Term
| what is the major cell type in the liver? how are they arranged? |
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Definition
| hepatocytes, which are arranged in plates - where there is a central vein w/hepatocytes around, each in contact with blood in sinusoids on at least 2 sides. on the 3rd side they are in contact with the bile canaliculi. |
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Term
| what characterizes the endothelial cells in the liver? |
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Definition
| endothelial cells line the intra-hepatic sinusoids. they are similar to the endothelium in the glomerular capillary (fenestrated/no basement membrane). there is intimate contact between what is in the sinusoids and what gets out between the cells. |
|
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Term
| what is the space of disse? |
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Definition
| the area between a hepatocyte and a sinusoid |
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Term
| what are some of the functions of the kupffer cells in the liver? |
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Definition
| these are found in the sinusoids and are *phagocytic to foreign particles/infecting organisms as well as a source of cytokine production. |
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Term
| what are some of the functions of the stellate cells in the liver? |
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Definition
| the stellate cells are sometimes called the fat storing/ito cells and are major players in regeneration, growth hormone production and cytokines. they are also involved in fibrogenesis and stages of cirrhosis. |
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Term
| what does it mean to say the liver can "regenerate"? |
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Definition
| the liver can restore up to 75% of its own lost tissue in response to environmental toxins/infections/hepatic threats. hepatocytes are long-lived and do not regularly divide but can proliferate in a hyperplastic compensatory reponse to meet the demands of the body (not true regeneration). |
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Term
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Definition
| these are bipotential cells which can give rise to hepatocytes or cholangiocytes (parenchymal cells of bile system) and may assist in regeneration if the mature hepatocytes are too impaired. |
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Term
| what are the 4 methods of addressing a liver subject to destruction by chronic liver disease? |
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Definition
| 1) transplantation of a whole organ. 2) transplantation of isolated hepatocytes from a cadaver/living donor. 3) transplantation of hematopoietic bone marrow progenitor cells/adipose tissue-derived mesenchymal cells. 4) fetal hepatocytes |
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Term
| what are the overall functions of the liver? |
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Definition
| bile production (exocrine: salts emulsify fats w/pigments such as bilirubin), storage (of glycogen/fat/vitamins/copper/iron), nutrient interconversion, detoxification (ammonia removal, conversion to urea), phagocytosis (old RBC/WBCs removed along with some bacteria), and synthesis (albumins, fibrinogen, globulins, heparin, clotting factors) |
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Term
| what does the liver's design boil down to? |
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Definition
| maintenance of a constant environment in the body through chemical/metabolic homeostasis - however this means dynamic changes in factors such as blood flow, metabolites etc. |
|
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Term
| what does it mean for the liver to maintain a dynamic equilibrium? |
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Definition
| the rate of inflow appropriately matches the rate of efflux and there is movement through the system |
|
|
Term
| where is the liver located in the body? |
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Definition
| in the URQ of the abdominal cavity, inferior to the diaphragm |
|
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Term
| how vulnerable is the liver to trauma? why? |
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Definition
| the liver is soft tissue, extremely vascular, not totally covered by visceral peritoneum, and extends down below the ribs - therefore it is very vulnerable to trauma, particularly with rib damage and in children. |
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Term
| what is the functional subunit of the liver? |
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Definition
|
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Term
| what is the liver lobule composed of? |
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Definition
| hexagonal structure with a central vein, inside which the portal triad (renal artery, portal vein, bile canal) is found. the hepatocytes are arranged in cords and separated by sinusoids and there is no basement membrane (practically no intervening connective tissue between sinusoids and hepatic tissue) |
