UW Cholesterol gallstones Flashcards
3 types of gallstones?
Cholesterol
Pigment:
a) brown (aka mixed)
b) black
Cholesterol stones are formed when the ability of bile salts to solubilize cholesterol is overwhelmed by …..
high concentrations of cholesterol in bile.
Cholesterol stones appearance?
yellow to pale gray and hard
black pigment gallstones are composed of …
calcium salts of unconjugated bilirubin (calcium bilirubinate)
pigment gallstones appearance?
soft, and are dark brown to black.
Brown pigment stones typically arise secondary to .2
bacterial (eg, Escherichia coli) or helminthic (eg, Ascaris lumbricoides, Clonorchis sinensis) infection of the biliary tract.
why infections of billiary tracts leads to formation of brown gallstones?
infection of the biliary tract results in the release of beta-glucuronidase by injured hepatocytes and bacteria (microbial enzyme).
function of beta-glucuronidase?
This enzyme hydrolyzes bilirubin glucuronides and increases the amount of unconjugated bilirubin.
what blirubin increases in the presence of beta-glucoronidase?
unconjugated
liver fluke C sinensis is common in what countries?
East Asian countries
apart from infection in what cases pigment gallstones may also occur?
when excess bilirubin is excreted, such as with chronic hemolytic anemia.
endogenous beta-glucuronidase in the biliary tract does what?
A small amount of conjugated bilirubin normally becomes deconjugated
When large amounts of conjugated bilirubin are excreted into the bile, enough becomes deconjugated to promote black pigment stone formation.
.
what conditions leads to black stones?
chronic hemolysis (sickle cells, spherocytosis) Increased enterohepatic cycling of bilirubin (eg ileal disease)
What tissue attaches gallbladder to liver?
The cystic plate is a fibroareolar tissue that attaches the superior surface of the gallbladder to the liver.
in which squares of liver lies gallblader?
lies on the cystic plate (gallbladder bed) under the liver segments IVB and V.
Most common gallstones?
cholesterol
Cholesterol presentation on xray?
Radiolucent with radiopaque areas due to calcifications.
Cholesterol stones composition?
Cholesterol monohydrate crystals and calcium carbonate
Black stones presentation on xray?
Radiopaque
Brown stones presentation on xray?
Radiolucent
Black stones composition?
calcium bilirubinate
Hemolysis –> what stones?
black
infection –> what stones?
brown
what solubilizes cholesterol in bile? 2
Bile salts and phosphatidylcholine
what conditions (incr and decr) predispose for cholest. stones formation since cholesterol cannot be dissolved?
incr. cholesterol concentration;
decr. bile salts;
decr. phosphatidylcholine.
Risk factors for gallstone formation?
Obesity rapid weight loss female sex glucose intolerance hypomotility of the gallbladder (eg, pregnancy, prolonged fasting).
Obesity. Stones?
Cholesterol
Rapid weight loss. stones?
Cholesterol
female sex. stones?
Cholesterol
glucose intolerance. Stones?
Cholesterol
hypomotility of the gallbladder (eg, pregnancy, prolonged fasting). stones?
Cholesterol
pregnancy, stones?
Cholesterol
prolonged fasting, stones?
Cholesterol
total parenteral nutrition (TPN) leads to what enteral physiologic changes? 2
decreased CCK release and subsequent biliary stasis.
enteral passage of what substances leads to trigger to CCK?
enteral passage of fat and amino acids into the duodenum
in what part of intestines fat and amino acids stimulate CCK?
duodenum
extensive resection of the ileum can have disruption to …..
the normal enterohepatic circulation of bile acids
extensive resection of the ileum –> disruption to the normal enterohepatic circulation of bile acids –> what result on gallbladder?
leading to inadequate solubilization of biliary cholesterol and formation of cholesterol crystals.
cirrhosis. stones?
black
Why advanced liver disease can impair cholesterol conversion to bile acids?
due to the diminished synthetic ability of injured hepatocytes, leading to supersaturation of the bile with cholesterol
cirrhosis increase risk of cholesterol gallstones. what symptoms seek?
hepatocellular dysfunction!!!
how changes cholesterol levels in total parenteral nutrition (TPN)?
