Liver Pathology 1 Flashcards
Jaundice
- -Yellow discoloration of skin from retention of bilirubin
- -Shows when total serum bilirubin approaches 2-3 mg/dl
Icterus
Yellow discoloration of sclera from retention of bilirubin
Bilirubin metabolism
Reticuloendothelial cells convert heme to bilirubin–> transported to liver and complexed to albumin–> conjugated w/glucuronic acid in liver cells –> excreted in bile
Unconjugated bilirubin
- -Water insoluble
- -Bound to albumin
- -Toxic to tissues
- -Not excreted in urine
Conjugated bilirubin
- -Water soluble
- -Not tightly bound to albumin
- -Not toxic to tissues
- -Excreted in urine when present at high levels
Cholestasis
Impaired secretion of bile
Causes of unconjugated hyperbilirubinemia
- -Increased bilirubin production (hemolysis)
- -Impaired hepatic bilirubin uptake (Gilbert Syndrome)
- -Impaired bilirubin conjugation ( Crigler-Najjar syndrome)
Causes of conjugated hyperbilirubinemia
- -Extrahepatic cholestasis (biliary obstruction)
- -Intrahepatic cholestasis
- -Excretion defect (Dubin-Johnson syndrome, Rotor syndrome)
Physiologic neonatal jaundice
- -Unconjugated hyperbilirubinemia
- -Normal neonatal alt. in bilirubin metabolism including increased bilirubin production, decreased bilirubin clearance (immature UDP-glucuronosyltransferase) and increased enterohepatic circulation.
Tx for physiologic neonatal jaundice
Phototherapy
Organ system affected by high bilirubin?
–Bilirubin can deposit in brain (bilirubin induced neurologic dysfunction)
Gilbert’s syndrome
–Decreased gluconyltransferase activity–> Increased unconjugated bilirubin w/o overt hemolysis. No clinical consequences.
Gilbert syndrome inheritance and how common is it?
- -Autosomal recessive or autosomal dominant.
- -Very common
Lab findings in Gilibert syndrome
Increased unconjugated bilirubin
Hepatocellular cholestasis morphology
Bile within hepatocytes, feathery degeneration of hepatocytes
Canalicular cholestasis morphology
Canalicular bile stasis, feathery degeneration of hepatocytes
Acute cholangitis morphology
- -Extrahepatic biliary obstruction
- -canalicular bile stasis
- -bile within distended bile ducts
- -feathery degeneration of hepatocytes
- -portal tract edema
- -bile duct proliferation w/in portal tracts
- -ascending cholangitis
Hepatitis A virus
- -Preferentially infects liver cells
- -Doesn’t cause chronic hepatitis
- -Injury due to cellular immune response
- -Majority asymptomatic
What forms of hepatitis have vaccines available?
- -A
- -B
How is hepatitis A diagnosed?
Serology
Hepatitis B virus
- -Preferentially infects liver cells
- -Potential to cause chronic hepatitis
- -Injury due to cellular immune response
- -Virus in fluids and blood
How is hepatitis B transmitted?
Parenteral, sexual/close contact, perinatal
Hepatitis A presentation
- -Most asymptomatic
- -Some present with acute hepatitis
- -1% develop acute liver failure and may die
Hepatitis B diagnosis
Serology (include nucleic acid testing if necessary)
Hepatitis B presentation
- -70% asymptomatic
- -30% develop clinical hepatitis
- -90% resolve
- -0.1-0.5% develop acute fulminant hepatitis with liver failure and may die
Carrier state for hepatitis B
- -Persistent HBV infection w/o necroinflammatory disease
- -Typically occurs from result of exposure at childbirth or exposure as a young child
- -+ HBsAg > 6 months
What indicates recovery from chronic HBV infection?
Negative test for HBsAg
Delta hepatitis virus (HDV)
- -Can have acute coinfection with HBV and HDV (will look like HBV)
- -Acute coinfection usually transient and self-limited.
- -Can convert mild chronic HBV into acute liver failure, cause acute hepatitis to occur in HBV carrier, lead to chronic hepatitis
In patients with HBV, when should HDV testing be considered?
- -Risk factors (IV drug use, from endemic country)
- -Unusually severe or protracted acute hepatitis
- -Acute hepatitis of undetermined origin in chronic HBV carrier
Hepatitis C RNA type, transmission, and cell type preferentially infects
- -Single stranded RNA
- -Spread parenteral (primarily blood), sexual/close contact, and rarely perinatally).
- -Liver cells
What causes hepatocellular injury in HCV?
–Patients cellular immune response and subsequent lysis of cells
Do most people with HCV develop chronic or acute hepatitis?
Chronic (80%)
–accounts for almost half of liver disease in US.
What do some HCV patients develop?
Extrahepatic autoimmune manifestations/syndromes (Cryoglobulinemia, membranoproliferative glomerulonephritis, thyroiditis)
How do you diagnose HCV?
HCV antibody screen and reflex to HCV RNA by PCR–> Anti-HCV antibodies develop approx. 10 wks after infection, but don’t confer recovery or immunity
How do you diagnose HDV?
Nucleic acid testing to detect viral DNA
How do you diagnose HEV?
Serology
Hepatitis E virus (HEV)
- -Preferentially infects liver cells
- -Hepatocellular injury due to patients cellular immune response
- -Very prevalent in underdeveloped countries, rare in US
- -Doesn’t cause chronic hepatitis
- -Generally self limited
What group of ind. with HEV have a higher mortality rate?
Pregnant women
