GI12 - Diseases of the Liver and Biliary Tract

What are the major functions of the liver?

Carbohydrate metabolism, fat metabolism, protein metabolism, bile synthesis, and detoxification.

What pattern of liver cell death is described as zonal necrosis?

Zonal necrosis is a pattern of liver cell necrosis occurring in specific regions of the liver lobule.

What is centrilobular necrosis?

Centrilobular necrosis is zonal necrosis around the terminal hepatic vein, mainly due to ischemic injury and drug or toxic reactions.

What causes centrilobular necrosis?

Centrilobular necrosis is mainly caused by ischemic injury and drug or toxic reactions.

What is piecemeal necrosis in the liver?

Piecemeal necrosis is necrosis next to the portal tract in which only part of the hepatocyte cytoplasm and nucleus become necrotic.

Where does piecemeal necrosis occur in the liver?

Piecemeal necrosis occurs next to the portal tract.

What is bridging necrosis in the liver?

Bridging necrosis is necrosis that extends across the liver lobule.

What is a Councilman body?

A Councilman body is a hepatocyte undergoing apoptosis, often surrounded by normal parenchyma.

What is fibrosis in the liver?

Fibrosis is repeated chronic liver damage with scarring; severe fibrosis equals cirrhosis.

What is cirrhosis?

Cirrhosis is repeated bouts of inflammation and cell damage leading to diffuse fibrosis.

What is the most important drug/toxin cause of cirrhosis?

Alcohol is the number 1 drug/toxin cause of cirrhosis.

What infections are primary causes of cirrhosis?

Hepatitis B and hepatitis C.

What metabolic or immune-related categories can cause cirrhosis?

Metabolic diseases and autoimmune diseases can cause cirrhosis.

What other conditions can cause cirrhosis?

Biliary obstruction and vascular disease.

What happens to normal liver architecture in cirrhosis?

Loss of normal liver architecture.

What defines micronodular cirrhosis?

Nodules <3 mm.

What defines macronodular cirrhosis?

Nodules >3 mm.

What is mixed cirrhosis?

Combination of micro- and macronodular patterns.

What metabolic complications occur in cirrhosis?

Ascites; edema; bleeding; jaundice.

What vascular complication occurs in cirrhosis?

Portal hypertension.

What dysplastic complication can arise in cirrhosis?

Liver cancer.

What is jaundice?

Elevated serum bilirubin.

What causes jaundice?

Extravascular hemolysis; hepatocyte dysfunction (e.g., hepatitis); bile flow obstruction (e.g., gallstone).

How does hemolysis cause jaundice?

Increased bilirubin production from RBC breakdown.

How does hepatocyte dysfunction cause jaundice?

Impaired bilirubin metabolism (e.g., hepatitis).

How does bile obstruction cause jaundice?

Blocked bile flow (e.g., impacted gallstone) → bilirubin accumulation.

What skin and mucosal findings occur in jaundice?

Yellow skin; yellow mucosa; yellow sclera.

What stool and urine findings occur in jaundice?

Dark urine; pale stool; steatorrhea.

Which disorders cause unconjugated hyperbilirubinemia?

Crigler–Najjar syndrome; Gilbert syndrome.

Which disorders cause conjugated hyperbilirubinemia?

Dubin–Johnson syndrome; Rotor syndrome.

What is Crigler–Najjar syndrome type I?

Autosomal recessive absence of UGT1A1 → inability to conjugate bilirubin → fatal neonatal kernicterus.

Which enzyme is absent in Crigler–Najjar type I?

UGT1A1 (uridine diphosphate glucuronosyltransferase).

What is Crigler–Najjar syndrome type II?

Less severe hereditary unconjugated hyperbilirubinemia with markedly reduced enzyme activity → not fatal.

What is Gilbert syndrome?

Mild fluctuating unconjugated hyperbilirubinemia → ~30% reduced bilirubin conjugation activity.

What causes hereditary conjugated hyperbilirubinemia?

Deficiency of canalicular membrane transporters.

Which diseases cause hereditary conjugated hyperbilirubinemia?

Dubin–Johnson syndrome; Rotor syndrome.

What is portal hypertension?

Portal venous pressure gradient >5 mmHg.

What are esophageal varices?

Dilated varicose veins in the esophagus.

Why is liver infarction rare?

Dual blood supply (portal vein + hepatic artery).

What causes passive hepatic congestion?

Congestive heart failure.

What causes “nutmeg liver”?

