ACUTE LIVER FAILURE

ANATOMY & PHYSIOLOGY

The liver is the largest organ in the body, normally weighing about 1.5kg

The liver is the main organ of metabolism and energy production; its other main functions include:

1. Bile production

2. Storage of iron, vitamins and trace elements

3. detoxification

4. conversion of waste products for excretion by the kidneys

ANATOMY & PHYSIOLOGY

The liver is functionally divided into two lobes, right and left. The external division is marked on the front of the liver by the falciform ligament, which joins the coronary ligament at the superior margin of the liver.

The right lobe is separated from the other lobes by the gallbladder fossa and the fossa for the inferior vena cava on the visceral surface of the liver.

The left lobe includes the caudate and quadrate lobes. It is separated from these two lobes by the attachment of the ligumentum teres, and the fissures for the ligumentum teres and the ligamentum venosum.

The caudate lobe lies between the fissure for the ligamentum venosum and the fossa for the inferior vena cava.

The quadrate lobe is partly covered by the gallbladder in normal patients; anatomically, it lies between the fissure for the ligamentum teres and the gallbladder fossa.

The liver is unusual in that it has a double blood supply; the right and left hepatic arteries carry oxygenated blood to the liver, and the portal vein carries venous blood from the GI tract to the liver.

DEFINITION

The development of prolonged prothrombin time and encephalopathy within 8 weeks of symptom onset in patient with no previous liver disease

U.S. annual incidence about 2,000 cases per year (1)

A rare disorder with high mortality and resource cost

CAUSES of Acute Liver Failure

Acute liver failure occurs when liver cells are damaged significantly and no longer able to function. Acute liver failure has many potential causes, including:

Acetaminophen overdose. Taking too much acetaminophen (Tylenol, others) is the most common cause of acute liver failure in the United States. In the U.S., acetaminophen hepatotoxicity most common

Cancer - Cancer that begins in your liver or cancer that spreads to your liver from other places in your body can cause your liver to fail.

Prescription medications. Some prescription medications, including antibiotics, nonsteroidal anti-inflammatory drugs and anticonvulsants.

Hepatitis and other viruses. Hepatitis A, hepatitis B and hepatitis E can cause acute liver failure. Other viruses that can cause acute liver failure include Epstein-Barr virus, cytomegalovirus and herpes simplex virus.

Autoimmune hepatitis — a disease in which your immune system attacks liver cells, causing inflammation and injury.

Ischemia- ischaemic injury as a result of systemic hypotension in sepsis or cardiac failure, or Budd-Chiari syndrome.

Wilson’s Disease Toxins like the poisonous wild mushroom Amanita phalloides, which is sometimes mistaken for

edible species.

Vascular diseases, such as Budd-Chiari syndrome

*Diseases of the veins in the liver. Vascular diseases, such as Budd-Chiari syndrome, can cause blockages to form in the veins of the liver and lead to acute liver failure.

Pregnancy – acute fatty liver of pregnancy and the HELP syndrome (hemolysis, elevated liver chemistries, low platelets)

RISK FACTORS for developing ALF are as follows:

People that take an extremely large dose of acetaminophen

Failure to follow dosage instructions for prescription medications and over-the-counter pain relievers and herbal medicines.

Failure to get vaccinated for Hepatitis A and B.

Failure to exercise caution when handling needles or cleaning up bodily fluids or blood.

Failure to inform one’s doctor of all prescription drugs, herbal remedies and over-the-counter medications

Consumption of excessive amounts of alcohol.

Obesity – (While obesity is not known to cause ALF, studies show that obese and severely obese patients had significantly poorer outcomes when they developed acute liver failure.)

Failure to follow manufacturer’s instructions when using aerosol sprays, pesticides, cleaning fluids and other toxic chemicals.

CLINICAL MANIFESTATIONS

Anorexia, nausea, vomiting, malaise, right upper quadrant discomfort

Dark urine, pale stool, icterus

Transaminases rise within 10 – 12 hours, often to dramatic levels AST > ALT, peak at day three and rapidly improve

Jaundice develops quickly, total bilirubin not as high as that seen in other causes of ALF

PATHOPHYSIOLOGY

A sudden massive necrosis of hepatocytes results in dramatic clinical manifestation of liver failure and multiple organ dysfunction syndrome including the kidneys, lungs and circulatory system.

Hallmarks of this disorder are clinical encephalopathy, rapid decrease in coagulation ability, cerebral edema and multiorgan failure.

In addition to the loss of function of hepatocyte, key mediators such as interleukin increases, tumor necrosis factors and others have been identified as one of the pathogenisis of multiple organ dysfunction. Microvascular obstruction the cellular debris from the damagedliver may impair tissue O2 extraction and lead to lactic acidosis and circulatory failure.

Ammonia levels are high in ALF, the encephalopathy appears to be more related to hypoxia. Cerebral edema may result from fluid overload.

Failure of the liver to manufacture the coagulation I, II, V, VII, IX, & X causes severe bleeding and is also great risk for disseminated intravascular coagulation.

A prolonged prothombin time is characterized by and is closely r/t severity of organ damage.

Cytotoxic edema is the consequence of impaired cellular osmoregulation in the brain, resulting in astrocyte edema. Cortical astrocyte swelling is the most common observation in neuropathologic studies of brain edema in acute liver failure. In the brain, ammonia is detoxified to glutamine via amidation of glutamate by glutamine synthetase. The accumulation of

glutamine in astrocytes results in astrocyte swelling and brain edema. There is clear evidence of increased brain concentration of glutamine in animal models of acute liver failure. The relationship between high ammonia and glutamine levels and raised ICH has been reported in humans.

