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84 Cards in this Set
- Front
- Back
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What is cirrhosis?
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hepatic fibrosis with regeneration of hepatocytes, creates nodules of liver parenchyma
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What causes cirrhosis?
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injury to hepatocytes, remodeling of hepatic architecture, fibrous bands extend between portal tracts and central veins, diffuse process involving the entire liver
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What are the circulatory effects of cirrhosis?
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shunting of blood away from liver, shunting of blood in liver away from sinusoids
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What are the clinical manifestations of cirrhosis?
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loss of liver parenchyma, circulatory alterations, active parenchymal disease
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What causes most of the problems of cirrhosis?
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circulatory changes
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What does micronodular cirrhosis look like?
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small regenerative nodules of uniform size separated by delicate fibrous bans
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What does macronodular cirrhosis look like?
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larger nodules of varying][ size separated by coarser fibrous tissue
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What do you see in active cirrhosis?
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evidence of ongoing parenchymal disease, irregular limiting plates of nodules
can have steatosis, hyaline inflammation or necrosis |
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What causes most cirrhosis?
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alcoholic liver disease
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What are the major clinical effects of portal hypertension?
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ascites, varices, splenomegaly, hepatic encephalopathy, endocrine
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What are the major clinical manifestations of hepatocyte failure?
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jaundice, coagulopathy
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What causes portal hypertension in cirrhosis?
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increased resistance to flow of blood from portal circulation, increased portal venous/hepatic arterial anastamoses, fibrosis narrows sinusoids, comrpression of hepatic veins by nodules
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What are the other causes of portal hypertension?
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thormbosis of veins, obstruction of veins by neoplasms, severe right heart failure, constrictive pericarditis
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What is ascites?
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fluid accumulation in peritoneal cavity
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What are the causes of ascites?
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increase in hydrostatic pressure in portal circulation, hypoalbuminemia, sodium retention, flow of lymph into peritoneal cavity
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What causes sodium retention in ascites?
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sequestration of blood in portal system, decreased systemic blood volume, increased aldosterone and ADH
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What complications are associated with portal hypertension?
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ascites, varices, hypersplenism
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What causes varices?
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nastamoses between portal and systemic circulation in hemorrhoidic plexus in anus, GE junction, also around umbilical vein
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What are the complications of varices?
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massive bleeding, shunting of blood away from the liver
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What results from shunting of blood away from the liver?
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higher circulating endogenous estrogens, increased plasma levels of substances absorbed by the bowel, decreased clearance of drugs detoxed by the liver, decreased clearnce of enteric bacteria
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What are the results of higher levels of endogenous estrogens?
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gynecomastia and testicular atrophy in men, palmar erythema, spider angiomas
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What are the results of increased plasma levels of substances absorbed from the bowel?
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increased levels of amonia to hepatic encephalopathy fetor hepaticus
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What are the results of hepatic encephalopathy?
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CNS disturbances, impaired NT, rigidity, hyperreflexia, asterixis
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What is asterixis?
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rapid extension-flexion of head and extremities
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What is fetor hepaticus?
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msuty body odor due to mercaptens, produced from methionine by GI bacteria
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What causes hypersplenism?
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chronic congestion of the spleen, with enlargement, increased destruction of erythrocytes, leukocytes, platelets
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What are the results of hypersplenism?
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anemia, leukopenia, thrombocytopenia
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What proteins are lost most prominently in cirrhosis?
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albumin and clotting factors
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What are the results of hypoalbuminemia?
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ascites, edema, coagulopathy
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What are the late stage decreased proteins?
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glucose and bilirubin conjugation
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What is hepatorenal syndrome?
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decreased renal function with advanced liver disease, no intrinsic morphologic renal abnomralities
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Why are cirrhotic patients more vulnerable to hemorrhage?
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decreased production of clotting factors, thrombocytopenia due to hypersplenism, varices
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How does alcohol produce liver problems?
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steatosis in proportion to the dose
chronic injury due to repeated injury and other factors |
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What happens in severe steatosis?
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liver is grossly enlarged, yellow and greasy, uniform macrovesicular change in liver cells
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What does the liver look like grossly with alcoholic hepatitis?
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steatosis, fibrosis
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What are the hallmark changes of alcoholic hepatitis?
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steatosis, Mallory's hyaline, inflammation with hepatocyte necrosis, centrilobular fibrosis
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What do the early changes of alcoholic cirrhosis look like?
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micronodular changes, swollen by steatosis
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What do the later changes of alcoholic cirrhosis look like?
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organ shrinks, nodules become irregular, macronodular pattern
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How much alcohol do you need to consume/day to definitely get cirrhosis?
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160g
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Why does cirrhosis develop with viral hepatitis?
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progression of chronic hepatitis, patients who survive fulminant hepatitis
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What disease causes most viral hepatitis?
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HCV
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What are the metabolic causes of cirrhosis?
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primary hemocrhomatosis, Wilson's, alpha-1-antitrypsin deficiency
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What are the rarer causes of metabolic cirrhosis?
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tyrosinemia, galactosemia, hereditary fructose intolerance
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What is primary hemochromatosis?
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autosomal recessive, excessive absorption of iron with deposition of hemosiderin in organs, esp liver, pancreas, spleen, and heart
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Where is the genetic defect of primary hemochromatosis?
