EXTRAHEPATIC CHOLESTASIS Diseases of the Gallbladder and Biliary Tree Dr.

Franco By: Group 2Big

Classification of Jaundice Based on the Underlying Derangement of Bilirubin Metabolism: 1. Predominantly Unconjugated - Overproduction (hemolysis) - Decreased Hepatic Uptake (sepsis) - Decreased Bilirubin Conjugation (Gilberts) 2. Predominantly Conjugated - Impaired Hepatic Excretion - Extrahepatic Biliary Obstruction

- common among Asians 2. Compression of Bile Ducts- extraductal Malignancy- lymphoma/gastric malignancy Inflammation pancreatitis 3. Hepatobiliary Tuberculosis Pathophysiology of Obstructive Jaundice

EXTRAHEPATIC BILIARY OBSTRUCTION (CHOLESTASIS) SURGICAL JAUNDICE *Surgical jaundice-these conditions require surgery *Mistakenly diagnosed as liver disease *Pancreatic head-most common location of pancreatic tumor 1. Intraductal Obstruction Gallstone (secondary CBD stone) Primary CBD stone - formed stones inside the CBD Malignancy- inta or extrahepatic - most common: cholangiocarcinoma and pancreatic head tumor Biliary Malformation - biliary atresia in neonates / choledochal cyst which manifest early in childhood or may be silent, which may manifest only in adulthood Stricture (iatrogenic / trauma) Infection (ascaris / amoebiasis forming abscess) Sclerosing Cholangitis

Bile Flow Obstruction Bilirubin and bile acids dammed back into the liver Bilirubin and BA enter the bloodstream Skin serum conjugated bilirubin above 30umol/L results to detectable jaundice; 60umol/L is obvious jaundice serum bile acids deposited in skin cause pruritus, usually seen in patients with severe disease; cannot be relieved by antipruritic meds Urine serum conjugated bilirubin - water soluble; excreted by the kidneys resulting to a dark-colored urine *Indirect hyperbilirubinemia- no darkening of urine

Stool low or absent excretion in the bowel; low urobilin makes the stool light-colored (acholic); usually seen in malignancy or in children with biliary atresia low bile acids lead to defective fat absorption and malabsorption of vitamin ADEK Vit K malabsorption results to a prolonged protime activity ->bleeding Biochemical Changes Increased plasma conjugated bilirubin Marked increase in alkaline phosphatase- very sensitive; produced primarily in the bile canaliculi *Increased pressure leads to increased alkaline phosphatase Transaminases (SGPT/SGOT)- not much elevated *Acute or sudden obstruction in the biliary treeSGPT *Acute hepatitis- SGPT Effects of Biliary Tract Obstruction Effects on Biliary Tracts 1. Increased Biliary Pressure 2. Proximal Dilatation cornerstone of surgical jaundice takes 1-2 weeks to become dilated appreciated by UTZ, MRI, MRCP presence of dilation means there is obstruction 3. Canalicular Changes hepatocyte damage Bile thrombi seen microscopically causing significant damage to the hepatocytes Bile salt deposition 4. Cholangitis infection of the bile Effects on the Liver 1. Hepatocyte Damage decreased bile secretion (by inhibition) and impaired elimination of drugs minimal or no bile production 2. Reticuloendothelial Cell Damage Kupffer cells damage 3. Fibrosis and Cirrhosis 4. Atrophy / Hyperplasia Complex Systemic Effects 1. Malnutrition decreased intake d/t abdominal pain 2. Coagulopathy prothrombin time, platelet count and platelet dysfunction

3. Poor Wound Healing d/t defective collagen formation prone to wound dehiscence and infection 4. Prone to systemic sepsis (Cholangitis) and wound infection a. Endotoxemia d/t defective collagen formation increased endotoxin absorption from the SI Increased intestinal capillary permeability endotoxin is easily absorbed in the intestinal tract decreased phagocytic activity of Kupffer Cells b. Immune Deficiency 5. Renal Failure (Hepatorenal Syndrome) excess bilirubin leads to bilirubin nephropathy sepsis ACUTE CHOLANGITIS Dreaded effect of obstruction

