Gallstone diseaseGallstone disease

Gallstone diseaseGallstone disease Bile Bile

Volume = 500-1500 ml/dayVolume = 500-1500 ml/day Hepatocytes and canalicular cellsHepatocytes and canalicular cells Bile salts + bilirubine + cholesterol + phospholipidsBile salts + bilirubine + cholesterol + phospholipids Bile flow depends onBile flow depends on: :

Its hepatic secretion;Its hepatic secretion; Contraction of the gall bladderContraction of the gall bladder Activity of the Oddi sphincterActivity of the Oddi sphincter

ColecistokininColecistokininee (CCK) (CCK) postprandial contraction of the gallbladder and relaxation of the Oddi postprandial contraction of the gallbladder and relaxation of the Oddi sphincter (vagal nerve facilitates this action)sphincter (vagal nerve facilitates this action)

Bile saltsBile salts Cholesterol-derived steroids synthesized in the hepatocyteCholesterol-derived steroids synthesized in the hepatocyte Function:Function:

InducInduce bile flow;e bile flow; Lipid transport;Lipid transport; Binds calcium ions in the bile;Binds calcium ions in the bile; In the jejunum – bile salts take part in the digestion and absorbtion of lipids. In the last 200 cm of the ileum In the jejunum – bile salts take part in the digestion and absorbtion of lipids. In the last 200 cm of the ileum

bile salts are reabsordeb by active transport – 95 %, and the rest end up in the colon – secondary bile saltsbile salts are reabsordeb by active transport – 95 %, and the rest end up in the colon – secondary bile salts

BilirubinBilirubinee Results from the destruction of RBC (75%) and from the hepatic turnover of the heme molecule Results from the destruction of RBC (75%) and from the hepatic turnover of the heme molecule

and of the haemoproteines (25%);and of the haemoproteines (25%); Haem is released from the haemoglobin and the iron and the globine are processed to be Haem is released from the haemoglobin and the iron and the globine are processed to be

reused;reused; Biliverdine, the first pigment resulted from the heme and it is reduced to unconjugated Biliverdine, the first pigment resulted from the heme and it is reduced to unconjugated

bilirubine (it must be linked to albumin because it is not soluble in water)bilirubine (it must be linked to albumin because it is not soluble in water) Unconjugated bilirubine is extracted from the blood by the hepatocytes and conjugated using Unconjugated bilirubine is extracted from the blood by the hepatocytes and conjugated using

glicuronic acid – direct bilirubine (water soluble) – conjugation is catalyzed by glicuronic acid – direct bilirubine (water soluble) – conjugation is catalyzed by glicuroniltransferase;glicuroniltransferase;

In the intestine bilirubine is reduced by the bacterial population in mesobilirubinogen, In the intestine bilirubine is reduced by the bacterial population in mesobilirubinogen, stercobilirubinogen and urobilinogen which are oxidized to urobiline; stercobilirubinogen and urobilinogen which are oxidized to urobiline;

Part of the urobilinogen is reabsorbed from the intestine and reaches the blood flow to be Part of the urobilinogen is reabsorbed from the intestine and reaches the blood flow to be excreted in urine.excreted in urine.

Gallstone diseaseGallstone disease 2 types of gallstones2 types of gallstones

Cholesterol – based: 70-80%Cholesterol – based: 70-80% Pigmentary – black or brown Pigmentary – black or brown

20-30%20-30% CholesterolCholesterol 3 necessary conditions3 necessary conditions

Oversaturation of cholesterol in the bileOversaturation of cholesterol in the bile Cholesterol is insoluble in water – micelae of bile salts Cholesterol is insoluble in water – micelae of bile salts

phospholipidic vesicles (lecitine) - when cholesterol concentration phospholipidic vesicles (lecitine) - when cholesterol concentration in the bile increases above the transport capacity cholesterol in the bile increases above the transport capacity cholesterol crystals precipitate out of the phospholipid vesicles. crystals precipitate out of the phospholipid vesicles.

Obesity, oral contraceptives, more than one pregnancy, Obesity, oral contraceptives, more than one pregnancy, dislipidemiadislipidemia

NucleationNucleation Pronucleation factors (immunoglobins, glicoproteins, Pronucleation factors (immunoglobins, glicoproteins,

fibronectines, orosomucoid) have a more important effect than fibronectines, orosomucoid) have a more important effect than antinucleation factors (glicoproteins, apolipoproteins, antinucleation factors (glicoproteins, apolipoproteins, citokeratine). citokeratine).

