Diseases of the gall-bladder and biliary tract based on www.harrisonsonline.com images.MD, Gallstones Grant Sanders, Andrew N Kingsnorth BMJ 2007;335:295-9 NEJM and and many others Dr. Fenyvesi Tamás 04/10/2017 11 „Become a doctor, no lectures required.” Saying Goodbye to Lectures in Medical School — Paradigm Shift or Passing Fad? Richard M. Schwartzstein, M.D., and David H. Roberts, M.D. NEJM 2017;377:605 2 Secretion of the bile in the. hepatic lobuli : ductuli---interlobular ducti—right and and left ductus hepaticus ; Here joins the ductus cysticus, The common ductus choledochus -ampulla Vateri-duodenum 33 44 . The bile is a pigmented isotonic fluid: water 82%,bile acids 12%, lecithin and other phospholipids 4%, Non esteric cholesterol 0,7%, etc ( ions, proteins, mucus,metabolites) 55 The primary bile acids : cholic- and chenodeoxicholic-acid derived from cholesterole and excreded in conjugation with glycin or taurin. They are detergents in watery solution, above 2mM concentration they form aggregates (micellum) 66 The enterohepatic circulation is a basic phenomenon Bile acids (b.a)are reabsorbed from the whole intestine in a passive way and actively from the jejunum Tha b.a.reserv is ~ 2-4g , 5-10 recirculations daily loss about 0.3-0.6g synthesis is being hinderd by reabsorbed b.a. ( 7 α-hydroxylase ) 77 . [email protected] 88 Function of the g.b. and of the Oddi sphincter The O.s. controlls the excretion of bile and stops reflux from the duodenum The g.b. function is controlled by cholecystokinin from duodenum mucosa (amino acids and fat…) g.b. contraction choledochus peristaltics O.s. resistance decrease increase of bile flow 99 Functioning of the gall bladder and of the Sphincter of Oddi: In an interdigestiv period 4-8/min phasic anterograde peristaltic contraction: minute „gall injections” into the duodenum, cleansing the sphincter of food remnants and small stones 1010 Storage and excretion from the gall bladder 1111 Muscular layer of the gallbladder 12 12 Mechanism of gallbladder function 13 13 Cholelithiasis First description 1341 Padua: Gentile de Foligno 40 yo < women 20%- , men 8%- prevalence cristallic structure formed from normal and pathol component of bile cholest and mixed stones 8 0% 70% cholest, Ca salts, bile acids, pigments Pigment stones 20% Ca bilirubin complex only 10% cholest 1414 About 10-15% of the adult Western population will develop gallstones, with between 1% and 4% a year developing symptoms. 1515 Cholesterol stones • Most prevalent in the bladder • >90% cholesterol • Minimal Ca larger than the pigment stones 1616 Pigment stones (calcium bilirubinate) 1. Demographic-genetic factors: Asia! 2. Chronic haemolysis 3. Alcoholic cirrhosis 4. Chronic bile infections 5. old age Increased conjugated bilirubin in the bile ducts causes precipitation 1717 Pathophysiology of cholesterol gallstone formation 18 18 19 19 Gallstones occur when there is an imbalance in the chemical constituents of bile that results in precipitation of one or more of the components. Why this occurs is unclear, although certain risk factors are known. 2020 21 21 gall bladder stasis, sludge and stone formation 22 22 10-15% prevalence in the US population Surprisingly it leads to ~1.000 death/year It is highly prevalent in American Indians Yearly~ 500 000 cholecystectomies the cost is ˃ 6 Mld $ (or as used in theUS billion) 2323 Conditions to stone formation 1. formation lithogenic bile Obesity, high calory diet, clofibrate increase in HMG-CoA reductase enzyme activity decrease cholic acid secretion Increase of cholesterin/cholic acid relation 2424 2. Instabile cholesterole-rich vesicules, cholesterol monohydrate cristals 3. Cholesterol nucleus formation 4. Bile sludge formation (semilunar layer at the wall of the g-bladder) pregnancy, very calory poor diet 2525 5. Disease of the ileum or postop Malabsorption of bile acids Decrease in bile acid pool, Secretion of bile-salts 7α-hydroxylase activity 2626 6. Increase of age Increase in cholesterole secretion, Decrease of bile acid pool And secretion of bile acid salts 2727 7. Gall bladder hypomotility causes sludge/stone formation a. Parenteral feeding b. starvation c. pregnancy d. some drugs: octreotide somatostatin analogue, clofibrate 2828 8. decreased bile-acid secretion a.primer biliary cirrhosis b.chronic intrahepatic cholestasis 9. Etc a, high calory/fat diet b. spine trauma(?) 