Because of impaired production of urea, blood urea does not represent the degree of kidney impairment. Inflammation and infection
About 60% of all ALF patients fulfil the criteria for systemic inflammatory syndrome irrespective of presence or absence of infection. This often contributes towards multi organ failure. Impaired host defence mechanism, due to impaired opsonization, chemotaxis and intracellular killing, substantially increases risk of sepsis. Bacterial sepsis mostly due to gram positive organisms and fungal sepsis are observed in up to 80% and 30% patients, respectively. Metabolic derangements
Hyponatraemia is an almost universal finding due to water retention and a shift in intracellular sodium transport from inhibition of Na/K ATPase. Hypoglycaemia (due to depleted hepatic glycogen store and hyperinsulinaemia), hypokalaemia, hypophosphataemia and metabolic alkalosis are often present, independent of renal function. Lactic acidosis occurs predominantly in paracetamol (also known as acetaminophen) overdose. Haemodynamic and cardio-respiratory compromise
Hyperdynamic circulation, with peripheral vasodilatation from low systemic vascular resistance, leads to hypotension. There is a compensatory increase in cardiac output. Adrenal insufficiency has been documented in 60% of ALF cases, and is likely to contribute in haemodynamic compromise. There is also abnormal oxygen transport and utilization. Although delivery of oxygen to the tissues is adequate, there is a decrease in tissue oxygen uptake, resulting in tissue hypoxia and lactic acidosis.Pulmonary complications occur in up to 50% of patients. Severe lung injury and hypoxemia result in high mortality. Most cases of severe lung injury are due to ARDS, with or without sepsis. Pulmonary haemorrhage, pleural effusions, atelectasis, and intrapulmonary shunts also contribute to respiratory difficulty.
Definition
Acute liver failure is defined as "the rapid development of hepatocellular dysfunction, specifically coagulopathy and mental status changes (encephalopathy) in a patient without known prior liver disease".page 1557The diagnosis of acute liver failure is based on physical exam, laboratory findings, patient history, and past medical history to establish mental status changes, coagulopathy, rapidity of onset, and absence of known prior liver disease respectively.page 1557The exact definition of "rapid" is somewhat questionable, and different sub-divisions exist which are based on the time from onset of first hepatic symptoms to onset of encephalopathy. One scheme defines "acute hepatic failure" as the development of encephalopathy within 26 weeks of the onset of any hepatic symptoms. This is sub-divided into "fulminant hepatic failure", which requires onset of encephalopathy within 8 weeks, and "subfulminant", which describes onset of encephalopathy after 8 weeks but before 26 weeks. Another scheme defines "hyperacute" as onset within 7 days, "acute" as onset between 7 and 28 days, and "subacute" as onset between 28 days and 24 weeks.page 1557

Treatment
General concerns
Because ALF often involves the rapid deterioration of mental status and the potential for multiorgan failure, patients should be managed in the intensive care unit. For patients not at a transplant center, the possibility of rapid progression of ALF makes early consultation with a transplant facility critical. Accordingly, plans for transfer to a transplant center should begin in patients with any abnormal mentation. Early institution of antidotes or specific therapy may prevent the need for liver transplantation and reduce the likelihood of poor outcome.