Hallmark: Charcots Triad (70% of cases) 1. Abdominal Pain (epigastric, RUQ) 2. Jaundice 3. Fever *Reynolds Pentad- severe suppurative cholangitis Charcots triad + hypotension + altered mental status *Watched closely and lead to an emergency surgery Three possible routes of entry of bacteria: 1. Portal vein 2. Retrograde flow form the duodenum through the Ampulla of Vater 3. Enteric lymphatics that drain to the liver Predominant Organisms: Escherichia coli (no. 1)- gram negative bacteria Klebsiella pneumonia Bacteroides fragilis- anaerobic bacteria Gram-positive enterococci *Give antibiotics covering Gram negative and anaerobic bacteria Diagnosis: Based on Initial Clinical Setting (Hx and PE) *Murphys sign - deep inspiration or cough during subcostal palpation of the RLQ causes pain and inspiratory arrest Laboratories: CBC (Leukocytosis) Conjugated Hyperbilirubinemia 2

Increase Alkaline Phosphatase Transaminases Mildly Elevated if acute onset

Parameter

Ultrasound ( best choice) *cheap and detects gall stones *may not request for bilirubin test Other lab work-up to determine the underlying cause Endoscopic Retrograde Cholangiopancreatography (ERCP) performed with a side-viewing duodenoscope that allows identification of the major papilla - bile duct is cannulated under endoscopic and fluoroscopic guidance Percutaneous transhepatic cholangiography (PTC) - initiated by advancing a 22-gauge needle under fluoroscopic guidance centrally toward the liver hilum and gently injecting contrast as the needle is withdrawn slowly - small needle reduces hepatic trauma and likelihood of bleeding despite the potential need for multiple needle passes to cannulate a bile duct, particularly when the bile ducts are not dilated - UTZ guidance and CT guidance can be used to access nondilated bile ducts CT- important in diagnosing malignancy MRI- only once cholangitis is controlled Treatment: 1. Hydration 2. Correct Prothrombin deficiency NPO give IV Vit K 3. Antibiotics 2nd generation cephalosporins ampicillin, metronidazole In severe infections, give superantibioticsImipenems and tazobactams 4. Surgical Drainage *usually, patients are treated medically *control infection first then operate when stable Clinical and Laboratory Features Extrahepatic cholestasis ( Surgical Jaundice ) VS Intrahepatic Cholestasis ( Icteric Liver Disease ) *There is a need to differentiate the two for proper management *Hepatitis most common cause of jaundice; has prodromal symptoms: body malaise ->fever->jaundice

History

Surgical Jaundice/Biliary Obstruction Abdominal Painsignificant complaint; high epigastric pain, moderate to severe Fever, Rigors

Icteric Liver Disease

Viral prodrome: anorexia, malaise, myalgia, fever then jaundice Known viral exposure

Physical examination

Laboratory studies

Prior Biliary Surgery- Hx of BT or injection stricture/ recurrent drug use stones Older Age Exposure to known hepatotoxin Family history of liver disease High-grade fever Low-grade feverhepatitis Abdominal Stigmata of portal tenderness- d/t hypertension: peritonitis prominent Palpable abdominal abdominal veins, hepatomegaly/splen mass- distended omegaly(with portal GB/hydrops GB Abdominal surgical hypertension), scar- previous biliary ascites, asterixis, gynecomastia, surgery Keyser- Fleisher Ringwhitish ring around the pupil in cirrhosis/chronic liver disease Predominant Predominant elevation of serum elevation of serum alkaline aminotransferases phosphatase relative to alkaline relative to phosphatase aminotransferases Prothrombin time Prolonged (INR) normalizes prothrombin time with Vit K that does not administration normalize with Vit K Leukocytosis Thrombocytopenia Elevated serum Serologies indicative amylase or lipase of specific liver level disease Transaminases not SGPT- specific to liver elevated/mildly disease elevated SGOT- not specific to (SGPT/SGOT) liver disease 3

Common Conditions Causing Surgical Jaundice CHOLEDOCHOLITHIASIS (stone in the CBD) A. Primary Stones - stones primarily formed in the bile ducts - causative factors: Stasis Biliary Ascariasis Bile Infection *primary stones are brownish to black, soft and friable, sludge-like (muddy); findings of mummified ascaris; stones are found 2 years after cholecystectomy B. Secondary Stones - stones coming from the gallbladder and carried to the CBD *secondary stones have characteristics similar to GB stones; hard and multifaceted; do not conform with the shape of the CBD