|
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Term
| what are the different zones of the liver lobule? |
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Definition
| starting from the outer ring, the periportal, then the mid, then the central zone. |
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Term
| how does the liver function as a reservoir? |
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Definition
| the liver is expandable and contractible in terms of blood volume which can either store some extra blood or release extra blood ("autotransfusion"), depending on the body's needs. |
|
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Term
| what does (extrinsic) parasympathetic innervation to the liver accomplish? |
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Definition
| promotion of storage and increased blood flow from the small intestine to the liver |
|
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Term
| what does (extrinsic) sympathetic innervation to the liver accomplish? |
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Definition
| removal of blood from storage and reduction of blood flow from the small intestine to the liver - increases dumping of blood from the liver and into general circulation (via alpha adrenergic receptors and angiotensin system) |
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Term
| is the extrinsic control of the liver (control of reservoir function) essential to life? |
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Definition
| no, as demonstrated with liver transplants - but the pt is more brittle to drastic changes in extracellular fluid compartment because no buffer function |
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Term
| how much blood flow to the liver is from the portal vein? what characterizes this blood in particular? |
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Definition
| 60-80%, this blood carries nutrients from the gut, drugs and toxins as it drains from the colon, spleen, and pancreas (insulin/glucagon/somatostatin/pancreatic polypeptide) |
|
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Term
| how much blood flow to the liver is from the hepatic artery? what characterizes this blood in particular? |
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Definition
| ~20%, but this is the only blood which the liver can regulate via extrinsic mechanisms due to innervation. it supplies O2 to the liver and biliary system. |
|
|
Term
| is the liver equally perfused? |
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Definition
| no, blood coming from portal circulation tends to go to the L side of the liver due to less resistance |
|
|
Term
| how much of cardiac output goes to the liver? |
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Definition
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|
Term
| what are the 3 intrinsic control mechanisms of the liver? |
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Definition
| myogenic response, metabolic response, and hepatic arterial buffer response |
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Term
| what is the myogenic intrinsic response in the liver? |
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Definition
| epithelial cells have local control over vascular tone by N02, CO2, and H2S (all vasodilators), and endothelin (vasoconstrictor) |
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|
Term
| what is the metabolic intrinsic response in the liver? |
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Definition
| hepatic arterial blood flow is increased by decreased portal O2 tension, pH, and postprandial hyperosmolarity. |
|
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Term
| what is the arterial buffer intrinsic response in the liver? |
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Definition
| adenosine (vasodilator) is released constantly around hepatic arterioles/portal venules which will also build up if blood builds up, acting as a natural correcting agent for up to a 25% decrease in portal blood flow. if the flow in the portal vein is increased, adenosine is washed out and it has less of a vasodilatory effect. |
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Term
| what is ohm's law, and how does it apply to flow in the liver? |
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Definition
| ohm's law: change in pressure is a function of resistance and rate of flow (change in P = R x Q). therefore in the liver, if you want to keep pressure and flow constant, resistance needs to be changed (which is normally very low in the liver). this resistance is accomplished by recruiting additional sinusoids to take overflow, preventing backup of pressure. there is no constant sinusoid size, they reflect the flow. |
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Term
| what is the role of the liver in lymph production in the body? |
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Definition
