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Liver III
Liver III pathology-Bernardino
| Question | Answer |
|---|---|
| a distinct group of liver disease attributable to disorders of metabolism, can be either acquired or inherited | Metabolic Liver Disease |
| this type of metabolic liver disease is non-alcoholic fatty liver disease | acquired |
| examples of this type of metabolic liver disease include: hemochromatosis, wilsons disease, and alpha 1 antitrypsin disease | inherited metabolic liver disease |
| a group of conditions that have in common the presence of hepatic steatosis (fatty liver). affected individuals do not consume alcohol or do so less than 20g Etoh/week. | non-alcoholic fatty liver disease |
| what is the pathogenesis of non-alcoholic fatty liver disease? | hepatic fat accumulation, hepatic oxidative stress. you have increased fat due to non-esterified fatty acids due to non-oxidized fatty acids. |
| what are the clinical features of nonalcoholic fatty liver disease | generally asymptomatic with simple steatosis |
| what other metabolic derangements are related to non-alcoholic fatty liver disease? | obesity, insulin resistance, diabetes |
| what is the frequent cause of death in non-alcoholic fatty liver disease? | cerebrovascular disease |
| are the serum transaminase levels in NAFLD elevated or depressed? | elevated |
| describe the AST/ALT ratio in NASH and Acohoic steatohepatitis | <1 in NASH >2 in alcoholic steatohepatitis |
| what is the treatment goal in NAFLD? | reverse steatosis and prevent cirrhosis. |
| what is the pattern of liver injury in NAFLD? | steatosis accompanied by minor, non-specific inflammation. It is generally a stable condition without significant clinical problems. |
| what is the rate of hepatocyte injury in non-alcoholic steatohepatitis? | hepatocyte injury may progress to cirrhosis in 10-20 percent of cases. |
| this is a morphology of NAFLD where on a histological specimen you see droplets of fat, predominantly triglycerides, accumulate within the hepatocytes | steatosis |
| this morphology, along with cirrhosis, in NAFLD is described as steatosis with multifocal parenchymal inflammation, mallory bodies, hepatocyte death, and perivenular fibrosis, | steatohepatitis |
| this disesae is described as excessive iron accumulation of the body iron | iron overload |
| what are the two classes of iron overload? | hemochromatosis, hemosiderosis |
| this is a hereditary disease of iron overload and is autosomal recessive | hemochromatosis |
| this is a disease of iron overload where there is acquired deposition of iron deposition, usually due to a secondary cause (ex: iron overload) | hemosiderosis |
| hereditary hemochromatosis results from mutation in this gene | gene encoding HFE, transferrin receptor 2 or hepcidin |
| in a normal individual during iron metabolism, transferrin levels are saturated only by how much? | fifty percent |
| in hemochromatosis, is transferrin highly saturated? | yes |
| what is the underlying mechanism of hemochromatosis? | absorption of iron is increased, and you have no physiologic mechanism to get rid of the extra iron so it accumualtes, and transferrin saturation levels are increased. serum ferritin is increased as well. |
| describe the physiology of iron metabolism in the interocyte | iron goes to the SI, is reduced, enters enterocyte cells, gets re-oxidized by ferroprotein (which is bound to Hephaestin) on the BL side, and attaches to transferrin. |
| high transferrin saturation is sensed by what protein? what happens then? | HFE protein on the hepatocytes. the HFE protein stimulates the liver cells to produce Hepcidin, which binds to ferroprotein, internalizes and degrades it. |
| hepcidin, by binding to ferrorprotein, regulates iron metabolism by (increasing/decreasing) abnsorption | decreasing |
| increased activity of iron transport is indicated by what? | high transferrin saturation |
| this gene, which is involved in iron metabbolism is on the short arm of chormosome six, and shares sequence homology with MHC class I molecules. it regulates intestinal absorption o fdietary iron. | the HFE gene. |
| describe the morphology of hemochromatosis | depositoin of hemosiderin in liver, get golden yellow hemosiderin granules in cyoplasm of hepatocytes, which stain blue with prussian blue stain. other organs affected: pancreas, pituitary, heart, adrenal gland..etc. get cirrhosis, pancreatic fibrosis |
| list some complicaitons of hemochromatosis | hypopituitarism, skin pigmentation, cardiac failure, hepatocellular carcinoma, cirrhosis, diabetes, arthropathy, testicular atrophy |
| this is an AR disorder with a wide range of age of onset presentation, marked by accumulation of toxic levels of copper in organs, mostly liver, brain, and eye | wilsons disease |
| what is the most common presentation of copper accumulation in the liver as seen in wilsons disease? | acute or chronic liver disease |
| what is the most common presentation of copper accumulation in the brain, as seen in wilsons disease? | neuropsychiatric disturbance (mild behavioral change, frank psychosis or a parkinson disease like syndrome such as tremor). |
