Relation of Renal Impairment and Haemorrhagic Diathesis to Endotoxaemia in Fulminant Hepatic Failure

Wilkinson, Stephen; Gazzard, B. G.; Arroyo, Vicente; Moodie, Helen; Williams, Roger

doi:10.1016/s0140-6736(74)92711-1

Cited by 190 publications

(79 citation statements)

References 18 publications

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“…It has been well known that non-septic endotoxemia appears in patients with fulminant hepatic failure (Wilkinson et al 1974) or cirrhotic patients (Wilkinson et al 1976). Wilkinson et al (1974) reported that 14 of 22 consecutive patients with fulminant hepatic failure had endotoxemia and there was statistically significant correlation between the occurrence of endotoxemia and the development of renal failure and DIC.…”

Section: Discussionmentioning

confidence: 99%

Endotoxemia in liver diseases: Detection by a quantitative assay using chromogenic substrate with perchloric acid pretreatment.

Yajima

Fukuda

Otsuki

et al. 1985

Tohoku J. Exp. Med.

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Section: Discussionmentioning

confidence: 99%

Endotoxemia in liver diseases: Detection by a quantitative assay using chromogenic substrate with perchloric acid pretreatment.

Yajima

Fukuda

Otsuki

et al. 1985

Tohoku J. Exp. Med.

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“…53 b. Microglial activation and its contribution to the development of astrocyte swelling and brain edema in ALF While the precise pathophysiological mechanisms responsible for the development of astrocyte swelling/brain edema in AHE have not been fully elucidated, it was recently proposed that microglial activation and the subsequent synthesis and release of pro-inflammatory cytokines are involved. 38,43,47,56 Microglia are well-known to induce inflammatory responses in brain, 57 as they represent the primary resident immune cells of the CNS. Microglia can be activated by a wide number of factors, including glutamate, pro-inflammatory cytokines (derived as a consequence of liver necrosis and/or sepsis), LPS, as well as by extracellular potassium.…”

Section: Inflammation In Hepatic Encephalopathymentioning

confidence: 99%

Neuroinflammation in Hepatic Encephalopathy: Mechanistic Aspects

Jayakumar

Rao

Norenberg

2015

Journal of Clinical and Experimental Hepatology

102

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Hepatic encephalopathy (HE) is a major neurological complication of severe liver disease that presents in acute and chronic forms. While elevated brain ammonia level is known to be a major etiological factor in this disorder, recent studies have shown a significant role of neuroinflammation in the pathogenesis of both acute and chronic HE. This review summarizes the involvement of ammonia in the activation of microglia, as well as the means by which ammonia triggers inflammatory responses in these cells. Additionally, the role of ammonia in stimulating inflammatory events in brain endothelial cells (ECs), likely through the activation of the toll-like receptor-4 and the associated production of cytokines, as well as the stimulation of various inflammatory factors in ECs and in astrocytes, are discussed. This review also summarizes the inflammatory mechanisms by which activation of ECs and microglia impact on astrocytes leading to their dysfunction, ultimately contributing to astrocyte swelling/ brain edema in acute HE. The role of microglial activation and its contribution to the progression of neurobehavioral abnormalities in chronic HE are also briefly presented. We posit that a better understanding of the inflammatory events associated with acute and chronic HE will uncover novel therapeutic targets useful in the treatment of patients afflicted with HE. ( J CLIN EXP HEPATOL 2015;5:S21-S28) H epatic encephalopathy (HE) is the major neurological complication of severe liver disease. It presents in two forms, chronic HE and acute HE. Chronic HE (portal-systemic encephalopathy) usually occurs in patients with alcoholic liver cirrhosis and is characterized by impaired neurological function, including changes in personality, altered mood, diminished intellectual capacity, and abnormal muscle tone and tremor. 1 Acute HE (AHE, acute liver failure, ALF; fulminant hepatic failure) generally occurs following massive liver necrosis due to viral hepatitis (hepatitis B and C), hepatic neoplasms, vascular causes, or exposure to acetaminophen and other hepatotoxins. AHE is associated with the abrupt onset of delirium, seizures, and coma.The principal pathological change in chronic HE is characterized by Alzheimer type II astrocytosis, 2,3 which is characterized by astrocytes possessing enlarged, pale nuclei, often occurring in pairs, with the nuclei frequently displaying prominent nucleoli. Cerebral edema and associated increase in intracranial pressure leading to brain herniation are the characteristic features of AHE which occurs in upto 80% of patients with AHE 4-6 and represents the most frequent cause of death in these patients (70% mortality). 4,7 While the basis for the edema in AHE is poorly understood, astroglial swelling (cytotoxic edema) dominates the pathology in experimental animals, [8][9][10][11] as well as in humans. 12 Of interest, no significant or consistent morphologic changes have been identified in neurons or other neural cells. Such findings prompted the suggestion that HE fundamentally represents a pr...

