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Flashcards in Liver and Biliary Tract Deck (82)
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Hepatic Failure

  • when 80-90% of hepatic function is lost.
  • mortality is 80%. 
  • presentation: jaundice, hypoalbuminemia with systemic edema, hyperammonemia, fetor hepaticus (odor from mercaptan formation), hyperestrogenemia from impaired estrogen metabolism (have palmar erythema, spider angiomata, hypogonadism, gynecomastia).
  • complications: coagulopathy, multiple organ failure, hepatic encephalopathy (from porto-systemic shunting and loss of hepatocellular function.  excess ammonia ⇒ brain edema, disturbances in consciousness, limb rigidity, hyperreflexia, asterixis), hepatorenal syndrome (↓ renal perfusion pressure, renal vasoconstriction, sodium retention, impaired free-water excretion), hepatopulmonary syndrome (from intrapulmonary vascular dilation and functional shunting from pulmonary arteries to veins, have hypoxia, V/Q mismatch).


Acute Liver Failure

  • liver illness associated with encephalopathy within 6 months of initial diagnosis.
  • from hepatic necrosis from drug/toxin injury, viral hepatitis, autoimmune damage.


Chronic Liver Disease

  • most common cause of failure.
  • ends in cirrhosis


Hepatic Dysfunction without Overt Necrosis

  • viable hepatocytes can't perform normal metabolic functions.


Liver Cirrhosis

  • from alcohol abuse, viral hepatitis, non-alcoholic steatohepatitis.  biliary disease and hemochromatosis less common.
  • 20% are cryptogenic cirrhosis = unknown cause.
  • characteristics = bridging fibrosis (links portal tracts with central veins), parenchymal nodules (hepatocyte regeneration when encircled by fibrosis), disrupted hepatic parenchymal architecture.
  • pathogenesis: hepatocyte death, ECM deposition, vascular reorganization.
    • types I and III collagen deposited in space of Disse.  sinusoidal endothelium loses fenestration. new vascular channels link portal triads to central veins.
    • fibrosis from proliferation and activation of stellate cells, promoted by PDGFreceptor beta.  causes ↑ collagen synthesis and ↑ intrahepatic vascular resistance.
    • stellate cells and fibroblasts activated by: TNFalpha and IL-1beta, TFG-beta, direct toxin stimulation, disruption of ECM.
  • presentation: silent until advanced.  anorexia, weight loss, weakness, debilitation.  precipitated by infection or GI hemorrhage.
    • death from progressive liver failure, complication of portal HTN, hepatocellular carcinoma.


Portal Hypertension

  • from ↑ flow into portal circulation and/or ↑ resistance to portal blood flow.
  • prehepatic = from thrombosis, portal vein narrowing, ↑ splanchnic arterial circulation, massive splenomegal with ↑ splenic vein blood flow.
  • intrahepatic = cirrhosis, schistosomiasis, massive fatty change, granulomatous disease, or nodular regenerative hyperplasia.
  • posthepatic = right-sided heart failure, constrictive pericarditis, hepatic vein obstruction.
  • consequences: ascites, portosystemic shunts, splenomegaly
    • ascites = have hypeatic sinusoidal hypertension from hypoalbuminemia, hepatic lymph in peritoneum, splanchnic vasodilation causes hypotension so retain sodium and water, have intestinal capillary transudation.
    • portosystemic shunts = from ↑ portal pressure.  flow reversed from portal into systemic circulation.  usually at esophagogastric varices, can rupture and have massive hematemesis.  also at rectum (hemorrhoids), and falciform ligament/umbilicus (caput medusa).
    • splenomegaly = from long-standing congestion.  can get thrombocytopenia from hypersplenism.


Bilirubin and Bile Formation

  • heme degraded to biliverdin to bilirubin, then bound to albumin, delivered to liver, conjugated to glucuronic acid by UGT1A1 ⇒ water soluble bilirubin glucuronides excreted in bile, deconjugated in gut, degraded to urobilinogen and fecally eliminated.
  • 20% urobilinogen reabsorbed and go to liver.



  • yellow sclera discoloration.



  • yellow skin discoloration.
  • bilirubin production exceeds hepatic uptake, conjugation, and/or excretion.
  • unconjugated hyperbilirubinemia = excess production or diminished uptake and/or conjugation.
  • conjugated hyperbilirubinemia = defective excretion


Unconjugated Bilirubin

  • water insoluble.  usually bound to albumin.
  • small amount circulates free and can diffuse into tissues (neonatal brain).
  • unbound fraction increases with severe hemolysis or when drugs displace from albumin.


