IUHS Student-2-Student USMLE Step 1 Recall
Biliary Tract
Cholelithiasis (Gallstones)
there are two main types of gallstones...in the west, about 80% are cholesterol monohydrate stones, containing more than 50% of crystalline cholesterol monohydrate...
the remainder are composed predominantly of bilirubin calcium salts and are designated pigment stones...
the prevalence rate of cholesterol gallstones approach 75% in native americans...the prevalence of gallstones increases throughout life...the prevalence in white women is about twice as high as in men (exceeding 50% by age 80 years)...with both aging and gender, hypersecretion of biliary cholesterol appears to play the major role...
estrogenic influences, including oral contraceptives and pregnancy, increase the expression of hepatic lipoprotein receptors and stimulate hepatic hydroxymethylglutaryl coenzyme A (HMG CoA) reductase activity...thus, both cholesterol uptake and biosynthesis, respectively, are increased...
cholesterol is rendered soluble in bile by aggregation with water soluble bile salts and water insoluble lecithins, both of which act as detergents...when cholesterol concentration exceed the solubilizing capacity of bile (supersaturation), cholesterol can no longer remain dispersed and nucleates into solid cholesterol monohydrate crystals...cholesterol gallstone formation involves a tetralogy of simultaneous defects...
bile must be supersaturate with cholesterol...gallbladder hypomotility promotes nucleation...cholesterol nucleation in bile is accelerated...mucus hypersecretion in the gallbladder traps the crystals, permitting their agglomeration into stones...
biliary hypersecretion of cholesterol appears to be the primary defect, mediated possibly by enhanced delivery to plasma cholesterol in circulating lipoproteins to bile and abnormal regulation of hepatic cholesterol biosynthetic pathways...
the
abundant free cholesterol is toxic to the gallbladder, exceeding the ability of
the mucosa to detoxify it by esterification...hypomotility, mucin hypersecretion,
and resultant sequestration of gallbladder bile promote nucleation and
agglomeration...
gallstones may be present for decades before symptoms develop, and 70-80% of patients remain asymptomatic throughout their lives...it appears that asymptomatic patients convert to symptomatic ones at the rate of 1-3% per year, and the risk diminished with time...
prominent among symptoms is biliary pain, which tends to be constant, or an excruciating "colicky" (spasmodic) pain due to the obstuctive nature of gallstones in the gallbladder or biliary tree proper...
inflammation of the gallbladder, in association with stones, also generates pain...
more severe complications include empyema, perforation, fistuals, inflammation of the biliary tree (cholangitis), and obstructive cholestasis or pancreatitis with ensuant problems...the larger the calculi, the less likely they are to enter the cystic or commmon ducts to produce obstruction...it is the very small stones, or "gravel", that are the more dangerous...a large stone may occasionally erode directly into an adjacent loop of small bowel, generating intestinal obstruction ("gallstone ileus")...on occasion, progressive mucosal removal of luminal lipids in obstructed, uninflamed gallbladder may leave clear mucinous secretions, so called hydrops or mucocelle of the gallbladder...
Pigment
Stones
pigment gallstones are mixtures of insoluble calcium salts of unconjugated bilirubin along with inorganic calcium salts...
unconjugated bilirubin is normally a minor component of bile but increases when infection of the biliary tract leads to release of microbial beta-glucuronidases, which hydrolyze bilirubin glucuronides...
thus, infection with E.coli, ascaris lumbricoides, or in asia, the liver fluke opisthorchis sinensis increases the likelihood of pigment stone formation...
alternatively, intravascular hemolysis leads to increased biliary excretion of conjugated bilirubin...since a low level (about 1%) of bilirubin glucuronides is deconjugated in the biliary tree even normally, the aqueous solubility of free bilirubin may easily be exceeded under hemolytic conditions, such as sickle cell anemia...
pigment gallstones are trivially classified as black and brown...in general, black pigment stones are found in sterile gallbladder bile, and brown stones are found in infected intrahepatic or extrahepatic ducts...
Cholesterol Stones
cholesterol stoens arise exclusively in the gallbladder and contain cholesterol contents ranging form 100% down to around 50%...
pure choleserol stones are pale yellow and round to ovoid and have a finely granular, hard external surface, which on transection reveals a glistening radiating crystallin palisade...with increasing proportions of calcium carbonate, phosphates, and bilirubin, the stones exhibit discoloration and may be lamellated and gray-white to black on transection...
most often, multiple stones are present that range up to several centimeters in diameter...rarely there is a single much larger stone that may virtually fill the fundus...surfaces of multiple stones may be rounded or faceted owing to tight apposition...stones composed largely of cholesterol are radiolucent; sufficient calcium carbonate is found in 10-20% of cholesterol stones to render them radiopaque...
Cholesterolosis
a incidental finding, pertinent to cholesterol biology but not directly related to gallstone formation is cholesterolosis...
cholesterol normally entering the gallbladder mucosa by free exchange with the lumen may be esterified by acyl CoA; cholesterol acyltransferase...
cholesterol hypersecretion by the liver promotes excessive accumulation of cholesterol esters within the lamina propria of the gallbladder...
the mucosal surface is studded with minute yellow flecks, producing the "strawberry gallbladder"...