Vasogenic factors- An increase of intracranial blood volume and cerebral blood flow is a factor in acute liver failure. The increased cerebral blood flow results because of disruption of cerebral autoregulation. The disruption of cerebral autoregulation is thought to be mediated by elevated systemic concentrations of nitric oxide, which acts as a potent vasodilator.

The development of cerebral edema is the major cause of morbidity and mortality in patients with acute liver failure. The etiology of this intracranial hypertension (ICH) is not fully understood, but it is considered to be multifactorial.

Briefly, hyperammonemia may be involved in the development of cerebral edema. Brain edema is thought to be both cytotoxic and vasogenic in origin.

Cytokine profiles are also deranged. Elevated serum concentrations of bacterial endotoxin, tumor necrosis factor–alpha (TNF-α), and interleukin (IL)–1 and IL-6 have been found in fulminant hepatic failure

Multisystem organ failure- Another consequence of fulminant hepatic failure is multisystem organ failure, which is often observed in the context of a hyperdynamic circulatory state that mimics sepsis (low systemic vascular resistance. therefore, circulatory insufficiency and poor organ perfusion possibly either initiate or promote complications of fulminant hepatic failure(acute liver failure).

Acetaminophen hepatotoxicity -ALF secondary to drug-induced liver injury may occur as an idiosyncratic drug reaction or, as in the case of paracetamol (acetaminophen), in a dose-dependent manner. Paracetamol is predominantly metabolised in the liver through glucuronidation and sulphation, with a small amount metabolised by the cytochrome P450 system. A toxic intermediate, N-acetyl-p-benzoquinone imine (NAPQI), generated via the P450 pathway is subsequently conjugated by glutathione. In the setting of paracetamol overdose, glutathione stores may become depleted, resulting in direct hepatocyte injury via NAPQI. Induction of the P450 system through chronic alcohol use or barbiturates and depletion of glutathione stores in settings such as nutritional deficiency may result in a greater propensity to develop paracetamol hepatotoxicity. Paracetamol is predominantly metabolised in the liver through glucuronidation and sulphation, with a small amount metabolised by the cytochrome P450 system. A toxic intermediate, N-acetyl-p-benzoquinone imine (NAPQI), generated via the P450 pathway is subsequently conjugated by glutathione. In the setting of paracetamol overdose, glutathione stores may become depleted, resulting in direct hepatocyte injury via NAPQI. Induction of the P450 system through chronic alcohol use or barbiturates and depletion of glutathione stores in settings such as nutritional deficiency may result in a greater propensity to develop paracetamol hepatotoxicity.

*The cytochrome P450 superfamily (officially abbreviated as CYP) is a large and diverse group of enzymes that catalyze the oxidationof organic substances. The substrates of CYP enzymes include metabolic intermediates such as lipids and steroidal hormones, as well as xenobiotic substances such as drugs and other toxic chemicals. CYPs are the major enzymes involved in drug metabolism and bioactivation, accounting for about 75% of the total number of different metabolic reactions.

DIAGNOSTIC PROCEDURES

Diagnostic TEST

Blood & urine tests

Blood tests to determine how well your liver is functioning may include the prothrombin time test, which measures how long it takes for your blood to clot. If you have acute liver failure, your blood doesn't clot as quickly as it should.

Imaging tests; such as ultrasound

to evaluate your liver. Imaging tests may show liver damage and may help your doctor determine the cause of your liver problems.

Examination of liver tissue;

- liver biopsy- to remove a small piece of liver tissue (liver biopsy). Tests of the liver tissue may help your doctor understand why your liver is failing. - transjugular liver biopsy - if there is a risk of bleeding during biopsy

CT Scan for cerebral edema & hemorrhage

Esophagoduodenoscopy or "EGD“

Upper GI series, also upper gastrointestinal (GI) tract radiography

NURSING INTERVENTION

Patient Monitoring

Obtain pulmonary artery pressure, central venous pressure, & BP

Continuously monitor ECG for lethal dysrhythmias that may result from electrolyte and acid-base imbalances.

Monitor fluid volume status. Measure intake and output hourly.

Patient Assessment

Assess hydration status. Assess for signs and symptoms of bleeding. Note skin turgor on inner thigh or forehead, condition of buccal membranes, and development of edema and crackles.

Measure abdominal girth once each shift to determine progression of ascites.

Assess respiratory status.

Diagnostic Assessment

Review serial serum ammonia, albumin, bilirubin, platelet count, PT, PTT and ALT to evaluate hepatic function.

Review serial serum electrolytes.

Review urine electrolyte, BUN, and creatinine to evaluate renal function.

Patient Management

Administer intravenous crystalloids as ordered.

Administer potassium as ordered. Validate adequate urine output before potassium administration.

Sodium restriction of 0.5 g/day and fluid restriction to 1000 ml/day may be ordered.

Institute bleeding precautions. Avoid razor blades and use soft-bristled toothbrushes.

MEDICAL MANAGEMENT

Paracentesis may be performed if abdominal distention is severe.

Prepare for Liver Transplantation (treatment of choice)

Blood or plasma exchanges, charcoal hemoperfusion and corticosteroids (plasmapheresis)

Liver support system, such as hepatocytes within synthethic fiber columns, extracorporeal liver-assist devices, and bioartificial liver, until transplantation is possible

TREATMENTS FOR COMPLICATIONS

Relieving excess fluid in the brain - Cerebral edema caused by acute liver failure can increase pressure on your brain. Medications can help reduce the fluid buildup in your brain.

Screening for infections- Your medical team will take periodic samples of your blood and urine to be tested for signs of infection. If your doctor suspects that you have an infection, you'll receive medications to treat the infection.

Preventing severe bleeding – People with acute liver failure often develop bleeding ulcers in the gastrointestinal tract. Your doctor can give you medications to reduce the risk of bleeding. If you lose a lot of blood, you may require blood transfusions.