Lecture Notes on Cirrhosis

Overview of Liver Injury and Fibrosis

• Cell Injury and Death
  • Damaged cells lead to fibrotic tissue formation.
  • Dead tissue becomes thickened with protein, forming scar tissue.
• Alcoholic Liver Disease and Viral Attacks
  • Chronic injury leads to hepatocyte destruction and inflammation, resulting in fibrosis.
  • This condition is termed cirrhosis when it becomes irreversible.

Characteristics of Cirrhosis

• End-stage Liver Damage
  • Cirrhosis is often referred to as "end-stage" or "late-stage" liver damage.
• Regenerative Nodules
  • Injured liver cells cluster together to form nodules, which are characteristic of cirrhosis.
  • Nodules are surrounded by fibrotic tissue and collagen, leading to a bumpy liver texture.
• Histological Features
  • Regenerative nodules with surrounding fibrotic protein bands.

Fibrosis and Stellate Cells

• Stellate Cells Role
  • Located in the perisinusoidal space, they store vitamin A and are usually dormant.
  • Upon hepatocyte injury, they become activated, proliferate, and produce collagen (TGF-beta).
• Effects of Fibrosis
  • Compresses central veins and sinusoids, leading to portal hypertension.
  • Portal hypertension causes fluid buildup, leading to complications like ascites and splenomegaly.

Complications of Cirrhosis

• Hepatorenal Failure
  • Increased renal resistance and decreased blood flow lead to kidney failure.
• Hepatic Encephalopathy
  • Toxins like ammonia accumulate in the brain, causing confusion and tremors (asterixis).
• Estrogen Imbalances
  • Increased estrogen levels can lead to gynecomastia, spider angiomata, and palmar erythema.
• Jaundice and Hypoalbuminemia
  • Decreased ability to conjugate bilirubin leads to jaundice.
  • Reduced albumin production results in hypoalbuminemia, affecting blood volume.
• Coagulation Issues
  • Liver dysfunction leads to decreased clotting factor production, increasing bleeding risk.

Stages of Cirrhosis

• Compensated Cirrhosis
  • Early stage; liver still functions adequately; may be asymptomatic or exhibit nonspecific symptoms (e.g., weakness, fatigue).
• Decompensated Cirrhosis
  • Advanced stage; liver cannot function properly; symptoms include jaundice, pruritus, ascites, and hepatic encephalopathy.

Diagnosis and Lab Findings

• Diagnosis
  • Gold standard: liver biopsy for histological examination.
• Common Lab Findings
  • Elevated serum bilirubin, elevated liver enzymes (AST, ALT, ALP, GGT), and thrombocytopenia.

Treatment Approaches

• Prevent Further Damage
  • Identify and manage underlying causes (e.g., stop alcohol consumption, antiviral treatment for hepatitis).
• Advanced Cirrhosis
  • May require liver transplantation when liver function severely declines.

Summary of Key Points

• Cirrhosis is caused by chronic liver damage leading to fibrosis and scar tissue.
• Symptoms include jaundice, ascites, easy bruising, and hepatic encephalopathy.
• Diagnosis is through liver biopsy and lab tests; treatment focuses on managing the underlying cause and may involve liver transplant.