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“…Renal failure with characteristics similar to those of the HRS Definition of Hepatorenal Syndrome has also been described in patients with acute liver failure. 104 Hepatorenal syndrome is a syndrome that occurs in patients with chronic liver disease and advanced hePatients with cirrhosis show abnormalities in the systemic circulation during the course of their disease. patic failure and portal hypertension characterized by impaired renal function and marked abnormalities in In patients with compensated cirrhosis (i.e., without ascites) these abnormalities are characterized by in-the arterial circulation and activity of the endogenous vasoactive systems.…”

Section: In Cirrhosismentioning

confidence: 99%

Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis†

Arroyo¹,

Ginès²,

Gerbes³

et al. 1996

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During the last decade great advances have been made of water retention and dilutional hyponatremia in human cirrhosis. Finally, the field of spontaneous infection of concerning the pathogenesis and treatment of ascites. A new hypothesis on the mechanism of renal dysfunction ascitic fluid (spontaneous bacterial peritonitis) is also experiencing major changes. The demonstration of intestiand ascites formation in cirrhosis has been proposed 1 and this has greatly stimulated research in this area. The nal bacterial translocation in experimental models of cirrhosis, 12 the potential role of cytokines in some discovery of the important role played by the vascular endothelium in the homeostasis of systemic hemodynam-complications associated with this infection, 13 the identification of subgroups of cirrhotic patients predisposed to ics and renal function 2,3 has also opened an important field of research into pathophysiology, and evidence has develop spontaneous bacterial peritonitis, 14 and the effectiveness of selective intestinal decontamination in the been presented implicating endothelial factors in the pathogenesis of systemic circulatory dysfunction in cir-primary and secondary prophylaxis of spontaneous bacterial peritonitis 15,16 are the most relevant developments. rhosis 4,5 and hepatorenal syndrome (HRS). 6 The reintroduction of therapeutic paracentesis has greatly modifiedIn clear contrast to these advances, little attention has been paid to the standardization of the nomenclathe treatment of cirrhotic patients with tense or refractory ascites. 7 The transjugular intrahepatic portosys-ture and diagnostic criteria of different syndromes associated with ascites in cirrhosis. The existence of a temic shunt is another therapeutic tool of potential interest in the management of refractory ascites. 8 The uniform language, however, is essential in modern medicine. It facilitates communication among clinisynthesis of orally-active specific antagonists of the tubular effect of antidiuretic hormone and inhibitors of antidi-cians and researchers and ensures unambiguous diagnoses and more confident prognoses. Moreover, it uretic hormone release will probably add new drugs to the pharmacological armamentarium for patients with improves pathophysiological and therapeutic investigations, simplifies the analysis of therapeutic trials, cirrhosis and ascites. These ''aquaretic drugs,'' which normalize renal water metabolism in experimental cirrhosis and stimulates multicenter studies. and ascites, 9-11 are of potential interest for the treatment PREVIOUS CONSENSUS DEFINITIONS OF HEPATORENAL SYNDROME AND

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Relation of Renal Impairment and Haemorrhagic Diathesis to Endotoxaemia in Fulminant Hepatic Failure

Cited by 190 publications

References 18 publications

Endotoxemia in liver diseases: Detection by a quantitative assay using chromogenic substrate with perchloric acid pretreatment.

Endotoxemia in liver diseases: Detection by a quantitative assay using chromogenic substrate with perchloric acid pretreatment.

Neuroinflammation in Hepatic Encephalopathy: Mechanistic Aspects

Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis†

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