A clinical case of drug-induced hepatitis in an obese pregnant woman. View full version. Doppler ultrasound diagnostics during pregnancy: what is it

Hepatitis A is an acute cyclic viral infection with fecal-oral transmission of the pathogen, characterized by impaired liver function.

Synonyms
Hepatitis a.
ICD-10 CODE
B15 Acute hepatitis A.

EPIDEMIOLOGY

Hepatitis A - intestinal infection, severe anthroponosis. The source of infection is patients with inapparent and manifest forms of hepatitis A. Persons with subclinical, obliterated and anicteric forms of the disease have the greatest epidemiological significance, the number of which can many times exceed the number of patients with icteric forms of hepatitis A. Infection of contact persons is possible already from the end of the incubation period, most intensively continues during the prodromal (preicteric) period and persists in the first days of the height of the disease (jaundice). Total duration excretion of the virus with faeces usually does not exceed 2-3 weeks. In recent years, it has been shown that viremia in hepatitis A can be longer (78–300 days or more).

The fecal-oral mechanism of transmission of the pathogen is realized by the water, food and contact-household route with the absolute predominance of the water route, which provides outbreaks and epidemics of hepatitis A. The possibility of the blood-contact (parenteral) route of transmission of the hepatitis A virus (about 5%) from patients with manifest and inapparent forms of infection (post-transfusion infection with hepatitis A in patients with hemophilia, infection of intravenous drug users).

The sexual route of transmission of the pathogen is not excluded, which is facilitated by promiscuity, the presence of other STIs, non-traditional sexual intercourse (primarily oral-anal contacts).

It occurs predominantly in children and young adults; In recent years, cases of hepatitis A in people older than 30 years and even 40 years have become noticeably more frequent. The disease is characterized by seasonality (mainly summer-autumn period).

The frequency of ups and downs of the disease ranges from 5 to 20 years.

Susceptibility to hepatitis A is high.

CLASSIFICATION

Allocate inapparent (subclinical) and manifest forms of hepatitis A. The latter includes erased, anicteric and icteric forms. According to the severity of the flow, they distinguish between mild, moderate and severe forms, downstream - acute and protracted. Chronic forms of hepatitis A are not observed.

ETIOLOGY (CAUSES) OF HEPATITIS A

The causative agent - Hepatitis A virus (HAV) - belongs to the family Picornaviridae, the genus Hepatovirus. Opened in 1973 by S. Feinstone. HAV is a small virus containing ribonucleic acid (RNA), has one specific Ag (HAAg), which is highly immunogenic. There are four known HAV genotypes that belong to the same serotype, which is the reason for the development of cross-immunity. Anti-HAV IgM circulate in the blood from the first days of illness for a short time (2–4 months), and HAV IgG appearing later remain in the body for a long time.

The hepatitis A virus is highly persistent in the environment, but is susceptible to ultraviolet irradiation and boiling (dies after 5 minutes).

PATHOGENESIS

The entrance gate is the mucous membranes of the gastrointestinal tract. In the vascular endothelium of the small intestine and mesenteric lymph nodes, the primary replication of the virus occurs. This is followed by viremia (in the clinical picture it manifests itself as an intoxication syndrome), followed by dissemination of the pathogen into the liver (a consequence of the hepatotropy of the virus). HAV replication in hepatocytes leads to dysfunction of cell membranes and intracellular metabolism with the development of cytolysis and dystrophy of liver cells. Simultaneously with the cytopathic effect of the virus (leading in hepatitis A), a certain role is assigned to immune damaging mechanisms. As a result, clinical biochemical syndromes characteristic of hepatitis develop - cytolytic, mesenchymal inflammatory, cholestatic.

The pathogenesis of complications of gestation

The pathogenesis of complications of gestation in hepatitis A has not been studied enough, including because of their great rarity.

CLINICAL PICTURE (SYMPTOMS) OF HEPATITIS A IN PREGNANT WOMEN

Hepatitis A is characterized by polymorphism clinical manifestations and self-limiting nature with reversible structural and functional changes in the liver.

The inapparent form prevails in frequency, its diagnosis is possible only with the help of ELISA when examining contact and sick persons (in epidemic foci).

Manifest forms proceed with a successive change of periods: incubation, prodromal (preicteric in the icteric form of the disease), peak (icteric in the presence of jaundice), convalescence. Infrequently, but relapses and complications of infection are possible.

The average incubation period is 15–45 days. The prodromal period lasts 5–7 days, proceeds with a variety of clinical symptoms. According to the leading syndrome, it is customary to distinguish influenza-like (feverish), dyspeptic, asthenovegetative, and the most frequently observed mixed variant of the prodrome with the corresponding clinical manifestations.

1-4 days after the first signs of the disease, the color of the urine changes (up to Brown color varying intensity), feces (acholia) become discolored, acquiring the consistency and color of white (gray) clay. Already in the prodromal period, hepatomegaly is possible with liver tenderness on palpation. Sometimes the spleen is slightly enlarged.

The peak period lasts an average of 2-3 weeks (with fluctuations from 1 week to 1.5-2 months, with the development of relapse - up to 6 months or more). The beginning of this period in the icteric form is marked by icteric staining of the visible mucous membranes and skin. At the same time, the well-being of patients noticeably improves, the signs of the prodromal period soften or disappear altogether. At the same time, the enlargement of the liver may continue - patients are concerned about heaviness and fullness in the epigastric region, moderate pain in the right hypochondrium. In 1/3 of cases during this period, splenomegaly is noted.

With the disappearance of jaundice, recovery normal color urine and feces, a period of convalescence begins. Its duration ranges from 1–2 to 8–12 months (depending on the presence or absence of relapses, exacerbations, and the course of the disease).

Erased and anicteric forms of hepatitis A usually proceed easily, with few symptoms, with a quick recovery.

The frequency of protracted manifest forms does not exceed 5–10%; in these cases, an increase in either the peak period or the convalescence period (with or without relapses, exacerbations) is noted, followed by clinical and laboratory recovery.

Hepatitis A in pregnant women proceeds in the same way as in non-pregnant women. There is no risk of antenatal transmission of the pathogen.

Complications of gestation

In rare severe and prolonged forms of hepatitis A, premature birth, in isolated cases - spontaneous miscarriages. There may be a threat of abortion, premature or early outflow of OB. In pregnant women with hepatitis A, as in other extragenital diseases, somewhat more often than in the population, early toxicosis, preeclampsia develop (including during childbirth).

DIAGNOSTICS OF HEPATITIS A IN PREGNANCY

Anamnesis

The diagnosis of hepatitis is established on the basis of epidemiological prerequisites (contact with a patient with hepatitis A), anamnestic data (symptom complexes of the prodromal period), indications of dark urine and fecal acholia.

Physical examination

During an objective examination, the main symptoms are icterus of the visible mucous membranes (the frenulum of the tongue, sclera), skin, slight or moderate enlargement and sensitivity / tenderness of the liver on palpation, much less often - slight splenomegaly.

Laboratory research

The most constant and diagnostically significant biochemical sign of hepatitis is an increase in the activity of the hepatic cell enzyme ALT by 10 times or more compared to the norm. Hypertransferasemia is the main marker of cytolysis syndrome. The increase in ALT activity begins already at the end of the prodromal period, reaches a maximum during the height of hepatitis, gradually decreases and normalizes during the convalescence period, indicating recovery. Hyperfermentemia is characteristic not only of icteric, but also anicteric forms of hepatitis. Violation of pigment metabolism is marked by the appearance of urobilinogen and bile pigments in the urine, an increase in the content of bilirubin in the blood, mainly conjugated (bound, direct bilirubin). Mesenchymal-inflammatory syndrome is detected by the determination of protein sediment samples. In hepatitis, the thymol test rises, and the sublimate titer decreases. The degree of their deviation from the norm is proportional to the severity of the infection. In many cases, hypocholesterolemia is noted due to a decrease in its synthesis by damaged hepatocytes. For hepatitis occurring without bacterial layers, leukopenia, neutropenia, relative and absolute lymphocytosis and monocytosis, normal ESR (often 2–3 mm/h) are characteristic.

Verification of hepatitis A is achieved using ELISA. The diagnosis of hepatitis A is considered confirmed by the determination of anti-HAV IgM in the blood serum during the prodromal period and during the peak period. Anti-HAV IgG is usually detected already during the convalescence period.

Instrumental Research

When performing an ultrasound scan, sometimes determine diffuse changes liver and increased echogenicity. There are no characteristic signs of hepatitis on ultrasound.

Differential Diagnosis

Hepatitis A is differentiated primarily from other etiological forms of hepatitis (B and C, mixed hepatitis), since in 40–70% of cases of jaundice in pregnant women they have viral nature. The basis of their differentiation is the use and correct interpretation of the results of the ELISA. Sometimes it becomes necessary to differentiate viral hepatitis, including hepatitis A, from the so-called satellite hepatitis (with infectious mononucleosis, pseudotuberculosis, intestinal yersiniosis, leptospirosis, etc.). In these cases, the basis for distinguishing liver damage is correct assessment symptoms that are not just associated with hepatitis-satellite, but determine the clinical appearance of diseases. The final solution to the problem of differentiation of viral hepatitis and other infectious liver lesions is the use of appropriate specific bacteriological and serological methods research.

In some cases, the differential diagnosis of viral hepatitis and jaundice directly related to pregnancy is more difficult. With CHB, itching comes to the fore different intensity with usually mild jaundice. There is no hepatosplenomegaly in CGD, as well as intoxication. Hepatosis is characterized by leukocytosis and an increase in ESR. The content of conjugated bilirubin in serum increases slightly, there is no hyperenzymemia (ALT) in most cases. However, in some pregnant women, ALT activity is still elevated - such options are the most difficult for differential diagnosis. The cholesterol content is usually elevated. Finally, there are no markers of viral hepatitis in CGD (exceptions to this rule are possible if CGD develops against the background of chronic hepatitis B and C, i.e. with comorbidity, the frequency of which has been increasing everywhere in recent years).

The greatest difficulty arises in distinguishing severe forms hepatitis (usually hepatitis B) and Sheehan's syndrome - acute fatty gestosis of pregnant women. Their clinical similarity can be very significant.

