3/22 Gallbladder Disease - Corbett Flashcards
gallbladder
embryonic origin
origin of blood supply
stores ____
embryonic foregut
celiac trunk → common hepatic a → R hepatic a → cystic a
- sits in triangle of Calot
stores BILE
- water, inorganic electrolytes
- organic components synthesized by hepatocytes
- bile acits
- lecithin
- cholesterol
- conjugated bilirubin
factors affecting bile acid synthesis
reabsorption occuring mainly in ILEUM
BILE SYNTHESIS
body’s major route for getting rid of cholesterol
hepatocytes: cholesterol acted on by CYP7A1
- cholesterol undergoes modifications (removal of side chains, addition of COOH groups) → primary bile acids
intestine: primary bile acids become unconjugated and dehydroxylated → secondary bile acids
- **carcinogenic to enterocytes**
conjugation of bile acids
where
with what
why?
cholic acid and chenodeoxycholic acid are CONJUGATED w glycine and taurine in HEPATOCYTE
why?
unconjugated bile acid has pKa of 5
intestinal pH of 2-4 → unconj bile acid would be protonated and therefore unable to do its job of emulsifying
- conjugation solves this by dropping the pKa down so that conjugated bile acids remain charged in the intestine
- more hydrophilic/polar/soluble
*conjugated BA reabs only if apical Na-dep BA transporter present
functions of bile acids
- regulation of chol homeostasis
- allows for intestinal absorption of dietary fat, chol, fat soluble vitamins
- control bacterial overgrowth in intestine
- HORMONE to reg enterohepatic circ, fat/glucose/energy homeostasis
function of gallbladder
CONCENTRATION of hepatic bile (drops volume 80-90%)
- micelles take up bile → allows GB bile to stay isotonic to plasma even though more concentrated
gallstone disease
- cholelithiasis (gallstone)
- biliary colic
- acute cholecystitis
- choledocholithiasis (stone in common bile duct)
- acute cholangitis
types of gallstones
- cholesterol stones (80)
- over 50% chol
- crystalline chol + bile pigments, Ca salts
- pigment stones (20)
- brown (18)
- form in bile ducts (primary duct stones)
- risk: bile stasis, bacterial or parasitic inf (ascaris, clonarchis), SE Asia (beta glucuronidase production)
- black (2)
- develop exclusively in gallbladder
- occur in sterile bile → chronic liver disaes, ineff erythropoeisis, hemolysis of any kind
- risk: hyperbilirubinemia
- general risks for pigment stones: terminal ileum disease bilirubin → incr UC bili conc in bile
- Crohn’s
- ileal resection
- terminal ileitis
pathophys of cholesterol gallstones
why more in women?
-
cholesterol supersaturation
- diet, dyslipidemia, obesity (incr HMG CoA reductase activity)
- not enough bile salt and lecithin
- chol hypersecretion (correlates with age)
- nucleation promoted
- gallbladder hypomotility (incr time for crystals to form)
- hypersecretion of mucin (accel chol crystal nucleation in supersat bile → incr bile viscosity)
- growth
women 2-3x more likely to get gallstones
- estrogen → incr hepatic secretion of biliary chol
- progesterone → decr GB motility
biliary colic
repeated episodes of pain due to impacted gallstone in cystic duct → wall tension/pain on GB contraction
- resolves in 30-90min as GB relaxes and obstr relieved
- sporadic and unpredictable
- assoc w diaphoresis, n/v
epigastric or RUQ pain radiating to right scapular tip
acute cholecystitis
cystic duct obstruction (90% of time, secondary to gallstone)
- gallbl distention affecting blood flow and lymph drainage
- mucosal ischemia and necrosis
- bacteria maybe present
constant severe RUQ w radiation to scapula
Murphy’s sign: inspiratory pause on palpation of RUQ
scleral icterus (uncommon)
fever, n/v
chronic cholecystitis
signs and sx
- calcification of wall of gallbladder → “porcelain gallbladder”
- risk of cancer
- proliferation of mucosal epi
- fusion of folds w wall of gallbladder → formation of Rokitansky Aschoff sinuses
complications
choledocholithiasis
stones in CBD
common sx:
- more prolonged RUQ/epigastric pain
- n/v
complications:
-
acute cholangitis : stone causes CBD obstruction → dilation w bacterial overgrowth
- systemic inf/sepsis
- Charcot’s triad: fever, jaundice RUQ paiin
- Reynold’s pentad: fever, jaundice, RUQ pain, hypoTN, altered mental status
- tx: antibiotics, drainage
-
acute pancreatisis : gallstone in distal CBD → compresstion of septum between CBD and pancreatic duct → obstruction of common channel (ampulla of Vater) → bile reflux into PD
- incr pressure in pancreatic duct → PD injury, release of enzymes into glandular interstitium → pancreatic autodigestion
- mostly mild, resolve with conservative tx
pathogenesis of primary vs secondary CBD stones
secondary stones
- CBD stones that have migrated from gallbladder
- most common
primary stones
- assoc with bacterial infection
- decr solubility of UC bilirubin → stone formation
acute cholangitis
cause
triad
pentad
acute cholangitis : stone causes CBD obstruction → dilation w bacterial overgrowth
- systemic inf/sepsis
- Charcot’s triad: fever, jaundice RUQ paiin
- Reynold’s pentad: fever, jaundice, RUQ pain, hypoTN, altered mental status
tx: antibiotics, drainage
acute pancreatitis
(as a fx of choledocholithiasis)
acute pancreatisis : gallstone in distal CBD → compresstion of septum between CBD and pancreatic duct → obstruction of common channel (ampulla of Vater) → bile reflux into PD
- incr pressure in pancreatic duct → PD injury, release of enzymes into glandular interstitium → pancreatic autodigestion
- mostly mild, resolve with conservative tx
gallstone ileus
mechanical bowel obstruction (esp in elderly)
due to chronic impaction of stone in Hartmann Pouch → chronic infl and biliary enteric fistula
- gallstone passes through fistula and becomes impacted in ileum (narrowest part of int) →→→ OBSTRUCTION!!!
***air in the biliary tree is pathognomonic
atypical gallstone disease
acalculous cholecystitis
emphysematous cholecystitis
Mirizzi syndrome
acalculous cholecystitis
- pathogenesis unclear
- assoc with prolonged fasting → no CCK stimulus, retained bile extremely concentrated
- maybe due to lack of contractile response to CCK?
emphysematous cholecystisis (Clostridia or E coli)
- rapidly progressive
- early gangrene
- gallbladder perf
- high mortality
- SURGICAL EMERGENCY
Mirizzi syndrome
- stone lodged in cystic duct or Hartmann pouch → external compression of common hepatic duct causing sx of obstructive jaundice
- characteristics
- common hep duct obstruction w normal CBD distal
- contracted/thickened GB wall
gallbladder cancer
bile acid tx for gallstones
goal: dissolve bile stones
mech: decr cholesterol content of bile by reducing hepatic chol secretion
ursodeoxycholic acid
- oral med. absorbed, conjugated in liver, excreted in bile
- extensively recirculated in enterohep circulation w long half life
