quiz 5- liver tumors, GB, pancreas Flashcards
• What is biliary atresia? 2 types?
o Aka extrahepatic ductopenia and progressive obliterative cholangiopathy.
o Congenital: common bile duct blocked or absent. 1/10-15,000 (?? 1/300 in US); some die in hours-days
o Acquired: usu AI, a principal form of chronic liver transplant rejection
• What are ssx of congenital biliary atresia? Dx? Tx?
o initial sxs mb indistinguishable from neonatal jaundice
o Prolonged jaundice resistant to photo therapy
o progressive cholestasis: pruritus, fat-sol vit def, malabsorption →cirrhosis, portal HTN
o 1-6 wks: clay colored stools, dark urine, swollen abd, enlarged, hardened
o liver enzymes grossly markedly elevated
o hyperbilirubinemia is conjugated, doesn’t cause kernicterus
o dx: US
o tx: Kasai procedure (anastomosis), liver transplant (need by age 3); un tx → liver failure
• what causes biliary atresia? Pathogenesis?
o Unknown cause (both congenital and acquired?); congenital: part/all of bile duct missing
o Mb damage dt immune response: Reovirus 3, congenital CMV, EBV, AI, malformation
o → bile trapped in liver (can’t get to intestine) = biliary stasis
o → Proliferation of small bile ductules → fibrosis → cirrhosis
• What are Choledochal cysts? Morbidities?
o congenital cystic dilatations of bile ducts
o Often jxn bw common bile duct and pancreatic duct (empties into CBD > 1 cm proximal to ampulla)
o Western: 1/10^5- 2x10^6; Japan (asia): 1/1,000
o Children: pancreatitis, cholangitis, histo hepatocellular damage
o Adults: hepatic abscesses, cirrhosis, portal HTN, recurrent pancreatitis, cholelithiasis
o Cholangiocarcinoma, 9-28%, mb dt susceptibility to bile as carcinogen
• How are choledochal cysts dx? Sxs?
o most dx as kids (60-70% w sxs)
o Infants: jaundice and clay colored stools → workup for biliary atresia; palpable mass in the RUQ, HM
o Kids: intermittent biliary obstruction (RUQ mass, jaundice), recurrent bouts of pancreatitis (↑ amylase, lipase)
o Adults: 1+ severe complications; vague RUQ pn (mc); jaundice, cholangitis
o Triad (only 10-20%): mass, abd pn, jaundice
• What is pathophysiology of choledochal cyst?
o Abn union, pancreatic secretions reflux into CBD, enzymes activated
o → damage, weaken bile duct wall
o Defects in epithelialization and recanalization
o → formation of a choledochal cyst
• What are classes of choledochal cysts?
o I-V
o I: mc, 80-90%; saccular dilatations of CBD, segment r entire duct
o I and IV have subclasses: IA, IB, IC, IVA, IVB
• What is cholelithiasis?
o crystalline mass formed within gallbladder, made of bile components
o may pass distally into other parts of biliary tract: cystic duct, CBD, pancreatic duct, ampulla of Vater
• what are risk factors for gallstones?
o female, overweight, age near or > 40
o ↑ in N and S American Indians, Hispanics, N Euro
o ↓ melatonin, which inhibits cholesterol secretion from GB, ↑ conversion of cholesterol to bile, antioxidant
o Polyfactorial: inherited body chemistry, body wt, GBmotility, diet (↓fiber, ↑chol, ↑starch), rapid wt loss, constipation, fewer meals, less fish, ↓folate, Mg, Ca, vit C
o PPIs ↓ GB fxn
o mb ↓ risk: wine and whole-grain bread
• what are some risks of having gallstones?
o In ampulla of Vater: obstruct exocrine pancreas → pancreatitis
o In GB: acute cholecystitis
• What is acute cholecystitis?
o Bile retained in GB; Usu caused by cholelithiasis, esp cystic duct block
o 2nd infx: intestinal microorganisms, E coli, Klebsiella, Pseudomonas, Bacteroides fragilis, Enterococcus.