The correct differentiation of hepatitis and acute fatty preeclampsia in pregnant women is most facilitated by a detailed biochemical study, especially with indications for the treatment of a pregnant woman with tetracycline antibiotics in large doses in the third trimester of gestation. The liver in acute fatty gestosis of pregnant women is usually not enlarged, signs of DIC, hypoproteinemia (often with ascites), azotemia, and high leukocytosis are noted. The content of direct (conjugated) bilirubin increases moderately or slightly, the activity of cytolysis markers (ALT, AST) is low. The activity of alkaline phosphatase is increased, the sublimate test is reduced, however, these indicators have no differential diagnostic value, since they are also characteristic of hepatitis, as well as a decrease in prothrombin. On the contrary, hypoglycemia, which is almost not amenable to correction, and decompensated metabolic acidosis, which are characteristic of acute fatty gestosis of pregnant women and are uncharacteristic of hepatitis, are highly informative. Markers of hepatitis are absent, if we are not talking about comorbidity.

Currently, a rare variant of differential diagnosis is hepatitis and preeclampsia with liver damage. The latter is the extreme severity of preeclampsia with all its manifestations, steadily increasing over time with inadequate therapy for severe nephropathy. Biochemical signs of cytolysis, pigmentary disorders are moderately or slightly expressed in preeclampsia and do not correlate with the severity of other manifestations of pregnancy complications and the general condition of the patient.

Occasionally, errors in the diagnosis of viral hepatitis, primarily hepatitis A, occur in pregnant women with jaundice that occurs with severe early toxicosis. In this case, repeated "excessive" vomiting and dehydration come to the fore. The course of the complication, unlike hepatitis, does not have a cycle, jaundice is mild, the intoxication syndrome is insignificant, the liver and spleen remain within normal sizes. The content of bilirubin rarely exceeds the norm by more than 2 times and usually increases due to the non-conjugated (indirect, unbound) fraction. There is usually no increase in ALT activity, as well as no DIC. Often, toxicosis develops acetonuria, which does not happen with hepatitis. Finally, with early toxicosis, immunoserological markers of hepatitis are not determined.

When differentiating hepatitis A (and other hepatitis) with HELLP-syndrome, the reference points are considered to be the presence in the latter hemolytic anemia, thrombocytopenia, increased levels of unconjugated (indirect, free) bilirubin. Hypertension can help in the differential diagnosis, as with hepatitis A, a tendency to hypotension is noted (if the patient does not suffer from hypertension or renal disease).

Hepatitis A does not aggravate the course of the HELLP syndrome.

Indications for consulting other specialists

With the appearance of jaundice syndrome (icteric staining of visible mucous membranes and skin, darkening of urine, acholia feces, increased content bilirubin), hepatomegaly, splenomegaly, intoxication syndrome and fever, increased activity of hepatocellular enzymes (ALT) against the background of leukopenia and normal/reduced ESR, consultation of an infectious disease specialist and his joint observation of a pregnant woman with an obstetrician are indicated.

Diagnosis example

Viral hepatitis A, icteric form, severe course. Relapse from 05.05.2007. Pregnancy 32–34 weeks.

TREATMENT OF HEPATITIS A DURING PREGNANCY

Non-drug treatment

Most patients with hepatitis A, including pregnant women, do not need active drug therapy. The basis of the treatment of patients is considered a sparing regimen and a rational diet. During the height of the infection, bed rest is indicated. The volume of fluid consumed (preferably alkaline mineral) is important - at least 2-3 liters per day. Within 6 months after recovery, limit physical exercise and recommend a sparing (mechanically and thermally) diet with the exception of acute, fatty foods and alcohol.

Medical treatment

With severe intoxication, intravenous detoxification is carried out (saline solutions, 5% glucose solution, dextrans, albumin). A good effect is given by detoxifiers for oral administration: polyphepan ©, povidone, rehydron ©, etc.

During the period of convalescence, multivitamins, hepatoprotectors (silibinin, Essentiale©, etc.) are prescribed to restore disturbed metabolism. With posthepatitis biliary dyskinesia, antispasmodics are prescribed (better than atropine, including belladonna, belladonna) and choleretic agents.

Surgery

Surgical treatment of hepatitis A is not carried out. Termination of pregnancy in hepatitis is not indicated, as it can worsen the prognosis of the disease. Exceptions - the occurrence of placental abruption with bleeding, the threat of uterine rupture.

Prevention and prediction of complications of gestation

In the last 10-15 years hospitalization of patients with hepatitis A is optional. Patients can stay at home under the supervision of an outpatient doctor (with the exception of persons living in hostels, which is dictated by anti-epidemic considerations).

As for pregnant women with hepatitis A, they should be hospitalized in an infectious diseases hospital to monitor and timely identify the threat of complications of gestation and prevent adverse pregnancy outcomes. In the hospital, the pregnant woman should be observed by two attending physicians - an infectious disease specialist and an obstetrician.

Features of the treatment of complications of gestation

Complications of gestation that have arisen in a patient with hepatitis A in any trimester are corrected according to the principles adopted in obstetrics by appropriate methods and means. This also applies to complications during childbirth and the postpartum period.

Indications for hospitalization

Pregnant women with hepatitis, including hepatitis A, are hospitalized in an infectious diseases hospital according to clinical indications(for monitoring the course of gestation, prevention and timely correction of possible complications of pregnancy).

TREATMENT EFFECTIVENESS ASSESSMENT

Therapy for hepatitis A is well developed, most patients recover completely. Mortality does not exceed 0.2–0.4% and is associated with severe concomitant pathology.

With adequate management of a pregnant woman and proper joint supervision of an obstetrician and an infectious disease specialist, pregnancy outcomes in women with hepatitis A are also favorable (for the mother, fetus and newborn).

CHOICE OF DATE AND METHOD OF DELIVERY

The best tactic in relation to delivery of a patient with hepatitis A is considered urgent delivery per vias naturalis.

INFORMATION FOR THE PATIENT

Hepatitis A is an acute intestinal infection, therefore, one of the main conditions for one's own protection against it is strict observance of personal hygiene rules. In order to avoid sexual infection (very rare), it is necessary to exclude oral-anal sexual intercourse. With the development of the disease in a pregnant woman, hospitalization is mandatory. Determination of anti-HAV IgM in a newborn for 3-6 months does not indicate infection, since they are transmitted from the mother. Breastfeeding is permitted provided that all hygiene rules (nipple care, etc.) are observed. The use of hormonal contraceptives is permissible no earlier than 8-12 months after the disease. There are no contraindications for other contraceptives. Repeated pregnancy possible 1–2 years after hepatitis.

Hyperthermia is a protective physiological reaction of the body. Its appearance at the beginning of pregnancy is due to delayed heat transfer as a result of hormonal changes. In most cases, an increase in temperature during this period means the following:

• First trimester - physiological increase, colds.
• Second trimester - inflammation of the kidneys, infectious infection of the respiratory system.
• Third trimester - availability viral infections, acute appendicitis, abnormal liver function.

This classification allows us to divide the causes of hyperthermia into:

• physiological;
• diseases that allow outpatient treatment;
• disease requiring hospitalization.

Symptoms

Clinical manifestations of hyperthermia are expressed in an increase in body temperature. Its indicators have a direct relationship with the cause. With hyperthermia of pregnant women, the thermometer readings are between 37 and 37.5 degrees. There are no associated symptoms. This increase is due to the action of the hormone progesterone, the production of which increases during pregnancy.

The temperature caused by an infectious disease is accompanied by various symptoms.

Common signs of an infection in the body are:

• general malaise;
• runny nose;
• pain radiating to the eyes;
• headache;
• sore throat;
• hoarseness of voice;
• cough;
• shortness of breath;
• pallor of the skin;
• irritability;
• lower back pain;
• frequent painful urination.
• mental retardation;
• muscle hypotension.

Diagnosis of hyperthermia during pregnancy

Any increase in temperature requires a medical consultation and examination. To establish a diagnosis, expectant mother research needed:

• general blood analysis;
• general urine analysis;
• blood chemistry;
• analysis for human immunodeficiency virus, syphilis, hepatitis B and C;
• coprogram;
• fluorography;
• determination of hormones in the blood;
• ultrasound diagnostics of organs.

Complications

Hyperthermia is a protective function of the body. However, during pregnancy, it can cause disturbances in the development of the fetus. It depends on the duration of the temperature increase, its indicators and the gestational age. Hyperthermia during pregnancy is dangerous if the temperature exceeds 38 degrees and is maintained for several days. Hyperthermia provokes:

• Violation of the work of the heart and blood vessels of the mother due to intoxication.
• Detrimental effect on the placenta - placental insufficiency and fetal growth retardation develop.
• Increased uterine tone, which is fraught with spontaneous abortion.
• Congenital pathologies of development. An elevated temperature in the first half of pregnancy is fraught with the following pathological disorders: abnormal development of the central nervous system, heart and blood vessels; underdevelopment of any part of the body; mental retardation; muscle hypotension.

Treatment

What can you do

In some cases, the temperature can be lowered without medication. For this you need:

• Observe bed rest.
• Don't wrap up.
• Ventilate the room.
• Use a wet compress on the forehead and large veins(elbow and knee bends). The water must not be too cold or hot.
• Wipe the skin.
• Abundantly drink.

What does a doctor do

Treatment of hyperthermia is based on the elimination of its causes. Treatment of the underlying disease is carried out under the supervision of a physician. The temperature must be lowered if:

• the indicator fluctuates over 38 degrees in the first trimesters of pregnancy;
• 38 degrees accompany the third trimester of pregnancy, which is a significant burden on the heart and blood vessels;
• 37.5 degrees is kept constantly with concomitant diseases, its decrease will relieve exacerbations.

Taking antipyretics during pregnancy is carried out on the recommendation of a doctor. If necessary, antiviral and antibacterial drugs are prescribed.

Prevention

There are no specific measures to prevent a rise in temperature. The only rule, the implementation of which will help to avoid hyperthermia, is to maintain health during pregnancy. Therefore, you should not visit crowded places, contact with infected people and get cold. It is necessary to adhere to the observance of sanitary hygiene standards, organize a rational diet and drinking regimen.