Gallstone increaseGallstone increase Nucleae and cholesterol accumulation in the gallbladder leads to Nucleae and cholesterol accumulation in the gallbladder leads to

stasis and further gall stone development.stasis and further gall stone development.

PigmentaryPigmentary Made from mixtures of Made from mixtures of

calcium bilirubinate, calcium bilirubinate, bilirubine polymers, bile bilirubine polymers, bile acids. acids.

50% - radioopaques 50% - radioopaques Electron microscopy – Electron microscopy –

mixture of bacteria along mixture of bacteria along with bile pigmentswith bile pigments

Risk factors: Risk factors: Cirrhosis, bile stasis, Cirrhosis, bile stasis,

chronic haemolysis, chronic haemolysis, bacterial infectionbacterial infection

Bacterial β glicuronidase – Bacterial β glicuronidase – deconjugation of the deconjugation of the bilirubin-diglucuronid bilirubin-diglucuronid which is soluble to which is soluble to unconjugated bilirubine unconjugated bilirubine which forms a which forms a conglomerate with the conglomerate with the glicocalix and becomes a glicocalix and becomes a gallstone.gallstone.

Gallstone diseaseGallstone disease Incidence increases with age Incidence increases with age Drugs Drugs

ceftriaxone, clofibrate, oral contraceptives, estrogen ceftriaxone, clofibrate, oral contraceptives, estrogen suppliments, progesterone, octreotidesuppliments, progesterone, octreotide

SexSex EthnicityEthnicity

Pima indians - Arizona (70%), Canada, hispanicsPima indians - Arizona (70%), Canada, hispanics Masai Africa – 0% Masai Africa – 0%

ObesityObesity BMI>30kg/m2 - 2X risk increaseBMI>30kg/m2 - 2X risk increase Cholesterol hipersecretionCholesterol hipersecretion

Weight lossWeight loss Mobilizes cholesterol from fat deposits and it eliminates it Mobilizes cholesterol from fat deposits and it eliminates it

through bilethrough bile

Gallstone diseaseGallstone disease CLINICACLINICALL subjectivesubjective

AsymptomaticAsymptomatic Cholicative painCholicative pain

Spasm due to temporary obstruction of the cystic ductSpasm due to temporary obstruction of the cystic duct Sudden onset – epigastriumSudden onset – epigastrium,, right hypochondria right hypochondria Progrssive increase in intensityProgrssive increase in intensity 15 min 15 min to a few hoursto a few hours IradiaIradiates în the right lumbar area and the righ tes în the right lumbar area and the righ

interscapulo-vertebral areainterscapulo-vertebral area Reoccurs in days-months-yearsReoccurs in days-months-years

Symptoms related to a complicationSymptoms related to a complication Acute cholecystitisAcute cholecystitis JaundiceJaundice Acute pancreatitisAcute pancreatitis

ObjectiveObjective NormalNormal Tenderness - Tenderness - epigastriumepigastrium,, right hypochondria right hypochondria ComplicationComplication

Murphy sign – Acute cholecystitisMurphy sign – Acute cholecystitis Jaundice Jaundice

Gallstone Gallstone diseasedisease

DIAGNOSTICDIAGNOSTIC UltrasoundUltrasound Abdominal X-rayAbdominal X-ray

Gallstone diseaseGallstone disease

CTCT

ERCPERCP

echoendoscopechoendoscopiaia

Cholangio-MRICholangio-MRI ScintigraphyScintigraphy

Gallstone diseaseGallstone disease DifferentialDifferential Gastric diseaseGastric disease

Peptic ulcer, GERD, Hiatal Peptic ulcer, GERD, Hiatal herniahernia Liver diseaseLiver disease

Hydatic cyst, cirrhosis, hepatocarcinoma, Hydatic cyst, cirrhosis, hepatocarcinoma, cholangiocarcinomacholangiocarcinoma

Pancreatic diseasePancreatic disease Chronic pancreatitis, pancreatic tumorsChronic pancreatitis, pancreatic tumors

Bowel diseaseBowel disease Irritable bowel syndromeIrritable bowel syndrome, appendicitis, appendicitis

Kidney diseaseKidney disease Kidney stone, pielonefritisKidney stone, pielonefritis