Serum triglyceride levels may rise on TPN, but TPN does not contain significant amounts of cholesterol, and serum cholesterol levels do not usually change significantly.
cholesterol stones - due to lack of enteral stimulation and decr. release of CCK.
gastrin effect on gallstones?
none
what catalyzes the rate-limiting step in the synthesis of bile acids?
Cholesterol 7α-hydroxylase
Cholesterol 7α-hydroxylase catalyzes what?
Rate-limiting step in the synthesis of bile acids
what medications increase cholesterol content in bile, which increases the risk of gallstones?
Fibrate (fenofibrate, gemfibrozil)
what does fibrate?
upregulate lipoprotein lipase, resulting in increased oxidation of fatty acids
fibrate effect on cholesterol stone formation and why?
fibrates inhibit cholesterol 7α-hydroxylase, which catalyzes the rate-limiting step in the synthesis of bile acids
fibrate effect on bile acid?
decreased productio
Estrogens increase the biosynthesis of cholesterol by upregulating ….
upregulating hepatic HMG-CoA reductase activity
estrogen medication effect on cholesterol gallstones?
increase the amount of cholesterol secreted in bile and contribute to formation of gallstones
Aromatase function?
Aromatase catalyzes the conversion of androgens to estrogen
Inhibition of aromatase leads to ….
lead to reduced gallstone formation (aromatase catalyzes conversion of androgens to estrogens)
β-glucuronidase does what on bilirubin?
deconjugates bilirubin, and the resulting free bilirubin precipitates with calcium in the bile to form pigmented gallstones
Decreased activity of β-glucuronidase on gallstones formation?
Decreased activity of this enzyme would reduce the formation of pigmented stones but would not affect the formation of cholesterol gallstones.
HMG-CoA reductase does what in cholesterol synthesis?
catalyzes the conversion of HMG-CoA to mevalonate, the rate-limiting step in cholesterol synthesis
decr HMG-CoA reductase activity on cholest stones?
Decreased activity would reduce cholesterol synthesis and the amount of cholesterol secreted in bile, discouraging cholesterol stone formation
what medications for cholest stones?
hydrophilic bile acids (eg, ursodeoxycholic acid)
effect of hydrophilic bile acids (eg, ursodeoxycholic acid)?
reduces cholesterol secretion and increases biliary bile acid concentration.
This improves cholesterol solubility and promotes gallstone dissolution
Bile acid sequestrants (eg cholestyramine) net result on gallstones?
The net result is no significant change in the risk of gallstones.
Bile acid sequestrants (eg cholestyramine) effect on enterohepatic recirculation of bile acids?
Decrease enterohepatic recirculation of bile acids (increase gallstone risk).
Bile acid sequestrants (eg cholestyramine) effect on conversion of cholesterol to bile acids and motility?
stimulate the conversion of cholesterol to bile acids and increase biliary motility (decrease gallstone risk).
Progesterone on bile acids?
progesterone reduces bile acid secretion
Estrogen on cholesterol?
Estrogen increases cholesterol secretion
Progesterone on bile emptying?
Progesterone slows gallbladder emptying
what gallbladder actively absorbs?
water from bile
conditions that cause gallbladder hypomotility result in …..
excessive dehydration of bile –> bile becomes concentrated –>viscous biliary sludge.
viscous biliary sludge results from what?
hypomotility result in excessive dehydration of bile –> bile becomes concentrated
Biliary sludge symptoms?
asymptomatic
biliary colic (RUQ abdominal pain associated with nausea)
also precursor to stone formation (particularly cholesterol stones).
Complications such as acute cholecystitis and cholangitis can also occur in patients with biliary sludge.
