Liver Function and Hepatic Failure

Study Notes

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

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

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

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 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