| the liver produces one half of all lymph formed in the body and comes from the sinusoids (protein concentration in the lymph is only slightly lower than plasma protein concentration) |
|
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Term
| how does protein enter the space of disse? why is this important? what factors can affect this functionality? |
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Definition
| protein can enter the space of disse from the sinusoids through pores in its fenestrated endothelium. this is a low pressure system which allows lymph flow and contact between hepatocytes and blood. any interruption of this system can have pathologic consequences and therefore alcohol/hormones which affect the endothelial fenestration are important to regulate - cholesterol builds up (fatty liver), nutrients/toxins cannot be processed, and materials for synthesis are lacking. |
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Term
| what ensures that only 1% of bacteria entering the portal blood from the intestines is able to incur damage? |
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Definition
| kupffer cells located in the periportal zone phagocytose and digest bacteria coming through the hepatic sinuses. |
|
|
Term
| what is most important in maintenance of normal liver function? |
|
Definition
|
|
Term
| what characterizes blood flow in the liver? |
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Definition
| the liver recieves 20-40% of cardiac output, but only ~20% of blood entering the liver is through the hepatic artery. (majority of blood comes from the portal venous system). |
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|
Term
| what are the logistics of damage and storage in terms of blood flow to the liver? |
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Definition
| the most oxygenated portion of the lobule is the periphery, where blood first enters. this sets the scene for distribution of different enzymes which are placed according to their optimal O2 level (in the least oxygenated areas, right next to the central vein, you find the enzymes for glycolysis). peripheral cells are the first to be hit by toxins - but also the first to be replenished after a fast. |
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Term
| why does bile not back up in the liver? |
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Definition
| b/c it flows counter to the flow of blood in the sinusoids (low pressure system) |
|
|
Term
| why might the liver be a risk as a food source? |
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Definition
| it has high levels of vit A which can become toxic |
|
|
Term
| where is the site of new bile synthesis? how does it flow in the liver? |
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Definition
| the liver, which secretes bile acids (synthesized/extracted from portal blood) into the canaliculi which feed into the gall bladder. as bile flows counter to blood, it allows for rapid filtration of drugs/toxins, clearing them from systemic circulation |
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|
Term
| what is the process of bile formation? |
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Definition
| cholesterol (from diet/liver synth) is converted to cholic or chenodeoxycholic acid and becomes conjugated bile acid when combined with glycine/taurine. bile salts (mostly Na+) are then secreted into bile. secondary bile salts (from bacterial deconjugation/dehydroxylation in the intestine) then form lithocholic acid and deoxycholic acid -> causes them to be more lipid soluble and have a higher affinity for cholesterol. |
|
|
Term
| how efficient is bile recirculation? |
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Definition
| very, 95-99% of bile is recycled via enterohepatic circulation which occurs primarily in the ileum |
|
|
Term
| what are the functions of bile in the small intestine? |
|
Definition
| detergent: takes large fat particles, and breaks them down to be reabsorbed. micelle formation: transports fat globules across small intestine epithelial membrane (have a slight negative charge to trap them) |
|
|
Term
|
Definition
| solutes the kidney can't handle: bile pigments, phospholipids, fatty acids, and electrolytes (heavy metals). |
|
|
Term
| how is protein processed in the liver? |
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Definition
| excess nitrogen from excess protein is made into urea in the liver via the urea cycle. urea is nontoxic, but can turn extracellular parts of tissues into sludge, so the kidneys excrete it w/urine. a small amount of protein escapes reabsorption in the small intestine and is converted to ammonia by bacteria in the colon, which is then taken up by portal circulation and entered into the urea cycle. |
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|
Term
| where does bilirubin/billiverdin come from? |
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Definition
| bilirubin is released by senescent erythrocytes into the blood then taken up by hepatocytes and bond to intracellular proteins. glucuronide is the water soluble, conjugated form of bilirubin that is excreted into bile via the bile canaliculus by carrier-mediated transport |
