Helen Moodie

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.

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).

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.