The invention relates to medicine, namely to diagnostic methods. The essence of the method: the patient's blood serum is examined, applied to a glass slide, covered with a coverslip and dried at 37-38 o C for 1.5-2 hours. The crystals formed in the patient's blood serum are compared with the crystals of model composites, which are previously obtained by enriching the serum blood of a healthy person with enzymes trypsin, amylase, lipase. In the presence of crystals in the form of cellular or dendritic networks, hypertrypsinemia is diagnosed, in the presence of subparallel lamellae - hyperamylasemia, in the presence of bubble chambers with processes - hyperlipasemia. The method provides high information content and reliability. 11 ill., 1 tab.

The invention relates to medicine and can be used in the treatment of diseases of the pancreas. The timely determination of violations of pancreatic enzyme production, the diagnosis of hyperenzymemia (the release of lipase, amylase, trypsin) continue to cause difficulties in the practice of doctors of various specialties (therapists, gastroenterologists, surgeons, endocrinologists, etc.). Often, an attack of acute pancreatitis is not recognized in a timely manner, but is interpreted as a clinic of an acute abdomen, due to perforation of a stomach ulcer, an attack of acute cholecystitis, acute appendicitis, intestinal obstruction. This leads to tactical errors (Henderson J. Pathophysiology of the digestive system. - St. Petersburg, 1997, p. 197-224). Violation of the external secretion of the pancreas (PG) can also be observed in chronic pancreatitis, as well as in other diseases of the gastrointestinal tract, in which the pancreas suffers for the second time, with the development of complications after operations on the pancreas and nearby organs. There are known cases of violation of the external secretion of the pancreas (primarily, an increase in the blood levels of lipase, amylase, trypsin enzymes) during cardiovascular bypass surgery, heart transplantation, kidney transplantation. rise pain syndrome in acute pancreatitis and exacerbation of chronic pancreatitis, it is accompanied by an increase in the content of amylase, lipase, and trypsin enzymes in the blood (Zimmerman Y.S. Chronic pancreatitis. Guidelines . - Perm, 1990; Loginov AS, Speransky MD, Astashenkova K. Yu. Screening methods for rapid diagnosis of liver and pancreas diseases. Guidelines. - M., 1987; Grigoriev P.Ya., Yakovenko E.P. Diagnosis and treatment of diseases of the digestive system. - M.: Medicine, 1996). Diagnosis of hyperenzymemia provides valuable information about the violation of the external secretion of the pancreas. The most important in the diagnostic process is the study of the content of enzymes in plasma of blood serum (SC), the determination of the content of α-amylase, lipase, trypsin. α-amylase is produced by the pancreas and salivary glands. Hyperamylasemia is observed in many diseases, but is most pronounced in acute pancreatitis. Lipase catalyzes the breakdown of glycerides, higher fatty acids. It is produced in the pancreas, lungs, and intestines. An increase in the activity of serum lipase may be a consequence of the pathology of the pancreas, lungs, intestines, stomach, leukocyte blood germ. Trypsin is produced in the pancreas, from which, as part of the pancreatic juice (in the form of trypsinogen), it enters the duodenum and is involved in the digestion of food proteins. When the pancreas is damaged, trypsin activity increases sharply, especially in acute pancreatitis. Diagnosis of violations of the enzyme-forming function of the pancreas is carried out by quantitative determination of the content of enzymes in blood serum - α-amylase, lipase, trypsin, as well as in other biological fluids. In this case, various methods for the quantitative determination of enzymes are used (Medical laboratory technologies. Handbook. T.2. - St. Petersburg, 1999; Biochemical methods of research in the clinic. - M., 1969). Lipase activity is determined in most methods on the basis of titrimetric determination of the amount of fatty acids released under the action of the enzyme. These methods differ in the substrate used: olive oil, tween, terbutyrin (Biochemical research methods in the clinic. Handbook. - M., 1969, p. 186-191). The disadvantage of these methods is their low specificity, tk. these substrates are hydrolyzed not only by lipase, but also by other hepatic esterases. The titrimetric method for determining lipase is based on the titration of fatty acids released as a result of enzymatic hydrolysis, the photometric method is associated with the introduction of special reagents into the reaction mixture. As a unified method, a turbidimetric method is used, in which olive oil is used as a substrate (Reference. Medical laboratory technologies. T.2. - St. Petersburg, 1999, pp. 39-41). Principle: Spectrophotometric determination of the change in turbidity of an olive oil suspension under the action of lipase. Reagents: olive oil, aluminum oxide, copper sulfate, ethyl alcohol, sodium salt of deoxycholic acid, hydrochloric acid. Special equipment: spectrophotometer with temperature-controlled cuvette. Determination course: Before determination, the studied blood serum and reagents are warmed up to the measurement temperature. 3 ml of a working emulsion of olive oil is poured into the cuvette, 0.1 ml of blood serum is added, mixed (without shaking) and placed in a thermostat at 30 o C or 37 o C, after 2 minutes the extinction (E1) is measured against distilled water or air at wavelength of 340 nm in a cuvette with an optical path length of 10 mm, then the cuvette is again placed in a thermostat at the same temperature and after 5 minutes the extinction (E2) is measured, calculating ΔE for 1 min. The calculation of lipase activity is carried out according to the formula

The disadvantages of the method:
- violation of the nativeness of the SC (heating, connection with the reagent);
- the use of reagents requiring additional processing;
- the use of expensive equipment;
- indirect determination of the presence of lipase.

Trypsin is determined in blood serum by determining its activity according to Erlanger et al. in the modification of V.A. Shornikova (Biochemical methods of research in the clinic. - L., 1969, p. 206-208). The method is based on trypsin cleavage of a synthetic colorless substrate - benzoylarginine-p-nitroanilide - with the formation of colored p-nitroaniline, the amount of which is determined calibrimetrically. Disadvantage of the method:
- the use of reagents is accompanied by the complexity and high cost of the method;
- use of a spectrophotometer;
- carrying out calculations;
- the unreliability of the results. The most common in recent years is the determination of trypsin using the Bio-LA CHEMA-test kit (Kasafirek E., Chavko M., Bartik M.: Coll. Czechisiov. Chem. Commum. 36, 4070, 1971) - by the photometric method. The method is based on the ability of trypsin to hydrolyze the chromogenic substrate. N-alpha-tosyl-L-arginine-4-nitroanilide. The resulting 4-nitroanilide is determined photometrically (kinetic method). kinetic way. Reagents: Tris buffer 3.4 mmol, calcium chloride 1.7 mmol/vial, substrate L-pack 10 mmol/l, standard solution 4-nitroaniline 500 µmol/l. The composition of the incubation mixture:
Tris buffer, pH 8.2 (25 o C) - 40.6 mmol / l,
L-TAPA - 0.94 mmol / l,
CaCl - 20.6 mmol / l. The volume ratio of serum:incubation mixture is 1:16. Auxiliary reagent:
acetic acid solution - 1.75 mmol / l. Definition progress:
1. Prepare a buffer solution with a reagent. 2. Prepare a working solution (mix reagent - 1 share of reagent 2 and 9 shares of buffer solution). Measure the optical density in the range of 30-90 seconds and calculate the change in optical density per minute (ΔA). Measure the absorbance of the standard against the blank (A2). Formula calculation

The disadvantages of the method:
1. Violation of serum nativeness.

2. Using a photometer. 3. Preparation of working and buffer solutions. Method for determining α-amylase activity
The biological fluids are divided into three main groups:
1. Reductometric, based on the determination of sugars formed from starch. 2. Amyloclastic, based on determining the amount of undigested starch by its reaction with iodine. 3. Chromolytic, based on the use of substrate-dye complexes, which, under the action of α-amylase, decompose to form a water-soluble dye (Handbook. Medical laboratory technologies. V.2. - St. Petersburg, 1993, pp. 19 and 20). Disadvantages of the above methods:
- use of substrates;
- Violation of the nativeness of blood serum;
- use of an indirect reaction (starch + iodine);
- complexity and unreliability. We used as a prototype a unified amyloclastic method with a persistent starch substrate (Karavey's method) (Handbook. Medical laboratory technologies. V.2. - St. Petersburg, 1999, pp. 20 and 21). Principle: α-amylase hydrolyzes the breakdown of starch to form end products that do not give a color reaction with iodine. The activity of α-amylase is judged by the decrease in color intensity. Reagents:
1. Benzoic acid. 2. Sodium hydrogen phosphate (Na 2 HPO 4). 3. Starch, soluble for nephelometry or Lintner (specially available as a substrate). 4. 154 mM (0.9%) sodium chloride solution: Dissolve 9 g of NaCl in a small amount of distilled water in a 1 L volumetric flask, then make up to the mark. 5. Substrate buffer solution, pH 7.0: 13.3 g of sodium hydrogen phosphate and 2 g of benzoic acid are dissolved in 250 ml of 154 mm sodium chloride solution and brought to a boil. Suspend 0.2 g of soluble starch in a small amount of cold distilled water and add to the boiling buffer solution. Boil for 1 minute, cool and dilute to 500 ml with distilled water. The substrate buffer solution should be clear and stable at room temperature for 10-12 days. 6. Potassium iodide (KI). 7. Potassium iodate (KIO 3). 8. Potassium fluoride (KF). 9. Concentrated HCl. 10. 0.01 n. iodine solution: 0.036 g of KIO 3 + 0.45 g of KI are dissolved in 40 ml of distilled water and 0.09 ml of concentrated HCl is added slowly with stirring. Dissolve 5 g of potassium fluoride in 50 ml of distilled water, filter into a volumetric flask, add 40 ml of iodine solution and top up with distilled water to a volume of 100 ml. Store in a dark glass container. Valid for a month. If potassium fluoride is not added to the working solution of iodine, then it should be prepared daily from 0.1 N. solution I. Progress of determination:
- 0.5 ml of the substrate-buffer solution is placed in a test tube, heated for 5 minutes at a temperature of 37 o C, add 0.01 ml of blood serum. - Incubate for 7.5 minutes at a temperature of 37 o C. The incubation time must be accurately counted by a stopwatch from the moment biological fluid(blood serum) into a starch substrate. Immediately after incubation, add 0.5 ml of 0.01 N. iodine solution and bring the volume with distilled water to 5 ml. - Photometrically in a cuvette with an optical path length of 10 mm at a wavelength N (3.3-8.9 mg / s l) 630-690 nm (red light filter) against distilled water. Make a calculation:
The activity of α-amylase is expressed in milligrams or grams of 1 starch hydrolyzed by 1 liter of biological fluid for 1 s of incubation at 37 o C. The calculation is made according to the formula

,
where A is the activity of α-amylase, mg/s l;
Ek - extinction of the control sample,
Eo - extinction of the experimental sample;
0.2 - the amount of starch introduced into the experimental and control samples, mg;
10 5 - coefficient of intersection per 1 liter of blood serum;
7.5 60 - crossover ratio per 1 s of incubation.

