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Gallstone disease. Gallstone disease. Bile Volume = 500-1500 ml/day Hepatocytes and canalicular cells Bile salts + bilirubine + cholesterol + phospholipids Bile flow depends on : Its hepatic secretion; Contraction of the gall bladder Activity of the Oddi sphincter
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Gallstone disease • Bile • Volume = 500-1500 ml/day • Hepatocytes and canalicular cells • Bile salts + bilirubine + cholesterol + phospholipids • Bile flow depends on: • Its hepatic secretion; • Contraction of the gall bladder • Activity of the Oddi sphincter • Colecistokinine (CCK) postprandial contraction of the gallbladder and relaxation of the Oddi sphincter (vagal nerve facilitates this action) • Bile salts • Cholesterol-derived steroids synthesized in the hepatocyte • Function: • Induce bile flow; • Lipid transport; • 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 bile salts are reabsordeb by active transport – 95 %, and the rest end up in the colon – secondary bile salts • Bilirubine • Results from the destruction of RBC (75%) and from the hepatic turnover of the heme molecule and of the haemoproteines (25%); • Haem is released from the haemoglobin and the iron and the globine are processed to be reused; • 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) • Unconjugated bilirubine is extracted from the blood by the hepatocytes and conjugated using glicuronic acid – direct bilirubine (water soluble) – conjugation is catalyzed by glicuroniltransferase; • In the intestine bilirubine is reduced by the bacterial population in mesobilirubinogen, stercobilirubinogen and urobilinogen which are oxidized to urobiline; • Part of the urobilinogen is reabsorbed from the intestine and reaches the blood flow to be excreted in urine.
Gallstone disease • 2 types of gallstones • Cholesterol – based: 70-80% • Pigmentary – black or brown 20-30% • Cholesterol • 3 necessary conditions • Oversaturation of cholesterol in the bile • Cholesterol is insoluble in water – micelae of bile salts phospholipidic vesicles (lecitine) - when cholesterol concentration in the bile increases above the transport capacity cholesterol crystals precipitate out of the phospholipid vesicles. • Obesity, oral contraceptives, more than one pregnancy, dislipidemia • Nucleation • Pronucleation factors (immunoglobins, glicoproteins, fibronectines, orosomucoid) have a more important effect than antinucleation factors (glicoproteins, apolipoproteins, citokeratine). • Gallstone increase • Nucleae and cholesterol accumulation in the gallbladder leads to stasis and further gall stone development.
Pigmentary • Made from mixtures of calcium bilirubinate, bilirubine polymers, bile acids. • 50% - radioopaques • Electron microscopy – mixture of bacteria along with bile pigments • Risk factors: • Cirrhosis, bile stasis, chronic haemolysis, bacterial infection • Bacterial β glicuronidase – deconjugation of the bilirubin-diglucuronid which is soluble to unconjugated bilirubine which forms a conglomerate with the glicocalix and becomes a gallstone.
