Circulatory, respiratory, cerebral, and renal derangements in acute liver failure: pathophysiology and management.
Many of the hemodynamic abnormalities seen in acute liver failure (ALF) have now been characterized. A lowered systemic vascular resistance with a raised cardiac output are prominent features, which in part are modulated by nitric oxide (NO). At a cellular level, oxygen supply and utilization are impaired by changes in vascular tone, plugging of nutritive vessels, and pathological shunting. The use of N-acetylcysteine (NAC) and prostacyclin, a vasodilator, have been shown to increase oxygen utilization in the microcirculation. NAC may act by enhancing the effect of NO on guanylate cyclase, increasing the formation of cyclic 3',5'-guanosine monophosphate (cGMP), and thereby resulting in vasodilatation. This suggests that despite overproduction of NO in ALF, there is a short-age/ failure of utilization at a cellular level. Appropriate management of these patients should be based on a good knowledge of the underlying pathophysiology, and thus on monitoring, during the course of the disease.
Ellis
A
A
Institute of Liver Studies, King's College Hospital, London, United Kingdom.
Wendon
J
J
D001775:Blood Circulation; D001929:Brain Edema / Q000628:therapy; D002318:Cardiovascular Diseases / Q000150:complications; D002560:Cerebrovascular Circulation; D006439:Hemodynamics; D006801:Humans; D007022:Hypotension / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D017114:Liver Failure, Acute / Q000150:complications / Q000503:physiopathology / Q000628:therapy; D051437:Renal Insufficiency / Q000628:therapy