The disadvantages of the method:
1. Labor intensity. 2. Use (preparation) of complex reagents. 3. Duration of the study. 4. Exposure to toxic substances. 5. Violation of the nativeness of the studied enzyme. 6. Use of a photometer (instrument complexity). 7. Unreliability of the definition. Tasks:
1. Simplify the sample preparation method. 2. Increase information content by isolating microtypes of crystals characteristic of selective hyperenzymemia. 3. To improve the accuracy and quality of diagnosing disorders of the exocrine function of the pancreas. The essence of the invention lies in the fact that for the diagnosis of disorders of the exocrine function of the pancreas (hyperfermentemia), blood serum is applied to a glass slide, covered with a coverslip, dried at a temperature of 37-38 o C, kept in the open air for 1.5-2 hours, then follow in transmitted light and in the presence of cellular or dendritic networks - hypertrypsinemia is diagnosed, subparallel lamellae - hyperamylasemia, bubble chambers with processes - hyperlipasemia. The method is carried out as follows:
1. Blood is taken from a vein - 3.0 ml, centrifuged to obtain serum. 2. Serum in the form of drops with a volume of 0.01-0.02 ml each is applied to a glass slide, covered with a cover glass. 3. Dry in a thermostat at a temperature of 37-38 o C for 1.5-2 hours. 4. Keep outdoors for 1.5-2 hours. 5. Under a microscope in transmitted light, the picture of crystallization is studied and, if there are crystals in the form of cellular or dendritic networks in the preparation, hypertrypsinemia is diagnosed, subparallel lamellae - hyperamylasemia, bubble chambers with processes - hyperlipasemia. We previously examined the reference crystallograms, for which the blood serum of a healthy person, placed in a container of quartz, was enriched with enzymes - amylase, lipase, trypsin. Photo 1 (a-d) shows the reference crystallograms (CG) of the blood serum of a healthy person, enriched with enzymes. KG is made with crystals in the form of a cellular mesh and a dendritic mesh when the blood serum (SC) is supersaturated with the enzyme trypsin; model composite of hypertrypsinemia, trypsin concentration was 1200 and 1800 mmol/l, respectively, photo 1 (a, b); crystals from subparallel lamellae upon supersaturation of SA with the enzyme amylase, model composite of hyperamylasemia, amylase concentration was 94 mmol/l h, photo 1c; crystals from bubble chambers with processes when supersaturation of SK with lipase enzyme, model composite of hyperlipasemia, lipase concentration - 5.4 c.u., photo 1 g. The method was tested on 800 patients. Examples
Example 1, photo 2 (a, c). Patient I., case history (IB) 1819. Diagnosis: acute pancreatitis. Photo 2 a-c shows CG of the blood serum of patient I., there are bubble chambers with processes (a, b), a dendritic mesh (c). Technology: blood was taken from the vein of patient I. in the amount of 3 ml, the blood was centrifuged to obtain serum. Drops of SC (5) with a volume of 0.01 ml each were applied to a glass slide, each drop was covered with a cover slip and dried in a thermostat for 1.5 hours at a temperature of +37 o C. The drug was kept in the open air for 2 hours, then studied in a passing light under a microscope. Crystals were found, represented by bubble chambers with processes, a dendritic network. At the same time, the level of lipase and trypsin was determined in the patient's SC, which turned out to be elevated and amounted to 3.4 c.u., respectively. (norm 0.8 c.u.), 630 mmol/l (norm 220 mmol/l). The suspected hyperenzymemia (hyperlipasemia and hypertrypsinemia) was confirmed. Example 2, photo 3 (a, b). Patient Zh., medical history 9680. Diagnosis: chronic recurrent pancreatitis, painful form. Photo 3 a, b shows the CG of the blood serum of patient Zh., there is a dendritic network (a), subparallel lamellae (b). Technology: 3 ml of blood was taken from the vein of patient Zh., which was centrifuged to obtain SC. Drops of SC (3) with a volume of 0.02 ml each were applied to a glass slide, each was covered with a cover slip and dried in a thermostat for 2 hours at a temperature of +38 o C. The preparation was kept in the open air for 1.5 hours, then microscoped. Crystals were found - a dendritic network and subparallel lamellae. At the same time, trypsin and amylase levels were determined in the patient's SC, which turned out to be elevated and, respectively, amounted to 780 mmol/l (norm 220 mmol/l) and 72 mmol/l.h. (norm 18.5 mmol / l. H.). The suspected hyperenzymemia (hypertripsinemia and hyperamylasemia) was confirmed. Example 3, photo 4 (a, b). Patient G., case history 10620. Diagnosis: peptic ulcer duodenal ulcer, complicated by cicatricial deformity of the bulb, suspicion of chronic pancreatitis. Photo 4 a, b shows the CG of the blood serum of patient G., there is a dendritic mesh (a) and a mesh mesh (b). Technology: 3 ml of blood was taken from the vein of patient G., which was centrifuged. Drops of SC (4) with a volume of 0.02 ml each were applied to a glass slide, each was covered with a cover slip and dried in a thermostat for 2 hours at a temperature of +38 o C. The drug was kept in the open air for 1.5 hours, then studied in transmitted light . Crystals were found - a dendritic network and a cellular network. At the same time, the level of trypsin in the patient's SC was determined, which turned out to be elevated and amounted to 630 mmol/l (the norm is 220 mmol/l). The suspected hyperenzymemia was confirmed. Example 4, photo 5 (a, b). Patient M., medical history 10972. Diagnosis: chronic recurrent pancreatitis, stage of fading exacerbation, erosive reflux esophagitis, chronic gastroduodenitis. Photo 5 a, b shows the CG of the blood serum of patient M., there are bubble chambers with processes. Technology: 3 ml of blood was taken from the vein of patient M., the blood was centrifuged. Drops of SC (3) with a volume of 0.02 ml each were applied to a glass slide and dried in a thermostat for 2 hours at a temperature of +38 o C. The drug was kept in the open air for 2 hours, then microscoped. Found crystals in the form of bubble chambers with processes. At the same time, the level of lipase was determined in the SC, which turned out to be elevated and amounted to 2.1 c.u. (norm 0.8 c.u.). The alleged hyperenzymemia (hyperlipasemia) was confirmed. Example 5, photo 6 (a, b). Patient O., case history 9418. Diagnosis: chronic gastroduodenitis, postcholecystectomy syndrome. Chronic pancreatitis, pain form. Photo 6 a, b shows the CG of the blood serum of patient O., there are subparallel lamellae (a) and a mesh (b). Technology: 3 ml of blood was taken from the vein of patient O., which was centrifuged. Drops of SC (5) with a volume of 0.01 ml each were applied to a slide, each drop was covered with a slide and dried in a thermostat at a temperature of +37 o C for 2 hours. The preparation was kept in the open air for 1.5 hours, then microscoped. Crystals were found - subparallel lamellas and a cellular grid. At the same time, the content of amylase and trypsin was determined in the SC, which turned out to be elevated and, accordingly, amounted to 28.5 mmol/L. hours and 290 mmol / l. The suspected hyperenzymemia (hyperamylasemia and hypertrypsinemia) was confirmed. Example 6, photo 7. Patient V., medical history 1443. Diagnosis: chronic gastroduodenitis, chronic cholecystitis, suspicion of chronic pancreatitis. Photo 7 shows the CG of the blood serum of patient V., there is a dendritic mesh. Technology: drops of SC from patient V. were applied to a glass slide (5 drops), each with a volume of 0.02 ml. Each drop was covered with a cover slip and dried in a thermostat for 1.5 hours at a temperature of +38 o C. The sample was kept in the open air for 1.5 hours and examined under a microscope. Crystals in the form of a dendritic network were found. At the same time, the level of trypsin was determined in the SC, which turned out to be elevated and amounted to 285 mmol/l (the norm is 220 mmol/l). The alleged hyperenzymemia (hypertripsinemia) was confirmed. Example 7, photo 8 (a, b). Patient B., case history 9389. Diagnosis: duodenal ulcer in the stage of incomplete remission. Catarrhal reflux esophagitis. Chronic recurrent pancreatitis, pain form. Photo 8 a, b shows CG of blood serum, there are bubble chambers with processes (a) and subparallel lamellae (b). Technology: 4 drops of patient B.'s SC, each with a volume of 0.01 ml, were applied to a glass slide, each was covered with a coverslip and dried in a thermostat at a temperature of +37 o C for 1.5 hours. The sample was kept in the open air for 1.5 hours and microscoped. Crystals were found: bubble chambers with processes and subparallel lamellae. At the same time, the level of lipase and amylase was determined in the SC, which turned out to be elevated and amounted to 1.2 c.u., respectively. e. (norm 0.8 c.u.) and 39.8 mmol / l.h. (Norm 18.5 mmol / l.h.) The alleged hyperenzymemia (hyperamylasemia and hyperlipasemia) was confirmed. Example 8, photo 9 (a, b). Patient Zh., medical history 13200. Diagnosis: chronic pancreatitis, period of exacerbation. Photo 9 (a, b) shows the CG of the blood serum of patient G., there are subparallel lamellae. Technology: blood from a vein in the amount of 3 ml was taken from a patient Zh., centrifuged. Drops of SK (4) each with a volume of 0.01 ml were applied to a glass slide. Each drop was covered with a cover slip and dried in a thermostat for 1.5 hours at a temperature of +38 o C. The sample was kept in the open air for 1.5 hours, then examined under a microscope in transmitted light. Crystals in the form of subparallel lamellae were found. At the same time, the level of amylase in the SC was determined, which turned out to be elevated and amounted to 45 mmol/l.h. The alleged hyperfermentemia (hyperamylasemia) was confirmed, which indicates a violation of the exocrine function of the pancreas. Example 9, photo 10 (a, b). Patient B., medical history 12228. Diagnosis: chronic pancreatitis, stage of incomplete exacerbation. Chronic erosive gastritis, catarrhal bulbitis. Photo 10 a, b shows the CG of the blood serum of patient B., subparallel lamellae (a) and bubble chambers with processes (b) are visible. Technology: drops of SC (3) of patient B. were applied to a glass slide, each with a volume of 0.01 ml. Each drop was covered with a cover slip and dried in a thermostat at a temperature of +37 o C for 1.5 hours. The sample was kept in the open air for 2 hours and microscoped. Subparallel lamellae and bubble chambers with outgrowths were found. At the same time, the level of amylase and lipase was determined in the patient's SC, which turned out to be elevated and, respectively, amounted to 78 mmol/l.h. and 3.8 c.u. (norm of amylase - 18.5 mmol / l.h. and lipase - 0.8 y. e.). The expected hyperenzymemia (hyperamylasemia and hyperlipasemia) was confirmed. Example 10, photo 11. Patient Sh., medical history 10767. Diagnosis: duodenal ulcer with localization of the ulcer on the back wall of the duodenal bulb, HP-associated, stage of exacerbation. reactive pancreatitis. Photo 11 shows the CG of the blood serum of patient III, there are subparallel lamellae. Technology: drops of the patient Sh.'s SC were applied to a glass slide (5 drops), each with a volume of 0.01 ml. Each drop was covered with a cover slip and dried in a thermostat for 2 hours at a temperature of +38 o C, the sample was kept in the open air for 1.5 hours and microscoped. Subparallel lamellas were found. At the same time, the level of amylase was determined in the SC, which turned out to be elevated and amounted to 48 mmol/l.h. (norm - 18.5 mmol / l.h.). The suspected hyperenzymemia (hyperamylasemia) was confirmed. The implementation method allows:
1. Simplify the definition of hyperenzymemia. 2 Eliminate the use of complex chemicals and instruments. 3. Reduce the cost of diagnostics. 4. Creates the possibility of express diagnostics of disorders of the exocrine function of the pancreas. 5. Provides high information content. 6. Increases the reliability of obtaining results.

