Liver Function and Hepatic Failure

Liver Functions and Hepatic Failure

• The liver has a significant impact on health status and has numerous functions
• Hepatic failure is the most severe consequence of liver disease, with a high mortality rate (most patients die within weeks or months)
• Hepatic failure may occur suddenly due to fulminant hepatitis B or follow years of low-grade hepatitis C infection
• Approximately 90% of hepatic function must be destroyed before failure occurs
• Clinical features of hepatic failure include:
  • Jaundice due to failure to excrete bilirubin
  • Ascites due to increased portal pressure and blood osmotic pressure
  • Fector hepatitis (liver breath) due to accumulation of volatile waste products such as ammonia

Hepatic Encephalopathy

• A complex neurologic syndrome characterized by memory lapses and personality changes
• Characteristic sign: asterixis (rapid extension-flexion motion of the hand and extremities)
• Results from accumulation of toxins in the blood when the liver fails to transform or detoxify the blood
• Toxins accumulate, leading to osmotic pressure increase, brain swelling, and cerebral edema, potentially causing herniation and death
• Ammonia is a key toxin implicated in causing many symptoms of hepatic encephalopathy
  • Normally converted to urea by the liver, but in liver failure, ammonia reaches the brain, altering cerebral metabolism and interfering with neurotransmitters

Hepatorenal Syndrome

• A complication of advanced liver disease, characterized by renal failure associated with advanced liver disease
• Pathophysiology involves a sudden decrease in blood volume, leading to decreased GFR, tubular necrosis, and renal vasoconstriction
• Characteristics include:
  • Blood volume expansion
  • Hydrogen ion accumulation
  • Electrolyte imbalance

Hepatitis

• Inflammation of the liver, caused by various factors, including viral infection, drug reactions, and infectious disorders
• Types of hepatitis include:
  • Hepatitis A (formerly infectious hepatitis)
    • Caused by small RNA-containing virus
    • Transmitted through fecal-oral route, contaminated food, or water
    • No carrier state or chronic hepatitis
  • Hepatitis B (formerly serum hepatitis)
    • Caused by double-stranded DNA virus
    • Transmitted through contact with infected blood, body fluids, or contaminated needles
    • Can produce acute hepatitis, chronic hepatitis, and fulminant hepatitis
    • May lead to chronic liver disease and liver cancer
  • Hepatitis C (formerly non-A, non-B hepatitis)
    • Caused by single-stranded RNA virus
    • Most cases of post-transfusion hepatitis, and most common blood-borne infection in the US
    • Chronic hepatitis occurs in 50-80% of cases, and may lead to cirrhosis and liver cancer
  • Hepatitis D (delta)
    • A defective RNA virus that co-infects with HBV
    • Increases severity of HBV infection
  • Hepatitis E
    • Common in developing countries
    • Clinically resembles Hepatitis A
    • Does not cause chronic or carrier state
  • Hepatitis G
    • Not much known, possibly related to post-transfusion hepatitis

Liver Injury and Cirrhosis

• Liver injury mechanisms include:
  • Direct cellular injury
  • Induction of immune responses against viral antigens
• Pathophysiology of hepatitis includes:
  • Hepatic cell necrosis
  • Scarring leading to fibrosis
  • Kupffer cell hyperplasia and infiltration with phagocytic cells
  • Cell injury promoted by cell-mediated immunity
• Cirrhosis:
  • An irreversible inflammatory disease disrupting liver function and structure
  • Leading cause of death in the US
  • Represents the end stage of chronic liver disease
  • Characteristics include:
    • Disrupted liver architecture and function
    • Nodular regeneration and fibrosis
    • Portal hypertension and ascites
    • Liver hard, firm, and cobbly when palpated
  • Causes of cirrhosis include:
    • Alcoholic cirrhosis (Laennec's cirrhosis)
    • Biliary cirrhosis (primary and secondary)
    • Post-necrotic cirrhosis