Morphometric parameters of hepatocytes in experimental complete extrahepatic bile duct obstruction

Authors

DOI:

https://doi.org/10.15587/2519-4798.2020.193845

Keywords:

experimental biliary tract obstruction, cholestasis, hepatocyte, liver morphology, morphometry

Abstract

Liver changes observed in complete extrahepatic bile duct obstruction (CEBDO) with consideration to its morphometric parameters, may reflect the upcoming decompensation of liver function and may serve as objective criteria for the disease prognosis.

The aim. To study the morphological changes of hepatocytes in experimental CEBDO using macro- and micromorphometry.

Materials and methods. In 41 rats, the CEBDO was done by ligation and transection of the common bile duct. The time points were on postoperative Day 1, 3, 7, 14, 21, 28 and 35. Control group included 10 non-operated rats. The total blood bilirubin (TB), liver volume (LV), the area of hepatocytes (AH), the hepatocyte nuclear-cytoplasmic ratio (HNCR), the hepatocyte bulk density (HBD) were investigated. The LV and HBD parameters were used to calculate the total volume of hepatocytes (TVH).

Results. The highest mortality was recorded on Day 22-35 of the experiment (7 out of 11 animals). Bilirubin level was significantly higher than in the control group with its maximum on Day 1 (295±100 vs. 8±6, μmol/l, p<0.001). The highest LV value was observed on Day 14 (14.1±1.1 vs. 8.4±1.4cm³, p<0.01). The processes prevailing in the livers were cell proliferation, fibrosis with gradual displacement of hepatocytes by proliferating bile ducts, and complete loss of normal liver histostructure. The proportion of hepatocytes in the liver (HBD) was progressively decreasing from 0.94 (Control) to 0.44 (Day 35). In spite of that, the TVH level was initially increased (max 9.7±0.36cm³ on Day 3 vs. 8.3±0.26cm³ on Day 1, p<0.05), but after Day 14 it decreased, with no significant differences from the Control group on Day 21(8.2±1.2 vs. 7.9±1.6cm³, p>0.05), with its lowest level (5.0±0.9cm³) on Day 35 (p<0.05 compared with max value on Day 3). The HNCR index, which reflects proliferative activity of hepatocytes, had its maximum on Day 14 (0.53±0.01 vs. 0.21±0.05 in Control group, p<0.001).

Conclusions. In experimental CEBDO, reduction of the HBD index less than 60 % and reduction of TVH less than the value of a normal liver are accompanied by highest mortality, i.e., are a sign of hepatic decompensation. That was preceded by the maximum proliferative activity of hepatocytes, the criterion of which is the HNCR index

Author Biographies

Ivan Mamontov, Kharkiv Medical Academy of Postgraduate Education Amosova str., 58, Kharkiv, Ukraine, 61176

PhD, Associate Professor

Department of Surgery and Proctology

Igor Ivakhno, Kharkiv City Clinical Hospital No. 17 Moskovsky ave., 195, Kharkiv, Ukraine, 61037 Kharkiv Medical Academy of Postgraduate Education Amosova str., 58, Kharkiv, Ukraine, 61176

PhD, Teaching Assistant, Doctor-Pathologist

Department of pathology

Tamara Tamm, Kharkiv Medical Academy of Postgraduate Education Amosova str., 58, Kharkiv, Ukraine, 61176

MD, Professor, Head of Department

Department of Surgery and Proctology

V’yacheslav Panasenko, Kharkiv National Medical University Nauky ave., 4, Kharkiv, Ukraine, 61022

Assistant

Department of Histology, Cytology and Embryology

Volodymyr Padalko, V. N. Karazin Kharkiv National University Svobody sq., 4, Kharkiv, Ukraina, 61022

PhD, Senior Researcher, Associate Professor

Department of General and Clinical Pathology

Ismat Zulfugarov, Kharkiv Medical Academy of Postgraduate Education Amosova str., 58, Kharkiv, Ukraine, 61176