Lung diseaseLung disease Pneumonia, Pneumonia, pleural effusionpleural effusion

Heart diseaseHeart disease Myocradial infarctionMyocradial infarction

Gallstone diseaseGallstone disease

ComplicationsComplications Chronic colecystitis Chronic colecystitis Acute colecystitis Acute colecystitis Lytiasis of the main bile Lytiasis of the main bile

ductduct Acute pancreatitisAcute pancreatitis CCholangitisholangitis FistulaeFistulae IleusIleus Gallbladder cancerGallbladder cancer Mirrizi Mirrizi syndrome syndrome Porcelain gallbladderPorcelain gallbladder

Gallstone diseaseGallstone disease

TreatmentTreatment Wait and seeWait and see MedicalMedical

Ursodezoxicolic acid Ursodezoxicolic acid Small gallstonesSmall gallstones 15% of the cases 15% of the cases 6-12 Months6-12 Months Recurrence - 50% at 5 aniRecurrence - 50% at 5 ani

SurgicalSurgical

Gallstone diseaseGallstone disease Extracorporeal sound wave lithotripsy Extracorporeal sound wave lithotripsy

High surgical risk patientsHigh surgical risk patients Cholesterol gallstonesCholesterol gallstones Small stones 4-30 mmSmall stones 4-30 mm Permeable cystic ductPermeable cystic duct < 4 stones< 4 stones 15% of patients15% of patients Side effectsSide effects

Petechiae, ecchymosisPetechiae, ecchymosis PainPain HematuriaHematuria NauseaNausea

Gallstone diseaseGallstone disease Percutaneous Percutaneous therapytherapy

Gallstone diseaseGallstone disease ERCPERCP

Acute cholecystitis Acute cholecystitis 90-95% due to lytiasis90-95% due to lytiasis 80% - obstruction of cystic duct80% - obstruction of cystic duct Gallbaldder – inflamed, distended - Gallbaldder – inflamed, distended -

pain. pain. Most cases – spontaneous remission, Most cases – spontaneous remission,

but sometimes - peritonitis.but sometimes - peritonitis. HistologyHistology

Subserosal oedema, haemmorhage, Subserosal oedema, haemmorhage, necrosis of the mucosanecrosis of the mucosa

Later – polymorphonucleary infiltrateLater – polymorphonucleary infiltrate FibrosisFibrosis Sometimes – gangrene and perforation 3 Sometimes – gangrene and perforation 3

days-2 weeks from first symptomsdays-2 weeks from first symptoms

Acute cholecystitis Acute cholecystitis Obstruction theoryObstruction theory

Sudden accumulation of bile in the gallbladder – parietal Sudden accumulation of bile in the gallbladder – parietal ischemiaischemia

Bile stasis – increase in bile concentration – chemical irritation Bile stasis – increase in bile concentration – chemical irritation – aseptic inflammation– aseptic inflammation

Progressive parietal ischemia – necrosisProgressive parietal ischemia – necrosis Cystic duct obstruction Cystic duct obstruction

Pancreatic enzymes theoryPancreatic enzymes theory Activation of pancreatic enzymes that backflowed to the Activation of pancreatic enzymes that backflowed to the

gallbladder – chemical irritation.gallbladder – chemical irritation. Septic theorySeptic theory

Hematogeneous pathway (portal or systemic);Hematogeneous pathway (portal or systemic); Septic backflow;Septic backflow;

Acute cholecystitis Acute cholecystitis

Alytiasic acute cholecystitisAlytiasic acute cholecystitis 5-10% of cases5-10% of cases Patients with:Patients with:

Severe traumaSevere trauma Burns Burns Long-term Long-term parenteral nutritionparenteral nutrition Major surgery outside the biliary treeMajor surgery outside the biliary tree

EtiologyEtiology Bile stasis and ischemiaBile stasis and ischemia

More severe than lytiasic acute cholecystitisMore severe than lytiasic acute cholecystitis Gangrene, empyema, perforationGangrene, empyema, perforation

Acute cholecystitis Acute cholecystitis

DiagnosisDiagnosis Pain in right hypochondriaPain in right hypochondria Murphy signMurphy sign FevreFevre Leucocitosis Leucocitosis

>12-13000/mm3>12-13000/mm3 US US

Gallstone Gallstone Oedematous gallbladder Oedematous gallbladder

walls >5 mmwalls >5 mm Enlarged gallbladder Enlarged gallbladder

Also possibleAlso possible Nausea, vomitingNausea, vomiting ChillsChills Gallbladder palpable Gallbladder palpable USUS