Gallstone disease • Incidence increases with age • Drugs • ceftriaxone, clofibrate, oral contraceptives, estrogen suppliments, progesterone, octreotide • Sex • Ethnicity • Pima indians - Arizona (70%), Canada, hispanics • Masai Africa – 0% • Obesity • BMI>30kg/m2 - 2X risk increase • Cholesterol hipersecretion • Weight loss • Mobilizes cholesterol from fat deposits and it eliminates it through bile
Gallstone disease • CLINICAL • subjective • Asymptomatic • Cholicative pain • Spasm due to temporary obstruction of the cystic duct • Sudden onset – epigastrium, right hypochondria • Progrssive increase in intensity • 15 min to a few hours • Iradiates în the right lumbar area and the righ interscapulo-vertebral area • Reoccurs in days-months-years • Symptoms related to a complication • Acute cholecystitis • Jaundice • Acute pancreatitis • Objective • Normal • Tenderness - epigastrium, right hypochondria • Complication • Murphy sign – Acute cholecystitis • Jaundice
DIAGNOSTIC Ultrasound Abdominal X-ray Gallstone disease
Gallstone disease • CT
Cholangio-MRI Scintigraphy
Gallstone disease • Differential • Gastric disease • Peptic ulcer, GERD, Hiatal hernia • Liver disease • Hydatic cyst, cirrhosis, hepatocarcinoma, cholangiocarcinoma • Pancreatic disease • Chronic pancreatitis, pancreatic tumors • Bowel disease • Irritable bowel syndrome, appendicitis • Kidney disease • Kidney stone, pielonefritis • Lung disease • Pneumonia, pleural effusion • Heart disease • Myocradial infarction
Gallstone disease • Complications • Chronic colecystitis • Acute colecystitis • Lytiasis of the main bile duct • Acute pancreatitis • Cholangitis • Fistulae • Ileus • Gallbladder cancer • Mirrizi syndrome • Porcelain gallbladder
Gallstone disease • Treatment • Wait and see • Medical • Ursodezoxicolic acid • Small gallstones • 15% of the cases • 6-12 Months • Recurrence - 50% at 5 ani
Gallstone disease • Extracorporeal sound wave lithotripsy • High surgical risk patients • Cholesterol gallstones • Small stones 4-30 mm • Permeable cystic duct • < 4 stones • 15% of patients • Side effects • Petechiae, ecchymosis • Pain • Hematuria • Nausea
Gallstone disease • Percutaneous therapy
Gallstone disease • ERCP
Acute cholecystitis • 90-95% due to lytiasis • 80% - obstruction of cystic duct • Gallbaldder – inflamed, distended - pain. • Most cases – spontaneous remission, but sometimes - peritonitis. • Histology • Subserosal oedema, haemmorhage, necrosis of the mucosa • Later – polymorphonucleary infiltrate • Fibrosis • Sometimes – gangrene and perforation 3 days-2 weeks from first symptoms
Acute cholecystitis • Obstruction theory • Sudden accumulation of bile in the gallbladder – parietal ischemia • Bile stasis – increase in bile concentration – chemical irritation – aseptic inflammation • Progressive parietal ischemia – necrosis • Cystic duct obstruction • Pancreatic enzymes theory • Activation of pancreatic enzymes that backflowed to the gallbladder – chemical irritation. • Septic theory • Hematogeneous pathway (portal or systemic); • Septic backflow;
Acute cholecystitis • Alytiasic acute cholecystitis • 5-10% of cases • Patients with: • Severe trauma • Burns • Long-term parenteral nutrition • Major surgery outside the biliary tree • Etiology • Bile stasis and ischemia • More severe than lytiasic acute cholecystitis • Gangrene, empyema, perforation
Acute cholecystitis • Diagnosis • Pain in right hypochondria • Murphy sign • Fevre • Leucocitosis >12-13000/mm3 • US • Gallstone • Oedematous gallbladder walls >5 mm • Enlarged gallbladder • Also possible • Nausea, vomiting • Chills • Gallbladder palpable • US • Liquid aroung the gallbladder • Abscess
Acute cholecystitis • Differential • Perforated peptic ulcer • Acute pancreatitis • Acute apendicitis • Digestive tract perforations • Peritonitis • Acute kidney disease • Acute lung disease • Gonococic perihepatitis • Hepatomegaly with sudden distension of the capsula of Glisson
Complication Gangrenous acute cholecystitis Emphysematous acute cholecystitis - Clostridium perfringens, E. coli, streptococus Acute cholecystitis
