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Zhuraeva Mohigul Azimjanovna, Oleynik Vladimir Michaylevich, Babich Svetlana Michaylovna, Andijan state medical Institute E-mail: [email protected]
PECULIARITIES OF SECRETION OF DIGESTIVE PEPTIDASES OF THE STOMACH AND PANCREAS IN CHRONIC VIRAL HEPATITIS C
Abstract. It remains unclear the question of multidirectional changes in secretory and endocrine activity of the digestive glands of the stomach and pancreas in chronic liver diseases. At the same time, the study of changes in the endocrine function is of interest for practical diagnosis. as in diseases of the stomach and pancreas, and the violation of their function in chronic liver diseases. A comprehensive assessment of the state of the pancreas in the group of patients with chronic viral liver lesions revealed a violation of the functional state of the organ in 80% of cases with chronic hepatitis and in 96.3% of cases - with liver cirrhosis.
Keywords: endocrine activity, stomach, pancreas, chronic viral liver, chronic hepatitis, amylase and lipase, stimulated secretion, liver cirrhosis.
Despite the long period since the sixties of the last century, the study of the influence of chronic liver diseases on the changes in the functional state of the stomach and pancreas, to date there is no clear idea of changing their exosecretion and incretion. It remains unclear the question of multidirectional changes in secretory and endocrine activity of the digestive glands of the stomach and pancreas in chronic liver diseases. At the same time, the study of changes in the endocrine function is of interest for practical diagnosis. as in diseases of the stomach and pancreas, and the violation of their function in chronic liver diseases. A comprehensive assessment of the state of the pancreas in the group of patients with chronic viral liver lesions revealed a violation of the functional state of the organ in 80% of cases with chronic hepatitis and in 96.3% of cases - with liver cirrhosis [4; 6].
With combined infection with hepatitis B and C viruses, more pronounced changes in the proteinase activity of the blood (activity of trypsin and kallikrein), a more distinct decrease in antitryptic activity were noted. Exocrine function of the pancreas in patients with hepatitis was also impaired to a greater extent, which was manifested in some studies by a decrease in basal and stimulated secretion, enzyme secretion (especially trypsin and amylase) and bicarbonate production [4; 6], in others - by an increase in the activity of amylase and lipase. Disorders of external secretion increase with the severity of the main clinical and biochemical syndromes. The content of glucagon and somatostatin in the blood of patients with chronic hepatitis was increased [5; 6].
In alcoholic liver disease, exocrine pancreatic secretion tends to increase with the severity of liver damage, but does not correlate with the severity of chronic pancreatitis. It is as-
sumed that alcohol abuse and the influence of hepatitis virus have an equal pathogenic effect on the liver and pancreas [3].
Levels of pancreatic enzymes - serum and pancreatic amylase, and serum lipase levels increase with the progression of liver disease in patients diagnosed with viral hepatitis. Pancreatic disease, asymptomatic in most cases, can be an extrahepatic manifestation of chronic viral hepatitis. It is suggested to reduce liver metabolism of amylase and lipase from the blood in patients with chronic infectious liver diseases, especially in patients with liver cirrhosis, which can lead to the accumulation of these enzymes in the blood [12; 18].
As for the stomach, it was shown that in patients with liver cirrhosis, the average rate of free and total acidity, as well as pepsinogen 1 in serum were lower than under normal conditions. Also in the gastric mucosa, a decrease in blood flow was noted, and the gastrin content was significantly lower than in the group of healthy patients. Whereas the concentration of serum gastrin and somatostatin in patients with liver cirrhosis was significantly higher [7].
In another study on dogs with liver disease was revealed hypergastrinemia and frequent manifestations of gastrointestinal disorders, which can be caused by ulceration. The paper suggests that the liver is important for inactivation of some forms of gastrin. Therefore, hypergastrinemia is involved in the pathogenesis of gastrointestinal ulceration associated with liver dysfunction [15].
Purpose of research. To study the features of changes in the content of blood hydrolases, incretilli stomach and pancreas, in chronic viral hepatitis C and to analyze the mechanisms of these changes.
Material and methods. 112 men and women aged 20 to 70 years were examined. For comparison, a group of healthy 42 people with no markers of HCV infection was formed, and liver samples were normal. Of the examined 70 had positive serological markers, 38 had markers related to post-HCV infection, 32 had markers related to chronic HCV infection. In all examined in serum by IFA (standard sets ofJSC "Vector-best", Russia) was determined: pepsinogen-1 (PG1) and pepsinogen- II (PG II). Biochemical methods were used to determine amylase pancreatic (standard sets ofJSC "Vector-best", Russia) and lipase pancreatic "HUMAN", Germany. In all patients hepatic samples were studied: alanine transaminase (ALT), aspartate aminotransferase (AST), total and direct bilirubin.
