SUMMARY The effects of intravenously administered endotoxin on the hepatic and systemic circulation as well as on the coagulation system were evaluated in normal rats (n = 26), in rats with experimental portal hypertension (n = 15), and in rats with portacaval anastomosis (n = 22). Endotoxin (15 mg/kg) in the normal rat leads to a prompt increase of transaminase activity and to a hyperdynamic circulation with a consequent increase in the total hepatic blood flow. In a later phase (6 h postoperatively) the hepatic artery dilated with a consequent hepatic arterial hyperperfusion. The coagulation system was affected with signs of consumption coagulopathy.In the rats with portal hypertension and portacaval collaterals as well as in those with portacaval anastomosis, the endotoxin injection resulted in acute liver necrosis within 12 to 15 hours. The hepatic artery became overdilated with a cardiac output fraction of 25 % (normal 5-5 %). Blood extravasates and thrombi, rich in fibrin, were detected in the liver. It is suggested that this exaggeration of the endotoxin effect was due to an impaired clearance function of the reticuloendothelial system, probably as consequence of portacaval collateral circulation. It is concluded that endotoxins (1) damage the liver even in a normal organism; (2) are potent to induce acute liver necrosis, if the reticuloendothelial system is altered; (3) have to be taken into consideration as contribution to the pathogenesis of acute as well as chronic liver diseases.Endotoxaemia is of increasing interest in the pathogenesis of acute hepatic failure and its complications. It is proposed that endotoxins coming from the intestine are insufficiently cleared from the portal venous system because of an impairment of the reticuloendothelial system. Endotoxins may then be responsible for both the intravascular coagulation and renal failure which are part of the picture of acute liver failure (Wilkinson, Gazzard, Arroyo, Moodie, and Williams, 1974). Gans, Mori, Lindsey, Kaster, Richter, Quinlan, Dineen, and Tan (1971) discussed these problems in connexion with their experiments concerning the anhepatic dog and suggested from the results that bacteria from the intestine or their products, no longer adequately eliminated by the liver reticuloendothelial system, are contributing significantly toward the pathogenesis of hepatic failure.

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SummaryThe fibrinogen synthesis rate in patients with cirrhosis of the liver is enhanced. To confirm this, both experimental and clinical investigations were carried out. The fibrinogen synthesis rate was studied, using the incorporation rate of 14-C-Leucine into thrombin clottable plasma protein in the setting of experimental portal hypertension caused by gradual occlusion of the portal vein. Under these conditions the plasma distribution space increased to 148% of the control (day 6). This was dependent on the amount of the portocaval shunt volume. While plasma fibrinogen concentration remained unaltered, the plasma fibrinogen pool increased to 154% of the controls. At the same time, the fibrinogen synthesis rate increased to 159%. In relation to liver weight per 100 gm body weight the rate of synthesis was much more enhanced (211 % of control). During the decline to normal plasma volume, due to a decrease of portocaval shunt volume, the fibrinogen synthesis was inhibited (61% of control).Under clinical conditions in patients with cirrhosis and portal hypertension, the pathophysiological state is in important aspects comparable to the experimental model. A group of 28 patients with cirrhosis was investigated from the same point of view. In these patients the plasma volume and the plasma fibrinogen pool was markedly increased, depending again on the portocaval shunt volume but not on the portal pressure. From these data it is concluded that in patients with cirrhosis fibrinogen synthesis is enhanced.

6 patients with severe self-poisoning were treated by charcoal-haemoperfusion in our centre up to now. In four of them (all suffering from sleeping drug overdosage) the treatment was successful. Two patients with intoxications by agrochemicals died in spite of haemoperfusion. Side effects of haemoperfusion were drops of blood pressure and platelet count, depletion of immune bodies, and adsorption of remedies. Up to now, the indication for haemoperfusion has to consider these secondary actions of encapsulated charcoal as inevitable.