Capillarization, sinusoidal

After experimental distal occlusion of the hepatic arteries in rats necrotic areas were observed. However, these necroses were bypassed by vessels similar to the capillarized sinusoids observed in the cirrhotic liver in humans. These vessels acted as sinusoidal shunts in the embolized territories (Tancredi et al. 1999) and were the reason for the resulting viable tumor cells after TACE treatment (Fan et al. 1998). Based on these results, the antitumor effect of TACE showed a mean partial response rate of 26.9%, while the mean complete response rate was only 6% (Camma et al. 2002). To improve the therapeutic results for large liver tumors and increase the survival rates, it is still necessary to eliminate the remaining viable tumor cells at the tumor-host interface. 

The central event in the development of liver fibrosis is the enhanced sinusoidal deposition of extracellular matrix proteins that are mainly produced by activated HSC [86, 112, 113] and to a minor extent by endothelial cells [44-46] and hepatocytes [114, 115]. So far, no evidence has been found that KC are directly involved in the production of extracellular matrix proteins [39]. The accumulation of extracellular matrix proteins is caused by a disturbed balance between the synthesis and the degradation of the matrix proteins. This imbalance leads to a 5 to 10-fold increase in the total amount of matrix molecules and to an altered composition of the extracellular matrix. In contrast to normal livers, the sinusoids in fibrotic livers are stuffed with the fibrillar collagens type I and III. This colla-genization of the sinusoids, referred to as sinusoidal capillarization, causes severe disturbances of the blood flow and an impaired exchange of proteins between the liver cells and blood. Furthermore, this capillarization is accompanied by a loss of fenestration of the sinusoidal endothelial lining, which further hampers the diffusion of proteins between plasma and hepatic cells. 

Another important criterion is to determine whether the nodular transformation in the liver is complete or incomplete. This morphological characteristic can be found both in progressive and stationary cirrhoses. In complete cirrhosis, the parenchyma is completely partitioned by connective tissue septa. The collapse of fibres (due to portocentral bridging necroses) results in the development of portocentral septa (= passive septa). Due to the spreading of the inflammation to the periportal parenchyma, septa develop and branch out from the portal fields (= active septa). Generally, they lead to capillarization of the sinusoidal walls as well. (s. fig. 35.7) Incomplete cirrhosis only displays the formation of short septa (= subsepta), so that there are areas of incomplete (partial) subdivision of the parenchyma. 

TIMP). Both factors reduce further degradation of connective tissue. The hepatocytes are now multilayered instead of normal single-layered cell plates and lose their microvilh. Fenestration of the sinusoids disappears, whereas the sinusoidal extracellular matrix increases, leading to capillarization of the sinusoids, (s. pp 406, 526) In this way, the distance between the hepatocytes and the blood becomes greater, and the clearance of macromolecular substances is reduced. Stronger flow resistance in the liver leads to portal hypertension. Portoportal and portocentral bands of connective tissue form, in which portosystemic intrahepatic shunts develop. 

Accumulation of both fibrillar and basement membrane-like collagens Increase of laminen and fibronectin Thickening of connective tissue septae Capillarization of the sinusoids Sclerosis Aging of fibrotic tissue... 

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