Chapter 16 Liver & Biliary Tract

CIRRHOSIS: three top causes 1. alcohol 60-70% (but only about 10% of alcoholics end up in cirrhotic liver failure) 2. cryptogenic ~15% 3. viral hepatitis 10%

Jaundice and Cholestasis (Table 16-3) jaundice - bilirubin > 2.0 mg/dL. Referred to as hyperbilirubinemia. (normal <1.2 mg/dL) in serum. cholestasis - elevated bilirubin, bile salts, and cholesterol in serum. Also causes jaundice. Occurs when bile flow in the liver, or after the liver, is impeded. Bile plugs form in liver. Other substances from liver cells are released, esp. alkaline phosphatase. lab testing (Table 16-2) for liver cell function: Measures of hepatocyte integrity: ........ AST (aspartate aminotransferase - normally AST>ALT. AST a general marker for liver injury. ...... ALT (alanine aminotransferase) - high concentration in liver cells (also muscle). In liver injury lots of ALT released which exceeds AST levels

portal hypertension: caused by increased resistance to blood flow through liver sinusoids due to fibrosis. Features: 1. ascites - 500 ml fluid with up to 3 gm/dL of largely albumin 2. portal-systemic venous shunts - periumbilical (caput medusae) and esophageal varicosities (about 65% of patients with advanced cirrhosis) 3. splenic congestion (splenomegaly) - can be massive (> 1 kg)

Yellowing of skin from excessive bilirubin is jaundice & yellowing of eye sclera is icterus. kernicterus - neurological injury of brain from excessive neonatal unconjugated bilirubin.

4. hepatic encephalopathy

mechanisms for jaundice (Table 16-3) - 1-3, below, result in elevated unconjugated hyperbilirubinemia: 1. excess prod. of bilirubin (excessive hemolysis or resorption of rbcs from injury) seen in hemolytic anemia 2. reduced hepatic cell uptake of bilirubin (liver disease) 3. impaired conjugation in the liver cell (liver disease) 4&5 causes conjugated hyperbilirubinemia:

INFLAMMATORY DISORDERS Viral hepatitis (Table 16-4) Essential knowledge! General considerations: By convention, the term hepatitis refers to inflammation of viral origin. Understand the carrier state, asymptomatic vs. clinically apparent disease and acute vs chronic hepatitis. Types: HAV - (Fig 16-5) no persistent state, permanent damage minimal. Can cause death, however in elderly HBV - (Figs 16-6 & 16-7) HCV - (Fig 16-8) - mutates readily and IgG does not confer immunity!

4. decreased hepatocellular excretion HDV - superinfection more serious than coinfection 5. impair bile outflow - obstruction Acute versus Chronic Hepatitis:

DRUG & TOXIN INDUCED LIVER DISEASE (Fig 16-14) Alcoholics - 85% have steatosis (fatty liver), up to 35% have hepatitis, 10% develop cirrhosis. Tends to be micronodular (hobnail) (versus macronodular seen in viral hepatitis) alcoholic hepatitis - characteristics - what leads up to cirrhosis 1. hepatocyte swelling - ballooning degeneration 2. Mallory bodies - accumulation of cytokeratins in hepatocytes 3. neutrophilia - especially intense around Mallory bodies (fig 16-16) 4. fibrosis - concentrated in sinusoidal and perivenule. 80 - 160 gm ethanol a day (~8-16 beers/day or 7-14 drinks). Often accompanied by malnutrition

TUMORS & TUMOR-LIKE CONDITIONS OF THE LIVER: Benign hemangioma - most common liver cell adenoma uncommon. Associated with oral contraceptives. Sometimes causes a medical emergency by bleeding into the peritoneum.

Primary carcinoma hepatocellular - HBV strongly linked, parasites (flukes), & mold toxins (Aspergillus & Fusarium)

Non-alcoholic fatty liver: not as severe as alcoholic. Seen predominantly in obese individuals with type II diabetes and elevated serum lipids.

DISORDERS OF GALLBLADDER 1. Cholelithiasis (Table 16-8)(Fig. 16-37) 50-100% cholesterol based. Predisposing factors: 1. supersaturated bile (with cholesterol) 2. nucleation

INBORN ERRORS OF METABOLISM Hemochromatosis - iron overload secondary more common than primary

3. crystals of cholesterol must remain to aggregate

Wilson Disease copper toxicity - may cause severe liver damage.

2. Cholecystitis - obstruction most frequent cause. Bacterial causes mostly gram negative.

alpha1-antitrysin deficiency 3. Carcinoma of the gallbladder more common than bile ductal carcinoma. gallstones present in 60-90%. Over age 60. Slightly more common in females. 95% adenocarcinoma. Reye syndrome kids under age 4 mainly. 25% die. Association with aspirin in doubt.