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144 Cards in this Set
- Front
- Back
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LIVER - LEE - FRIDAY FEB 9
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PRIMARY BILIARY CIRRHOSIS (BPC)
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what type of disease is primary biliary cirrhosis?
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chronic cholestatic liver disease
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what is it characterized by (3)?
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1) destruction of intrahepatic bile ducts; 2) portal inflammation; 3) scarring
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what is progression like?
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slow, with eventual development of cirrhosis and liver failure
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who gets primary biliary cirrhosis?
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middle aged women (90-95% women, with peak incidence between 40 and 50 years of age)
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what is onset like?
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extremely insidious, and patients may be symptom free for many years
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what are often presenting symptoms (3)?
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1) pruritus; 2) increasing skin pigmentation; 3) cholestatic jaundice
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what type of non-liver lesion is seen in 30% of patients?
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xanthoma
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levels of what substances are elevated in blood (2)?
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1) serum alkaline phosphatase; 2) cholesterol
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what antibodies are seen, and in what % of patients?
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antimitochondrial antibodies are seen in more than 90% of patients
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what is the pathogenesis?
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autoimmune
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what are classic pathologic findings (3)?
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1) florid duct lesions; 2) presence of granulomas (25%); 3) ductopenia (absence of bile ducts in portal triads)
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what are florid duct lesions like?
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classic destructive bile duct lesion with marked lymphoplasmacytic infiltrate
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what are seen in advanced stages?
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fibrosis, cirrhosis
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what are treatments (2)?
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1) ursodeoxycholic acid (UDCA) - significantly increases survival free of transplant; 2) liver transplant (one of best indications for liver transplant)
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PRIMARY SCLEROSING CHOLANGITIS (PSC)
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what type of syndrome is PSC, and what is it characterized by?
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chronic cholestatic ysndrome characterized by: 1) inflammation of and; 2) obliterative fibrosis of intrahepatic nad extrahepatic bile ducts
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what happens to preserved segments?
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dilation
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who gets PSC?
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predominantly young men (70% are males under 45)
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what disease is seen in many PSC patients, and what % have it?
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ulcerative colitis (70% of PSC patients) - PSC seen in 4% of UC patients
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what substance has high levels in blood?
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alkaline phosphatase
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what is seen in radiographic studies?
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beading - multifocal irregular structures and dilations
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what are three pathologic freatures?
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1) periductal fibrosis/inflammation; 2) bile duct proliferation; 3) ductopenia
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what is seen in advanced stages?
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fibrosis and cirrhosis
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what is a complication of PSC?
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cholangiocarcinoma
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what is the treatment for PSC?
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liver transplantation
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ASCENDING CHOLANGITIS
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what can ascending cholangitis result from, and what does it most commonly result from?
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results from any lesion creating obstruction to bile flow, most commonly from choledocholitiasis
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what else can cause it (4)?
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indwelling stents/catheters, tumors, acute pancreatitis, and benign structures
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what infectious organisms are usually involved?
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gram negative aerobes
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what symptoms generally occur (4)?
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1) fever; 2) chills; 3) abdominal pain; 4) jaundice
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what is the underlying pathology?
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acute inflammation of the wall of bile ducts
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where do neutrophils infiltrate into?
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the luminal space
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EXTRAHEPATIC BILIARY ATRESIA
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who gets extrahepatic biliary atresia (and what % of this group)?
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30% of infants with neonatal cholestasis
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what is this the most frequent cause of?
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death from liver disease in early childhood
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what type of jaundice is this, and what happens to urine/stools?
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obstructive type jaundice, with dark urine and pale stools
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what is the course like?
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progressive fibrosis and subsequent cirrhosis development
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what happens to ducts and where?
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periportal ductular proliferation and fibrosis, cholestasis
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what are small or absent?
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extrahepatic bile ducts
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what are treatments for extrahepatic biliary atresia (2)?
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1) hepatic porto-enterostomy (Kasai procedure); 2) liver transplantation (50-60% of children referred for transplantation, living related donors)
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when does death typically occur if lesion cannot be corrected?
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by one or two years of age
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CAUSES OF IRON OVERLOAD
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how can hereditary hemochromatosis arise (3)?
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1) idiopathic; 2) primary; 3) genetic
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what can iron overload be secondary to (3)?