| describe normal copper metabolism. | Cu is absorbed in the small intestine, gets to the liver via portal vein, then is transported across bile canalicular membnrane via ATP7B gene, and forms ceruloplasmin-Cu complex. most of Cu in circulation is bound to this, the rest is bound to albumin. |
| copper is transferred to the whole body when it is complexed with what protein? | albumin |
| what is the pathogenesis of wilson's disease? | copper causes toxic liver injury, through the production of radical oxygen species |
| what is the mechanism/pathogenesis of copper accumulation in the liver? | there is a mutation in the ATP7B gene on chr. 13, so you cannot transport copper across the bile canalicular membrane. gene encodes a transmembr Cu transporting ATPase expressed on hepatocyte analicular membrane |
| a deficiency in the ATP7B protein causes what? | decrease in copper transport into the bile, impairs the incorporation of copper into ceruloplasmin, and decreased ceruloplasmin levels that may be secreted into blood. |
| in wilsons disease, what are the hepatic changes you see? | steatosis, acute hepatitis, chronic cirrhosis |
| in wilsons disease, what are changes you see to the brain? | toxic injury, which primarily affects the basal ganglia, particularly the putamen, which shows atrophy andcavitations. |
| in wilsons disease, what changes do you see to the eye? | kayser-Fleischer ring, which is a green to brown deposit of copper in descemet's membrane in the lumbus of the cornea. |
| how do you diagnose wilsons disease? | decrease in serum ceruloplasmin, increased hepatic copper content (>250 micrograms/dry weight), incrased urinary copper excretion. |
| what is the most sensitive and accurate diagnostic test for wilsons disease? | increased hepatic copper content |
| what is the most specific screening test for wilsons disease? | increased urinary excretion of copper |
| this is an amino acid glycoprotein syntehsized mainly by hepatocytes, and is a member of the serine protease inhibitor (serpin) family. the gene is on ch. 14, and has 75 different forms | alpha 1 antitrypsin |
| Pi_ denotes what in allelic variants of alpha 1 antitrypsin? | Pi is protease inhibitor and the blank is for the alphabetic letter denoting the position on the gel. |
| this is the wild allelic variant of alpha 1 antitrypsin. it produces normal levels of functional alpha 1 antitrypsin | PiM |
| the wild type genotype of alpha 1 antitrypsin would be... | PiMM |
| this is an autosomal recessive diorder marked by very low levels of alpha 1 antitrypsin | alpha 1 antitrypsin deficiency |
| in this allelic variation, you have moderate reduction in serum concentratoins of alpha 1 antitrypsin, without clinical manifestations | PiS |
| homozygotes of this allele for alpha 1 antitrypsin only have 10% of the normal circulating alpha 1 antitrypsin levels | PiZ |
| homozygotes for this allele of alpha 1 antitrypsin are rare varients with undetectable levels. | Pi null |
| list some consequences of alpha 1 antitrypsin deficiency | pulmonary emphysema due to destructive proteases that are normally inhibited by alpha 1 antitrypsin, cutaneous penniculitis, arterial aneurysm, bronchiectasis, wegeners granulomatosis |
| what is the pathogenesis of liver disease in alpha 1 antitrypsin deficient variants? | deficiency variants cause accumulation of alpha 1 antitrypsin in the hepatocytes. there is a selective defect migration of this secretory protein from ER to golgi apparatus. in PiZ, abonormally folded protein polymerizes, creating ER stress.to apoptosis. |
| once the alpha 1 antitrypsin protein accumulates in the ER, what happens? | it triggers a series of events, including autophagic response, mitochondrial dysfunction and possible activation of pro-inflammatory NfKb causing hepatocyte damage. only 10-15% of PiZZ individuals develop overt clinical disease. |
| what is the morphology of alpha 1 antitrypsin deficiency? | presence of alpha 1 antitrypsin globules in hepatocytes, fatty change, mallory bodies, severe cholestasis in infants with neonatal hepatitis caused by alpha 1 antitrypsin. |
| what are some diseases where you see mallory bodies | alcoholic liver disease, non-alcoholic steatohepatitis, wilsons disease, alpha 1 antitrypsin deficiency |
| in this diseaes, there are spherical nodules iwthout fibrosis, and can lead to portal hypertension. it occurs in association with conditions affecting intrahepatic blood flow, and also occurs in HIV patients. | nodular regenerative hyperplasia |
| in this disease, there is well-demarcated, poorly encapsulated central gray-white depressed stellate scar. fibrous septa radiate to the periphery, and the scar has large vessels with fibromuscular hyperplasia. long term use of anabolic hormones and contra | focal nodular hyperplasia |
| list the benign neoplasms of the liver | cavernous hemangioma, hepatic adenoma |
| this is the most common benign tumor of the liver of the blood vessels, and should not be mistaken for a metastatic tumor, and a blinded percutaneous biopsy should not be done because it can lead to XS bleeding | cavernous hemangioma |
