Endotoxemia of cirrhosis: an observation not substantiated.

Physiologic similarities between cirrhotic and septic patients have implicated systemic endotoxemia as a possible mediator of the hemodynamic, neurologic, and hematologic complications observed in patients with cirrhosis of the liver. The recently reported high prevalence of endotoxin in ascites, as well as in portal and systemic plasma, has further incriminated endotoxin of gut origin as the responsible agent. Limulus amebocyte lysate tests were performed upon peripheral plasma of 38 cirrhotic patients; portal plasma and ascites were assayed in 14 and 11 of these patients, respectively. No endotoxin was detectable. We believe that the ubiquity of endotoxin, with the attendant opportunities for specimen contamination, is the most likely explanation for the recently reported high prevalence of endotoxin in the plasma and ascites of cirrhotic patients.

Tyrosine metabolism in cirrhosis.

The aim of this study was to define the enzyme defect responsible for tyrosinemia in cirrhotic patients. The principal hepatic degradation pathway for tyrosine, tyrosine leads to p-hydroxyphenylpyruvic acid equilibrium homogentisic acid leads to CO2 was studied in 18 cirrhotic patients and eight controls. The classic method employed in elucidation of hereditary tyrosinosis was sued. Metabolic intermediates on the pathway were measured in the basal state, and following oral loading doses (50 mg/kg BW) of tyrosine, PHPA, and homogentisic acid. Cirrhotic patients showed a significant increase (p = 0.005) in fasting plasma tyrosine and in basal PHPA excretion and impaired tolerance to all three metabolites when compared to normals. Fifteen of the 18 cirrhotic patients showed tyrosine intolerance which was not accompanied by change in distal metabolites compared to their basal levels. Nevertheless 13 of the 18 did exhibit intolerance of either PHPA or homogentisic acid. We conclude that in contrast to the single complete defect in hereditary disorders of tyrosine metabolism, cirrhotic patients have partial defects at tyrosine transaminase, PHPA oxidase, and homogentisic acid oxidase, the initial step being rate-limiting.

Portal pseudoperfusion: an angiographic illusion.

Much confusion regarding the hemodynamics following interposition mesosystemic shunts prevails. Many authorities have claimed that portal venous perfusion continues following interposition mesocaval shunts. In 1971, a prospective, randomized trial comparing the distal splenorenal shunt with a variety of interposition mesosystemic shunts (primarily mesocaval or mesorenal) was begun. Visceral angiography was utilized to assess the early and late postoperative hemodynamic changes following both selective and nonselective shunts. None of the patients with patent interposition shunts retained portal perfusion present preoperatively. Searching for an explanation for this hemodynamic discrepancy, we examined two patients of the randomized trial angiographically. Both patients had excellent portal perfusion preoperatively, yet following interposition shunting (one mesocaval and one splenocaval), neither maintained portal perfusion of the liver. Celiac artery injections produced opacification of the entire splenoportal axis; however, it is shown that such portal venous opacification occurred in a retrograde direction by selective hepatic arterial injections demonstrating hepatofugal portal venous flow. Additionally, two nonrandomized patients received interposition mesorenal shunts and exemplify this phenomenon, entitled "portal pseudoperfusion". The explanation for conflicting literature reports lies in the misinterpretation of venous phase celiac and non-selective SMA arteriography in determining the direction of portal flow. A narrative of preoperative and postoperative angiograms of four patients will clarify the mechanism of "portal pseudoperfusion" and demonstrate that interposition shunts totally siphon portal venous perfusion. Clues to the detection and techniques to avoid this phenomenon will be presented.

Deranged tyrosine metabolism in cirrhosis.

In normal individuals, the main route for tyrosine degradation is the hepatic pathway tyrosine→4-hydroxyphenylpyruvic acid→homogentisic acid→CO(2). Quantitatively minor pathways, in large part extrahepatic, are: tyrosine→tyramine→octopamine and tyrosine→dopa→catecholamines.In cirrhosis, the main hepatic pathway is blocked to varying degrees at the first three stages. This appears to be due to lack of activity of the enzymes tyrosine transaminase, PHPA oxidase, and HGA oxidase, the first step being rate limiting. Hypertyrosinemia and tyrosine intolerance result.With the main hepatic pathway partially blocked, an abnormally large amount of tyrosine passes into the normally minor extrahepatic pathway leading to the false neurotransmitters tyramine and octopamine. Overproduction of these amines ensues and they accumulate in the body fluid.The false neurotransmitters can displace catecholamines from their storage sites in the peripheral and central nervous system, and thereby disrupt adrenergic processes in arterioles, kidneys, and brain. Their accumulation in cirrhotic patients may play a role in the pathogenesis of hepatic encephalopathy, hepatorenal syndrome, and hyperdynamic circulation.

Splenic artery ligation in distal splenorenal shunts.

Splenic artery ligation, a simple surgical procedure expected to decrease splenic flow and portal pressure in patients with cirrhosis of the liver, was performed concomitantly with a distal splenorenal shunt procedure in six patients and as the main surgical procedure in two patients. Immediate cessation of bleeding was achieved in the four patients in whom the splenic artery was ligated to reduce intraoperative bleeding. However, three of the seven patients with previous gastroesophageal hemorrhage rebled from various postoperatively. Symptoms of splenic infarction were observed in six patients, resulting in thrombosis of the splenic vein and/or of the distal splenorenal shunt in four patients and necessitating splenectomy in one. This incidence of thrombosis of the distal splenorenal shunt is much higher than the overall incidence of 5 per cent observed at our institution. It is thus concluded that the splenic artery should not be ligated in cirrhotic patients with patent distal splenorenal shunts, since splenic arterial collateral vessels have already been reduced by the gastric devascularization, an integral component of the distal splenorenal shunt.