taken 45-60 minutes before meals, with increased acidity - 1.5 hours before meals or immediately after meals; with reduced secretion - during meals or 15-30 minutes before taking it. In diseases of the liver and biliary tract, mineral water is recommended to be taken heated up to 36-42 ° C 3 times a day 1 hour before meals. The course of treatment with mineral water is 4-6 months. Mineral water can be used for tubage, in order to improve the outflow of bile. Mineral waters of weak or medium mineralization such as Essentuki 4.17, Slavyanovskaya, Smirnovskaya, Borjomi, Jermuk, Arzni are used.

At present, Donat Mg mineral water has appeared in Russia, which is a carbonic magnesium-sodium-hydrocarbonate-sulfate natural healing mineral water with a total mineralization of over 13 g/l. The mineral carbonic spring Donat Mg is located on the territory of the balneo-climatic resort Rogaška Slatina in Slovenia. The content of Mg ions in this water exceeds 1000 mg/l and, together with a high concentration of free carbon dioxide of natural origin and a set of other cations and anions (sodium, potassium, calcium, lithium, bromine, fluorine, iodine, bicarbonate, sulfate, silicic acid) create an amazing chemical "cocktail" of biologically active macro- and microelements. Being a universal regulator of metabolic processes in the body, magnesium has a positive effect on all organs and systems (cardiovascular, nervous, muscular, bone, bronchopulmonary, urinary, endocrine). Magnesium has the most significant effect on the gastrointestinal tract, improving the peristalsis of the stomach, intestines, stimulating bile secretion. Mineral water Donat Mg for dysfunctional disorders of the biliary tract is dosed at the rate of 3-5 ml / kg of weight per 1 intake of water without gas (water at room temperature can be used).

Thus, early diagnosis and timely treatment of biliary tract dysfunction can prevent more severe pathology of the biliary system. A wide arsenal of drugs provides the opportunity to choose the most effective and safe drug or combination of drugs, depending on the pathogenetic features of biliary dysfunction.

N. A. Korovina,
I. N. Zakharova, doctor of medical sciences, professor
S. V. Shishkina
F. N. Izzadust
RMAPO, Moscow