2929 Pregnancy a. in the third trimester the cholesterole saturation of the bile increases b. the gall bladder contraction on food intake decreases This leads to sludge formation in 20-30 % gall-stones in 5-12% 3030 1.Demography North Europe, USA> Asia, Family, inherited traits 2.Obesity Normal b.a. storage and secretion, but increased cholesterole bile secretion 3.Weight loss tissue cholest mobilization leads to increased biliary cholest secretion 3131 4. Female sex hormones a. estrogens stimulate hepatic lipoprotein receptors, stimulate cholesterole absorption, biliar cholesterole secretion, decreases chenodeoxycholic a. synthesis b. anticoncipients decrease c.a. secretion and cholesterol esterification 3232 Diagnostics 1.Ultrasound 2.CT 3.MR cholangiopancreatography 4.Nuclear cholangio -cholecystography 5.percutaneous transhepatic cholangiography 6.ERCP 3333 Dg of gallstones Abdominal ultrasound is the method of choice ( a stone and a „shadow”) 2 mm is detectable, the false pozitive and false negative ratio 2-4% 3434 US scan shows highly reflective echoes within the gallbladder (arrows), which indicate gallstones and shadowing .( RadiologyInfo.org) 35 Acalculous cholecystitis with dilated gallbladder and thickened gallbladder wall 36 36 Appearance of gallstones 37 37 Appearance of gallstones 38 38 Cholesterol stones 39 39 Cholangiography 40 40 41 41 Cholangiography 42 42 Gall stones are common but often do not give rise to symptoms. Pain arising from the gall bladder may be typical of biliary colic, but a wide variety of atypical presentations can make the diagnosis challenging. BMJ 2001;323:1170-3 N.B. angina pectoris P.D.White 43 Stone in ductus choledochus g.bladder stone to the ductus cysticus 44 Asymptomatic gallbladder diseases Cholelithiasis is defined as asymptomatic^ when gallstones do not relate to symptoms such as pain or complications such as acute cholecystitis, cholangitis, or pancreatitis The estimated prevalence of gallstones is 10– 25 % and 50–80 % of the patients are asymptomatic at the diagnosis 4545 Symptoms of cholelithiasis Most common right upper quadrant pain Usually not waxing and waning like intestinal colic the stone may occlude the cistic duct, or the common bile duct (this leads to jaundice) It may radiate to the right scapula. It is often causing cholecystitis 4646 Moderate increase serum bilirubin ( normal values 5-21 µµµmol/l) conjugated with glucuronic acid : „direct” bilirubin Fever is a sign of complication (-itis) epigastrialial fullness, flatulence Possible precipitating cause fatty food or „gobbling” 4747 Management of gall stones 1. Surgical Operate on asymptomatic? indications a. repeat colics, quality of life b. events in history: cholecistitis, pancreatitis etc c. different complications acut cholecystitis, porcelain g.bladder, small stones (?) , statistics on gall bladder cancer…. 4848 The„gold standard”) technique is laparoscopic cholecystectomy from a study of 4.000 cases 1.complications 4% 2. „upgrade” to laparotomy 5% 3. lethality < 0,1% 4. injury to ducts 4% intraop cholangio 30 % postop ERCP 1,5% 4949 History of laparoscopic cholecystectomy 50 50 1. Who should undergo LC? 2. How should common bile stones be managed? 3. In what stage of technological development is LC? 4. Is LC safe and feasible? 5. Is it beneficial to the patients? 6. What are the special aspects to be considered during LC? 7. What are the training recommendations for LC? Consensus Conference 2015 5151 Indications for laparoscopic cholecystectomy 52 52 Conservative management of cholelithiasis UDCA and CDCA decrease the HMG-CoA reductase activity the cholesterol synthesis decreases in the liver UDCA decreases the stone formation and some of the stones dissolve, but very expensive , and difficult compliance and the stones recur in 50% extracorporeal shock-wave lithotripsy (electrohidraulic, piezoceramic, electromagnetic) practically disapeared with laparoscopy 5353 Evacuation of gallstone fragments after shockwave lithotripsy 54 54 Acute @ chronic cholecystitis Acute: ductus cysticus obstruction by stone 1. mechanical inflammation from stretch 2. chemical infl. from lysolecithin and other tissue products 3. bacterial infl. 50-85% of cases 5555 Characteristic symptoms starts as bile colic irradiates to the right scapula vomiting, exsiccosis fever, even chills , a RUQ pain may cause a sudden halt in inspiration (Murphy sign) A „triad”: RUQ tenderness fever leukocytosis Laboratory signs : many 5656 Some cases without gall-stones 5-10 % causes: traume , burns after delivery adenocarcinoma vasculitis diabetes torsion of the gall-bladder 5757 Complications of cholecystitis Empyema: d.cysticus obstruction hydrops : long-standing obstruction, usually one big stone in the bladder palpable!! Must be operated on 5858 Gangrena and perforation ischemia of the dilated bladder , abscess may develop urgent operation „free” perforation is rare :lethality 30% Fistule formation :mostly cholecysto- duodenal. Air in the bile ducts or contrast reflux during barium meal Gall-stone ileus big stones to the duodenum through a fistule porcelain gall-bladder carcinoma !! 5959 Treatment of cholecystitis