Acute cholecystitis • Perforation • Localized peritonitis • Abscess located under the liver • Generalized peritonitis • Choleperitonitis • Fistulae • Duodenum, colon, stomach • Ileus • In the main bile duct
Acute cholecystitis • Treatment • Medical • Pain • Hidroelectrolitic balance • Stop oral food intake • ± NG tube • Antibiotherapy • Cefalosporines • Type A penicilinestip A+aminoglicozides ± metronidazole • Carbapenemes
Acute cholecystitis • Surgical • Cholecystectomy • Laparoscopic • Open • Timing of the procedure • 60% spontaneous remission • Early – first 72-96 hours • Secondary – after 4-6 weeks • Cholecystectomy • Severely altered state of patients
Main bile duct litiasis • 7-15% of patients with galbladder litiasis also present main bile duct litiasis • types • Secondary • Primitive • Associated with stasis and infection • Stasis can be due to • Strictures • Stenosis of the papila • Oddi sphincter disfunction
Main bile duct litiasis • Severe complications • Jaundice • Cholangitis • Acute pancreatitis
Main bile duct litiasis • Jaundice • Possibly no pain • Frequent episodes of jaundice • Obstacle+spasm+oedema • Stasis – increased pressure in the bile canaliculy
Main bile duct litiasis • colicative pain+(fever)+jaundice • Hypochromic stools • Hyperchromic urine • Pruritus • Laboratory • Serum • Bilirubine • Alkalyne phosphatasis • Cholesterol is increased • Increased bile salts • ALAT,ASAT almost normal • Urine • Urobilinogen - absent • Bile salts – increased • Conjugated bilirubine • Stool • Stercobilinogen, urobiline
Main bile duct litiasis • Paraclinical • NG tube – no bile • US • Gallstones in main bile duct • Biliary ducts - dilated • ERCP • CT
Main bile duct litiasis • Echoendoscopy • Cholangio - MRI
Main bile duct litiasis • Differential • Prehepatic jaundice • Serum • Unconjugated bilirubine • Normal hepatic tests • Urine • Urobilinogen – increased • Absence of bilirubine • Stool – increased stercobiline • US – normal bile ducts • Hepatic jaundice • Hepatitis, cirrhosis • Conjugation defficit and elimination defficit • Serum • Unconjugated and conjugated bilirubine increased • Bile salts increased • Increased cytolisis • Urine • Conj bilirubine, bile salts, urobilinogen • US – bilre duct not dilated
Main bile duct litiasis • Endoscopic • Baloon probe • Sphincterotomy
Surgical Laparoscopic or open Cholecystectomy Cholangiography Extraction of the gallstones Transcystic Transcoledocian Choledocoscopy Cholangiography Kehr drain Bilo-digestive anastomosis Transduodenal sphicterotomy
CHOLANGITIS • Bacterial infection of bile ducts – no obstruction, no clinical symptoms • Not every obstruction leads to cholangitis • Obstruction – increased bile duct pressure – bacterial proliferation – systemic disease • Charcot triade: colicative pain, jaundicem, fever. • Most common: E. Coli, Klebsiella, Pseudomonas, Enterococi, Proteus. Bacteroides fragilis, Clostridium perfingens • Supurative cholangitis is used for severe disease associated with sepsis: • Abdominal pain • Jaundice • Fever • Confusion • shock • 90% - i.v. antibiotics • Severe cholangitis or lack of response to antibiotics – decompression of the main bile duct: • Endoscopically • Percutaneously • Surgicaly
Biliary fistulae • Biliodigestive • Biliobiliary • Old litiasis patient with frequent inflammatory episodes • Inflammed gallbladder adheres to an organ which is in the vicinity – necrosis – perforation • First an acute episode and then a decrease in symptoms after fistula occured • Gallstones can pass through the fistula and cause • Vomiting and nausea • Ileus • Bouvert piloro-duodenal obstruction • Cholangitis • Main bile duct litiasis
Abdominal X-ray • Air in the main bile duct • Air-fluid levels • Radioopaque gallstone • Barium meal • Contrast passes into the main bile duct • US • Gallbladder stones • Radioopaque stones abnormally located • Endoscopy, echoendoscopy, CT
Mirrizi syndrome • ERCP • US • Cholecystectomy
Porcelain gallbladder • Calcification of the walls of the gallbladder • Complication • Gallbladder cancer • Profilactic cholecystectomy