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1) anemia and ineffective erythropoiesis; 2) liver disease; 3) high iron intake
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what are two examples of iron overload secondary to anemia and ineffective erythropoiesis?
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1) thalassemia major; 2) sideroblastic anemia
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what are two examples of iron overload secondary to liver disease?
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1) alcoholic cirrhosis; 2) following portacaval anstomosis
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what are three examples of iron overload secondary to high iron intake?
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1) multiple transfusions; 2) prolonged excessive ingestion; 3) prolonged consumption of iron-laden alcoholic beverage
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HEREDITARY HEMOCHROMATOSIS
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how is hereditary hemochromatosis inherited?
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autosomal recessive
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what is it characterized by?
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excessive accumulation of body iron in organs such as liver, pancreas
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what are three very common manifestations?
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1) micronodular cirrhosis (all fully developed cases); 2) diabetes mellitus (75-80%); 3) skin pigmentation (75-80%)
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what other manifestations were mentioned (3)?
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1) cardiac failure; 2) testicular atrophy; 3) arthropathy
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when do symptoms generally appear?
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in fifth to sixth decade of life
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what sex predominates, and why?
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males - 5-7 to 1 with earlier presentation - because of physiologic blood loss in women
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what is the name of the hemochromatosis gene, and what does it encode?
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called HFE, and located on the short arm of chromosome 6, encodes an HLA class I-like molecule that regulates intestinal absorption of dietary iron
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what mutation is present in 85-90% of cases, and what race is it common in?
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C282Y mutation (common in Northern Eyrompeans)
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what is penetrance in homozygous cases?
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20%
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why is there dysregulation of enteric uptake?
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problem with "sensing" circulating iron levels by the crypt epithelial cells with mutant HFE
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what is the early pathology like?
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progressive increase in hepatocellular hemosidering pgiment
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what are the late changes (2)?
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1) marked hemosiderin deposition in hepatocytes and bile duct epithelium; 2) fibrosis and eventually cirrhosis
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how is the disease diagnosed (3)?
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1) HFE gene molecular analysis; 2) quantitive measurement of tissue iron content in liver; 3) screening of family members by biochemical/genetic studies
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what is the treatment?
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phlebotomy
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what disease often develops in patients with hereditary hemochromatosis, and what % get it?
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hepatocellular carcinoma (up to 30%)
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WILSON'S DISEASE
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how is Wilson's disease acquired, and what type of disease is it?
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rare (genetic) autosomal recessive disorder of copper mettabolism - accumulation of toxic levels of copper in may tissues and organs
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where in particular does copper accumulate (3)?
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1) liver; 2) brain; 3) eye
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where is the WD gene, and what does it encode?
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the WD gene is on chromosome 13, and encodes a transmembrane copper-transporting ATPase, located on the hepatocyte canalicular membrane
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what is the pathogenesis of WD?
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defective biliary excretion of copper
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what can happen to the liver (3)?
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1) acute fulminant hepatitis; 2) chronic hepatitis; 3) cirrhosis
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what is seen in the eye?
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Kayser-Fleischer ring; greenish-brown ring at periphery of cornea
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what is the first indication in 40% of cases?
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neurological signs
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what problem can occur in the blood (15% of cases), and why?
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Coombs-negative hemolytic anemia caused by rapid release of copper from the liver
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what are the two most important tools in diagnosing Wilson's disease?
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1) inrease in hepatic copper content; 2) slit-lamp examination for Kayser-Fleischer rings
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what is the problem with genetic analysis?
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over 30 mutations, not widely available
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what are other signs that can help in diagnosis (2)?
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1) decrease in serum ceruloplasmin; 2) increased urinary excretion in copper
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what are two treatments for Wilson's disease?
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1) liver transplantation; 2) copper chelation agents: D-penicillamine
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ALPHA-1-ANTITRYPSIN DEFICIENCY
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how is this disease inherited, and who is it most commonly diagnosed in?
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autosomal recessive disorder and the most commonly diagnosed genetic liver disease in infants and children
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what are the two main problems that develop?
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1) pulmonary emphysema; 2) liver disease
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what type of molecule is alpha-1-antitrypsin, and what is its major function?
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a glycoprotein, with a major function of inhibiting proteases, particularly neutrophil elastase, cathespin G, and proteinase 3 at sites of inflamamtion
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what is the predominant site of synthesis of alpha-1-antitrypsin?
