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120 Cards in this Set
- Front
- Back
what percentage of cardiac output does the liver recieve? through what vessles
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25% - through the portal vein and hepatic artery (blood exits liver through hepatic vein)
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the appearance of which varies with age: hepatocytes or their nuclie?
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Nuclie vary in their size and number per hepatocyte
Hepatocyte size remains pretty constant |
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what are liver macrophages called
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Kupffer cells
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what is the function of stellate cells
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to metabolize and store Vit A, to transform into collagen producing myofibroblasts when there is liver inflammation
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what is the most common cause of chronic liver dz?
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Hep C (57%) >EtOH (24%0 > NASH (9%)>Hep B (4%)
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what is the most common cause of cirrhosis in the US
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EtOH (60-70%) > cryptogenic cirrhosis (10-15%) > Viral Hepatitis (10%) > biliary dz (5-15%) > hemachromatosis (5%) > wilson's dz & alpha 1antitrypsin dz (rare)
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Name 5 responses to injury seen in the liver
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1. degeneration and intracellular accumulation
2. inflammation 3. fibrosis 4. regeneration 5. necrosis and apoptosis |
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what is the difference between ballooning and feathery degeneration?
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Ballooning = severly swollen hepatocytes with irregularly clumped cytoplasmic organelles and large clear spaces
Feathery = similar to ballooning, but retained biliary material (cholestatic liver injury) makes hepatocytes foamy yellow |
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give definition and causes of microsteatosis:
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muliitple droplets that do not displace the nucleus
acute fatty liver of pregnancy, valproic acid, tetracycline, salicylates, yellow phosphorus, EtOH |
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give definition and causes of macrosteatosis
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single large droplet that displaces the nucleus
obesity, DM, hep C, methotrexate, amiodarone, EtOH |
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name causes of each type of zonal necrosis; centrilobular vs periportal
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centrilobular = ischemia, drugs/toxins, (bromobenzene, CCL4, acetominophen, halothene, rifampin)
periportal = ecclampsia |
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what is the most common cause of massive hepatic necrosis?
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Acetominophen (38% of cases in US)
Other drugs include: halothane, rifampin, isoniazid, MAOIs, CCL4, mushroom Amanita phalloides |
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which viruses cause massive hepatic necrosis
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Hep A & B (NOT C)
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Hepatic encephalopathy is associated with elevated blood levels of what
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Ammonia
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what is hepatorenal syndrom
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The appearance of renal failure in patients with severe chronic liver disease, in whom there are no intrinsic morphologic or functional causes for the renal failure
Renal abnormalities include: Na retention, impaired free water excretion, dec reanl perfusion and GFR Maybe caused by dec renal perfusion pressure, constriction of afferent renal arteriole onset signaled by drop in urine output, rising BUN and creatinine, hyperosmolar/low Na urine (no prot/sediment) |
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what are the most common cuases of cirrhosis
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alcohol abuse (60-70%) and viral hepatitis (10%)
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list causes of each type of portal hypertension:
-prehepatic -posthepatic -intrahepatic |
-prehepatic: obstructive thrombosis and narrowing of the portal vein and massive splenomegaly
-posthepatic: severe right sided heart failure, constrictive pericarditis, hepatic vein outflow obstruction -intrahepatic: cirrhosis (most cases of portal HTN), schistosomiasis, massive fatty change, sarcoidosis, miliary TB, and nodular regenerative hyperplasia |
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what are the 4 major consequences of portal HTN
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ascites, formation of portosystemic venous shunts, congestive splenomegaly, hepatic encephalopathy
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what does bile help eliminate
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hydrophobic substances such as bilirubin, cholesterol, xenobiotics
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how is bilirubin formed
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1. bilirubin is the end product of heme degradation (mostly from old RBCs)