| this is a benign mass of hepatocytes, and more frequent in women who use OCP, and regresses if OCP use is stopped. adenomatosis occurs in MODY, with HNF1 mutation. | hepatic adenoma |
| what is the significance of a hepatic adenoma? | it can be mistaken as a carcinoma, has a tendency to rupture, and can cause intraperitoneal hemorrhage. rarely, it may transform into a carcinoma (beta catenin gene mutation) |
| list the malignant tumors of the liver | hepatoblastoma, angiosarcoma, hepatocellular carcinoma, cholangiocarcinoma. |
| this is the most common liver of childhood, and can be fatal if not treated. associated with syndromes of FAP, Beckwith Wiedeman syndrome. It is activated with WNT/B-catenin signaling pathwya | Hepatoblastoma |
| this malignancy of the liver is associated with exposure to vinyl chloride, arsenic and thorotrast. the latency period after exposure (can develop decades later) can be several decades, and it is a highly aggressive neoplasm (death within one year) | angiosarcoma of liver |
| in this malignancy of liver, the pathogenesis is repeated cycles of cell death and regeneration. Get accumulation of mutations during continuous cycles of cell division and may damage DNA repair mechanisms and eventually transform hepatocytes. | hepatocellular carcinoma. |
| what are the four main etiologic factors of hepatocellular carcinoma? | chronic viral infection (HBV, HCV), chronic alcoholism, non-alcoholic steatohepatitis, food contaminants, particularly aflatoxxin. |
| describe the gross morphology of hepatocellular carcinoma | pale center with surrounding liver, solitary large mass, multifocal with varying sizes or diffusely infiltrative. strong propensity for invasion of vascular structures. |
| describe the histology of hepatocellular carcinoma | well to moderately differentiated and are recognizable as hepatocytes in origin, poorly differentiated tumors, take on pleiomorphic appearance with anaplastic giant cells, can be small or resemble a spindle cell carcinoma. |
| this occurs in 5% of HCC patients, occurs in young adults, (20-40 years of age), occurrence rate is equal in males and females, and has an unknown etiology. there is no underlying chronic liver disease, and prognosis is good. | fibrolamellar variant of HCC |
| this is a malignancy of the biliary tree, arising from bile ducts within and outside the liver. it is the second most common malignant hepatic tumor after HCC. | cholangiocarcinoma |
| what are some risk factors for cholangiocarcinoma | primary sclerosing cholangitis, congenital fibropolycystic disease of biliary tree, HCV infection, previous exposure to thorotrast |
| what is the pathogenesis of cholangiocarcinoma | signaling pathways involving apoptotic pathways. MCL-1, an anti-apoptotic protein is activated or enhanced through overexpression of IL6. P53 expression is decreased thereby cells escape death. signaling pathways involving cellular regulation. |
| what are some congenital fibropolycystic diseases of the biliary tree that present as risk factors for cholangiocarcinoma? | choledocal cysts, caroli disease |
| this is a congenital dilation of the CBD, nonspecific symptoms of jaundice and abdominal pain before age 10. 20& present in adulthood. may be segmental or cylindrical dilation of CBD. predisposes you to stone formation, stenosis, and stricture | choledocal cysts |
| in this disease, there are larger ducts of the intrahepatic biliary tree and they are segmentally dilatd and may contain insipissated bile | carolid disease |
| what are two classificaitons of cholangiocarcinoma? | intrahepatic, extrahepatic |
| in this classification of cholangiocarcinoma, it occurs within the liver and mixed variants an occur. there are separate tumor masses of HCC and CCCA within the same liver . | intrahepatic |
| in this classification of CCA, lesions occur outside the liver, they are mostly adenocarcinomas which may or may not secrete mucin, uncommonly have squamous features, and there are abundant fibrous stroma. it occurs within the biliary tree | extrahepatic |
| describe the hoistology of CCA | neoplastic glandlar and tubular structures lined by cuboidal to low columnar cells. dense colagenous stroma separating the glandular elements. |
| this classification of CCA is not detected until late in the course, there is obstruciton of bile flow and symptomatic liver mass. | intrahepatic CCA |
| in this classification of CCA, there is hilar and distal tumors present with symptoms of biliary obstruciton, cholangitis, and right upper quadrant pain | extrahepatic CCA |
| what is the prognosis of CCA? | there is only a two year survival rate in 15%. six months is the median time for diagnosis to death even after surgery |
| these diseases are more common than primary hepatic neoplasia. they commonly originate from colon, breast, lung, and pancreas. typically liver metastasis are multifocal. if oslitary, may be resected surgically. there can be massive involvement of liver | metastatic tumors. |
| which are more common, metastatic liver tumors or primary liver tumors? | metastatic liver tumors |
Created by:
aferdo01
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