Hepatic Encephalopathy and Ammonia

Cerebral Edema and Hepatic Encephalopathy

• Ammonia, a by-product of protein metabolism and intestinal bacterial action, accumulates in the brain and alters cerebral metabolism, leading to hepatic encephalopathy.
• The liver's inability to convert ammonia to urea in liver failure causes neurologic signs, including rigidity, hyperreflexia, and seizures.
• Fatal coma may occur due to hepatic encephalopathy.

Hepatorenal Syndrome

• Hepatorenal syndrome is a complication of advanced liver disease, characterized by renal failure.
• The pathophysiology of hepatorenal syndrome involves a sudden decrease in blood volume, leading to decreased GFR, tubular necrosis, and renal vasoconstriction.
• The liver's inability to remove vasoconstrictive substances, such as angiotensin, vasopressin, and catecholamines, contributes to renal vasoconstriction.

Hepatitis

• Hepatitis refers to inflammation of the liver and can be caused by viral infections, drug reactions, infectious disorders, and other factors.
• Hepatitis A is caused by a small RNA-containing virus and is transmitted through the fecal-oral route.
• The incubation period for HAV is 2-4 weeks, and individuals may be contagious for up to 2 weeks before the onset of symptoms.

Hepatitis A

• Hepatitis A is a self-limiting disease that usually runs its course within 4 months after exposure.
• HAV does not cause a carrier state or chronic hepatitis.
• By mid-adult life, about half of people in developed countries have blood anti-HAV antibodies as evidence of infection.

Hepatitis C

• Hepatitis C is the most common blood-borne infection in the US, affecting approximately 3.9 million Americans.
• Chronic hepatitis occurs in 50-80% of cases, and HCV is the most common cause of chronic liver disease, cirrhosis, and liver cancer worldwide.
• There is no vaccine available for HCV due to the over 50 subtypes of the virus.

Hepatitis D

• Hepatitis D is a defective RNA virus that cannot infect hepatocytes on its own and requires co-infection with HBV.
• The Delta agent often increases the severity of HBV infection and can convert mild HBV infection into severe, fulminant disease.

Hepatitis E

• Hepatitis E is common in developing countries and clinically resembles hepatitis A.
• It does not cause chronic or carrier states and has a high mortality rate (20%) among pregnant women.

Cirrhosis

• Cirrhosis is a leading cause of death in the US and represents the end stage of chronic liver disease.
• Normal liver architecture and function are disrupted with the development of diffuse fibrosis and nodular regeneration.
• Obstruction can cause portal hypertension, leading to increased resistance to flow in the portal venous system and blood shunting.

Causes of Cirrhosis

• Alcoholic cirrhosis (Laennec's cirrhosis) occurs after years of alcohol abuse and begins with fatty infiltration of the liver.
• Biliary cirrhosis can be primary (autoimmune disease) or secondary (develops with prolonged partial or complete obstruction of the common bile ducts or branches).
• Post-necrotic cirrhosis can result from severe liver disease, drugs, or toxins.