Claim

A method for diagnosing a violation of the external secretory function of the pancreas, including the study of the patient's blood serum, applied to a glass slide, covered with a coverslip, dried at 37-38 o C for 1.5-2 hours, followed by the study of crystals, characterized in that model composites are previously created by enriching the blood serum of a healthy person with enzymes, with the crystals of which the crystals of the patient's blood serum are compared, and diagnosing hyperenzymemia: in the presence of crystals in the form of cellular or dendritic networks, hypertrypsinemia is diagnosed, in the presence of subparallel lamellae - hyperamylasemia, in the presence of bubble chambers with processes - hyperlipasemia.

MM4A Early termination of a patent of the Russian Federation for an invention due to non-payment of the fee for maintaining the patent in force by the due date

Hyperfermentemia (with a predominant increase in ALT activity by 30-50 times) is recorded during the entire icteric period, then there is a gradual decrease in its level. The protein-synthetic function of the liver in HBV is impaired in the severe course of the disease, which is manifested by a decrease in the sublimate test, albumin content, prothrombin index, activity (3-lipoproteins. Indicator thymol test usually does not increase.

There are no significant abnormalities in the peripheral blood. the number of leukocytes is normal or low.

The recovery period can last up to six months. Clinical and biochemical changes disappear slowly. The content of bilirubin in the blood serum normalizes relatively quickly (within 2-4 weeks), and increased activity enzymes are stored from 1 to 3 months. In a number of patients, a wave-like nature of hyperenzymemia can be observed during the period of convalescence. It should be taken into account that the recurrence of the disease with enzymatic exacerbation and hyperbilirubinemia requires the exclusion of HDV infection.

Clinical variants of HBV can be very diverse: icteric, anicteric, erased, inapparent (subclinical). It is difficult to judge the frequency of each of them, since usually only the icteric variant is diagnosed and, accordingly, recorded. Meanwhile. according to epidemiological studies, the anicteric variant is found 20-40 times more often than the icteric one.

One of the features of the icteric variant of HBV is the severity of the cholestatic syndrome in some cases. At the same time, intoxication is insignificant, the main complaint of patients is itching of the skin; jaundice is intense, with a greenish or gray-green tint of the skin, persists for a long time. The liver is significantly enlarged, dense. Acholic feces, dark urine for a long time. In the blood serum - high bilirubinemia. elevated cholesterol and alkaline phosphatase activity. and the level of hyieralatemim is relatively low (5-10 norms). The icteric period can be delayed up to 2-4 months, the full normalization of biochemical changes occurs even later.

HBV can be mild, moderate, or severe.

The most informative for assessing the severity of viral hepatitis is the syndrome of hepatic intoxication, which is manifested by weakness, adynamia, loss of appetite, vegetovascular disorders, and in some cases, impaired consciousness. It is the severity of intoxication (in combination with the results laboratory research, primarily prothrombin activity) characterizes the severity of hepatitis.

59. Breslau N., Lipton R.B., Stewart W.F. et al. Comorbidity of migraine and depression: Investigating potential etiology and prognosis. Neurology. 2003; 60:1308-12.

60. Lake A.E., Saper J.R., Hamel R.L. Comprehensive inpatient treatment of refractory chronic daily headache. headache. 2009; 49:555-62.

61. Saper J.R., Lake A.E. Inpatient strategies for refractory migraine. In: Shulman E.A., Levin M., Lake A.E. et al. Refractory migraine. Mechanisms and management. New York: Oxford University Press; 2010: 314-41.

62. Franzini A., Messina G., Leone M. et al. Occipital nerve stimulation (ONS). Surgical technique and prevention of late electrode migration. Acta Neurochir. (Wien). 2009; 151:861-5.

63. Silberstein S.D., Dodick D.W., Saper J. et al. Safety and efficacy of peripheral nerve stimulation of the occipital nerves for the management of chronic migraine: results from a randomized, multicenter, double-blinded, controlled study. Cephalalgia. 2012; 32:1165-79.

Received 04/12/14 Received 04/12/14

UDC 616.153.1-008.61-02:616.37]-036.1

Krasnovsky A.L.1, Grigoriev S.P.1, Zolkina I.V.1, Loshkareva E.O.1, Brutskaya L.A.2, Bykova E.A.1 ASYMPTOMIC PANCREATIC HYPERFERMENTEMIA

‘Department of Internal Medicine, State Budgetary Educational Establishment of Higher Professional Education Russian National Research Medical University. N.I. Pirogov. 117997, Moscow; 2FGBUZ "Central Clinical Hospital of the Russian Academy of Sciences". 117593, Moscow, Russia

For correspondence: Krasnovsky Alexander Leonidovich, Ph.D. honey. in Medicine, Assistant of the Department of Internal Diseases, Faculty of Medicine and Biology. Email:

Correspondence to: Aleksandr Krasnovskiy - MD, PhD, assistant of department of internal diseases of medicobiologic faculty. Email:

♦ Asymptomatic elevations in pancreatic enzymes often lead to a misdiagnosis of chronic pancreatitis and unnecessary treatment. Meanwhile, in many such cases, hyperenzymemia is benign. The article describes the possible causes of pancreatic hyperenzymemia in practically healthy people and proposed a diagnostic search algorithm in this clinical situation.

Key words: asymptomatic pancreatic hyperenzymemia; Gullo syndrome; pancreas;

hyperamylasemia; macroamylasemia; amylase; lipase; trypsin; chronic pancreatitis

Krasnovskiy A.L.1, GrigoriyevS.P.1, Zolkina I.V.1, Loshkareva E.O.1, Brutskaya E.O.2, Bykova E.A.1

THE ASYMPTOMATIC PANCREATIC HYPERFERMENTATION

‘The N.I. Pirogov Russian national research medical university Minzdrav of Russia, 117997 Moscow, Russia

2The central clinical hospital of the Russian academy of sciences, 117593 Moscow, Russia

♦ The asymptomatic increase of the level of enzymes of pancreas often results in such incorrect diagnosis as chronic pancreatitis and in prescription of unnecessary treatment. Meanwhile, in many similar cases hyperenzymemia has a benevolent nature. The article discusses possible causes of pancreatic hyperenzymemia in healthy persons. The algorithm of diagnostic search in this clinical situation is proposed.

Keywords: asymptomatic pancreatic hyperenzymemia; Gullo's Syndrome; pancreas; hyperamylasemia; macroamylasemia; amylase; lipase; trypsin; Chronic pancreatitis

An increase in the serum level of pancreatic enzymes is usually regarded as a manifestation of pancreatic diseases, primarily of an inflammatory or tumor nature, less often as a manifestation of the pathology of other organs (see table).

In recent years, the study of the level of pancreatic enzymes has entered the screening panel of biochemical analyzes, in connection with this, asymptomatic pancreatic hyperenzymemia is increasingly incidentally detected, and standard methods diagnostics (history taking, physical examination, transabdominal ultrasound of the abdominal organs) do not reveal any pathology that explains laboratory abnormalities. There is currently no generally accepted algorithm for diagnostic search in such cases. At the same time, the results of a number of studies, which formed the basis of the recommendations of leading experts in the field of pancreatology, can help the clinician in making tactical decisions.

In 1978, A. Warshaw and K. Lee described 17 cases with chronic hyperamylasemia without clinical manifestations and other signs of pancreatic disease. In 1988, the same group of authors already described 117 similar cases, suggesting that laboratory abnormalities in these patients are not associated with pancreatic pathology.