Conjugated Bilirubin

  • water-soluble, non-toxic, loosely bound to albumin.
  • excess is renally excreted.


Neonatal Jaundice

  • transient, mild unconjugated hyperbilirubinemia until 2 weeks of age.
  • hepatic metabolic machinery doesn't develop until about 2 weeks.
  • exacerbated by breast-feeding from bilirubin-deconjugating enzymes in breast milk.


Crigler-Najjar Syndrome Type 1

  • autosomal recessive.
  • total absence of UGT1A1 causes jaundice with high serum levels of unconjugated bilirubin, normal liver histology.
  • need liver transplantation or will get kernicterus (fatal neurologic damage).


Crigler-Najjar Syndrome Type 2

  • autosomal dominant.
  • less severe UGT1A1 deficiency.
  • not usually lethal but can get kernicterus.


Gilbert Syndrome

  • autosomal recessive. 6-10% population.
  • mild, fluctuating unconjugated hyperbilirubinemia, 30% ↓ UGT1A1 activity.
  • exacerbated by infection, strenuous exercise, fasting.


Dubin-Johnson Syndrome

  • autosomal recessive.
  • defective hepatocyte secretion of conjugated bilirubin from absent MDR2 (does bilirubin glucuronide transport).
  • liver is brown, accumulated pigment granules.
  • jaundiced but have normal life expenctancy.


Rotor Syndrome

  • autosomal recessive.
  • defective hepatocellular bilirubin uptake or excretion.
  • jaundiced with normal life expectancy.



  • impaired bile formation or flow ⇒ accumulation of intrahepatic bile pigments.
  • extrahepatic = duct obstruction
  • intrahepatic = hepatocellular dysfunction or canalicular obstruction.
  • consequences: jaundice, pruritus, xanthomas (skin accumulations of cholesterol), intestinal malabsorption, ↑ serum levels alkaline phosphatase and GGT.
  • morphology: bile pigment accumulates in hepatic parenchyma ⇒ dilated bile canaliculi and hepatocye degeneration.
    • obstruction ⇒ distended proliferating bile ducts in portal tracts, edema, periductular neutrophils.
      • prolonged ⇒ bile lakes, portal tract fibrosis, and cirrhosis.


Progressive Familial Intrahepatic Cholestasis (PFIC)

  • autosomal recessive disorders from mutated ATP-dependent transporter proteins.
  • PFIC-1 = Bylder disease or Benign recurrent intrahepatic cholestasis.
  • PFIC-2 = mutated ABCB11 gene for bile salt export pump in canaliculi.
    • have cholestasis, extreme pruritus, growth failure, progession to cirrhosis in 1st decade.
    • GGT levels normal.
  • PFIC-3 = mutated ABCB4 gene for MDR3 protein for biliary phosphatidycholine secretion.
    • ↑ GGT levels from biliary epithelium damage by bile salts.


Byler Disease

  • PFIC-1.  mutated ATP8B1 gene impairs bile secretion.
  • cholestasis in infancy, progesses to liver failure by aduthood.
  • no damage to canaliculi or biliary tree, normal GGT, normal bile ducts.


Benign Recurrent Inrahepatic Cholestasis

  • mild form of PFIC-1.  affects ATP8B1 gene.  
  • intermittent attacks of cholestasis, doesn not progress to chronic liver disease.


Hepatitis A Virus

  • aka HAV.  related to picornavirus.
  • 25% acute hepatitis.
  • ssRNA virus causing benign, self-limited disease.
  • transmission: fecal-oral
  • incubation: 2-4 weeks.
  • damage from CD8+ T cell response.
  • does not progress to chronic liver disease.
  • detection: anti-HAV IgM in acute infection.  IgG remains with immunity.