|
|
Term
| what is the transport route of bile from the liver? |
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Definition
| 1) hepatocytes actively transport bile into bile canaliculi (choleresis: production/secretion of hepatic bile). 2) intrahepatic/extrahepatic bile ducts transport bile and secrete into it a watery HCO3 rich fluid - important because it keeps the bicarbonate from building up on the luminal side opposite to the cells. (secretin stimulates the cholangiocytes of the tubules to produce this, along with glucagon and VIP). 3) between meals, 1/2 of hepatic bile is diverted to the gall bladder. |
|
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Term
| what happens to bile extrahepatically? |
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Definition
| bile drains into the hepatic ducts, 1/2 of which moves by passive forces through the cystic duct and into the gall bladder. between meals, the sphincter of oddi is usually contracted and creates resistance to flow - allowing bile to move to the gall bladder, which is relaxed between meals in the absence of CCK. |
|
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Term
| what happens with bile if there is a long period of fasting? |
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Definition
| there may be a build up through the common bile duct and a small bit can be secreted into the intestine when the gall bladder is full. |
|
|
Term
| what are the steps of bile release during normal digestion? |
|
Definition
| 1) chyme w/fat enters small intestine. 2) I cells in the intestinal mucosa secrete CCK. 3) CCK travels through the bloodstream then stimulates the muscular layer of the gall bladder wall to contract. 4) bile travels down the cystic duct and bile ducts to the duodenum where the sphincter of oddi relaxes b/c of CCK. |
|
|
Term
| what is the function of the gall bladder? |
|
Definition
| the gall bladder stores and concentrates the bile acids/pigments BUT *does not concentrate the fluid content of the bile b/c as Na and Cl are reabsorbed across the mucosal surface of the gall bladder, you have water following in *isoosmotic amounts (the number of electrolytes overwhelms the amount of other particles that are in there and osmolarity is maintained close to body osmolarity). |
|
|
Term
| how does the small intestine affect the composition of bile? |
|
Definition
| the small intestine, along with its secretion of CCK, also secretes secretin - which precipitates secretion of HCO3 and shut down dumping of low pH substances into the duodenum |
|
|
Term
| how does the form of the gall bladder inform its function? |
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Definition
| the gall bladder has many folds, allowing it to expand and has copious mucus secretion - allowing protection of its surface from the bile. |
|
|
Term
| how much bile is usually stored in the gall bladder after a time of digestion? what is its osmolarity? |
|
Definition
| 40-60 mL of bile is stored in the gall bladder after a time of digestion and it is isotonic |
|
|
Term
| what determines the amount of bile stored in the gall bladder? |
|
Definition
| the length of an overnight fast |
|
|
Term
| when is the most significant amount of bile discharged by the gall bladder? |
|
Definition
| during the 1st hour of a meal |
|
|
Term
| what does the sphincer of oddi do during meal processing? |
|
Definition
| the sphincter of oddi is open and there is no preferential movement of bile into the gall bladder (no storage there) – it moves down through duct |
|
|
Term
| what is the enterohepatic circulation of bile salts? |
|
Definition
| the process of recycling bile from the intestine back to the liver, transported by albumin and dependent upon caloric intake (low calories, less circulation) |
|
|
Term
|
Definition
| anything that causes contraction of the gall bladder (such as CCK) |
|
|
Term
|
Definition
| substances which increase secretion of bile |
|
|
Term
|
Definition
| when the bile system is slowed down - can lead to gall stones |
|
|
Term
| what kind of gland is the pancreas? |
|
Definition
| mixed, both exocrine and endocrine - but here we are only talking about the exocrine portion (which classify it as a vital organ). |
|
|
Term
| why is the pancreas considered a vital organ? |
|
Definition
| b/c it produces proteolytic enzymes we cannot live w/o |
|
|
Term
| what is the location of the pancreas? |
|
Definition
| head is encircled by the duodenum (possible pathology), the tail is very close to the spleen, and it all lies around the level of L2 |
|
|
Term
| where does the pancreatic duct empty into? |
|
Definition
| the 2nd part of the duodenum, where it forms the *ampulla of vater, where the pancreatic duct meets the bile duct and both are controlled by the sphincter of oddi. |
|
|
Term
| what is the blood supply to the pancreas? |
|
Definition
| the splenic artery supplies the neck, body, and tail and the superior mesenteric artery supplies the superior pancreaticoduodenal artery which supplies the head. the portal vein drains the whole thing. |
|
|
Term
| what is the autonomic innervation of the pancreas? |
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Definition