Result of passive hepatic congestion from congestive heart failure.

What causes iron overload disorders?

Metabolic defect → excess iron absorption or abnormal storage regulation.

What is genetic hemochromatosis?

Autosomal recessive iron overload disorder.

When does hereditary hemochromatosis usually present?

Rarely before age 40.

What liver complications occur in hemochromatosis?

Cirrhosis; ~200-fold increased cancer risk.

What pancreatic complication occurs in hemochromatosis?

Pancreatic fibrosis.

What cardiac complication occurs in hemochromatosis?

Cardiomyopathy.

What skin finding occurs in hemochromatosis?

Skin pigmentation.

What is Wilson disease?

Autosomal recessive mutation in copper-transport ATPase → copper accumulation.

What liver manifestations occur in Wilson disease?

Chronic hepatitis; cirrhosis.

What neurologic/psychiatric manifestations occur in Wilson disease?

Psychiatric disorders.

What ocular sign occurs in Wilson disease?

Kayser-Fleischer rings (pigmented rings in the cornea)

What is hepatic adenoma?

Benign liver tumor associated with estrogen → common in women of childbearing age.

What is the histologic appearance of hepatic adenoma?

Cells resemble normal hepatocytes with minor variation.

What is a liver hemangioma?

Common benign vascular tumor that can grow large.

What is hepatocellular carcinoma (HCC)?

Malignant tumor of hepatocytes.

What is the gender distribution of HCC?

Male > female.

What is the prognosis of HCC?

Poor prognosis (can lead to death in 6-8 months)

What are major risk factors for HCC?

Hepatitis B or C carrier state; any cirrhosis; aflatoxins from Aspergillus.

What is hepatic angiosarcoma?

Malignant vascular tumor of the liver → poor prognosis.

Which cancers commonly metastasize to the liver?

Lung; breast; colon; stomach.

What is cholestasis?

Blockage of bile flow from the liver.

What mechanisms cause cholestasis?

Extrahepatic obstruction; intrahepatic bile duct obstruction; hepatocyte bile secretion defects.

What symptom commonly occurs in cholestasis?

Yellow discoloration of skin and sclera.

What is ascending cholangitis?

Bacterial infection of the biliary tree.

Which bacteria commonly cause ascending cholangitis?

Coliforms; enterococci.

What symptoms occur in ascending cholangitis?

Fever; chills; abdominal pain; jaundice.

What is primary biliary cholangitis?

Autoimmune destruction and granulomatous scarring of small/medium intrahepatic bile ducts.

What is primary sclerosing cholangitis?

Inflammation and fibrosis of intrahepatic and extrahepatic bile ducts (usually large ducts)

What disease is strongly associated with primary sclerosing cholangitis?

Ulcerative colitis.

What cancer is associated with primary sclerosing cholangitis?

Cholangiocarcinoma.

What is cholangiocarcinoma?

Malignancy of the biliary tree arising from bile ducts inside or outside the liver → very poor prognosis.

(intrahepatic or extrahepatic)

What is acute cholecystitis?

Acute gallbladder inflammation → right upper quadrant pain; usually caused by gallstones.

(acute, sudden onset with sharp pain)

What complications can occur in acute cholecystitis?

Infection; perforation → biliary peritonitis.

What is chronic cholecystitis?

Chronic gallbladder inflammation usually caused by gallstones.

What structural change occurs in chronic cholecystitis?

Thickened gallbladder wall.

What is porcelain gallbladder?

Calcification of the gallbladder wall in chronic cholecystitis.

What may accumulate in chronic cholecystitis?

Mucus.

What is cholelithiasis?

Presence of gallstones.

Is cholelithiasis usually symptomatic?

Usually asymptomatic.

What demographic pattern is associated with gallstones?

Older age; female > male.

What is the classic gallstone risk profile?

The 5 F’s: “Fat, forty, female, fertile, fair skin”

What causes cholesterol gallstones?

Insufficient bile salts to keep cholesterol dissolved.

What are pigment stones composed of?

Insoluble bilirubin pigment and calcium salts.

What is the main malignant tumor of the gallbladder?

Gallbladder carcinoma.

How common are benign gallbladder tumors?

Rare.

What is the gender distribution of gallbladder carcinoma?

Female >>> male.

What percentage of gallbladder carcinomas are associated with gallstones?

~90%.

How does gallbladder carcinoma spread?

Invades liver or metastasizes.

Why is gallbladder carcinoma prognosis poor?

Usually detected late because of late onset of symptoms