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

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.

Keywords: Ascites; Lymphangiogenesis; Nitric oxide; Portal hypertension.

Figure 1

Lymphatic vascular systems in normal and pathological conditions. A filtrate (essentially plasma) escapes from blood vessels into the interstitial space of the surrounding tissues. The lymphatic vascular system removes this excess interstitial fluid and returns it to the bloodstream. The lymphatic vascular system consists of closed-ended capillaries and larger collecting lymphatic vessels. The lymphatic capillaries are composed of a single layer of lymphatic endothelial cells and absence of a continuous basement membrane, making it highly permeable to fluid and macromolecules. Smooth muscle cells (SMCs) are absent in the lymphatic capillaries but are present in the collecting lymphatic vessels. The collecting lymphatic vessels have intraluminal valves that prevent lymphatic backflow. Insufficient lymphatic drainage results in lymphedema and ascites.