Term
| What is the inheritance pattern of Wilson's disease? |
|
Definition
|
|
Term
|
Definition
| acts as a pro-oxidant and promotes the generation of free radicals |
|
|
Term
| Wilson's disease is termed _____ degeneration. |
|
Definition
|
|
Term
| At what age does Wilson's disease manifest? |
|
Definition
|
|
Term
| What are the hepatic manifestations of Wilson's disease? |
|
Definition
| chronic hepatitis, cirrhosis, massive necrosis, fulminant failure |
|
|
Term
| What are the neurologic manifestations of Wilson's disease? |
|
Definition
| injury of basal ganglia, incoordination, dystonia, psychiatric disorders |
|
|
Term
| What are the hematologic manifestations of Wilson's disease? |
|
Definition
|
|
Term
| What are the opthalmologic manifestations of Wilson's? |
|
Definition
| kayser-fleischer rings (corneal limbus) |
|
|
Term
| How do hepatocytes help control copper levels? |
|
Definition
| transported into the trans-golgi network where it is incorporated into apo-ceruloplasmin to form ceruloplasmin which is secreted into circulation (90-95% of plasma copper). Transported into bile canaliculi to be excreted |
|
|
Term
| What gene encodes for the copper-transporting ATPase? |
|
Definition
|
|
Term
| Does a defect int he ATP7B gene interfere with secretion into plasma copper or excretion into bile? |
|
Definition
|
|
Term
| How do you diagnose Wilson's disease? |
|
Definition
| low serum ceruloplasmin, high non-ceruloplasmin serum copper, high urinary copper, high hepatic copper, opthalmologic evaluation, measurement of copper concentration in liver biopsies |
|
|
Term
| What is the most accurate test for Wilson's disease? |
|
Definition
| measurement of copper concentration in liver biopsies |
|
|
Term
| Can you diagnose Wilson's disease by genetic testing? |
|
Definition
| yes the ATP7B gene (but i'ts impractical because there are more than 300 mutations) |
|
|
Term
| What's the inheritance pattern of alpha1antitrypsin deficiency? |
|
Definition
|
|
Term
| What does alpha1antitrypsin do? |
|
Definition
| protease inhibitor (Pi), inhibits neutrophil elastase and other proteases |
|
|
Term
| There are at least ____ allelic variants of alpha 1 antitrypsin deficiency. |
|
Definition
|
|
Term
| Describe the homozygotic and heterozygotic states of alpha-1-antitrypsin deficiency. |
|
Definition
PiZZ (homozygotes)= 10% of normal levels
PiMz (hetero)= intermediate levels
PiMM= normal genotype |
|
|
Term
| How does the genetically mutated version of alpha1antitrypsin cause alpha1antitrypsin defieciency? |
|
Definition
| single aa substitution causes protein to be abnormally folded and therefore cannnot move from ER to the Golgi apparatus. Accumulates in teh ER which may induce autophagocytosis resulting in hepatocellular destruction |
|
|
Term
| How do you stain for alpha1antitrypsin deficiency? |
|
Definition
| mutated alpha 1 antitrypsin appear as PAS-positive cytoplasmic globes |
|
|
Term
| How do you diagnose alpha-1 antitrypsin deficiency? |
|
Definition
| liver biopsy, serum protein electrophoresis (decreased alpha-1-antitrypsin band) |
|
|
Term
| What are the manifestations of alpha1antitrypsin deficiency? |
|
Definition
liver: neonatal hepatitis (10-20%), chronic hepatitis, cirrhosis, hepatocellular carcinoma
lung:emphysema |
|
|
Term
| What percent of patients with alpha-1-antitrypsin deficiency develop hepatocellular carcinoma? |
|
Definition
|
|
Term
| How is iron lost by the body? |
|
Definition
| epithelial desquamation, minor hemorrhages, menstruation |
|
|
Term
| How is iron transported in the blood? |
|
Definition
|
|
Term
|
Definition
readily available in circulation: ferritin
poorly available in macrophages and tissues: hemosiderin |
|
|
Term
|
Definition
| excessive accumulation of iron (hemosiderin) |
|
|
Term