| sympathetic fibers from the splanchnic nerves provide inhibitory signals from the pancreatic/celiac plexus (slow down blood supply) while parasympathetics stimulated both exocrine and endocrine secretions from the vagus. |
|
|
Term
| why is the pancreas referred to as the "hermit of the abdomen"? |
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Definition
| the pancreas is hard to palpate as it lies in retroperitoneal space and life threatening lesions are difficult to find until they are very advanced - often until its large endocrine/exocrine capacity is compromised pancreatic disease goes unnoticed. |
|
|
Term
| how long does it take for severe malabsorption deficiencies to result due to pancreatic damage? |
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Definition
| severe malabsorption deficiencies result only when 90% of exocrine pancreas is destroyed |
|
|
Term
| where do the liver and gallbladder refer pain? |
|
Definition
| R shoulder (phrenic nerve) |
|
|
Term
| where does the pancreas refer pain? |
|
Definition
| directly behind the pancreas, LLQ/umbilicus |
|
|
Term
| what are the two main kinds of cells in the pancreas, responsible for its exocrine secretions? |
|
Definition
| 1) acinar cells of intercalated ducts which respond to secretin and produce bicarb. 2) basophilic cells which produce digestive enzymes in response to CCK. *caveat - when secretin and CCK are present, this potentiates the secretion of digestive enzymes. |
|
|
Term
| how is bicarb produced in the pancreas? |
|
Definition
| CO2, H2O, and carbonic anhydrase are present in large amounts, creating carbonic acid which quickly dissociates into HCO3- and H+. H+ diffuses into the blood stream and combines with mostly Cl- to create HCl buffers ("acid tide"). the HCO3 progresses to the lumen of the ducts and to the intestine. |
|
|
Term
| what is the major stimulus for bicarb production? what facilitates this? |
|
Definition
| secretin - which is released by S cells when the vagal nerve senses low pH in the intestine |
|
|
Term
| what are the major stimulants for bicarb release in the GI? |
|
Definition
| secretin, cholecystokinin, gastrin, and ACh |
|
|
Term
| what are the major inhibitors for bicarb release in the GI? |
|
Definition
| atropine, somatostatin, pancreatic polypeptide, and glucagon |
|
|
Term
| at what pH is secretin release from the duodenal mucosa? |
|
Definition
|
|
Term
| what are the digestive enzymes produced by the acinar cells in the pancreas? |
|
Definition
| trypsin, chymotrypsin, elastase, carboxypepdidase (protein digestion), lipase (fat digestion), amylase (polysaccharide digestion), and ribonuclease/deoxyribonuclease (nucleic acid digestion) |
|
|
Term
| what is the major stimulus for pancreatic digestive enzyme secretion? |
|
Definition
| CCK - which causes relaxation of the sphincter of oddi/contraction of the gall bladder |
|
|
Term
| what is the only enzyme secreted by the pancreas in its active form? |
|
Definition
| amylase - which functions at a pH of 7 to hydrolyze starch and glycogen to glucose, maltose, maltotriose and dextrins |
|
|
Term
| what is the role of enterokinase in combination with pancreatic digestive enzymes? |
|
Definition
| enterokinase (from the duodenal epithelium) converts trypsinogen to trypsin, which can then activate all the other proenzymes to their active form |
|
|
Term
| how is the pancreas protected from its own digestive enzyme production? |
|
Definition
| antiproteolytic enzyme is secreted by the acinar cells which keeps trypsinogen from becoming trypsin |
|
|
Term
| what are the 2 patterns of pancreatic secretion? |
|
Definition
| basal and meal associated |
|
|
Term
| what characterizes the basal secretion by the pancreas? |
|
Definition
| there is a resting level of secretion during the inter-digestive period at a very low rate (bursts of secretion for 10-15 min every 1-2 hrs). these pancreatic enzymes are not activated b/c there is no stimulation of S cells or CCK. |
|
|
Term
| what characterizes the meal secretion by the pancreas? |
|
Definition
| when stimuli cease, there is a decrease in pancreatic secretions to a minimal level (b/c no hormonal/vagal stimulation) |
|
|
Term
| what are the 3 phases of pancreatic secretion? |
|
Definition
| cephalic phase (vagal stimulation/gastrin release from stomach signals pancreatic acinar cells), gastric phase (vago-vagal reflexes and gastrin relase while food is in stomach, accounts for <20% of release), and intestinal phase (precursors are present to stimulate release of secretin and CCK (hormonal), and this accounts for >70% of total secretion) |
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|
Term
| what are the protective mechanisms to keep digestive secretions from damaging the body? |
|
Definition
| 1) proteolytic/membrane digesting enzyme are produced in pro- forms. 2) digestive enzymes are compartmentalized in acinar cells away from lysosomal enzymes. 3) trypsin inhibitor production by the pancreas. 4) enterokinase (activating enzyme) is produced physically separate from the pancreas; and the liver produces the inhibtors a1-antitrypsin and a2-macroglobulin which are found in the blood. |
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