23
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      The lymphatic vascular system in liver diseases: its role in ascites formation

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The lymphatic system is part of the circulatory system and plays a key role in normal vascular function. Its failure plays a crucial role in the development and maintenance of various diseases including liver diseases. Lymphangiogenesis (the growth of lymphatic vessels) and changes in the properties of lymphatic vessels are associated with pathogenesis of tumor metastases, ascites formation, liver fibrosis/cirrhosis and portal hypertension. Despite its significant role in liver diseases and its importance as a potential therapeutic target for those diseases, the lymphatic vascular system of the liver is poorly understood. Therefore, how the lymphatic vascular system in general and lymphangiogenesis in particular are mechanistically related to the pathogenesis and maintenance of liver diseases are largely unknown. This article summarizes: 1) the lymphatic vascular system; 2) its role in liver tumors, liver fibrosis/cirrhosis and portal hypertension; and 3) its role in ascites formation.

          Related collections

          Most cited references25

          • Record: found
          • Abstract: found
          • Article: not found

          Toxic injury to hepatic sinusoids: sinusoidal obstruction syndrome (veno-occlusive disease).

          The term veno-occlusive disease of the liver refers to a form of toxic liver injury characterized clinically by the development of hepatomegaly, ascites, and jaundice, and histologically by diffuse damage in the centrilobular zone of the liver. The cardinal histologic features of this injury are marked sinusoidal fibrosis, necrosis of pericentral hepatocytes, and narrowing and eventual fibrosis of central veins. Recent studies suggest that the primary site of the toxic injury is sinusoidal endothelial cells, followed by a series of biologic processes that lead to circulatory compromise of centrilobular hepatocytes, fibrosis, and obstruction of liver blood flow. Thus we propose a more appropriate name for this form of liver injury--sinusoidal obstruction syndrome. This review encompasses historical perspectives, clinical manifestations of sinusoidal obstruction syndrome in the setting of hematopoietic cell transplantation, histologic features of centrilobular injury, and a discussion of the pathophysiology of sinusoidal injury, based on both animal and clinical investigations.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Microlymphatics and lymph flow.

            A careful review of several different organs shows that with the information available today the beginnings of the microlymphatics in the tissue consist of endothelialized tubes only. Lymphatic smooth muscle within the collecting lymphatics appears further downstream, in some organs only outside the parenchyma. This particular anatomic picture has been observed in many different mammalian organs and in humans. The nonmuscular, so-called initial, lymphatics are the site of interstitial fluid absorption that requires only small and transient pressure gradients from the interstitium into the initial lymphatics. A fundamental question concerns the mechanism that causes expansion and compression of the initial lymphatics. I presented several realistic proposals based on information currently on hand relevant to the tissue surrounding the initial lymphatics. To achieve a continuous lymphatic output, periodic (time variant) tissue stresses need to be applied. They include arterial pressure pulsations; arteriolar vasomotion; intestinal smooth muscle contractions and motilities; skeletal muscle contraction; skin tension; and external compression, such as during walking, running, or massage, respiration, bronchiole constriction, periodic tension in tendon, contraction and relaxation of the diaphragm, tension in the pleural space during respiration, and contractions of the heart. The nonmuscular initial lymphatic system drains into a set of contractile collecting lymphatics, which by way of intrinsic smooth muscle propel lymph fluid. The exact transition between noncontractile and contractile lymphatics has been established only in a limited number of organs and requires further exploration. Retrograde flow of lymph fluid is prevented by valves. There are the usual macroscopic bileaflet valves in the initial and collecting lymphatics and also microscopic lymphatic endothelial valves on the wall of the initial lymphatics. The latter appear to prevent convective reflow into the interstitium during lymphatic compression. Many of the lymph pump mechanisms have been proposed in the past, and most authors agree that these mechanisms influence lymph flow. However, the decisive experiments have not been carried out to establish to what degree these mechanisms are sufficient to explain lymph flow rates in vivo. Because individual organs have different extrinsic pumps at the level of the initial lymphatics, future experiments need to be designed such that each pump mechanism is examined individually so as to make it possible to evaluate the additive effect on the resultant whole organ lymph flow.(ABSTRACT TRUNCATED AT 400 WORDS)
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              LYVE-1 is not restricted to the lymph vessels: expression in normal liver blood sinusoids and down-regulation in human liver cancer and cirrhosis.

              Lymphatic vessel endothelial hyaluronan receptor (LYVE)-1 is thought to be restricted to lymph vessels and has been used as such to show that tumor lymphangiogenesis occurs on overexpression of lymphangiogenic factors in mouse tumor models. However, these studies have not yet been corroborated in human tumors. Here we show, first, that LYVE-1 is not exclusive to the lymph vessels. Indeed, LYVE-1 is also present in normal hepatic blood sinusoidal endothelial cells in mice and humans. Surprisingly, LYVE-1 is absent from the angiogenic blood vessels of human liver tumors and only weakly present in the microcirculation of regenerative hepatic nodules in cirrhosis, though both vessels are largely derived from the liver sinusoids. Second, we propose a novel approach to identify lymphatics in human and murine liver. By combining LYVE-1 and Prox 1 (a transcription factor) immunohistochemistry, we demonstrate that lymphatics are abundant in cirrhosis. In contrast, in human hepatocellular carcinoma and liver metastases, they are restricted to the tumor margin and surrounding liver. The absence of intratumor lymphatics in hepatocellular carcinomas and liver metastases may impair molecular and cellular transport in these tumors. Finally, the presence of LYVE-1 in liver sinusoidal endothelia suggests that LYVE-1 has functions beyond the lymph vascular system.
                Bookmark

                Author and article information

                Journal
                Clin Mol Hepatol
                Clin Mol Hepatol
                CMH
                Clinical and molecular hepatology
                The Korean Association for the Study of the Liver
                2287-2728
                2287-285X
                June 2013
                27 June 2013
                : 19
                : 2
                : 99-104
                Affiliations
                Section of Digestive Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.
                Author notes
                Corresponding author: Yasuko Iwakiri. 1080 LMP, 333 Cedar Street, Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT 06520, USA. Tel. +1-203-785-6204, Fax. +1-203-785-7273, yasuko.iwakiri@ 123456yale.edu
                Article
                10.3350/cmh.2013.19.2.99
                3701854
                23837133
                8b414807-1c8a-4f3f-9565-b22d21097753
                Copyright © 2013 by The Korean Association for the Study of the Liver

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 10 May 2013
                : 16 May 2013
                Categories
                Review

                Gastroenterology & Hepatology
                lymphangiogenesis,ascites,portal hypertension,nitric oxide
                Gastroenterology & Hepatology
                lymphangiogenesis, ascites, portal hypertension, nitric oxide

                Comments

                Comment on this article