Liver vasculature system

Figure 6.2 The vasculature supplying and draining the liver and its relationship to the systemic circulation. Source. From Ref. 3.

Hepatorenal syndrome, functional renal failure in the setting of cirrhosis in the absence of intrinsic renal disease, occurs in patients with cirrhosis as a result of intense vasoconstriction within the renal cortical vasculature. It is common and develops in approximately 40% of patients with cirrhosis and ascites within 5 years. The resultant reduction in blood supply to the kidneys causes avid sodium retention and oliguria. The vasoconstriction that occurs in the kidneys is in stark contrast to the state of systemic vasodilation that is characteristic of chronic liver failure. The pathophysiologic mechanism responsible for these effects is unknown, but is linked to the systemic vasodilation, hypovolemia, and hyperkinetic circulation seen in chronic liver failure. ... 

FIGURE 6.2 The vasculature supplying and draining the liver and its relationship to the systemic circulation. From Timbrell, J.A., Biotransformation of xenobiotics. From General and Applied Toxicology, 2nd edition, edited by Ballantyne, Marrs and Syversen, Stockton Press, U.S.A. 

Estrogens have a number of functions and not only feminization. Sites of (human) expression include the ovaries, testes, placenta, fetal (but not adult) liver, adipose tissue, chondrocytes and osteoblasts of bone, vasculature smooth muscle, and several sites in brain, including parts of the hypothalamus, limbic system, and cerebral cor-tex °. As discussed later, regulatory mechanisms differ considerably in these tissues. P450 19A1 is also expressed in some tumors, particularly those derived from these tissues. 

In summary, several enzyme systems have been shown to be capable of metabolizing organic nitrates. Some of these systems, for example, CYP and the GSTs, are found abundantly in the liver, and may be the primary enzymes used for the detoxification of these compounds. The principal metabolic products are nitrite and nitrate ions, rather than NO itself. In the vasculature a microsomal enzyme exists that converts nitroglycerin to NO. The identity of this enzyme remains to be defined, although it is unlikely to be either a GST or CYP. 

A recently described multicellular model that may offer promise is the formation of liver buds from pluripotent stem cells cultured with endothelial cells and mesenchymal stem cells (Takebe et al., 2013). This coculture system self-organizes into a 3D bud of cells with a complex vasculature and shows improved hepatic function compared to 2D controls. Despite this, the authors report a lack of biliary cell formation suggesting that this model, while being a step forward, requires independent reproduction and further development before fully recapturing the complex architecture of the liver. 

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