In 1996, L. Gullo (Lucio Gullo) described a series of 18 cases of increased activity of pancreatic enzymes (isolated or combined 2-15-fold increase in total amylase, pancreatic amylase, lipase or trypsin) in apparently healthy people. Accidentally detected hyperfermentemia was the reason for an in-depth examination, however, with a detailed history taking, a thorough physical and laboratory-instrumental examination, including ultrasound and computed tomography, abdominal organs, and

performing endoscopic retrograde cholangiopancreatography (ERCP), the pathology explaining the increased activity of pancreatic enzymes could not be identified. Prof. Gullo continued to follow most of these patients from 1987 to 2006 and stated that persistent hyperenzymemia persisted during this period in the absence of overt pancreatic disease or other known causes. The author came to the conclusion that the increase in the activity of pancreatic enzymes in these patients is benign, in connection with which he called the described anomaly chronic non-pathological pancreatic hyperenzymemia, or benign pancreatic hyperenzymemia, or Gullo's syndrome. In most cases, with this syndrome, the level of at least two pancreatic enzymes is increased, in other cases there is an isolated increase in the activity of amylase or lipase, often small (1.5-4 times). After stimulation with secretin, there is a further increase in the initially increased levels of pancreatic enzymes, while the Wirsung duct expands to the same extent as in healthy volunteers without hyperenzymemia. Therefore, it is impossible to associate benign hyperenzymemia with stenosis of the pancreatic ducts.

In 2000 prof. Gullo described several families in which at least two blood relatives, including children, had an asymptomatic increase in the activity of pancreatic enzymes. He designated this condition as "familial pancreatic hyperenzymemia". He later described 15 more cases of benign pancreatic hyperenzymemia in children. In this context, the results of the study by E. Tsianos et al. . They measured the level of total amylase, as well as isoenzymes (B- and P-isoamylase) in 92 volunteers in England, divided into 3 ethnic subgroups.

Causes of pancreatic hyperenzymemia with clinical manifestations

State group

Diseases and provoking factors

Pathology of the pancreas and other abdominal organs

Malignant neoplasms

Multisystem diseases

Diseases of other organs and other conditions

Taking medications

Acute pancreatitis or exacerbation of chronic pancreatitis, obstruction of the pancreatic duct (stones, tumors), acute cholecystitis, consequences of endoscopic retrograde cholangiopancreatography, abdominal surgery, cardiac surgery, liver transplantation, secondary pancreatitis in diseases of the abdominal cavity and small pelvis (gastric ulcer perforation, intestinal obstruction, mesenteric thrombosis, peritonitis, obstruction of the afferent loop of the small intestine after gastrectomy , periampullary diverticula, inflammatory diseases intestine, gastroenteritis, salpingitis, ectopic pregnancy, endometriosis), dissecting aneurysm of the descending aorta, abdominal trauma, liver disease (viral hepatitis, cirrhosis of the liver)

lung cancer, ovarian cancer, thyroid gland, colon, prostate, kidneys, mammary glands, hemoblastosis

AIDS, critical conditions in resuscitation patients (including various types of shock, acidosis, intracranial hemorrhages), acute porphyria, SLE and other rheumatic diseases, toxic epidermal necrolysis, leptospirosis, sarcoidosis

Diseases of the salivary glands (mumps, duct stones and tumors of the salivary glands, Sjögren's disease), macro-amylasemia and macrolipasemia, renal failure (decreased clearance of pancreatic enzymes), alcoholism (acute alcohol intoxication), pheochromocytoma, thrombosis

Paracetamol, corticosteroids, azathioprine, ephedrine, ritodrine, cytostatics, roxithromycin, cyclosporine, clozapine, pentamidine, didanosine, opiates

Note. SLE - systemic lupus erythematosus.

Native English, Asian, and West Indian subjects. Serum amylase activity has been found to be higher in immigrants than in native English. The authors concluded that these differences in serum amylase activity may be genetically determined and named this condition ethnic hyperamylasemia. They also emphasized the need to develop ethnic standards in order to avoid diagnostic and tactical errors.

In a specially designed study, the activity of pancreatic enzymes (lipase, total amylase, pancreatic amylase, trypsin) was determined daily for five consecutive days in 42 patients diagnosed with Gullo's syndrome. All patients showed pronounced fluctuations in the content of enzymes, and in 33 (78.6%) of them it normalized within a few days, then increased again. Gullo proposed to consider such variability as a diagnostic criterion for benign pancreatic hyperenzymemia, and to include the determination of the level of the corresponding enzymes daily for five days in the examination plan for such patients.

A report on the study by E. Gaia881 et al. is currently being prepared for publication. . They summarized the results of a 5-year follow-up of 183 patients with benign pancreatic hyperenzymemia. In 74.9% of them, the levels of lipase and both isoenzymes of amylase were increased, in 7.2% - only lipase, in 6.3% - only amylase, and the level of lipase increased to a greater extent. They also stated a significant variability in the activity of enzymes up to their temporary normalization.

At the same time, Gullo drew attention to the fact that in several cases an asymptomatic increase in the activity of pancreatic enzymes was combined with Gilbert's syndrome, with an asymptomatic increase in the level of CPK or transaminases in the absence of obvious liver disease. He also observed a patient with benign hyperamylasemia, in whom clinically, as well as according to ultrasound and CT of the abdominal organs, no pathology of the pancreas was detected. Eight years later, at age 56, this patient developed jaundice and was diagnosed with pancreatic cancer. Discussing such cases, Prof. Gullo pointed out that it is not possible to confirm or refute the presence or absence of causal relationships between the detected pathology and pancreatic hyperenzymemia. In this regard, he proposed to make it a rule to follow up patients with presumably benign pancreatic hyperenzymemia for at least 1-2 years before the diagnosis, in the absence of clinical and laboratory and instrumental data confirming another disease, can be finally established.

Ya. Re77DN et al. showed that chronic asymptomatic pancreatic hyperenzymemia only in half of the cases is truly benign, i.e. does not have a detectable morphological substrate. They examined in detail 75 patients aged 19 to 78 years who had an asymptomatic increase in the activity of one or more pancreatic organs for at least six months.

enzymes (exclusion criteria were the presence of kidney failure and celiac disease). The examination plan included (one or more studies): MSCT of the abdominal organs with contrast enhancement (44 patients), magnetic resonance cholangiopancreatography (MRCP - 50 patients), endoscopic ultrasound (16 patients). Laboratory examination included a clinical blood test, determination of the level of trans-aminases, gamma-glutamyl transpeptidase (GGTP), total bilirubin, alkaline phosphatase (AP), total protein, albumin, globulins, cholesterol, triglycerides, calcium, CA 19-9, as well as a study on macroamylasemia by selective precipitation. Chronic pancreatitis was diagnosed in 20 (26.7%) patients, 5 (5.7%) patients had intraductal papillary mucinous tumors, 3 - pancreatic ductal adenocarcinoma, 2 - Crohn's disease, 4 - chronic viral hepatitis , 3 - macroamylasemia, 1 case each - autoimmune pancreatitis and benign pancreatic cyst, 2 cases - serous cystadenoma. Only 4 cases revealed familial hyperenzymemia and 31 (41.3%) - chronic non-pathological hyperenzymemia. The authors concluded that the "watch and wait" tactics in chronic asymptomatic pancreatic hyperenzymemia is unacceptable, careful diagnostic search to identify the cause, which can be found in most of these patients.

In the study by A. Amodio et al. 160 patients (age 49.6 ± 13.6 years) were included, who had a long-term (more than six months) increase in the activity of pancreatic enzymes in the absence of clinical manifestations. Exclusion criteria were based on known causes of pancreatic hyperenzymemia: previously diagnosed pancreatic disease, liver cirrhosis, celiac disease, renal failure, endometriosis, cholelithiasis with clinical manifestations, diabetes mellitus, previous endoscopic procedures involving the papilla of Vater, surgical interventions on the stomach duodenum or biliary tract in history, as well as alcohol consumption >40 g per day. All patients included in the final analysis underwent MRI of the abdominal organs, MRCP with secretin stimulation. Laboratory examination included determination of the level of total amylase, pancreatic amylase and lipase (first-degree relatives were also examined), basic renal and hepatic parameters, tests for viral hepatitis B and C, serological tests for celiac disease, determination of cholesterol and triglycerides. An isolated increase in amylase activity was detected in 59 patients, lipase - in one, a combined increase in the activity of both enzymes - in 100 patients. Normal data on the results of MRCP before administration of secretin were determined in 117 (73%) patients, while after stimulation with secretin - only in 80 (50%). Pathological changes detected after stimulation with secretin: cysts (4 patients; 2.5%), diffuse dilation of the Wirsung duct (31; 19.4%), segmental dilatation of the Wirsung duct (11; 6.9%), diffuse dilatation of small ducts ( 41; 25.6%), focal dilation of small ducts (17; 10.6%), Santorini-

cele (5; 3.1%), tumors (5; 3.1%). In 14.4% of cases, the identified changes were regarded as clinically significant, as they influenced the management of these patients. Thus, 5 patients were operated on for identified endocrine tumors (3 patients), pancreatic cancer (1) and intraductal papillary mucinous tumor (1), another 18 patients remained under observation due to identified intraductal tumors (17) or endocrine tumor(one). In 20% of cases, changes in the pancreatic ducts are regarded as early manifestations of chronic pancreatitis. In 26 (19.5%) cases, familial asymptomatic pancreatic hyperenzymemia was detected, however, the frequency of anomalies of the ductal system according to the results of MRCP with secretin stimulation in this subgroup of patients did not differ from that in other patients. In 11 (6.9%) patients, viral hepatitis, renal failure or celiac disease were diagnosed for the first time, which could cause pancreatic hyperenzymemia. Thus, only in half of the patients with asymptomatic pancreatic hyperenzymemia, after a thorough examination, Gullo's syndrome was established, in the remaining cases, specific causes were identified. According to the authors, the results of their study suggest that in cases of asymptomatic pancreatic hyperenzymemia, it is necessary to perform MRCP with secretin stimulation, as well as an examination to rule out extrapancreatic causes of hyperenzymemia. The authors of other studies evaluating the informativeness of MRCP with secretin stimulation in asymptomatic pancreatic hyperenzymemia came to the same conclusions. The tactics of observation with the performance of repeated ultrasound of the abdominal organs after 3-6 months does not justify itself: although in most cases there will be no clinically significant complications of possible diseases during this time, diagnostic value Ultrasound after 3-6 months will be minimal.