| What do you call the disease state (multi-systemic cellular injury, fibrosis, dysfunction) caused by excessive accumulation of iron? |
|
Definition
|
|
Term
| What are secondary or acquired causes of hemochromatosis? |
|
Definition
| ineffective erythropoeis (most common: ex's are thalassemia, sideroblastic anemia, pyruvate kinase deficiency, myelodysplastic syndromes), parental administration (transfusions), increased oral intake (bantu siderosis) |
|
|
Term
| What is the inheritance pattern of hereditary hemochromatosis? |
|
Definition
|
|
Term
| Which mutations on what gene cause hereditary hemochromatosis? |
|
Definition
| HFE gene with C28Y, H63D mutations account for more than 90% of HH cases |
|
|
Term
| What race/ethnicity commonly has hereditary hemochromatosis? How common is it? |
|
Definition
| whites (northern european); homozygotes=1/200; heterozygotes=1/8 |
|
|
Term
| What gender is hereditary hemochromatosis more common in? |
|
Definition
| men 5:1. Occurs earlier in men (40s) than in women (50s) |
|
|
Term
| What is the classic triad of hereditary hemochromatosis? |
|
Definition
| cirrhosis, DM (pancreatic fibrosis, atrophy), and bronze skin pigmentation |
|
|
Term
| What are other manifestations of hereditary hemochromatosis? |
|
Definition
| joint pain (pseudogout), cardiomyopathy, arrythmia, heart failure, thyroid and adrenal insufficiency, hypogonadism, impotence, ammenorrea, early menopause |
|
|
Term
| What is the most common presenting complaint for patients with hereditary hemochromatosis? |
|
Definition
|
|
Term
| What stain can you use on liver specimens to look for hemochromatosis? |
|
Definition
|
|
Term
| How do you diagnose hemochromatosis? |
|
Definition
| increased transferrin saturation, elevated serum iron and ferritin, increased iron concentration in liver, genetic analysis (HFE gene) |
|
|
Term
| How do you treat hemochromatosis? |
|
Definition
| early phlebotomy, normal life expectancy |
|
|
Term
| Hemochromatosis increases your risk of hepatocellular carcinoma by... |
|
Definition
|
|
Term
| Whta is primary biliary cirrhosis? |
|
Definition
| autoimmune disease with antimitochondrial antibodies (in more than 90%) that cause destruction of bile ducts, chronic hepatitis, and biliary cirrhosis |
|
|
Term
| What is the typical patient with primary biliary cirrhosis? |
|
Definition
| female predominance >6:1; peak incidence is 40-50 years. Association with other autoimmune disorders |
|
|
Term
| What types of symptoms are associated with primary biliary cirrhosis? |
|
Definition
| those associated with cholestasis and portal hypertension |
|
|
Term
| What pattern of cirrhotic lobules is characteristic of primary biliary cirrosis on histological slide? |
|
Definition
|
|
Term
| What are common causes of secondary biliary cirrhosis in adults? |
|
Definition
| choledocholithiasis, malignant neoplasms (head of the pancreas, biliary tree), biliary strictures from surgical procedures |
|
|
Term
| What are the causes of secondary biliary cirrhosis in children? |
|
Definition
| biliary atresia, choledochal cysts, cystic fibrosis (mucovisidosis) |
|
|
Term
| What is primary sclerosing cholangitis? |
|
Definition
| segmental fibrosis and obliteration of intrahepatic and extrahepatic bile ducts |
|
|
Term
| What types of patients get primary sclerosing cholangitis? |
|
Definition
| males predominate 2:1; 3rd thru 5th decades of life; 70% of patients have ulcerative colitis (toxins released by inflamed gut may cause injury to the biliary tree) |
|
|
Term
| What are possible sequalae and outcomes of primary sclerosing cholangitis? |
|
Definition
| increased risk for cholangiocarcinoma. Progression to cirrhosis and liver failure is slow but inexorable |
|
|
Term
| What are congenital bile duct microharmartomas called? |
|
Definition
