Toxicology Exam 1 - Questions and Answers

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Toxicology Exam 1 - Questions and Answers The liver functions as the primary site of ___________________ for both physiological components and drugs. metabolism Damaging this function of the liver wi ... ll cause what? Metabolism Inability to metabolize/process waste products and eliminate drugs/toxins Damaging this function of the liver will cause what? Nutritional homeostasis Hyper or hypoglycemia, hypercholesterolemia Damaging this function of the liver will cause what? Filtration Endoxemia Damaging this function of the liver will cause what? Synthesis Clotting factor and vitamin D deficiencies Damaging this function of the liver will cause what? Bile acid synthesis/secretion Steatorrhea, jaundice, malnutrition Toxic damage to the liver usually presents either as... 1. Fatty liver (an accumulation of lipids that may or may not damage the liver functionally) 2. Necrosis (direct cellular death) 3. Altered blood flow 4. Alter/decrease bile acid secretion Necrosis usually occurs as a result of _____________________ or as a result of ____________________ to the hepatocyte. direct cellular injury; immune-mediated attack Perilobular (periportal, Zone 1) necrosis is often due to toxicants that... Present to the liver in their active form Zone 1 is typically more ______________________ than the other regions and is relatively rich in __________________. oxygenated; glutathione Cause a periportal specific necrosis due to high oxygen content which contributes to more reactive species and direct cellular damage Copper, iron, and other heavy metals Describe midzonal (zone 2) necrosis. May be the result of direct toxic action or may reflect the action of hepatotoxic metabolites Describe centrilobular (zone 3) necrosis. Often due to hepatotoxic metabolites that are formed within the lobule itself The centrilobular region is the most poorly ___________________ region of the lobule and is relatively rich in ____________________________. oxygenated; cytochrome P450 pathways Centrilobular specific poisons include... Carbon tetrachloride (or any halogenated hydrocarbon) APAP Describe carbon tetrachloride toxicity. Metabolized by the cytochrome P450 2E1 pathway to a reactive metabolite, causing lipid peroxidation centrilobularly Carbon tetrachloride toxicity is greater with... Induction of the cytochrome system (e.g. ethanol) In states of hypoxia In states of free radical scavenger (e.g. GSH) deficiency Describe APAP toxicity. Metabolized by the 2E1 pathway to N-acetylbenzoquinoneimine, a highly reactive, free-radical type intermediary (metabolite), causing centrilobular necrosis Necrosis may exhibit a ____________________ relationship. dose:response Carbon tetrachloride is a classic hepatotoxic agent that produces necrosis by __________________________ and through _______________________. direct tissue damage; biochemical lesions Other agents that may cause biochemical lesions include... Dimethylnitrosamine Galactosamine Fatty liver may occur by either increased ______________________ and/or decreased _____________________. TG synthesis; TG secretion Classic example of a hepatotoxin that produces fatty liver by interfering with VLDL production and inhibiting fatty secretions Carbon tetrachloride Other hepatotoxins that produce fatty liver include... Puromycin Tetracycline Ethanol Some evidence suggests that fatty liver, per se, is not directly __________________. However, increased TG within the cell does increase the risk of lipid ___________________ which does damage the cellular and organelle membranes leading to _________________. hepatotoxic; peroxidation; necrosis Agents that increase hepatotoxicity risk by causing lipid peroxidation include (again)... Carbon tetrachloride Chloroform Decreases in the bile flow will result in... Hyperbilirubinemia (jaundice) Commonly block transport of bile, resulting in cholestatic injury Manganese Anabolic steroids Other agents that cause cholestatic or biliary based hepatotoxicity include... Diclofenac Chlorpromazine Ethanol Manganese How do estrogens, androgens, and cyclosporin cause cholestatic or biliary based hepatotoxicity? Inhibit ATP-dependent bile acid transport How does colchicine cause cholestatic or biliary based hepatotoxicity? Inhibits tubulin-dependent bile acid secretion How does phalloidin cause cholestatic or biliary based hepatotoxicity? Inhibits actin-mediated contraction of biliary canaliculi sphincter This chronic hepatic condition results from deficiencies in the repair mechanisms of the liver and local hypoxia Cirrhosis Classic compounds that can cause hepatic cirrhosis include... Carbon tetrachloride Aflatoxins Ethanol Other agents that cause hepatic cirrhosis include... Arsenic Ethanol Pyrrolizidine alkaloids Vitamin A derivatives (isotretinoin and hypervitaminosis A) Retinoids are deposited into the _____________ of the liver, which are responsible for maintaining hepatocyte health, causing progressive fibrosis. Ito cells Hemorrhagic necrosis such as caused by _______________ and ________________________, will cause reduced blood flow to distal areas of the liver, thus causing ischemia and ultimate necrosis. beryllium; dimethylnitrosamine Other agents that alter hepatic blood flow include... Arsenic Dacarbizine Pyrrolizidine alkaloids Toxins that specifically cause liver-based cancers Aflatoxin Andro [Show More]

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