49. Basic etiology and pathogenesis of liver diseases. Hepatitis.

Basic etiology and pathogenesis of liver diseases. Hepatitis

Etiology of liver diseases

1. Viruses

• Cause hepatitis A, B, C, D, E

2. Toxins

• Alcohol
• Broken down by (1) catalase and (2) alcohol dehydrogenase to acetaldehyde and further acetate → consumes a lot of energy → decreased oxygen consumption in mitochondria → damages cell membranes and inhibits lipoprotein synthesis → increases levels of FA + steatosis of liver
• Acetate produced by catalase inhibits electron transport → less ATP
• High levels of acetaldehyde produced from alcohol dehydrogenase → stimulates synthesis of (3) cytochrome P450 enzymes → generate free radicals → cell damage

3. Drugs

• Antibiotics
• NSAIDs
• Metabolic hepatotoxicity or immune hepatotoxicity
• Drugs act as haptens and can cause autoimmune hepatitis

4. Alimentary
5. a) Malnutrition - ascites, hepatomegaly
6. b) Overeating - steatosis
7. Trauma

• Martial arts

6. Biliary

• Gallstones

7. Hypoxia

• Occurs in RHF → congestion of liver → hypoxia → cell death → increased bile → gallstones

8. Neoplastic diseases
9. a) Benign
10. b) Malignant

• Metastases (95% of the cases) or primary hepatocellular carcinoma

9. Metabolic

• Enzyme deficiencies/hyperactivity

Hepatitis

• Hepatitis - inflammation of the liver
• Causes:

1. Viral infection (main cause)
2. Reactions to chemical agents, drugs, and toxins
3. Disorders such as autoimmune diseases and infectious mononucleosis (glandular fever caused by EBV) that cause secondary hepatitis

• Hepatitis can be:

1. Acute hepatitis
2. Chronic hepatitis

• The clinical course of viral hepatitis involves a number of syndromes:
• Asymptomatic infection - only serological evidence of disease
• Acute symptomatic hepatitis
• Carrier state - without clinically apparent disease or with chronic hepatitis
• Chronic hepatitis - with or without progression to cirrhosis
• Fulminating disease - with rapid onset of liver failure

Acute viral hepatitis

• The known primary hepatotropic viruses include:

1. Hepatitis A virus (HAV)
2. Hepatitis B virus (HBV)
3. Hepatitis B-associated delta virus (HDV)
4. Hepatitis C virus (HCV)
5. Hepatitis E virus (HEV)

• There are two mechanisms of liver injury in viral hepatitis:

1. Direct cellular injury

• Hep A and E only

2. Immune responses against viral antigens in infected hepatocytes

• Hep B, C, and D
• Mast cell degranulation, histamine release, cytokine production, complement activation
• Further stimulation of complement, cell lysis and direct antibody attack against virus → damages hepatocytes → liver becomes edematous with collapsing capillaries → decreased blood flow → hypoxia → tissue scarring and fibrosis
• The manifestations of acute hepatitis can be divided into three phases:

1. Prodromal or preicteric period

• Marked by nonspecific symptoms
• Malaise, easy fatigability, nausea, loss of appetite