| von Meyenburg's complexes |
|
|
Term
| Polycycstic liver disease is associated with what other disease? |
|
Definition
| Autosomal dominant polycystic kidney disease |
|
|
Term
| What type of liver pathology is associated with autosomal recessive polycystic (kidney) disease? |
|
Definition
| congenital hepatic fibrosis with broad fibrous septa |
|
|
Term
| What is Caroli's disease? |
|
Definition
| larger intrahepatic bile ducts have segmental cystic dilatation while maintaining thier communication with the biliary tree (filled with inspissated bile, inflamed). Pure form is rare and si commonly associated with congenital hepatic fibrosis. Also related to choledocal cysts. |
|
|
Term
| Nutmeg liver is due to _____ _______. |
|
Definition
|
|
Term
| Caroli's disease is frequently complicated with... |
|
Definition
| cholangitis, intrahepatic lithiasis, and abscesses |
|
|
Term
| T/F Caroli's disease increases your risk of cholangiocarcinoma. |
|
Definition
|
|
Term
| What is congenital hepatic fibrosis? |
|
Definition
| asaoc with AR PKD. Liver is divided by broad fibrous septa. Abnormally-shaped bile ducts found within the septa that communicate with the biliary tree |
|
|
Term
| What is polycystic liver disease? |
|
Definition
| associated with AD PKD. Multiple cysts (few to hundreds) that do not communicate with the biliary tre (contain serous fluid and are not inflammed) |
|
|
Term
| Another name for the underlying pathology of nutmeg liver is... |
|
Definition
|
|
Term
| Wht is the effect of right sided heart failure on the liver? |
|
Definition
| congestion with centrilobular passive congestion |
|
|
Term
| What is the effect of left sided heart failure on the liver? |
|
Definition
| shock, centrilobular hypoxia and necrosis |
|
|
Term
| What does a right/left heart failure combo do to the liver? |
|
Definition
| centrilobular hemorrhagic necrosis |
|
|
Term
|
Definition
| cnetrilobular congestion with or without necrosis and hemorrhage that confers to the liver a variegated mottled appearance on gross examination referred to as the nutmeg liver |
|
|
Term
| What is cardiac sclerosis? |
|
Definition
| fibrous repair following centrilobular necrosis resulting in a pattern of centrilobular fibrosis |
|
|
Term
| T/F Liver infarcts are rare. |
|
Definition
|
|
Term
| What percent of blood comes from where to the liver? |
|
Definition
30-40% from hepatic artery
60-70% from portal vein |
|
|
Term
| T/F Interruption of the main hepatic artery can be tolerated. |
|
Definition
| true, except int he transplanted liver |
|
|
Term
| What is an infarct of Zahn? |
|
Definition
| thrombosis of a portal vein radicle that results in ischemia, dilatation and congestion of sinusoids and attenuation (flattening) of the surrounding hepatocytes. no necrosis (pseudoinfarct) |
|
|
Term
| A grossly visible, sharply demarcated area of congestion in the liver is characteristic for... |
|
Definition
|
|
Term
| What are the prehepatic causes of portal hypertension? |
|
Definition
| portal vein obstruction like pylephlebitis |
|
|
Term
| What are the intrahepatic causes of portal HTN? |
|
Definition
| cirrhosis (most common), nodular regenerative disease, veno-occlusive disease |
|
|
Term
| What are the posthepatic causes of portal HTN? |
|
Definition
| right sided heart failure, hepatic veins thrombosis (budd chiari) |
|
|
Term
| What are the manifestations of portosystemic shunts? |
|
Definition
| umbilical vein-caput medusae; coronary veins-esophageal varices; splenic vein-splenomegaly; inferior mesenteric veins-hemorroids; ascites |
|
|
Term
| What is Budd-Chiari syndrome? |
|
Definition
| thrombosis of 2 or more major hepatic veins, massive enlargement of the liver, severe portal hypertension, severe ascites |
|
|
Term
| What causes Budd-chiari syndrome? |
|
Definition