Liquid aroung the Liquid aroung the gallbladdergallbladder

AbscessAbscess

Acute cholecystitis Acute cholecystitis DifferentialDifferential Perforated peptic ulcerPerforated peptic ulcer Acute pancreatitisAcute pancreatitis Acute apendicitisAcute apendicitis Digestive tract perforationsDigestive tract perforations Peritonitis Peritonitis Acute kidney diseaseAcute kidney disease Acute lung diseaseAcute lung disease Gonococic perihepatitisGonococic perihepatitis Hepatomegaly with sudden distension of the Hepatomegaly with sudden distension of the

capsula of Glissoncapsula of Glisson

Acute cholecystitis Acute cholecystitis

ComplicationComplication Gangrenous acute Gangrenous acute

cholecystitischolecystitis Emphysematous acute Emphysematous acute

cholecystitis - cholecystitis - Clostridium Clostridium perfringens, E. coli, perfringens, E. coli, streptococusstreptococus

Acute cholecystitis Acute cholecystitis PerforationPerforation

Localized peritonitisLocalized peritonitis Abscess located under the liverAbscess located under the liver

Generalized peritonitisGeneralized peritonitis Choleperitonitis Choleperitonitis FistulaeFistulae

Duodenum, colon, stomachDuodenum, colon, stomach IleusIleus In the main bile ductIn the main bile duct

Acute cholecystitis Acute cholecystitis

TreatmentTreatment MedicalMedical

Pain Pain Hidroelectrolitic balanceHidroelectrolitic balance Stop oral food intakeStop oral food intake

±± NG tube NG tube AntibiotherapyAntibiotherapy

CefalosporinesCefalosporines Type A penicilinestip A+aminoglicozides Type A penicilinestip A+aminoglicozides ±±

metronidazolemetronidazole CarbapenemesCarbapenemes

Acute cholecystitis Acute cholecystitis SurgicalSurgical CholecystectomyCholecystectomy

LaparoscopicLaparoscopic OpenOpen

Timing of the procedureTiming of the procedure 60% spontaneous remission60% spontaneous remission Early – first 72-96 hoursEarly – first 72-96 hours Secondary – after 4-6 weeksSecondary – after 4-6 weeks

CholecystectomyCholecystectomy Severely altered state of patientsSeverely altered state of patients

Main bile duct lMain bile duct liitiasistiasis

7-15% of patients 7-15% of patients with galbladder with galbladder litiasis also present litiasis also present main bile duct main bile duct litiasislitiasis

typestypes SecondarySecondary PrimitivePrimitive

Associated with Associated with stasis and infectionstasis and infection

Stasis can be due toStasis can be due to StricturesStrictures Stenosis of the Stenosis of the

papilapapila Oddi sphincter Oddi sphincter

disfunctiondisfunction

Main bile Main bile duct lduct liitiasistiasis

Severe Severe complicationscomplications JaundiceJaundice CholangitisCholangitis Acute pancreatitisAcute pancreatitis

Main bile duct lMain bile duct liitiasistiasis JaundiceJaundice Possibly no painPossibly no pain Frequent episodes of Frequent episodes of

jaundicejaundice Obstacle+spasm+oedeObstacle+spasm+oede

mama Stasis – increased Stasis – increased

pressure in the bile pressure in the bile canaliculycanaliculy

Main bile duct Main bile duct lliitiasistiasis colicative pain+(fever)+jaundicecolicative pain+(fever)+jaundice

Hypochromic stoolsHypochromic stools Hyperchromic urineHyperchromic urine PruritusPruritus LaboratoryLaboratory

Serum Serum BilirubineBilirubine Alkalyne phosphatasisAlkalyne phosphatasis Cholesterol is increasedCholesterol is increased Increased bile saltsIncreased bile salts ALAT,ASAT almost normalALAT,ASAT almost normal

UrineUrine Urobilinogen - absentUrobilinogen - absent Bile salts – increasedBile salts – increased Conjugated bilirubineConjugated bilirubine

StoolStool Stercobilinogen, urobilineStercobilinogen, urobiline

Main bile duct Main bile duct lliitiasistiasis

ParaclinicalParaclinical NG tube – no bileNG tube – no bile USUS

Gallstones in main Gallstones in main bile ductbile duct

Biliary ducts - dilatedBiliary ducts - dilated ERCPERCP CTCT

Main bile Main bile duct duct

lliitiasistiasis EchoendoscopyEchoendoscopy Cholangio - MRICholangio - MRI

Main bile duct lMain bile duct liitiasistiasis DifferentialDifferential Prehepatic jaundicePrehepatic jaundice

SerumSerum Unconjugated bilirubineUnconjugated bilirubine Normal hepatic testsNormal hepatic tests

