Pathophysiology - Disorders of the Liver and Biliary System

Liver Failure – What is liver failure?

Destruction of hepatocytes to the point that the liver can no longer carry out normal physiological functions.

Causes of Liver Failure?

Cirrhosis, chronic active hepatitis, liver cancer.

What is cirrhosis?

Chronic, progressive nodular scarring of the liver leading to structural and functional changes.

Laennec’s Cirrhosis cause?

Alcohol or drug-induced; alcohol/drugs act as toxins to the liver.

How does alcohol damage the liver in Laennec’s cirrhosis?

Alcohol converts to acetaldehyde → inhibits protein removal, alters vitamin/mineral metabolism, accumulates fat → “fatty liver.”

Drug-related cirrhosis cause?

Toxic effect from street drugs or medications like Tylenol.

Cause of biliary cirrhosis?

Autoimmune destruction or obstruction of biliary ducts.

What does bile retention in biliary cirrhosis cause?

Inflammation; may involve gallstones or gallbladder.

Pathophysiology of cirrhosis (general)?

Fatty infiltration + inflammation → scarring; worsened by poor nutrition.

Effect of altered hepatocyte transport in cirrhosis?

Obstructed bile and blood flow.

What causes portal hypertension in cirrhosis?

Increased pressure from scarring obstructing circulation.

Manifestations of portal hypertension?

Pressure on abdominal/esophageal vessels; splenomegaly; increased breakdown of WBCs, RBCs, platelets → infection, anemia, bleeding risk.

Why does edema occur in cirrhosis?

Decreased albumin → altered osmotic pressure.

Why does sodium and water retention occur in cirrhosis?

Decreased metabolism of aldosterone.

Cause of hepatic encephalopathy in cirrhosis?

Inability to break down ammonia → ammonia accumulates in blood and travels to the brain.

Why do bleeding problems occur in cirrhosis?

Decreased synthesis of clotting factors.

What is hepatitis?

Inflammation of liver tissue with necrosis of hepatocytes; most commonly viral.

Types of hepatitis?

A, B, C, D, E, or autoimmune.

Etiology of hepatitis A and E?

Contaminated food and water.

Etiology of hepatitis B, C, D?

Blood and body fluids.

Primary pathophysiology of hepatitis?

Virally induced inflammation; immune response causes diffuse hepatocyte injury and necrosis.

What happens after hepatocyte injury in hepatitis?

Interrupted liver function followed by regeneration over time.

Example of serum antigen marker?

HBsAg (Hepatitis B surface antigen).

Prodromal phase of hepatitis?

Occurs 2 weeks after exposure; flu-like symptoms; highly transmissible.

Icteric phase of hepatitis?

Jaundice and liver-related manifestations lasting up to 6 weeks.

Recovery phase of hepatitis?

Symptoms resolve over weeks; liver may remain enlarged.

What is fulminant hepatitis?

Severe necrosis causing rapid liver failure; often chronic B or C.

What is biliary atresia?

Congenital absence or closure of extrahepatic bile ducts → bile retention, inflammation, duct destruction, cirrhosis; fatal by age 3 without transplant.

What is liver cancer commonly associated with?

Chronic cirrhosis, toxic exposure, alcohol use.

What is hepatocellular carcinoma?

Primary liver cancer arising from liver cells; nodular/massive/diffuse; spreads rapidly via hepatic/portal vein.

What causes jaundice?

Disturbed flow or accumulation of bile/bilirubin staining the skin, sclera, tissues.

When does jaundice appear (bilirubin level)?

When serum bilirubin is 3–4× normal.

What causes pruritus in jaundice?

Tissue irritation from bile/bilirubin accumulation.

Pre-hepatic jaundice cause?

Excessive RBC destruction → increased bilirubin.

Intrahepatic jaundice cause?

Actual liver disease prevents bilirubin removal.

Post-hepatic jaundice cause?

Obstruction of bile flow, often stones.

Neonatal jaundice cause and treatment?

Immature liver lacking enzyme for bilirubin conjugation; phototherapy converts bilirubin to excretable form.

What is ascites?

Accumulation of fluid in the peritoneal cavity.

Cause of ascites – portal pressure?

Increased portal venous pressure from inflammation.

Cause of ascites – osmotic disruption?

Decreased plasma proteins (albumin) disrupt colloid osmotic pressure → fluid shifts into peritoneal cavity.

RAAS role in ascites?

Aldosterone ↑ sodium/water retention; ADH ↑ water reabsorption.

Why do clotting disturbances occur in liver disease?

Low clotting factors + vitamin K malabsorption → bleeding tendency.

What are esophageal varices?

Dilated esophageal veins from portal hypertension.

Why are varices dangerous?

Easily ruptured from irritation (acid, vomiting, alcohol) → rapid blood loss.

What is hepatic encephalopathy?

Neurologic dysfunction due to ammonia accumulation.

Key signs of hepatic encephalopathy?

Agitation, confusion, asterixis (liver flap), fetor hepaticus, coma.

What is hepatomegaly?

Liver enlargement causing RUQ tenderness.

What liver enzymes elevate in hepatocellular damage?

Alkaline phosphatase, AST, ALT.

Why does urine get dark and stool become light in liver disease?

Urine: bilirubin in urine; stool: impaired fat absorption.

What is cholecystitis?

Inflammation of the gallbladder, usually from a gallstone blocking a duct.

What can severe cholecystitis lead to?

Necrosis and possible perforation.

Effect of blocked bile outflow in cholecystitis?

Bile accumulation in gallbladder.

What is cholelithiasis?

Gallstones formed from cholesterol sludge + calcium.

What promotes gallstone growth?

Stasis of bile allowing crystals to enlarge.

Where can gallstones cause obstruction?

Hepatic duct, cystic duct, common bile duct.

Clinical manifestations of gallbladder disease?

RUQ pain, nausea, vomiting; pain radiates to back/right shoulder; intolerance to fatty foods.

What is gallbladder cancer associated with?

Chronic irritation; often resembles inflammation; often found during surgery.