| hypercoagulable states (pregnancy, oral contraceptives, postoperative, postpartum states, deficiencies in antithrombin III, protein S or C, polycythemia vera, sickle cell disease), idiopathic |
|
|
Term
| What do you see histologically with Budd-Chiari syndrome? |
|
Definition
| centrizonal congestion/necrosis |
|
|
Term
| What is venoocclusive disease? |
|
Definition
| terminal venules obliteration, toxic damage to the sinusoidal endothelial cells, desquamation of endothelial cells that embolize into the terminal hepatic venules, extravasation of RBCs, subendothelial swelling, marked centrizonal congestion, necrosis and fibrosis |
|
|
Term
| What is the etiology of veno-occlusive disease? |
|
Definition
acute: after bone marrow transplantation
chronic: Jamaican bush tea (pyrrolizidine alkaloids found in many plants) |
|
|
Term
| What are the histological findings of veno-occlusive disease? |
|
Definition
| centrizonal congesiton/necrosis |
|
|
Term
| What are the symptoms/signs of preeclampsia/eclampsia? |
|
Definition
| HTN, proteinuria, edema, coagulation d/os, seizures. Leads to periportal fibrin deposits and periportal coagulative necrosis. Also parenchymal hemorrhage and infarcts and subcapsular hematoma, catastrophic rupture |
|
|
Term
| What is the acute fatty liver of pregnancy? |
|
Definition
| microvesicular steatosis that occurs in the third trimester due to fetal defect in oxidation of long-chain fatty acids that accumulate and cause liver toxicity in a susceptible mother. Lead to acute liver failure |
|
|
Term
| What percent of women with acute fatty liver of pregnancy have coexistent preeclampsia |
|
Definition
|
|
Term
| What is the intrahepatic cholestasis of pregnancy? |
|
Definition
| estrogen inhibits bile secretion in predisposed individuals in the third trimester leading to conjugated hyperbilirubinemia <5mg/dl and pruritis and jaundice. Resolves rapidly after delivery but increases your incidence of fetal distress, stillbirths, and prematurity |
|
|
Term
| Histologically the intrahepatic cholestasis of pregnancy looks like... |
|
Definition
|
|
Term
| What does focal nodular hyperplasia look like grossly? |
|
Definition
| hyperplastic nodule with central stellate scar |
|
|
Term
| What causes focal nodular hyperplasia? |
|
Definition
| hyperplastic response to localized increased blood flow (vascular malformations) that is more common in females and has questionable association with oral contraceptives |
|
|
Term
| What does nodular regenerative hyperplasia look like grossly/histologically? |
|
Definition
| regenerative nodules with the abscence of fibrosis. W/ reticulin stain you can see nodules surrounded by rims of compressed cords |
|
|
Term
| T/F Nodular regenerative hyperplasia affects the entire liver. |
|
Definition
|
|
Term
| What causes nodular regenerative hyperplasia? |
|
Definition
| congenital or acquired conditions that alter hepatic blood flow as well as antineoplastic drugs |
|
|
Term
| What is the clinical sequalae of nodular regenerative hyperplasia? |
|
Definition
|
|
Term
| What is the most common benign neoplasm of the liver? |
|
Definition
|
|
Term
| What is the appearance of cavernous hemangiomas? |
|
Definition
| red-blue soft nodules usually less than 2 cm and often directly beneath the capsule |
|
|
Term
| Cavernous hemangiomas are often mistaken for _____. |
|
Definition
|
|
Term
| What lesions of the liver can cause profuse bleeding upon biopsy? |
|
Definition
|
|
Term
| Describe hepatic adenoma's gross appearance. |
|
Definition
| well demarkated and often subcapsular |
|
|
Term
| What patient population/risk factors are there for hepatic adenoma? |
|
Definition
| more common in young women, related to the use of oral contraceptives and anabolic steroids and may regress on discontinuance |
|