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hepatocytes
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what is the encoding gene called, and what should we know about it?
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SERPINA1Z, located on chromosome 14, and is very polymorphic
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what genotype is seen in 90% of individuals?
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PiMM type
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what is the pathogenic mechanism for liver disease?
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defective secretion and excessive accumulation of abnormal A1AT peptides in hepatocyte
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what key pathological feature is found in hepatocytes, and what two properties must we know about these structures?
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PAS +, diastase-resistant globules in hepatocytes
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what other stain will be positive in this disease?
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immunohistochemical stain for alpha-1-antitrypsin
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what is the best method for diagnosing alpha-1-antitrypsin deficiency?
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serum A1AT phenotype determination (also can be diagnosed by serum quantification: 10% of normal level in PiZZ)
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what is the treatment for alpha-1-antitrypsin deficiency?
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liver transplantation
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HEPATOCELLULAR CARCINOMA (HEPATOMA)
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how common is hepatocellular carcinoma, and what % of primary liver tumors does it account for?
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one of the most common malignant tumors in the world, and 90% of all primary liver cancers
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what is the prevalence of HCC strongly linked to?
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prevalence of HBV infection
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what areas have the highest, and lowest incidence?
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highest incidence: Southeast Asia and Africa; lowest incidence: North America and Western Europe
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what % of cases have concurrent cirrhosis?
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60-90% (80% in North America)
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what % of cirrhotic livers have HCC in USA?
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5-10%
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why does cirrhosis lead to HCC?
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repeated cycles of cell death and regeneratio, accumulation of mutations and genomic instability
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in areas of high incidence, what % of cases is HBV documented in?
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80-90% of cases
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how much does risk increase for HBV carriers?
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200 fold
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how may HBV alter host genome?
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integrate HBV-DNA into host genome
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what regulatory element does HBV encode that may contribute to HCC, and how may it function?
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HBx protein - binds to p53 and interferes with growth suppression
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is HCV linked to hepatocellular carcinoma?
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there is compelling evidence that it is
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what if ingested may lead to hepatocellular carcinoma, and where does it come from?
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aflatoxin B1, a dietary toxin derived from the fungus Aspergillus flavus, found in moldy grains and peanuts - a highly carcinogenic toxin
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what gene in particular does this toxin mutate?
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p53
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what are endemic areas for HBV (2) that have increased rates of HBV?
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1) China; 2) South Africa
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what does HCC usually look like grossly?
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single mass in a cirrhotic liver, but can have multiple nodules or be diffusely infiltrative
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what does HCC look like microscopically?
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like liver
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what is elevated in the blood in 50-75% of cases?
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alpha-fetoprotein
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what are signs of HCC?
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sudden inrease in liver size and clinical deterioration in a cirrhotic patient
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OTHER LIVER NEOPLASMS
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what is the most common malignant neoplasm of the liver?
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metastatic cancer
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what are the most common primary sites (3)?
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1) breast; 2) lung; 3) colon
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what does metastatic cancer look like grossly?
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multiple nodules in a non-cirrhotic liver
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what is the most common genign tumor of the liver?
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hemangioma
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what is the etiology of cholangiocarcinoma in most cases?
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unknown
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what cause must we know that can lead to cholangiocarcinoma?
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chronic inflammation of the biliary tract
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what else can cause it (list)?
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primary sclerosing cholangitis, congenital fibropolycystic diseases of the biliary system, liver fluke in the Orient, hepatolithiasis in the Orient, recurrent pyogenic cholangitis in the Orient
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what type of cancer is cholangiocarcinoma, and what is pathology like?
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adenocarcinoma, with substantial fibrosis
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what is angiosarcoma of the liver associated with (3)?
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1) acsenic; 2) vinyl chloride; 3) Thorotrast
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who usually gets hepatocellular (liver cell) adenoma?
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young women with use of oral contraceptives
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what are presenting symptoms (2)?
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1) abdominal pain (usually due to hemorrhage); 2) rupture
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what does hepatocellular adenoma look like pathologically (what two things are missing)?
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looks like normal liver but there are no: 1) central veins; 2) portal areas
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how does focal nodular hyperplasia arise?
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probably hyperplastic and altered growth response to arterial malformation
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what is the pathology of focal nodular hyperplasia like, and what is one key feature?
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well demarcated but poorly encapsulated mass with a prominent central fibrous scar
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