F. Gallucd et al. compared baseline and final diagnoses in 51 patients with asymptomatic hyperamylasemia (alone or in combination with hyperlipasemia). Initially, chronic pancreatitis was diagnosed in 31 patients, recurrent - in 13, and in 7 patients the diagnosis remained unclear. All patients were examined at least three times with an interval of at least six months. In addition to collecting complaints and anamnesis, all patients underwent laboratory (total amylase, salivary and pancreatic isoamylase, pancreatic lipase, daily amilasuria, lipid profile, creatinine clearance, CA level 19-9) and instrumental examination (ultrasound of the abdominal organs, on average 3 studies each during the observation period; CT scan of the abdominal organs with contrast enhancement, repeated in 34 cases). In addition, ERCP was performed in 21 cases, MRCP was performed in 25, and endoscopic ultrasound was performed in 11 cases. In all patients, these instrumental studies did not reveal any clinically significant pathology. The final diagnoses were distributed as follows: salivary hyperamylasemia - 13 (25.4%) cases, macroamylasemia - 18 (35.2%), benign pancreatic hyperamylasemia - 20 (39.2%). Criteria for the diagnosis of benign pancreatic hyperamylasemia corresponded to those previously described by Gullo. The diagnosis of salivary hyperamylasemia was made in the case of an increase in the activity of total serum amylase, mainly due to salivary isoamylase (60%). In this case, the authors recommend referring the patient for a consultation with a dentist, ultrasound and/or scintigraphy of the salivary glands to look for the cause (sialolithiasis, salivary gland tumors, mumps, Sjögren's syndrome). Macroamylasemia was noted with an increase general level amylase with a normal level of lipase and normal or reduced amylasuria (normal 400-600 U / l) in combination with a decrease in the ratio of amylase clearance / creatinine clearance of less than 1%.

Macroamylasemia is a condition in which complexes of normal serum amylase with proteins or carbohydrates circulate in the blood (the presence of polymeric forms of enzymes or abnormal amylase is also possible, but the existence of such forms has not been proven). It should also be said that there are references to macrolipasemia in the literature. Clinical manifestations may be absent, sometimes abdominal pain is possible. In 1964, P. Wilding et al. described the clinical picture in a patient with long-term asymptomatic hyperamylasemia, which was explained by the binding of amylase to serum globulins. Then J. Berk et al. published data obtained from the observation of three patients with the same phenomenon, and proposed the term "macroamylasemia". This pathology is described in detail in the review by N.B. Gubergritsa et al. . This state arises due to the appearance in the blood

a stream of enzyme-active macromolecular complexes of proteins or carbohydrates with amylase (mainly salivary, S-amylase). Most often, macroamylase is a complex of amylase with a high molecular weight protein, usually IgA, less often IgG. Due to their large size, these complexes are poorly filtered by the kidneys and are retained in the bloodstream. The frequency of macroamylasemia, according to different authors, ranges from 0.4% in healthy people to 8.4% in patients with hyperamylasemia. There are three types of macroamylasemia. Type 1 - persistent hyper-amylasemia, high content macroamylase complex in serum and a decrease in the level of amylase in the urine; type 2 - also hyperamylasemia, a slight decrease in the level of amylase in the urine, the ratio of macroamylase and normal amylase in serum is much less than in type 1 macroamylasemia; type 3 - normal activity of amylase in serum, urine, as well as a low ratio of macroamylase and normal amylase in serum. A simple and affordable method for diagnosing macroamylasemia is to determine the ratio of clearances of amylase (Ka) and creatinine (Kk). For this, the concentration of creatinine and amylase in the daily urine, as well as creatinine and amylase in the blood, is determined (the analysis is taken in the morning on an empty stomach).

The indicator is calculated according to the following formula:

Ka / Kk \u003d A urine / A blood K blood / K urine 100%,

where And urine - the level of amylase in the urine; And blood - the level of amylase in the blood; To urine - the level of creatinine in the urine; To the blood - the level of creatinine in the blood. It is necessary to pay special attention to ensuring that the units of measurement of each indicator in urine and blood are brought into line. Decrease in the ratio of amylase and creatinine clearances less than 1% with preserved kidney function with high probability confirms the diagnosis of macroamylasemia, other forms of hyperamylasemia are characterized by an increase in this ratio of more than 1% (within the normal range, 1-4% or above normal).

In order to demonstrate the possibilities of verifying the cause of pancreatic hyperenzymemia, we present our observation of a 28-year-old patient in whom isolated hyperamylasemia was accidentally detected during examination before surgery for nasal septum deviation, as a result of which the patient was refused to perform the operation until the reasons for the increase in amylase activity were clarified. Good health, absence of comorbidities or habitual intoxications, abnormalities in physical examination, normal results laboratory tests, except for amylase, as well as the absence of pathology according to ultrasound of the abdominal organs, did not clarify the situation. Upon re-examination, the level of alpha-amylase in the blood is 360 U / l, in the urine - 200 U / l, the concentration of creatinine in the blood is 80 μmol / l, in the urine - 17.7 mmol / l (which is equal to 17,700 μmol / l - translation in the same units of measurement as blood creatinine). The Ka/Kk ratio in our patient was:

Ka / Kk \u003d (200/360) (80/17700) 100% \u003d 0.26%.

Based on the above data, a diagnosis of type 1 macroamylasemia was made, which, in the absence of other abnormalities and diseases, is not a contraindication for elective surgery.

A case of long-term (12 years) follow-up of a patient suffering from macroamylasemia is described by D.I. Abdulganieva et al. . The diagnosis was established on the 5th year of a stable increase in amylase activity, however, even after that, the patient continued to periodically undergo examination and treatment for chronic pancreatitis, which led to the development anaphylactic shock against the background of the introduction of an unnecessary drug (contri-feces). Thus, the timely and correct diagnosis of patients with asymptomatic laboratory abnormalities can actually have a significant impact on their further evaluation, treatment, and well-being.

Unfortunately, a decrease in the ratio of amylase and creatinine clearance occurs not only in macroamylasemia, similar changes are also observed in S-type hyperamylasemia. In addition, macroamylasemia types 2 and 3 may not be accompanied by a change in amylase clearance and its content in the urine. Therefore, for a reliable diagnosis of macroamylasemia, additional examinations. For the diagnosis of macroamylasemia, chromatography is used - column, accelerated liquid, thin-layer, ultracentrifugation, electrophoresis, isoelectric focusing, precipitation with polyethylene glycol, assessment of the thermal sensitivity of amylase, immunological methods (reaction with monoclonal antibodies, the use of antiserum to immunoglobulins - components of the macroamylase complex). Most-

Diagnostic algorithm for asymptomatic pancreatic hyperenzymemia.

The simplest and fastest methods for diagnosing macroamylemia are electrophoresis and the polyethylene glycol test. Unfortunately, none of the tests listed above are performed in the laboratories available to us. Apparently, both domestic and foreign clinicians face a similar problem, so macroamylasemia is often stated only on the basis of the absence of clinical manifestations in combination with a decrease in the ratio of amylase and creatinine clearances. At the same time, it must be remembered that macroamylasemia can sometimes coexist with diseases of the pancreas. Therefore, the suspicion of macroamylasemia does not eliminate the need for further examination of the patient to exclude pancreatic pathology and to search for other possible causes macroamylasemia (celiac disease, Crohn's disease, UC, rheumatoid arthritis, SLE, liver disease, HIV, lymphoma, thyroid cancer, renal cell carcinoma; in addition, macroamylasemia is often associated with Gilbert's syndrome).

Finally, we must not forget that asymptomatic hyperamylasemia may be a manifestation of paraneoplastic syndrome or ectopic amylase production (usually S-type) malignant tumors. Thus, the production of amylase by lung tumors, with multiple myeloma, pheochromocytoma and other tumors is described (see table). In this regard, in diagnostically unclear cases of pancreatic hyperenzymemia, it is necessary to consider the issue of conducting a detailed oncological search.

Based on the literature data, we propose a diagnostic algorithm for asymptomatic increases in the level of pancreatic enzymes (see figure). At the first stage, it is necessary to perform screening laboratory tests to exclude hepatitis, celiac disease, and renal failure as the causes of an increase in the level of pancreatic enzymes. An increase in the content of CA 19-9 increases alertness regarding possible cancer of the pancreas, to exclude pronounced structural changes in the pancreas, ultrasound of the abdominal organs is performed. At the same time, the level of total amylase, S- and P-isoamylase, lipase and trypsin is determined, as well as the daily excretion of amylase in the urine with the calculation of the ratio of amylase clearance and creatinine clearance. In the case of isolated hyperamylasemia due to the salivary fraction, it is necessary to exclude the pathology of the salivary glands. Due to the fact that an isolated increase in S-amylase activity may not be accompanied by an increase in amylasuria and a decrease in the ratio of amylase and creatinine clearances, after exclusion of the pathology of the salivary glands, an examination is necessary to diagnose possible macroamylasemia, as well as a detailed oncological search, since hyperamylasemia is often within the framework of paraneoplastic syndrome is represented by S-amylase.

A decrease in daily amylasuria, combined with a decrease in the ratio of amylase and creatinine clearances in the absence of complaints and other abnormalities during the examination, makes it possible to diagnose macroamylasemia. Further diagnostic search in this case depends on the possibilities of laboratory examination to confirm macroamylasemia and identify diseases associated with the development of macroamylasemia. In addition, the presence of macroamylasemia does not exclude concomitant pancreatic disease, therefore, regardless of whether macroamylasemia is confirmed or not, continued instrumental examination is indicated.