|
Term
| Hepatic adenoma is often mistaken for... |
|
Definition
|
|
Term
| What are the dangerous sequalae associated with hepatic adenoma? |
|
Definition
| can rupture causing hemoperitoneum; rarely undergo malignant transformation |
|
|
Term
| What patient population is hepatoblastoma found in? |
|
Definition
|
|
Term
| What are the cells of a hepatoblastoma like? |
|
Definition
| immature hepatocytes; some have mesenchymal elements (cartilage, osteoid, striated muscle) |
|
|
Term
| What's the only way to cure a hepatoblastoma? |
|
Definition
|
|
Term
| Angiosarcoma can be caused by exposure to... |
|
Definition
| poly-vinyl chloride (PVC), arsenic, and thorotrast |
|
|
Term
| How long is the latency period for angiosarcoma? |
|
Definition
| several decades, but after that it is highly aggressive and metastasizes widely |
|
|
Term
| What are the major types of primary liver carcinomas? |
|
Definition
| hepatocellular carcinoma (hepatoma) and cholangiocarcinoma |
|
|
Term
| Is hepatocellular carcinoma common in the US? |
|
Definition
| No. But can be upt to 20-40% of cancers in HBV endemic regions |
|
|
Term
| 85% of patients with hepatocellular carcinoma also have... |
|
Definition
|
|
Term
| At what age does hepatocellular carcinoma usually occur? |
|
Definition
|
|
Term
| T/F Hepatocellular carcinoma usually has a fairly good prognosis. |
|
Definition
|
|
Term
| What are the risk factors for hepatocellular carcinoma? |
|
Definition
| cirrhosis, HBV, HCV, EtOH, NASH, primary hemochromatosis, hereditary tyrosinemia, aflatoxins |
|
|
Term
|
Definition
| produced by food spoilage molds (aspergilus flavus) and activated in hepatocytes. Is a risk factor for hepatocellular carcinoma |
|
|
Term
| What serum protein is elevated in hepatocellular carcinoma? |
|
Definition
| alpha fetoprotein (60-75%) |
|
|
Term
| Hepatocellular carcinoma often occurs when there is a history of ____ and ____. |
|
Definition
| cirrhosis and chronic hepatitis |
|
|
Term
| Which liver cancer has a strong propensity for vascular invasion? |
|
Definition
|
|
Term
| What is the typical patient with fibrolamellar carcinoma? |
|
Definition
| young adult (20-40 yoa); equal male/female incidence. No association with underlying liver disease |
|
|
Term
| T/F Fibrolamellar carcinoma has a fairly good prognosis. |
|
Definition
| true: 76% are alive at 5 years |
|
|
Term
| T/F Fibrolamellar carcinoma causes a rise in serum alpha fetoprotein. |
|
Definition
| false! that is the case in hepatocellular carcionma tho |
|
|
Term
| What are the histological characteristics of fibrolamellar carcinoma? |
|
Definition
| fibrous bands, tumoral cells with abundant eosinophilic cytoplasm |
|
|
Term
| What do cholangiocarcinomas resemble? |
|
Definition
| adenocarcinomas arising in other organs |
|
|
Term
| What is the characteristic feature of cholangiocarcinomas? |
|
Definition
|
|
Term
| T/F Cholangiocarcinomas are associated with cirrhosis. |
|
Definition
|
|
Term
| T/F The prognosis of cholangiocarcinomas is fairly good. |
|
Definition
| false, most are usually detected late and cause death within 6 months |
|
|
Term
| What are the risk factors for cholangiocarcinoma? |
|
Definition
| primary sclerosing cholangitis, congenital hepatic fibrosis, caroli disease, choledochal cysts, liver flukes, thorotrast, and HCV |
|
|
Term
| Which are the most common cancers that metastsize to the liver? |
|
Definition
| breast, lung, colon, pancreas, |
|
|
Term
| What are the gross features of metastasis to the liver? |
|
Definition
| multiple implants that look like cannon balls with central necrosis, striking hepatomegaly, nodularity palpable on the free edge |
|
|
Term
| T/F Extensive metastasis to the liver may be clinically silent. |
|
Definition
|
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