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144 Cards in this Set

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