Chapter 18: Liver Flashcards
3 main types of hepatic failure
- acute liver failure (encephalopathy within 6 months of onset; including fulminant liver failure which is within 2 weeks)
- chronic liver disease leading to cirrhosis
- hepatic dysfunction without necrosis as in fatty liver of pregnancy
Definition of cirrhosis
- bridging fibrous septa (portal to portal or portal to lobular)
- parenchymal nodules resulting from hepatocyte regeneration and scarring
- disruption of architecture of entire liver
Posthepatic causes of portal hypertension
- right heart failure
- constrictive pericarditis
- hepatic vein outflow obstruction
Pathophysiology of cirrhosis
- increased resistance to blood flow at the level of the sinusoids due to contraction of smooth muscle cells and myofibroblasts, and disruption of blood flow due to scarring
- increased portal venous flow due to hyperdynamic circulation, particularly from increased slanchnic arterial blood flow
Basic causes of jaundice
- bilirubin overproduction
- hepatitis
- obstruction of biliary flow
What is UGT1A1?
- uridine diphosphate (UDP)-glucuronyl transferase that conjugates bilirubin the liver
- mutations cause hereditary unconjugated hyperbilirubinemia (Crigler-Najjar and Gilbert syndome)
Causes of jaundice
- excess extrahepatic production of bilirubin
- reduced hepatic uptake of bilirubin
- impaired conjugation of bilirubin
- decreased hepatocellular excretion of conjugated bilirubin
- impaired bile flow
Dubin-Johnson syndrome
- autosomal recessive defect in hepatic excretion of bilirubin
- excess conjugated bilirubin
Causes of cholestasis
- intra or extrahepatic obstruction of bile channels
- defects in hepatocyte bile secretion
What is the supposed underlying pathogenesis of autoimmune hepatitis?
- T cell-mediated autoimmunity
- IFN-gamma produced by CD4 cells causes hepatic damage, as do CD8 cells
- may be triggered by viral infections or drugs
What are the deleterious effects of alcohol on the liver?
- steatosis
- dysfunction of mitochondrial and cellular membranes
- hypoxia
- oxidative stress
What organs accumulate iron in hemochromatosis?
Liver, pancreas, joints, heart, other endocrine organs
How is iron toxic to the host?
- lipid peroxidation as iron catalyzes free radical reactions
- stimulation of collagen formation by activation of hepatic stellate cells
- interaction of ROS and iron with DNA, leading to cell injury or HCC
What is the main regulator of hepatic iron absorption?
Hepcidin; functions to lower plasma iron levels such that its absence causes iron overload
What mutations cause hemochromatosis?
-mutations in hepcidin, hemojuvelin, TfR2 and HFE, all of which decrease hepcidin expression