With increased amylasuria in combination with a normal ratio of amylase and creatinine clearance in patients with pancreatic hyperenzymemia, a detailed examination of the pancreas is necessary. The most sensitive method is secretin-stimulated MRCP; if this method is not possible, endoscopic ultrasound or contrast-enhanced CT can be used. Investigation of pancreatic enzyme levels in first-degree relatives to detect familial pancreatic hyperenzymemia is recommended, as well as daily determination of the patient's pancreatic enzyme levels for five consecutive days. In the absence of structural pathology of the pancreas, according to the results of instrumental studies, in combination with pronounced fluctuations in the activity of pancreatic enzymes from day to day, the most likely diagnosis is benign pancreatic hyperenzymemia (Gullo's syndrome). If no other pathology is detected during the 2-year follow-up period during repeated laboratory and instrumental examinations, the diagnosis of Gullo's syndrome becomes final.

LITERATURE (PP. 1-2 1, 24, 25 SEE IN REFERENCES)

22. Gubergrits N.B., Lukashevich G.M., Zagoreko Yu.A. Macroamylasemia - harmless delusion or dangerous ignorance? Su-chasna gastroenterology. 2006; 32(6): 93-9.

23. Abdulganieva D.I., Odintsova A.Kh., Cheremina N.A., Khafizova A.Kh. etc. Is hyperamylasemia always associated with chronic pancreatitis? Practical medicine. 2011; 55(7): 157-9.

1. Siegenthaler W., ed. Differential Diagnosis in Internal Medicine: From Symptom to Diagnosis. 1st English Ed. Stuttgart; New York: Thieme; 2007.

2. Frulloni L., Patrizi F., Bernardoni L., Cavallini G. Pancreatic hyperenzymemia: clinical significance and diagnostic approach. JOP. 2005; 6(6): 536-51.

3. Warshaw A.L., Lee K.H. Macroamylasemia and other chronic nonspecific hyperamylasemias: chemical oddities or clinical entities? Am. J. Surg. 1978; 135(4): 488-93.

4. Warshaw A.L., Hawboldt M.M. Puzzling persistent hyperamylasemia, probably neither pancreatic nor pathologic. Am. J. Surg. 1988; 155(3): 453-6.

5. Gullo L. Chronic nonpathologicalhyperamylasemia of pancreatic origin. gastroenterology. 1996; 110(6): 1905-8.

6. Gullo L. Benign pancreatic hyperenzymemia. Dig. LiverDis. 2007; 39(7): 698-702.

7. Gullo L., Ventrucci M., Barakat B., Migliori M., Tomassetti P., Pezzilli R. Effect of secretin on serum pancreatic enzymes and on the Wirsung duct in chronic nonpathological pancreatic hyperenzyme-mia. pancreatology. 2003; 3(3): 191-4.

8. Gullo L. Familial pancreatic hyperenzymemia. pancreas. 2000; 20(2): 158-60.

9. Gullo L., Migliori M. Benign pancreatic hyperenzymemia in children. Eur. J. Pediatr. 2007; 166(2): 125-9.

10. Tsianos E.B., Jalali M.T., Gowenlock A.H., Braganza J.M. Ethnic ‘hyperamylasaemia’: clarification by isoamylase analysis. Clin. Chim. acta. 1982; 124(1): 13-21.

11. Gullo L. Day-to-day variations of serum pancreatic enzymes in benign pancreatic hyperenzymemia. Clin. Gastroenterol. Hepatol. 2007; 5(1): 70-4.

12. Galassi E., Birtolo C., Migliori M., Bastagli L. et al. A 5-year experience of benign pancreatic hyperenzymemia. pancreas. 2014 Apr 16. .

13. Pezzilli R., Morselli-Labate A.M., Casadei R., Campana D. et al. Chronic asymptomatic pancreatic hyperenzymemia is a benign condition in only half of the cases: a prospective study. Scand. J. Gastro-enterol. 2009; 44(7): 888-93.

14. Amodio A., Manfredi R., Katsotourchi A.M., Gabbrielli A. et al. Prospective evaluation of subjects with chronic asymptomatic pancreatic hyperenzymemia. Am. J. Gastroenterol. 2012; 107(7): 1089-95.

15. Testoni P.A., Mariani A., Curioni S., Giussani A. et al. Pancreatic ductal abnormalities documented by secretin-enhanced MRCP in asymptomatic subjects with chronic pancreatic hyperenzymemia. Am. J. Gastroenterol. 2009; 104(7): 1780-6.

16. Donati F., Boraschi P., Gigoni R., Salemi S. et al. Secretin-stimulated MR cholangio-pancreatography in the evaluation of asymptomatic patients with non-specific pancreatic hyperenzymemia. Eur. J. Radiol. 2010; 75(2): e38-44.

17. Gallucci F., Buono R., Ferrara L., Madrid E. et al. Chronic asymptomatic hyperamylasemia unrelated to pancreatic diseases. Adv. Med. sci. 2010; 55(2): 143-5.

18. Bode C., Riederer J., Brauner B., Bode J. C. Macrolipasemia: a rare cause of persistently elevated serum lipase. Am. J. Gastroenterol. 1990; 85(4): 412-6.

19. Oita T., Yamashiro A., Mizutani F., Tamura A. et al. Simultaneous presence of macroamylase and macrolipase in a patient with celiac disease. RinshoByori. 2003; 51(10): 974-7.

20. Wilding P., Cooke W.T., Nicholson G.I. Globulin-bound amylase: a cause of persistently elevated levels in serum. Ann. Intern. Med. 1964; 60(6): 1053-9.

21. Berk J.E., Kizu H., Wilding P., Searcy R.L. Macroamylasemia: a newly recognized cause for elevated serum amylase activity. N. Engl. J. Med. 1967; 277(18): 941-6.

22. Gubergrits N.B., Lukashevich G.M., Zagoreko Yu.A. Macroamy-lasemia: is it harmless delusion or dangerous ignorance? Contemporary gastroenterology. 2006; 32(6): 93-9. (in Ukrainian)

23. Abdulganieva D.I., Odintsova A.Kh., Cheremina N.A., Khafizova A.Kh. et al. Whether always the hyperamylasemia is a consequence of chronic pancreatitis? Prakticheskaya Meditsina. 2011; 55(7): 157-9. (in English)

24. Crook M.A. Hyperamylasaemia: don'tforgetundiagnosedcarcino ma. Ann. Clin. Biochem. Published online before print November 5, 2013, doi: 10.1177/0004563213510490

25. Mariani A. Chronic asymptomatic pancreatic hyperenzymemia: is it a benign anomaly or a disease? JOP. 2010; 11(2): 95-8.

Received 05/25/14 Received 05/25/14

Increasing the rate of enzyme synthesis in cells.

An increase in the number of cells that synthesize the enzyme.

Increasing the permeability of cell membranes.

Necrosis (death) of cells.

The use of enzymes in medicine

For screening diagnostics- selective tests.

For diagnosing diseases(aspartic transaminase - for the diagnosis of myocardial infarction, alanine transaminase - for the diagnosis of liver diseases).

For differential diagnosis(acid phosphatase - prostate cancer, alkaline phosphatases - bone, cancer metastases).

For the treatment of diseases:

a) replacement therapy(for diseases of the gastrointestinal tract, pepsin, pancreatin, festal, panzinorm, mezim-forte are used - these are hydrolytic enzymes; enzyme inhibitors can be used for pancreatitis);

b) to treat diseases and eliminate pathological processes Enzymes are used to:

destruction of dead tissue (in the treatment of burns, ulcers, abscesses - trypsin, chymotrypsin, nuclease);

liquefaction of viscous secrets in the treatment of bronchitis (trypsin, chymotrypsin, broncholithin);

for smoothing postoperative scars (protease, lidase, nuclease);

for the destruction of blood clots (streptokinase, fibrinolysin).

The use of enzymes in dentistry: for the treatment of caries, pulpitis, periodontitis, gingivitis, aphthous stomatitis, oral ulcers.

Enzymes can be used both independently (tablets, powders, aerosols, solutions) and on a carrier, i.e. in an immobilized form (gels, ointments, pastes). Immobilized enzymes have a prolonged effect.

INTRODUCTION TO METABOLISM. CENTRAL METABOLIC WAYS.

Metabolism - a set of chemical reactions occurring in the cells of the body from the moment nutrients enter the body to the formation of end products of metabolism.

Metabolic functions:

supply of cells with chemical energy;

turning food molecules into building blocks;

the assembly of these blocks of cell components (proteins, lipids, nucleic acids);

synthesis and destruction of specialized biological molecules (heme, choline).

metabolic pathway - the sequence of chemical transformations of a substance. Metabolic pathways are multi-stage, interconnected, regulated, coordinated in space. They are linear (disintegration and synthesis of glycogen, glycolysis, etc.) and cyclic (tricarboxylic acid cycle, ornithine cycle):

P is an example of a linear metabolic pathway, where S is the initial substrate, P is the final product, A, B, C, D are metabolites (intermediate products).

Enzymes (enzyme), which determine the speed of the entire process as a whole, are calledkey , catalyze irreversible reactions, have a quaternary structure and are easily regulated.

2 sides of metabolism

catabolism - the process of splitting complex molecules into simpler ones, going with the release of energy.

Anabolism synthesis process complex substances from simpler ones, going with the expenditure of energy in the form of ATP.

Anabolism and catabolism are closely related:

at the levelsubstrates (sources of carbon)

at the levelenergy sources

catabolism  ATP  anabolism.

Direct conversion of the chemical energy of substrates into the energy of high-energy bonds of ATP is impossible. This process is divided into two stages:

S  chemical energy  ATP

Release Transformation

Consider stage 1 - energy release on the example of the general scheme of catabolism.

End products of exchange:

- formed by deamination;

SO- formed by decarboxylation;

O - is formed by the oxidation of hydrogen with oxygen in the respiratory chain (tissue respiration).

The stage of catabolism occurs in gastrointestinal tract and is reduced to reactions of hydrolysis of food substances. Chemical energy is dissipated as heat.

 stage (intracellular catabolism) occurs in cytoplasm and mitochondria. Chemical energy is partially dissipated in the form of heat, partially accumulated in the form of reduced coenzyme forms, and partially stored in macroergic bonds of ATP (substrate phosphorylation).

 The final stage catabolism takes place in mitochondria and reduces to the formation of end products of CO2 and H2O exchange. Chemical energy is partially dissipated in the form of heat, 40–45% of it is stored in the form of ATP (oxidative phosphorylation).