2. heme is oxidized to biliverdin (by heme oxigenase) 3. biliverdin is reduced to bilirubin (by biliverdin reductase) 4. bilirubin must bind to albumin for blood transport to liver (unconj is very insol) 5. bili is conj with glucuronic acid in ER (by bilirubin UDP-glucuronyltranserase UGT1A1) 6. bilirubin glucuronids are water soluble and excreted into bile 7. bilirubin glucuronides in bile are then deconj to colorless urobilinogens (by bacterial beta-glucuronidases) 8. urobilinogens are excreted in feces or resorbed (20% ) in the ileum and colon and returned to the liver |
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what is kernicterus and what causes it
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it is the accumulation of unconjugated bilirubin in the brain of infants, ususally caused by severe hemolytic disease of the newborn (erythroblastosis fetalis), which gives more unconjugated bilirubin that is displaced from albumin and can diffuse into tissues (freee unconj bili can also increase due to protein-binding drugs)
-conjugated bilirubin is water soluble and nontoxic, and can be excreted in urine |
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what type of bilirubin predominates in neonatal jaundice
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unconjugated (bilirubin system not fully mature until 2 weeks of age)
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what causes breastfed infants to exhibit jaundice more frequently
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the beta-glucuronides present in milk that deconj bili, increasing amount of unconjugated bili
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which hereditary hyperbilirubinemia is fatal without a liver transplant
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Crigler-Najjar type I (NO UGT1A1 enzyme)
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which hereditary hyperbilirubinemia hyperbilirubinemia are autosomal dominant
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Crigler-Najjar type II and Gilbert's syndrom
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which hereditary hyperbilirubinemia is due to MRP2 mutation giving impared excretion of bilirubin glucuronides
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Dubin- Johnson
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which hereditary hyperbilirubinemia is causes by a TA base repeat in the TATAA 5' promoter region
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Gilberts syndrome (gives decrease expression of UGT1A1)
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which hereditary hyperbilirubinemia gives pigmented cytoplasmic globules in the liver
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Dubin- Johnson
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what are some signs and symptoms of cholestasis
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Jaundice, pruritis (due to deposition of bile acids in skin), xanthomas (due to impaired excretion of cholesterol), increased serum alk phos, gamma glutamyl transpeptidase (GGT), and deficiencies of fat soluble ADEK
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why is serum alk phos elevated in cholestasis
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alk phos is an enz present in bile duct epi and in the canalicular membrane of hepatocytes that gets released into circulation when retained bile salts act as detergents
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how can the hepatic alk phos isozyme be distinguished from the bone isozyme
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the alk phos from bone will degrade when heated ("bone burns")
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which virus is
icosahedral capsid ssRNA- enveloped dsDNA enveloped ssRNA unenveloped ssRNA |
icosahedral capsid ssRNA- hep A
enveloped dsDNA- hep B enveloped ssRNA- hep C and Hep D unenveloped ssRNA- hep E |
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what is used in Hep B vaccination
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noninfections HBsAg
*protectino confirmed by identification of anti-HBs |
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what serum findings are indicative of chronic Hep B with possible progressive liver damage
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-Chronic replication of HBV virions characterized by circulating HBsAg, HBeAg, HBV DNA
-usually also have anti-HBs and anti-HBc |
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which acute hepatitis has a high mortality rate amongst pregnant women
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Hep E, about 20A% mortality
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what causes the acute icteric phase of hepatitis
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-conjugated hyperbilirubinemia, mostly Hep A and some Hep B
-accompanied by dark urine and light stools |
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what type of HBV transmission produces the msot individuals in a carrier state
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- vertical transmission: carrier state in 90-95%
-adult transmission: carrier state only in 1-10% |
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autoimmune hepatitis is most common in what patients
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Women (78%) especially young and perimenopausal
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what serum autoantibodies are elevated and which one is not
Positive? Negative? |
Positive: Type I (Most common) = antinuclear (ANN) and or antismooth muscle (SMA)
Type II (younger patients) = antiliver/kidney microsomes (antiLKM1) Negative: antimitochondrial (AMA), which is positive in what other conditions = primary biliary cirrhosis (PBC) |
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what is a histological feature of AI hepatitis?