Postgraduate student

Department of surgery and proctology

References

  1. Wu, W., Yang, Y., Huang, Q. (2001). Bilirubin metabolism after obstructive jaundice in rats. Zhonghua Gan Dan Wai Ke Za Zhi, 5, 288–291.
  2. Marques, T. G., Chaib, E., Fonseca, J. H. da, Lourenço, A. C. R., Silva, F. D., Ribeiro Jr, M. A. F. et. al. (2012). Review of experimental models for inducing hepatic cirrhosis by bile duct ligation and carbon tetrachloride injection. Acta Cirurgica Brasileira, 27 (8), 589–594. doi: http://doi.org/10.1590/s0102-86502012000800013
  3. Dondorf, F., Fahrner, R., Ardelt, M., Patsenker, E., Stickel, F., Dahmen, U. et. al. (2017). Induction of chronic cholestasis without liver cirrhosis – Creation of an animal model. World Journal of Gastroenterology, 23 (23), 4191–4199. doi: http://doi.org/10.3748/wjg.v23.i23.4191
  4. Wright, J. E., Braitwaite, J. L. (1964). The effects of ligation of the common bile duct in the rat. Journal of Anatomy, 98 (2), 227–233.
  5. Matenaers, C., Popper, B., Rieger, A., Wanke, R., Blutke, A. (2018). Practicable methods for histological section thickness measurement in quantitative stereological analyses. PLOS ONE, 13 (2), e0192879. doi: http://doi.org/10.1371/journal.pone.0192879
  6. Heinrich, S., Georgiev, P., Weber, A., Vergopoulos, A., Graf, R., Clavien, P.-A. (2011). Partial bile duct ligation in mice: A novel model of acute cholestasis. Surgery, 149 (3), 445–451. doi: http://doi.org/10.1016/j.surg.2010.07.046
  7. Prigge, J. R., Coppo, L., Martin, S. S., Ogata, F., Miller, C. G., Bruschwein, M. D. et. al. (2017). Hepatocyte Hyperproliferation upon Liver-Specific Co-disruption of Thioredoxin-1, Thioredoxin Reductase-1, and Glutathione Reductase. Cell Reports, 19 (13), 2771–2781. doi: http://doi.org/10.1016/j.celrep.2017.06.019
  8. Tietz, N. W. (Ed.) (1995). Clinical guide to laboratory tests. Philadelphia: WB saunders, 268–273.
  9. Yang, Y., Chen, B., Chen, Y., Zu, B., Yi, B., Lu, K. (2014). A comparison of two common bile duct ligation methods to establish hepatopulmonary syndrome animal models. Laboratory Animals, 49 (1), 71–79. doi: http://doi.org/10.1177/0023677214558701
  10. Ertor, B., Topaloglu, S., Calik, A., Cobanoglu, U., Ahmetoglu, A., Ak, H. et. al. (2013). The Effects of Bile Duct Obstruction on Liver Volume: An Experimental Study. ISRN Surgery, 2013, 1–7. doi: http://doi.org/10.1155/2013/156347
  11. Kordzaia, D., Jangavadze., M. (2014). Unknown bile ductuli accompanying hepatic vein tributaries (experimental study). Georgian Med News, 234, 121–129.
  12. Mamontov, I. М., Ivakhno, I. V., Tamm, T. I., Panasenko, V. O., Padalko, V. I., Zulfugarov, I. (2019). Morphological signs of the hepatic function decompensation with experimental complete obstruction of the extrahepatic bile ducts. World of Medicine and Biology, 15 (67), 162–166. doi: http://doi.org/10.26724/2079-8334-2019-1-67-162

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Published

2020-02-06

How to Cite

Mamontov, I., Ivakhno, I., Tamm, T., Panasenko, V., Padalko, V., & Zulfugarov, I. (2020). Morphometric parameters of hepatocytes in experimental complete extrahepatic bile duct obstruction. ScienceRise: Medical Science, (1 (34), 51–56. https://doi.org/10.15587/2519-4798.2020.193845

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Section

Medical Science