o GB wall inflamed; severe: → necrosis and rupture
o spreads to outer covering, irritates surrounding structures, diaphragm, bowel
• what are ssx of cholecystitis?
o RUQ pn (biliary colic), initially intermittent (mb referred, R scapula)→constant, severe pain o pain after fatty meals o ↓ fever, diarrhea, N/V o GB mb tender and distended o ↑AST,ALT, WBC
• What is acalculous cholecystitis?
o Less common, w/o stones
o mb no stones in debilitated trauma patients, CAD, immunosuppressed
o obstructing tumors or inadequate blood supply
o also anorexia nervosa: lack of stimulation of GB → bile stasis
o can progress more rapidly to gangrene and sepsis
• What is gross and microappearance of acute cholecystitis?
o US: 1.9 cm stone; thickening of GB wall consistent w chronic cholelithiasis
o Micro: extensive ulceration of mucosa, hemorrhage, edema, dense transmural infiltrate of Ns and mononuclear inflam cells
• What are the types of gallstones?
o On basis of composition
o Cholesterol: light yellow to dark green/brown; oval 2-3 cm in length, tiny dark central spot. At least 80% cholesterol by weight (too much), and not enough bile salts; > 80% in US
o Pigment: mc in developing world; ↑ w hemolytic anemia, cirrhosis, biliary tract infxs; small, dark, bilirubin and calcium salts; < 20% cholesterol; st xray
o Mixed stones: 20–80% chol; calcium (seen on xray) carbonate, palmitate phosphate, bilirubin, other bile pigments
• What are the size and consistency variations of gallstones?
o grain of sand to golf ball
o single large stone or many smaller ones
o Pseudoliths: aka sludge, thick, alone or w fully formed gallstones; presentation like lith
o composition affected by age, diet and ethnicity
• What are the risk factors for forming gallstones?
o Older: time-dependent process
o Female (3:1)- estrogen induces changes in lipid metabolism and GB function; ↑ risk preg, multiparous, OCPs, hormone tx
o Race and ethnicity- > 75% American Indian F > 40
o Genetics
o Obesity- alterations in lipid metabolism, ↑cholesterol synthesis dt ↑ activity of hydroxy-methyl-glutaryl- CoA (HMG CoA) reductase
o Crohn’s: ↓ ileal resorption of bile salts
o Total parenteral nutrition: → stasis and distension
o Rapid weight loss: 30-40% gastric bypass; removal of GB prophylactically
o ability of GB to effectively empty; presence of additional proteins and salts in the bile
• how does bacterial infx contribute to gallstones?
o Bile is normally sterile
o Infx: bacteria hydrolyze conjugated bilirubin → ↑unconjugated bilirubin → precipitation of calcium bilirubinate crystals
o Bacteria also hydrolyze lecithin to release fatty acids, may bind calcium and precipitate
o Claylike, “brown pigment stones”
o often form in bile ducts
• how do cholesterol stones form?
o Liver cells secrete cholesterol into bile w phospholipid (lecithin) in form of small spherical membranous, “unilamellar vesicles”, and bile salts (detergents)
o In GB: Bile salts dissolve unilamellar vesicles → soluble aggregates, “mixed micelles”
o Compared w vesicles (hold 1 molecule of cholesterol for every molecule of lecithin), mixed micelles have lower carrying capacity for cholesterol (about 1 for every 3 lecithin)
o → bile supersaturated w cholesterol, and cholesterol monohydrate crystals may form
• What are the main factors that determine whether cholesterol gallstones will form are?
o 1) the amount of cholesterol secreted by liver cells, relative to lecithin and bile salts
o 2) the degree of concentration and extent of stasis of bile in the gallbladder.