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prominent plasma cell infiltrate
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what histologic feature distinguishes drug-induced hepatitis from viral hepatis
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Nothing = they are histologically indistinguishable and serological markers must be used
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what is Reye syndrome and what causes it
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Reye syndrome is potentially fatal syndrome of mitochondrial dysfunction in the liver and brain in children who are give acetylsalicylic acid (aspirin) in certain virus induced fevers
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what are mallory bodies
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accumulations of eosinophilic cytokeratin intermediate filaments within the cytoplasm of degenerating hepatocytes
- they are characteristic of but not specific for alcoholic liver dz (also seen in PBC, Wilsons dz, HCC) |
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What % of alcoholics develop cirrhosis
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only 10-15% (women appear to be more susceptible to liver damage)
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Name the metabolic liver disease
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1. NAFL (non alcoholic fatty liver) and NASH (nonalcoholic steatohepatitis)
2. hemochromatosis 3. Wilsons dz 4. Alpha 1 antitrypsin |
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what is the prevalence of NASH
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presents in approximately 31% of men and 16% of women in the US.
-diagnosis of exclusion (no EtOH abuse but elevated aminotransferases &/or GGT) -strongly associated with obesity, dyslipidemia, hyperinsulinemia and insulin resistance and DMII |
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in what two organs does iron accumulate in hemochromatosis
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liver and pancrease
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what are 3 features of hemochromatosis
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micronodular cirrhosis (100%), diabetes mellitus (75-80%), skin pigmentation (75%-80%)
- may also be called "bronze diabetes" |
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what genetic defect is present in 70-100% of hemachromatosis patients?
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C282Y (cysteine-to-tyrosine substitution) due to a G845A (G to A transition) on the HFE gene (6p21.3)
this causes loss of the regulation of intestinal iron absorption |
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the HFE gene is in linkage disequilibrium with what
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HLA - A3
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how common is the C282Y mutation
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in caucasians, 1/220 are homozygous, and 1/9 are heterozygotes
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why is hemochromatosis less common than the frequency of mutations would suggest
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because the pentrance is only 20% in patients with homozygous mutations
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how much iron is typically accumulated before disease manifests itself
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after about 20g of storage iron have accumulated (normal iron storage ranges from 2-6 grams)
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what is hepatic iron concentration in normal livers and in hemochromatosis
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normal - iron content of unfixed liver < 1000ug/g dry weight
hemochromatosis - iron content of unfixed liver tissue >10,000 ug/g dry weight > 22,000 ug is associated with fibrosis and cirrhosis |
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why is the skin pigmented
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hemosiderin in dermal macrophages and increased epidermal melanin production
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what is the risk of hepatocellular carcinoma in hemochromatosis patients
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200x greater than in the general population
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what accumulates in Wilson dz (and in what organs)
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copper - in the liver, brain (putamen) and eyes
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mutations causing wilson disease are present on which gene
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ATPB7 on ch13, which encodes a transmembrane copper-transporting ATPase
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what special stains help demonstrate the copper
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rhodanine (copper) and orcein (for copper-associated protein)
copper content > 250ug per gram dry weight also helps makes the diagnosis |
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what are Kayser-Fleisher rings
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accumulation of green-brown copper deposits in Descemet's membrane in the limbus of teh cornea
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how is Wilsons disease diagnosed biochemically
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increased hepatic copper content and urinary excretion of copper
decreased serum ceruloplasmin serum copper levels are of no diagnostic value |
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what is the function of alpha 1 antitrypsin
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protease inhibitor "Pi" (particularly elastase, cathepsin G and proteinase 3, which are released from neutrophils)
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what is the notation for most common genotype and the A1AT genotype
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Normally (90%) have PiMM, A1AT have PiZZ (1/7000 people in the US) and have only 10% normal A1AT levels, but only 10% of PiZZ individuals develop clinical liver disease
the mutant A1AT polypeptide is abnormally folded, which causes retention in the ER of hepatocytes and causes an intense autophagocytic response that causes liver injury Pi-null have not detectable A1AT |
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what is the distinctive histologic feature of A1AT?
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eosinophilic PAS + diastase-resistant (because they are not made of glycogen) globules with in hepatocytes
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what is the risk of hepatocellular carcinoma in PiZZ individuals
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2-3%
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What is the treatment for A1AT disease affecting liver or lung?