Results and discussion. It was found that in the examined healthy individuals the indicators of amylase, lipase, pepsinogen-1 and pepsinogen- II in the blood were within normal limits (table. 1).
In persons with HCV postinfection (table. 1) indicators of liver tests were within the norm, but higher than in healthy ones. In the same individuals, despite the absence of an active HCV process, the blood levels of amylase and lipase were significantly higher than normal and compared to healthy ones. At the same time, pepsinogen-1 indicators were within normal limits, but were lower than in healthy, and pepsinogen-II indicators were slightly higher than in healthy, but within normal limits.
Table 1. - Changes in the content of gastric and pancreatic hydrolases in the blood of healthy and patients with viral hepatitis C
Serum markers Healthy Healthy HCV postinfection Chronic HCV infection
Liver function tests
AST (mmol/h*l) Norm 0.1-0.68 0.36 ± 0.04 0.47 ± 0.05 1.26 ± 0.13
ALT (mmol/h*l) Norm 0.1-0.68 0.21 ± 0.02 0.38 ± 0.04 0.89 ± 0.09
Total bilirubin (^mol/l) Norm 8.5-20.5 13.6 ± 1.2 18.3 ± 1.9 61.5 ± 6.7
Direct bilirubin (^mol/l) Norm 0-5.02 2.0 ± 0.1 3.9 ± 0. 4 34.2 ± 4.27
Blood hydrolases
Amylase pancreatic Norm 0-60 E/l 41.6 ± 5.8 85.2 ± 11.4 129.7 ± 15.2
Pancreatic lipase Norm 0-53 E/l 26.8 ± 3.7 69.5 ± 8.1 94.4 ± 12.6
Pepsinogen-I (^g /l) Norm 40-130 98.6 ± 12.5 48.9 ± 6.3 19.5 ± 2.3
Pepsinogen-II (^g/l) Norm 4-22 16.9 ± 1.8 18.4 ± 2.1 11.2 ± 1.4
In patients with chronic HCV infection rates of all considered hepatic samples were higher than normal. In these patients, there was a marked increase above the norm of amylase and lipase compared with patients with HCV postinfection. At the same time, pepsinogen-1 indicators were less than the lower limit of the norm and significantly lower than in persons with HCV post-infection. At the same time, pepsinogen-II levels were within normal limits, but were slightly lower than those with HCV post-infection.
The presented data demonstrate that in healthy individuals all the considered indicators were within the norm. At the same time, the blood levels of amylase and lipase are higher than normal in persons with HCV post-infection, and pep-
sinogen- 1 and pepsinogen-II are within normal limits, indicating the absence of significant changes in the function of the digestive glands of the stomach and a slight increase in the functional activity of the pancreas, which may be associated with a hidden form of pancreatitis.
In patients with chronic HCV infection, a marked increase in blood above the norm of amylase and lipase indicates an increase in the functional activity of the pancreas, and possibly a latent form of pancreatitis. The observed values below the norm of pepsinogen-1, which is produced by the main cells of the glands of the bottom and the body of the stomach, indicate a decrease in the enzymatic activity of the stomach, with a decrease in the concentration of serum
pepsinogen-1 (PG1) to values less than 40 ^g/l, observed with a marked decrease in the secretion of hydrochloric acid and the development of atrophic gastritis [10]. The available indicators within the norm of pepsinogen- II (PG II), which is produced by mucin-forming cells of the glands of all parts of the stomach, indicates the absence of changes in the mucin-forming function of the stomach. At the same time, the change in the ratio PG1 /PG2 (19.5/11.3) below the coefficient 3 is an additional indicator of the development of atrophic gastritis.
Thus, in patients with chronic HCV infection, there is a marked increase in the functional activity of the pancreas, which may be a manifestation of a hidden form of pancreatitis and a decrease in the functional activity of the digestive glands of the stomach, which may be a manifestation of a hidden form of atrophic gastritis. However, the mechanisms of these changes are not covered in the literature.
In our opinion, this is due to the physiological metabolism of the liver of low molecular weight peptides, in particular, CCK-8, which was shown by us in previous publications [1; 2] and which is confirmed by a number of other researchers [8; 9].
It is shown that the liver affects the metabolism of CCK-8 and this metabolic effect can vary significantly in liver diseases. It was found that CCK-8 is metabolized to a large extent in healthy individuals and to a lesser extent in patients with
liver cirrhosis. Due to this, the content of CCK-8 in the blood of patients with liver cirrhosis increases [17].
The physiological role of CCK-8 as a stimulator of pancreatic secretion is known [11; 16]. At the same time, the results of the study of the physiological role of cholecystokinin as a regulator of gastrin secretion show that CCK-8 can play a crucial role in inhibiting stimulated secretion of gastric acid and controls the production of gastric acid, gastrin content in blood plasma and somatostatin secretion [13].
It was found that cholecystokinin inhibits acid secretion by activation of type A CCC receptors and a mechanism including somatostatin production [14].