• What are bilirubin stones?
o Most bilirubin in bile is glucuronide conjugates, water soluble and stable,
o Some is unconjugated, like fatty acids, phosphate, carbonate, and other anions, tends to form insoluble precipitates with calcium
o Hemolysis/cirrhosis: ↑ unconj bili → stones
o Jet black color= black pigment stones (10-20% in US)
• What is cholesterolosis?
o abnormal deposition of cholesterol and TG filled M0s in GB lamina propria
o → bulge and lift the superficial epithelium overlying them.
o St assoc w chronic cholecystitis
o Mb localized or extensive and diffuse
o “strawberry gallbladder“= w diffuse mucosal involvement; hundreds of tiny (1mm or less) bright yellow dots (cholesterol); mucosa is red
o Asx, no clinical sig
o St find w chronic cholecystitis, cholelithiasis, but nor causative
o Both the pathogenesis and epidemiology is unknown
• What is chronic cholecystitis?
o pathogenesis not well understood.
o Mb hx repeated attacks of acute cholecystitis
o Bacteria in GB in 1/3 – ¼ cases
o F 30-50 (like acute)
o Usu assoc w cholelithiasis
o Asx, or like acute w chronic dz, biliary colic, fistula formation, GB hydrops, perforation
o Predisposes to GB CA
• What is gross appearance of chronic cholecystitis? Micro?
o GB mb enlarged, normal or shrunken
o GB wall is thickened, mucosal lining lost normal velvety, granular appearance; shaggy, roughened mucosal surface
o Fibrosis, necrosis, ulceration
o Outpouchings of mucosa thru muscle of GB wall (Rokitansky - Aschoff Sinuses)
o Micro: chronic inflam cells (M0s, Ls, plasma cels); surface epithelium lose normal delicate papillary appearance, fibrosis, chronic inflammation in the lamina propria; Rokitansky-Aschoff sinuses (pockets) in muscularis
• What is Porcelain gall bladder?
o calcification of GB dt persistent inflammation dt gallstones, exact cause not clear
o GB= porcelain-like vessel, dt fibrosis and calcification
o a morphological variant of chronic cholecystitis.
o Usu overweight F, ~40
o Tx: surgical removal (but if CA, fear of causing seeding)
o ↑ risk GB CA
• What is Choledocholithiasis?
o gall stone that has passed into CBD
o Obstruct bile flow → abd pn, jaundice
o Stagnant bile often becomes infected → ductal system into the liver →ascending cholangitis (emergency)
o If Obstruct pancreatic duct in ampulla of Vater → activate pancreatic digestive enzymes → acute pancreatitis
• What is MRCP? ERCP?
o MRCP: Magnetic resonance cholangiopancreatography;To visualize biliary and pancreatic ducts in non-surgical manner; see if gallstones are lodged in any of the ducts surrounding GB
o ERCP: Endoscopic retrograde cholangiopancreatography, for x-ray; combo endoscopy and fluoroscopy to dx biliary or pancreatic ductal do; see inside of stomach and duodenum, inject dyes into biliary ducts and pancreas; dx gallstones, inflammatory strictures, leaks from trauma and surgery, CA; dx or tx uses; Endoscopic sphincterotomy (both of the biliary and the pancreatic sphincters); Removal of stones; Insertion of stents, dilate strictures
• What is ascending/acute cholangitis? Ssx?
o Life-threatening, medical emergency
o infx of bile duct, usu dt bacteria ascending at jxn w duodenum
o esp if bile duct is already partially obstructed by gallstones (70-90%)/stricture
o ssx: jaundice, fever, abd pain, rigors, malaise; sever: ↓BP, shock; elderly mb atypical
o charcot’s triad: abd pn, jaundice, fever (20-70%)
o reynold’s pentad: Charcot + mental confusion, septic shock
• what is tx for acute cholangitis? Px? Micro?
o Tx: initial IV fluids/abx, tx underlying problem
o Px: Risk death, dt irreversible shock, multiple organ failure (dt severe infx); Mort rate 10-30%
o Micro: mb secondary sclerosing cholangitis, looks just like PSC (onion-skin)
• What is GB CA? incidence? Types?
o Aggressive; Strong assoc w gallstone dz, but w gall stones adenocarcinoma is rare
o 6,000 new cases of GB adenocarcinoma in US per yr (relatively uncommon)
o M:F 4:1 (2:1), avg 70 (50-60); N Indian, ppl of Americas
o Most are well differentiated adenocarcinomas
o Others: papillary adenocarcinoma, poorly differentiated adenocarcinoma, well differentiated adenocarcinoma w squamous metaplasia