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Liver - transplant
Lung - replace enzymes and smoking cessation |
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name 2 intrahepatic biliary tract disorders
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1. primary biliary cirrhosis(PBC)
2. secondary biliary cirrhosis (SBC) 3. primary sclerosing cholangitis(PSC) |
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which affects women 6x more
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PBC
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what causes secondary biliary cirrhosis
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uncorrected obstrxn of the extra hepatic biliary tree (gall stones, tumors, strictures)
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subtotal obstrxn of biliary tree may promote what types of secondary bacterial infections
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enteric organisms (coliforms and enterococci)
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what is the feature of primary biliary cirrhosis
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non-suppurative inflammatory destrxn of the medium sized intrahepatic bile ducts
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name early and late signs and sx of pbc
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early - pruritis, hepatomegaly, xanthomas, increased serum alk phos, and cholesterol
late - jaundice, portal HTN, varices, encephalopathy, hyperbilirubinemia |
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what antibodies are present in 90% of patients with PBC
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anti mitochondrial Ab against E2 subunit of pyruvate dehydrogenase complex (PDC-E2 protein)
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what is the histologic appearance of PBC
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lymphs and plasma cells in the portal tract with possible granuloma formation, fibrosis, and necrosis, bile stasis
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what are the features of primary sclerosising cholangitis
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inflammation and obliterative firbrosis of the intra and extrahepatic bile ducts with dilatino of preserved segments, seen as "beading" on barium radiographs
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PSC is associated with what GI condition
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Inflammatory Bowel Dz, most commonly ulcerative colitis ( 70% of PSC have UC, but only 4% of UC have PSC)
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what is the histologic buzz word in PSC
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onion skining fibrosis of the bile ducts
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Is PSC associated with increased risk for hepatocellular carcinoma
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YES
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what is the treatment for PSC and PBC
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liver transplant
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Of these 3 conditions: polycystic liver dz, congenital hepatic fibrosis, caroli dz
which has teh greater association with AD polycystic kidney dz |
polycystic liver dz
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Of these 3 conditions: polycystic liver dz, congenital hepatic fibrosis, caroli dz
which has the greatest association with AR polycystic kidney dz |
congenital hepatic fibrosis
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Of these 3 conditions: polycystic liver dz, congenital hepatic fibrosis, caroli dz
which is autosomal recessive |
congenital hepatic fibrosis, and caroli dz
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Of these 3 conditions: polycystic liver dz, congenital hepatic fibrosis, caroli dz
which has an increased risk of cholangiocarcinoma |
congenital hepatic fibrosis and caroli dz
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what are von meyenburg complexes
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clusters of dilated bile ducts in a fibrous hyalinized stroma (benign bile duct hamartoma)
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in what condition are bile ducts completely absent from an otherwise normal liver
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Alagille syndrome, (AD jagged1 gene mutations on ch20, a notch receptor ligand) also affects heart, skeleton, eye, and kidney as well as predisposes to hepatic carcinoma
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what is peliosis
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primary sinusoidal dilation, associated with oral contraceptives, danazol and anabolic steroids
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what causes Budd-Chiari Syndrome
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hepatic vein thrombosis (or obstruction of two ore more major hepatic veins)
associated iwth thrombogenic disorders,sometimes idiopathic, but endemic in Nepal (infectious association) |
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when is veno-occlusive disease seen
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weeks after a bone marrow transplant, but originally in Jamaican drinkers of bush tea (pyrrolizidine alkaloid)
subendothelial swelling and sloughing causes obstruction of sinusoidal blood flow and results in fibrosis and collagen deposition causing hepatic venule obliteration clinical diagnosis; hepatomegaly, ascites, weight gain, jaundice |
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What is HEELP syndrome
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Hemolysis
Elevated liver enzymes low platelets that may accompany preeclampsia (HTN, proteinuria, edema, +/- DIC) |
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Breifly contrast liver damage in graft versus host disease (GVHD) and rejection
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GVHD - following bone marrow transplant, donor lymphs attack hepatic epithelial cells, may also have endotheliitis
Rejection - following a liver transplant, host inflammatory cells attack portal tracts, and may alos have endotheliitis or obliterative arteritis giving ischemic liver parenchyma |
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Of these 3 conditions: focal nodular hyperplasia (FNH), nodular regenerative hyperplasia, hepatic adenoma
which occurs in women on oral contraceptives |
hepatic adenoma
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Of these 3 conditions: focal nodular hyperplasia (FNH), nodular regenerative hyperplasia, hepatic adenoma
which lacks portal tracts |