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HFE gene chromosome 6
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What are the clinical manifestations of primary hemochromatosis?
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cirrhosis, diabetes mellitus, skin pigmentation, cardiomyopathy, hepatocellular carcinoma
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What is the pathology of primary hemochromatosis?
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liver is enlarged and brown, cirrhosis is typically micronodular, hemosiderin in hepatocytes, Kupffer cells, biliary epithelium
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How do you find hemosiderin in hemochromatosis?
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Prussian blue stain
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What is Wilson's disease?
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autosomal recessive disorder of copper metabolism, defective excretion of copper into bile
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What is the pathogenesis of hemochromatosis?
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accumulation of 20 gm of iron, HLA-H on surface of intestinal cells, mechanism of excess intake not understood
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How is the excessive iron intake toxic to tissues?
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formation of free radicals, stimulation of collagen production, direct interaction with DNA: lethal cell injury, cancer
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how do you diagnose hereditary hemochromatosis?
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high levels of serum iron, ferritin iron concentration on liver tissue, testing for mutation, exclusion of secondary causes of iron overload
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What gene is defective in Wilson's?
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ATP8B on chromosome 13
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What does the ATP8B gene do?
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encodes transmembrane copper transporting ATPase on canalicular membrane
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Where does copper accumulate in Wilsons?
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liver, brain, eye
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What are the clinical manifestaitons of wilson's?
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liver disease in adolescence, cirrhosis, atrophy of basal ganglia, Kayser-Fleischer rings
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What are Kayser-Fleischer rings?
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deposits of copper in the cornea
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What happens with the BG atrophy?
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Parkinson's like movement disorder and psychiatric disturbances
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How do you diagnose Wilson's?
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low plasma levels of ceruloplasmin, increased urinary copper, quantitative copper concentration on liver tissue, molecular testing
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What is alpha one antitrypsin deficiency?
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autosomal recessive disorder, protease inhibitor is synthesized in the liver, not released into circulation
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What is the mutation for alpha-1-antitrypsin?
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PiZ homozygote, single AA substitution makes misfolding
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What does the PiZ mtuation do?
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ineffective transport from ER to Golgi
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What are the clinical manifestations of alpha-1-antitrypsin deficiency?
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neonatal cholestasis, hepatitis/cirrhosis, emphysema, increased risk fo hepatocellular carcinoma with cirrhosis
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How do you diagnose alpha-1-antitrypsin deficiency?
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low serum levels of A1AT, genetic testing, PAS positive cytoplasmic inclusions in hepatocytes
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What causes biliary cirrhosis?
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portal fibrosis, can progress to nodularity
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What are the pathologic features of biliary cirrhosis?
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edema of portal tracts, bile ductular proliferation, bile accumulation, intially in Zone 3
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What happens in extrahepatic biliary obstruction?
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obstruction of extrahepatic biliary ducts causes scarring, nodule formation
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What obstructs the biliary tract?
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gallstones, neoplasms of giliary tract, strictures of ducts, pancreatic disease with fibrosis
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How do you correct extrahepatic biliary obstruction?
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fix the biliary obstruction
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What is primary biliary cirrhosis?
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chronic progressive cholestatic liver disease with destruction of intrahepatic bile ducts
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Who gets primary biliary cirrhosis?
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middlea ged women
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What is the pathogenesis of primary biliary cirrhosis?
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elevation of anti-mitochondrial antibodies, hypergammaglobulinemia, abnormal cellular immunity
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What are the abnormal labs with primary biliary cirrhosis?
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elevated alkaline phosphatase, normalish ALT, AST
elevated serum lipids normal bilirubin until late antimitochondrial antibody to M2 antigen of pyruvate dehydrogenase complex |
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What is the natural history of primary biliary cirrhosis?
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insidious onset, presents with pruritis, fatigue
protracted course to cirrhosis, jaundice late |
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What is the early pathology of primary biliary cirrhosis?
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inflammatory destruction of interlobular bile ducts wtih granulomas
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What is the late pathology of primary biliary cirrhosis?
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fiborisis from portal areas becomes mroe prominent than inflammation, reduction in bile ducts, can get cirrhotic nodules
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What is primary sclerosing cholangitis?
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diffuse inflammatory disorder of extrahepatic and large intrahepatic bile ducts
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how gets primary sclerosing cholangitis?
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young men 30s-50s
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What is associated with primary sclerosing cholangitis?
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mostly IBD, UC
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What antibodies are associated with primary sclerosing cholangitis?
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HLA-DR
p-ANCA |
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What are the lab abnormalities of primary sclerosing cholangitis?
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elevated alkaline phosphatase, elevated bilirubin, ANA, pANCA
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What do you look for on a cholangiogram with primary sclerosing cholangitis?
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strictures, beading, dilation
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What is the natural history of primary sclerosing cholangitis?
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fatigue, cholestasis, protracted course to cirrhosis, increased risk of cholangiocarcinoma, bacterial cholangitis, biliary stones
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What is the pathology of primary sclerosis cholangitis?
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progressive fibrosis of bile ducts with concentric periductal "onion-skin" pattern
ultimate pattern of ducts with scarring biliary cirrhosis |