Hepatitis B Virus

  • aka HBV.  hepadnavirus.
  • dsDNA virus,causes acute, self-limited hepatitis, non-progressive chronic hepatitis, progressive chronic disease with cirrhosis, fulminant hepatitis with massive liver necrosis, asyptomatic carrier state.
  • Dane particle with outer surface protein and lipid envelope encasing electron-dense core.
  • 4 reading frames: HBcAg (core antigen), HBeAg (into bloodstream), HBsAg (surface antigen), HBx (for viral replication).
  • strong response by CD4+ and CD8+ IFN-gamma for resolution.  damage via CD8+ cells
  • related to cancer development (hepatocellular carcinoma).
  • transmission: parenteral, sexual contact, perinatal.
    • high prevalence = from childbirth.
    • intermediate-prevalence = minor cuts or breaks in mucus membranes.
    • low prevalence = IV drug abuse, unprotected sex.
  • incubation: 1-4 months.
  • 10% get chronic liver disease.
  • morphology: finely granular 'ground-glass' cytoplasm with HBsAg.
  • detection: HBsAg before symptoms (anorexia, fever, jaundice).  HBeAg and HBV DNA after HBsAG and before disease onset, persistence of HBeAg means chronic disease.  Anti-HBcAg IgM first, then anti-HBeAg IgM and anti-HBcAg IgG.  anti-HBsAg means end of acute disease and immunity.  
    • chronic carrier = HBsAg in serum for 6 months.
    • detect by HBsAg or Ab to HBcAg.


Hepatitis C Virus

  • aka HCV. flaviridae.
  • ssRNA, enveloped.  substantial genomic variability (quasispecies).  
  • E2 envelope protein targeted by Abs, also most variable.
  • antibodies don't cause immunity.  
  • 80-85% go on to chronic liver disease.  cirrhosis in 20-30%.
  • damage is immune mediated.
  • transmission: parenteral, intransal cocaine.
  • risk groups: IV drug abusers, multiple sexual partners.
  • incubation: 7-8 wks.
  • morphology: portal lymphoid aggregates, bile duct reactive changes, lobular regions of macrovesicular steatosis.
  • detection: HCV RNA in blood for 1-3 wks during active infection with transaminase elevation.  anti-HCV Ab in 50-70% in acute, 90% in chronic.
    • PCR for HCV RNA.
  • tx: for chronic use IFN-gamma and ribovarin.


Hepatitis D Virus

  • aka HDV.
  • circular defective ssRNA, requires host RNA polymerase activity.
  • only replicates and infects when encapsulated by HBsAg, so only when with HBV.
  • ranges mild to fulminant, chronicity rare (5% for co-infection, <70% with superinfection).
  • high prevalence in Africa, Middle East, Italy, and Amazon basin.
  • Dane-like particle with HBV envelope.  makes delta antigen.
  • incubation: 1-4 months.
  • detection: HDV RNA in blood and liver during infection, recent exposure has anti-HDV IgM, anti-HBcAg IgM = co-infection, HBsAg = superinfection
  • have a vaccine.


Hepatitis E Virus

  • aka HEV.  Calicivirus.
  • non-enveloped ssRNA, self-limiting, does not become chronic liver disease.
  • transmission: water-borne enteric infection (fecal-oral) via monkeys, cats, pigs, dogs.
  • epidemic in Asia, Africa, Mexico.
  • endemic in India = 30-60% acute hepatitis.
  • high rate of fatal fulminant hepatitis in pregnant women.
  • incubation: 4-5 wks.
  • detection: HEV antigen in hepatocytes (PCR), RNA and virions in stool and serum before onset.
    • IgG anti-HEV = immunity.


Hepatitis G Virus

  • aka HGV.
  • non-pathogenic RNA virus in 1-4% blood donors.
  • replicates in marrow and spleen.


Acute Asymptomatic Viral Hepatitis with Recovery

  • identified by ↑ transaminases or anti-viral Ab titers.
  • HAV and HBV frequently subclinical.


Acute Symptomatic Viral Hepatitis with Recovery

  • asymptomatic pre-icteric phase, symptomatic icteric phase, convalescence.
  • peak infectivity during last few days of asymptomatic days and first few symptomatic days.


Chronic Hepatitis

  • symptomatic disease with biochemical or serologic evidence of ongoing heptaic damage of more than 6 months.
  • HCV>>HBV or HDV
  • younger patients more likely to develop this, maternal-fetal transmission.
  • causes ongoing liver injury, cirrhosis, hepatocellular carcinoma, immune complex disease with vasculitis and glomerulonephritis.
  • 35% chronic HCV develop cryoglobulinemia.
  • morphology: mild to severe cirrhosis.  mild = limited to portal tracts.
    • extension of chronic inflammation from portal tracts with interface hepatitis, linking of portal-portal and portal-central regions = bridging necrosis.
    • continued loos of hepatocytes ⇒ fibrous septum formation, associated hepatocyte regeneration causes cirrhosis.
  • major cause of morbidity and mortality in HIV pts.  second most common cause of death in AIDs.