hepatic adenoma
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Of these 3 conditions: focal nodular hyperplasia (FNH), nodular regenerative hyperplasia, hepatic adenoma
which has a central stellate scar with large vessels and radiating fibrous septae containing bile ducts and lymphocytes |
FNH
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Of these 3 conditions: focal nodular hyperplasia (FNH), nodular regenerative hyperplasia, hepatic adenoma
which affects the entire liver |
nodular regen hyperplasia
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Of these 3 conditions: focal nodular hyperplasia (FNH), nodular regenerative hyperplasia, hepatic adenoma
which associated with the development of portal HTN |
nodular regen hyperplasia
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Of these 3 conditions: focal nodular hyperplasia (FNH), nodular regenerative hyperplasia, hepatic adenoma
which has a tendency to rupture (especially during prego with estrogen stim) |
hepatic adenoma
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what is the most common bening tumor of the liver
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hemangioma
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what mutation is seen in approximately 80% of hepatoblastomas
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activation of the Wnt/Beta- catenin signaling pathway (which stabilize beta-catenin mutations and cause carcinogenesis)
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primary liver angiosarcoma is associated is associated with what risk factors
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exposure to vinyl chloride, arsenic, and thorotrast (used in radiography of biliary tract)
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Vertical transmitted HBV increases the risk of hepatocellurlar (HCC) by how much
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200x risk of HCC by adulthood
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what carcinogen is found in moldy grains and peanuts
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dietary aflatoxins derived from the fungus aspergillus flavus
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What type of hepatocellular carcinoma occurs in young patients and has no association with HBV or cirrhosis
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firbrolamellar carcinoma- single, firm, large mass of well-differentiated hepatocytes seperated by dense collagen bands
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does it have better or worse prognosis than hepatocellular carcinoma
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better
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what lab value is elevated in 50-75% of patients with HCC
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alpha-fetoprotein
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what other conditions cause elevations of this marker
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yolk sac tumors, cirrhosis/hepatitis, massive liver necrosis, normal pregnancy, fetal distress, fetal neural tube defects
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what are risk factors for cholangiocarcinoma
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PSC, Caroli dz, choledochal cysts, congenital hepatic fibrosis, thorotrast exposure, liver fluke opisthorchis sinensis
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what are characteristic histologic features of cholangiocarcinoma
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well to moderately differentiated adenocarcinoma with dense collagenous stroma making the tumor firm and gritty
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does teh cholangiocarcinoma bile duct epithelium synthesize bile
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No. therefore the tumor is rarely bile stained
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what are the most common tumors that metastasize to the liver
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breast, colon, lung
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how much bile does the liver secrete each day
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up to 1 liter
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anatomically, how does the gallbladder differ from teh rest of the GI tract
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it lacks a muscularis mucosea and submucosa
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what is the most common anomaly of the gallbladder
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Phrygian cap- an inwardly folded fundus
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what % of gallstones are clinically silent
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>80%
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Are most gall stones radioopaque or radiolucent
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most are composed of cholesterol, which makes them radiolucent (opaque are calcium carbonate/black pigmented)
contrast this to renal stones (which ahve calcium) to make them radioopaque |
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what primary bacterial organism can cause an acalculus cholecystitis
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salmonella typhi and staphylococci
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what is a porcelain gallbladder and why is it significant
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it is extensive dystrophic calcification of the gallbladder wall that accompanies cancer
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what is choledocholithiasis
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stones with in the bile ducts or biliary tree (higher in Asia and usually pigmented stones d/t infections)
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what organisms cause ascending cholangitis
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gram negative aerobes: E. coli, Klebsiella, Clostridium, Bacteriodes, enterobacter, and group D streptococci
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what is the difference between Caroli Dz and choledochal cyst
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Caroli dz = cystic dilation of intrahepatic biliary tree
choledochal cyst = dilations of common bile duct |
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what are Klatskin tumors
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extrahepatic tumors arising in the common bile duct betweenthe cystic duct and the confluence of the left and right hepatic ducts at the liver hilus
notable for slow growing behavior, sclerosing characteristics and infrequent metastases |