Бауыр жеткіліксіздігінің жедел ағымы және оның салдары

Acute liver failure is the appearance of severe complications rapidly after the first signs (such as jaundice) of liver disease, and indicates that the liver has sustained severe damage (loss of function of 80–90% of liver cells). The complications are hepatic encephalopathy and impaired protein synthesis (as measured by the levels of serum albumin and the prothrombin time in the blood). The 1993 classification defines hyperacute as within 1 week, acute as 8–28 days, and subacute as 4–12 weeks; both the speed with which the disease develops and the underlying cause strongly affect outcomes.

The main features of acute liver failure are rapid onset jaundice, weakness, and eventually, changes in mental status that can begin as mild confusion but progress to coma, known as hepatic encephalopathy.

In ALF, hepatic encephalopathy leads to cerebral edema, coma, brain herniation, and eventually death. Detection of encephalopathy is central to the diagnosis of ALF. It may vary from subtle deficit in higher brain function (e. g. mood, concentration in grade I) to deep coma (grade IV). Patients presenting as acute and hyperacute liver failure are at greater risk of developing cerebral edema and grade IV encephalopathy. The pathogenesis remains unclear, but is likely to be a consequence of several phenomena. There is a buildup of toxic substances like ammonia, mercaptan, serotonin and tryptophan in the brain. This affects neurotransmitter level and neuroreceptor activation. Autoregulation of cerebral blood flow is impaired, and is associated with anaerobic glycolysis and oxidative stress. Neuronal cell astrocytes are susceptible to these changes, and they swell up, resulting in increased intracranial pressure. Inflammatory mediators also play important role. Unfortunately, signs of elevated intracranial pressure, such as papilledema and loss of pupillary reflexes, are not reliable, and occur late in the disease process. CT imaging of the brain is also unhelpful in detecting early cerebral oedema, but is often performed to rule out intra cerebral bleeding. Invasive intracranial pressure monitoring via subdural route is often recommended; however, the risk of complications must be weighed against the possible benefit (1% fatal haemorrhage). The aim is to maintain intracranial pressures below 25 mm Hg, and cerebral perfusion pressures above 50 mm Hg. 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.

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.

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.

In late pregnancy liver function decreases significantly, which can be easily monitored by blood tests. Early clinical manifestations of ALF in late pregnancy include hypodynamia, decrease in appetite, dark amber urine, deep jaundice, nausea, vomiting, and abdominal distention. Among patients whose deaths were attributed to ALF in late pregnancy, the majority had experienced vaginal deliveries.

Common causes for acute liver failure are paracetamol (acetaminophen) overdose, idiosyncratic reaction to medication (e. g. tetracycline, troglitazone), excessive alcohol consumption (severe alcoholic hepatitis), viral hepatitis (hepatitis A or B—it is extremely uncommon in hepatitis C), acute fatty liver of pregnancy, and idiopathic (without an obvious cause). Reye syndrome is acute liver failure in a child with a viral infection (e. g. chickenpox); it appears that aspirin use may play a significant role. Wilson's disease (hereditary copper accumulation) may infrequently present with acute liver failure. Acute liver failure also results from poisoning by the death cap mushroom (Amanita phalloides) as well as other amatoxin producing fungus species. Certain strains of Bacillus cereus—a common species of bacterium implicated as a frequent cause of food poisoning—can cause fulminant liver failure through the production of cereulide, a toxin which destroys the mitochondria in affected hepatocytes, resulting in cell death. While most instances of B. cereus infection are resolved by the body's immune system and do not affect the liver, severe cases resulting in liver damage can be fatal without immediate treatment or liver transplantation.

In the majority of acute liver failure (ALF) there is widespread hepatocellular necrosis beginning in the centrizonal distribution and progressing towards portal tracts. The degree of parenchymal inflammation is variable and is proportional to duration of disease. Zone 1 (periportal) occurs in phosphorus poisoning or eclampsia. Zone 2 (mid zonal), although rare, is seen in yellow fever. Zone 3 (centrilobular) occurs with ischemic injury, toxic effects, carbon tetrachloride exposure, or chloroform ingestion. In acute acetaminophen overdose, toxification occurs, mostly in Zone III which has the highest level of P450 micro enzymes. That fact along with Zone III's decreased oxygen level helps to explain why it is preferentially one of the initial sites of damage.