Thus, it can be assumed that in the norm of CCK-8, it is more utilized by the liver, and in chronic hepatitis C, its utilization in the liver is disturbed and the concentration in the blood increases. Due to what is noted above mechanisms stimulation of pancreatic secretion and the development of pancreatitis, with simultaneous inhibition of gastric secretion, and the development of atrophic gastritis.
Conclusion. In patients with chronic HCV infection by increment, an increase in the functional activity of the pancreas and the development of a hidden form of pancreatitis, with a simultaneous decrease in the functional activity of the digestive glands of the stomach, which is a sign of a hidden form of atrophic gastritis. We assume that CCK-8 is the main factor contributing to the development of these violations.
References:
1. Aleinik V. A., Babich S. M., change in pancreatic secretion with the introduction of different doses of trypsin in the peripheral and portal veins // F-l Theor.and wedge honey. 2012.- No. 5.- P. 9-12.
2. Babich S. M., Alejnik V A., Khodjimatov G. M. the Influence of protease inhibitors on the changes of utilization of penta-gastrin by the liver under the influence of trypsin// Therapeutic. Bulletin of Uzbekistan, 2016.- No. 3.- P. 70-74.
3. Kataev S. S., Vasilyeva N. S. Exocrine function of the pancreas in patients with chronic hepatitis and liver cirrhosis of different etiology. Klin Med.- M. 1993. 71 (6),- P. 37-42.
4. Morozova T. S. condition of pancreas in patients with chronic diffuse liver diseases of viral etiology and evaluation of the effectiveness of antiviral therapy. Izhevsk, 1997 the dissertation of candidate of medical Sciences.
5. Ushakova O. V. pancreatic dysfunction in chronic viral liver diseases. Stavropol 2011 abstract of the thesis of the candidate of medical Sciences.
6. Shlychkova A. A. Investigation of exocrine pancreatic function in patients with viral hepatitis B and C. Moscow, 2007 abstract of the thesis of candidate of medical Sciences. Akere A. et al. Upper gastrointestinal endoscopy in patients with cirrhosis: spectrum and prevalence of lesions // Annals of tropical medicine and public health, 2016.- V. 9.- No. 2.- 112 p.
7. Gregory G. L., La Russo N. F., Miller L.J. Hepatis processing of cholecystokinin peptides. 1. Structural specificity and mechanism of hepatis extraction // Amer. J. Physiol. 1986.- Vol. 250.- No. 3.- Pt 1.- P. 344-349.
8. Hoffmaster K. A., Zamek-Gliszczynski M. J., Pollack G. M., Brouwer K. L. Hepatobiliary disposition of the metabolically stable opioid peptide [D-Pen2, D-Pen5]-enkephalin (DPDPE): pharmacokinetic consequences of the interplay between multiple transport system // J. Pharmacol. Exp. Ther., 2004.- Vol. 311(3),- P. 1203-10.
9. Hunter F. M. et al. Serum pepsinogens as markers of response to therapy forHelicobacter pylori gastritis // Digestive diseases and sciences. 1993.- V. 38.- No. 11.- P. 2081-2086.
10. Ji B. et al. Human pancreatic acinar cells lack functional responses to cholecystokinin and gastrin // Gastroenterology. 2001.- T. 121.- No. 6.- C. 1380-1390.
11. Katakura Y. et al. Pancreatic involvement in chronic viral hepatitis // World Journal of Gastroenterology: WJG. 2005.-V. 11.- No. 23.- P. 3508-3513.
12. Konturek J. W. Cholecystokinin in the control of gastric acid and plasma gastrin and somatostatin secretion in healthy subjects and duodenal ulcer patients before and after eradication of Helicobacter pylori // Journal of physiology and pharmacology: an official journal of the Polish Physiological Society. 1994.- V. 45.- No. 4.- Suppl 1.- P. 3-66.
13. Lloyd K. C.K. et al. Somatostatin is released in response to cholecystokinin by activation of type A CCK receptors // Peptides. 1994.- V. 15.- No. 2.- P. 223-227.
14. Mazaki-Tovi M. et al. Serum gastrin concentrations in dogs with liver disorders // The Veterinary record, 2012.- V 171.-No. 1.- P. 19-19.
15. Niebergall-Roth E., Singer M. V. Central and peripheral neural control of pancreatic exocrine secretion // J Physiol Pharmacol. 2001.- T. 52.- No. 4.- Pt. 1.- P. 523-538.
16. Paloheimo L. I. et al. Plasma cholecystokinin and its precursors in hepatic cirrhosis // Journal of hepatology. 1997.-V. 27.- No. 2.- P. 299-305.
17. Yoffe B. et al. Hyperlipasemia associated with hepatitis C virus // Digestive diseases and sciences. 2003.- V. 48.- No. 8.-P. 1648-1653.
