Term
| What are the 3 ways of looking at liver structure? |
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Definition
| lobule, portal lobule, and acinus |
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Term
| Describe the classic lobule model of the liver. |
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Definition
| the classic model is the lobule - has the central vein in the middle |
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Term
| What is the portal lobule model? |
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Definition
| encompasses 3 lobules - has the portal canal at the center and 3 central veins as the points (makes a triangle) |
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Term
| Describe the liver acinus. |
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Definition
| encompasses 2 lobules - the distributing blood vessels are in the middle (the equator), and the central veins are the poles |
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Term
| Describes the 3 zones in the liver acinus model. |
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Definition
| 1 - the middle zone - closest to the outside edge of the lobule * 3 - closest to the central vein * 2 - in the middle of 1 and 3 |
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Term
| Functionally, what is the best model for liver? |
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Definition
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Term
| Which zone is most affected by xenobiotics? (i.e. most likely to be damaged) |
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Definition
| zone 3 - it gets less oxygen and nutrients and so these cells are less able to biotransform things - they get less xenobiotics, but they are much less able to biotransform what it does get |
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Term
| What are the main functions of the liver? |
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Definition
| glucose storage and synthesis, filtration (bacterial products), protein synthesis (albumin, clotting factors), bioactivation/detoxification, formation of bile (bilirubin, cholesterol, metals, xenobiotics) |
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Term
| What are hepatic cords? What is between them? |
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Definition
| cords of hepatocytes - sinusoids (filled with blood) |
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Term
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Definition
| kuppfer cells (macrophages), endothelial cells (allow small molecules in), and Ito cells - synthesize collagen and store vitamin A |
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Term
| Why is the liver susceptible to toxic injury? |
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Definition
| because it is the first organ to receive ingested toxins like metals, drugs, vitamins, etc |
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Term
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Definition
| a yellowish fluid that contains bile salts, bilirubin, cholesterol, phospholipids, metals, and other things |
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Term
| What are the functions of bile (3)? |
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Definition
| help in the uptake of nutrients from the small intestine, protection of the small intestine from oxidative insult, and the excretion of compounds (endogenous and xenobiotic) |
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Term
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Definition
| hepatocytes transport it to the canalicular lumen - these connect to larger ducts that eventually empty into the bile duct |
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Term
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Definition
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Term
| What cells have phase I and II enzymes? |
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Definition
| hepatocytes and biliary cells |
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Term
| Where are metals taken up? |
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Definition
| across the sinusoidal membrane by facilitated diffusion or receptor mediated endocytosis |
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Term
| Where are metals stored in the liver? |
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Definition
| bound to proteins or lysosomes |
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Term
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Definition
| by lysosomes through canalicular excretion - specific canalicular membrane transporter |
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Term
| Which metals are excreted by the liver? |
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Definition
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Term
| What is Wilson's disease? |
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Definition
| a genetic disease that results in accumulation of Cu in the liver and other tissue b/c the person can't export Cu into the bile |
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Term
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Definition
| it's the buildup of lipids in hepatocytes - hepatotoxins like CCl4 and ethanol can cause that |
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Term
| What 3 patterns of cell death can be seen in the liver? |
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Definition
| focal - random distributed death of single hepatocytes * zonal - death of hepatocytes in particular functional regions * panacinar - massive death of hepatocytes |
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Term
| What is canalicular cholestasis? What does it result in? What is it associated with? |
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Definition
| decrease in volume or impaired secretion of specific solutes into bile * pigment accumulation in the skin and eyes (jaundice) and urine becomes bright yellow or dark brown * cell swelling, cell death, and inflammation |
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Term
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Definition
| accumulation of excessive amounts of collagen ibers in response to direct injury or inflammation - after repeated insults result in scar tissue replacing heptocytes |
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Term
| What are 3 mechanisms of liver toxicity? |
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Definition
| disruption of the cytoskeleton, cholestasis, and mitochondrial damage |
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Term
| How does disruption of the cytoskeleton of hepatocytes occur? |
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Definition
| microcystin uptake into hepatocytes leads to hyperphosphorylation of cytoskeletal proteins - this leads to deformation of hepatocytes |
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Term
| How does mitochondrial DNA damage contribute to liver toxicity? |
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Definition
| mitochondrial DNA codes for several electron transport proteins |
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Term
| What diseases have drugs that cause direct mitochondrial damage? |
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Definition
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Term
| How does alcohol cause liver toxicity? |
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Definition
| it causes mitochondrial damage by shifting the bioactivation/detox balance for ethanol which leads to an accumulation of acetaldehyde within mitochondria |
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