Acute Cholecystitis
acute
calculous cholecystitis is an acute inflammation of the gallbladder,
precipitated 90% of the time by gallstone obstruction
of the neck or cystic duct...
it is the primary complication of gallstones and the most common reason for emergency cholecystectomy...
acute acalculous cholecystitis occurs in the absence of gallstones, generally in the severely ill patient...most of these cases occur in the following circumstances: (1) the postoperative state after major, nonbiliary surgery; (2) severe trauma (car accidents, war injuries); (3) severe burns; (4) multisystem organ failure; (5) sepsis; (6) prolonged intravenous hyperalimentation; and (7) the postpartum state...
Chronic
Cholecystitis
chronic cholecystitis may be a sequel to repeated bouts of mild to severe acute cholecystitis, but in many instances it develops in the apparent absence of antecedent attacks...since it is associated with cholelithiasis in more than 90% of cases, the populations of patients are the same as for cholelithiasis...
outpouchings of the mucosal epithelium through the wall (Rokitansky-Aschoff sinuses) may be prominent...superimposition of acute inflammatory changes implies acute exacerbation of a previously chronically injured gallbladder...
Choledocholithiasis
choledocholithiasis
is the presence of stones within the biliary tree,
occurring in about 10% of patients with cholelithiasis...in western nations,
almost all stones are derived from the gallbladder, although both cholesterol
and pigmented stones can form de novo in the biliary tree...
in the orient, there is a much higher incidence of primary ductal and intrahepatic stone formation, usually pigmented...
choledocholithiasis may be asymptomatic or may cause symptoms from (1) obstruction, (2) pancreatitis, (3) cholangitis, (4) hepatic abscess, (5) secondary biliary cirrhosis, and (6) acute cholecystitis...
Cholangitis
cholangits is the term used for bacterial infection of the bile ducts...cholangitis can result from any lesion creating obstruction to bile flow, most commonly choledocholithiasis..
uncommon causes include indwelling stents or catheters, tumors, acute pancreatitis, benign strictures, and rarely fungi, viruses, or parasites...bacteria most likely enter the biliary tract through the sphincter of Oddi; infection of intrahepatic biliary radicles is termed ascending cholangitis...
the bacteria are usually enteric gram negative aerobes such as E. coli, Klebsiella, Clostridium, Bacteroides, or Enterobacter and group D streptococci...
cholangitis usually generates fever, chills, abdominal pain, and jaundice accompanied by acute inflammmation of the wall of the bile ducts with entry of neutrophils into the luminal space...
intermittence of symptoms suggests bouts of partial obstruction...the most severe form of cholangitisis suppurative cholangitis, in which purulent bile fills and distends bile ducts, extending into the hepatic substance to cause liver absceses...b/c sepsis rather than cholestasis tends to dominate the picture, prompt diagnostic evaluation and intervention are imperative in these unstable patients...
Biliary Atresia
a major contributor to neonatal cholestasis is extrahepatic biliary atresia, representing one third of infants with neonatal cholestasis and occurring in approximately 1:10,000 live births...
extrahepatic biliary atresia is defined as a complete obstruction of bile flow due to destruction or absence of all or part of the extrahepatic bile ducts...
it is the single most frequent cause of death from liver disease in early childhood and accounts for 50-60% of children referrred for liver transplantation b/c of the rapidly progressing secondary biliary cirrhosis...
the salient features of extrahepatic biliary atresia include inflammation and fibrosing stricture of the hepatic or common bile ducts, peridutual inflammation of intrahepatic bile ducts, and progressive destruction of the intrahepatic biliary tree...
infants with extrahepatic biliary atresia present with neonatal cholestasis, discussed previously...these infants exhibit normal birth weight and postnatal weight gain, a slight female preponderance, and the progression of initially normal stools to acholic stools as the disease evolves...
Choledochal Cysts
choledochal cysts are congenital dilations of the common bile duct, presenting most often in children before age 10 years with the nonspecific symptoms of jaundice or recurrent abdominal pain typical of biliary colic...
approximately 20% of cases become symptomatic only in adulthood; these sometimes occur in conjunction with cystic dilation of the intrahepatic biliary tree (Caroli disease)...
the female to male ratio is 3 to 4:1...these uncommon cysts may take the form of segmental or cylindrical dilation of the common bile duct; diverticula of the extrahepatic ducts; or choledochoceles, which are cystic lesions that protrude into the duodenal lumen...
choledochal cysts predispose to stone formation, stenosis and stricture, pancreatitis, and obstuctive biliary complications within the liver...in the older patient, the risk of bile duct carcinoma is increased...
Adenomas of the Biliary Tract
adenomas are benign epithelial tumors representing localized neoplastic growth of the lining epithelium and are similar to adenomas found elsewhere in the alimentary tract...
inflammatory polyps are sessile mucosal projections with a surface of columnar epithelia cells covering a fibrous stroma infiltrated with chronic inflammatory cells and lipid-laden macrophages...
these lesions may be difficult to differentiate from neoplasms on imaging studies...
adenomyosis of the gallbladder is characterized by hyperplasia of the muscularis, containing intramural hyperplastic glands...
fatality high...1% survive past 5 years...
women predominant (3:1)...
stones very frequently...(90%)...
Carcinoma of the Gallbladder
carcinoma of the gallbaldder is slightly more common in women and occurs most frequently in the seventh decade of life...only rarely is it discovered at a resectable stage, and the mean 5-year survival has remained for many years at about 1%, despite surgical intervention...
gallstones are present in 60-90% of cases, but not 100%; in asia, where pyogenic and parasitic disease of the biliary tree is common, the coexistence of gallstones is much lower...
presumably, gallbladders containing stones or infectious agents develop cancer as a result of irritative trauma and chronic inflammation...carcinogenic derivatives of bile acids may also play a role...