S. P. Wilkinson

Endotoxaemia and renal failure in cirrhosis and obstructive jaundice.

An investigation into the possible role of endotoxins in the pathogenesis of renal failure in cirrhosis and obstructive jaundice showed the two to be closely related. None of the patients with cirrhosis who had endotoxaemia had other evidence of Gram-negative infection at the time of the study, and the endotoxaemia was therefore probably due to impaired hepatic clearance of toxins normally absorbed from the gastrointestinal tract. In contrast, bacteriological evidence of Gram-negative infection was found in most of the patients with obstructive jaundice and endotoxaemia.

RELATION OF RENAL IMPAIRMENT AND HAEMORRHAGIC DIATHESIS TO ENDOTOXAEMIA IN FULMINANT HEPATIC FAILURE

Abstract Endotoxaemia, as detected by the Summary Limulus lysate assay, was found in 14 of 22 consecutive patients with fulminant hepatic failure. In most cases there was no other evidence of gram-negative infection and the endotoxaemia may have been due to impaired hepatic clearance of toxins normally absorbed from the gastrointestinal tract. There were statistically significant correlations between the occurrence of endotoxaemia and the development of renal failure and intravascular coagulation, which may be explained by the known properties of endotoxin as a renal vasoconstrictor and an activator of Hageman factor.

Frequency and type of renal and electrolyte disorders in fulminant hepatic failure.

Of 48 patients with fulminant hepatic failure who progressed to grade III or IV encephalopathy 38 showed evidence of renal impairment. In 32 of these patients the underlying cause could be placed initially into one of three categories—prerenal uraemia (4 patients), acute tubular necrosis (16), and “functional renal failure” (12). The latter differed in several respects from that seen with liver failure secondary to cirrhosis. The frequency and type of renal impairment was the same in those patients in whom the fulminant hepatic failure had resulted from an overdose of paracetamol as in the other aetiological groups. Abnormalities in plasma electrolytes were common—in particular hypernatraemia occurred in 11 patients from an osmotic diuresis precipitated by hypertonic dextrose or fructose given intravenously, and from the sodium in the fresh frozen plasma used to correct the coagulation disturbance when renal excretion of this ion was inappropriately low.

Renal failure in otherwise uncomplicated acute viral hepatitis.

Twelve patients with otherwise uncomplicated acute viral hepatitis (two were HBsAg-positive) developed renal failure. Apart from dehydration due to repeated vomiting in one patient, no factor responsible for precipitating renal failure could be identified. The clinical course was characterised by renal failure with plasma urea concentrations reaching maximum values of 26-69 mmol/l (175-416 mg/100 ml). Ten patients needed dialysis for up to two weeks. Seven patients recovered completely, while the other five died from sepsis. The types of renal failure were similar to those described in fulminant hepatic failure and cirrhosis--namely, functional renal failure in five patients and acute tubular necrosis in seven. Two of the patients with functional renal failure later developed tubular necrosis. The mechanism responsible for renal failure in acute viral hepatitis is uncertain, though endotoxaemia may contribute.

Abnormalities of sodium excretion and other disorders of renal function in fulminant hepatic failure.

Renal function was evaluated in 40 patients with fulminant hepatic failure, They were divided into two groups on the basis of glomerular filtration rates greater than 40 ml/min or less than 25 ml/min. A number of patients in group 1 had markedly abnormal renal retention of sodium together with a reduced free water clearance and low potassium excretion which could be explained by increased proximal tubular reabsorption of sodium. The patients in group 2 had evidence that renal tubular integrity was maintained when the glomerular filtration rate was greater than or equal ml/min (functional renal failure), but evidence of tubular damage was present when this was less than 3 ml/min (acute tubular necrosis).

Hepatitis from dantrolene sodium.

The clinical course and histological changes in the liver during a presumed adverse reaction to the drug dantrolene sodium are described in four patients. After a typical prodrome one developed a moderately severe hepatitis-like illness. Another also had a prodrome but never became jaundiced. In the other two, abnormal liver function tests were detected on routine screening. In each case liver biopsy showed changes typical of an acute hepatitis, but the severity was unrelated to the clinical presentation. In addition, there were also changes in the portal tracts resembling ascending cholangitis. In each case liver function tests returned to normal after withdrawing treatment with dantrolene.

Ascites reinfusion using the Rhodiascit apparatus—clinical experience and coagulation abnormalities

The results of twenty-four ascitic reinfusions in twenty patients, using the Rhodiascit procedure, are reported. The procedure was of no value in the management of patients with spontaneous functional renal failure, but was of considerable value in accelerating hospital discharge of patients with tense ascites but good renal function. Complications of the procedure were few, but tests of blood coagulation became abnormal, the most likely cause of which was deposition of fibrin on to the filtration membrane.

Pathogenesis of renal failure in cirrhosis and fulminant hepatic failure

Acute renal failure in cirrhosis and fulminant hepatic failure represents a spectrum with ‘functional renal failure’ at one end and acute tubular necrosis at the other. In fulminant hepatic failure the development of renal failure is not necessarily a measure of the severity of liver damage. Functional renal failure is due to active renal vasoconstriction which may, at least in fulminant hepatic failure, be initiated by systemic endotoxaemia.

Renal retention of sodium in cirrhosis and fulminant hepatic failure

Abnormal renal retention of sodium is a characteristic finding in both cirrhosis and fulminant hepatic failure. In cirrhosis the pathogenesis varies according to the level of renal perfusion. When this is normal, hyperaldosteronism is probably the most important factor and this results from an increased release of renin by the kidney. The stimulus to the latter may be a shunting of blood from the outer cortical to juxtamedullary nephrons, although there is no direct relationship between the changes in intrarenal blood flow distribution and sodium excretion. The patients with hyperaldosteronism fail to escape from its sodium retaining effects because of impaired production of natriuretic hormone, which in turn is the result of a failure to expand the ‘effective’ extracellular fluid volume, because of ascites formation. In fulminant hepatic failure the site in the nephron of abnormal sodium retention appears to be predominantly the proximal tubule, but its cause is obscure.

Intracellular Electrolyte Abnormalities in Fulminant Hepatic Failure

The sodium, potassium, and water content of peripheral blood leukocytes was determined in 30 patients with fulminant hepatic failure. Although values for potassium were reduced, statistically significant increases were found in sodium and water content. Serial studies showed that, with recovery of liver function, the leukocyte sodium content fell initially to below normal, with values subsequently returning to the normal range some weeks later. Leukocyte sodium content was inversely correlated to the plasma sodium concentration, suggesting that a shift of sodium into the intracellular compartment might contribute toward the hyponatremia that was found in many patients.