UrineUrine Urobilinogen – increasedUrobilinogen – increased Absence of bilirubineAbsence of bilirubine

Stool – increased stercobilineStool – increased stercobiline US – normal bile ductsUS – normal bile ducts

Hepatic jaundiceHepatic jaundice Hepatitis, cirrhosisHepatitis, cirrhosis Conjugation defficit and elimination defficit Conjugation defficit and elimination defficit SerumSerum

Unconjugated and conjugated bilirubine increasedUnconjugated and conjugated bilirubine increased Bile salts increasedBile salts increased Increased cytolisisIncreased cytolisis

UrineUrine Conj bilirubine, bile salts, urobilinogen Conj bilirubine, bile salts, urobilinogen

US – bilre duct not dilatedUS – bilre duct not dilated

Main bile duct Main bile duct lliitiasistiasis

EndoscopicEndoscopic Baloon probe Baloon probe SphincterotomySphincterotomy

PercutaneousPercutaneous

SurgicalSurgical Laparoscopic or openLaparoscopic or open

CholecystectomyCholecystectomy CholangiographyCholangiography Extraction of the Extraction of the

gallstonesgallstones TranscysticTranscystic TranscoledocianTranscoledocian

CholedocoscopyCholedocoscopy CholangiographyCholangiography Kehr drain Kehr drain Bilo-digestive Bilo-digestive

anastomosisanastomosis Transduodenal Transduodenal

sphicterotomysphicterotomy

CHOLANGITISCHOLANGITIS Bacterial infection of bile ducts – no obstruction, no clinical Bacterial infection of bile ducts – no obstruction, no clinical

symptomssymptoms Not every obstruction leads to cholangitis Not every obstruction leads to cholangitis Obstruction – increased bile duct pressure – bacterial Obstruction – increased bile duct pressure – bacterial

proliferation – systemic diseaseproliferation – systemic disease Charcot triade: colicative pain, jaundicem, fever.Charcot triade: colicative pain, jaundicem, fever. Most common: E. Coli, Klebsiella, Pseudomonas, Enterococi, Most common: E. Coli, Klebsiella, Pseudomonas, Enterococi,

Proteus. Bacteroides fragilis, Clostridium perfingens Proteus. Bacteroides fragilis, Clostridium perfingens Supurative cholangitis is used for severe disease associated with Supurative cholangitis is used for severe disease associated with

sepsis:sepsis: Abdominal painAbdominal pain Jaundice Jaundice FeverFever ConfusionConfusion shockshock

90% - i.v. antibiotics90% - i.v. antibiotics Severe cholangitis or lack of response to antibiotics – Severe cholangitis or lack of response to antibiotics –

decompression of the main bile duct:decompression of the main bile duct: EndoscopicallyEndoscopically PercutaneouslyPercutaneously SurgicalySurgicaly

Biliary fistulaeBiliary fistulae BiliodigestiveBiliodigestive BiliobiliaryBiliobiliary Old litiasis patient with frequent inflammatory episodesOld litiasis patient with frequent inflammatory episodes Inflammed gallbladder adheres to an organ which is in the Inflammed gallbladder adheres to an organ which is in the

vicinity – necrosis – perforationvicinity – necrosis – perforation First an acute episode and then a decrease in symptoms First an acute episode and then a decrease in symptoms

after fistula occuredafter fistula occured Gallstones can pass through the fistula and cause Gallstones can pass through the fistula and cause

Vomiting and nauseaVomiting and nausea IleusIleus Bouvert piloro-duodenal obstructionBouvert piloro-duodenal obstruction CholangitisCholangitis Main bile duct litiasisMain bile duct litiasis

Abdominal X-rayAbdominal X-ray Air in the main bile ductAir in the main bile duct Air-fluid levelsAir-fluid levels Radioopaque gallstoneRadioopaque gallstone

Barium mealBarium meal Contrast passes into the Contrast passes into the

main bile ductmain bile duct USUS

Gallbladder stonesGallbladder stones Radioopaque stones Radioopaque stones

abnormally locatedabnormally located Endoscopy, Endoscopy,

echoendoscopy, CTechoendoscopy, CT

Mirrizi syndromeMirrizi syndrome ERCPERCP USUS CholecystectomyCholecystectomy

Porcelain gallbladderPorcelain gallbladder Calcification of the walls of the gallbladderCalcification of the walls of the gallbladder ComplicationComplication

Gallbladder cancerGallbladder cancer Profilactic cholecystectomyProfilactic cholecystectomy