Diagnostics Leukocytosis Laboratory Features of Obstructive Jaundice Ultrasound/ CT/ ERCP/ PTC/ T-tube Cholangiogram *Missed stone appreciated in t-tube cholangiogram, seen after surgery Treatment Treat Cholangitis Surgery Endoscopic Retrograde Cholangiopancreatograpghy

T- tube Cholangiogram

Clinical Features Abdominal Pain - most prominent feature - usually high epigastric area/ below xiphiod process - vary from biliary colic to severe and persistent *if persistent- it means it is impacted and needs surgery Cholecystitis - tender GB / (+) Murphys Sign Cholangitis - abdominal pain followed by jaundice then fever Pancreatitis (Gallstone Pancreatitis) - bile stone that lodges into the pancreatic dict *control pancreatitis first then operate after 5 days (+)History of Gallstone Disease Asymptomatic (found incidentally during cholecystectomy)

Management: Common Bile Duct Exploration (Indications) 1. Clinical - Presence or History of Jaundice - Cholangitis (Charcots Triad) - Pancreatitis 2. Diagnostic Procedure - Ultrasound finding of dilated ducts or stones noted in the CBD 3. Intraoperative Findings - Dilated CBD - Palpable Stones in the CBD - IOC showing stones in the CBD or a dilated duct 4

Surgical Treatment: Choledocholithiasis Cholecystectomy, CBDE, Choledocholithotomy Cholecystectomy, CBDE, Choledocholithotomy, TTube Insertion, Choledochoscopy Cholecystectomy, CBDE, Biliary-Enteric Bypass *presence of many stones/tendency for recurrenceanastomose biliary tree to the intestines for better bile flow ERCP, Sphincterotomy, CBD Clearance, Laparoscopic Cholecystectomy- one of the more common surgical procedures Transduodenal Sphincteroplasty Roux-En-Y Hepaticojejunostomy

chemical components of bile role of the gallbladder genetic, environmental, and metabolic factors

ACUTE SUPPURATIVE CHOLANGITIS Severe form Bile becomes pus Treatment-urgent 1. Medical Treatment of Cholangitis 2. Emergency Drainage Procedure - ERCP with Stenting of CBD to drain infected bile - PTBD-leave a tube inside the BD through the liver - Tube Cholecystotomy, choledocholithotomy, Ttube choledochostomy

Natural History A. Symptomatic Abdominal Pain (Recurrent) Fatty Food Intolerance Complications Cholecystitis Cholangitis Pancreatitis Gallstone Ileus- gall stone causing intestinal obstruction Hydrops GB cystic duct remains obstructed and the GB lumen may be distended with clear mucoid fluid; needs emergency surgery because GB might rupture Cholecystoenteric fistulae - occurs when a stone erodes through the gallbladder wall (usually the neck) and into a hollow viscus (duodenum, hepatic flexure of the colon, stomach, jejunum) Mirizzis Syndrome - rare complication in which a stone embedded in the neck of the gallbladder or cystic duct extrinsically compresses the common hepatic duct with resulting jaundice, bile duct obstruction, and, in some cases, a fistula. B. Asymptomatic Benign course 15% may develop symptoms after 10-15 years Complications occur in 20% Incidence of calculi in cancer of the GB (65-100%)stone is formed d/t stasis *small risk for malignancy with gall stones

GALLSTONES Formed from the constituents of bile Major components: Cholesterol calcium carbonate calcium bilirubinate *any imbalance leads to gall stone formation Most are mixed variety Factors in formation:

Cystic duct is obstructed by kinking or tumor Due to fibrosis of the sphincter of Oddi Following typhoid fever or systemic infection Among diabetics Severe dehydration, fever, fasting Inflammation of GB without stone

Indications for cholecystectomy for asymptomatic patients with stones: Stones > 2.5 cm (may develop cancer and complication) Diabetes Calcification (Porcelain Gallbladder- radiologic finding, more prone to develop GB cancer) Sickle Cell Disease Young Patients (<40 years old) Diagnosis History and PE Ultrasound of HBT (can demonstrate stones in 95% of cases and can detect cholecystitis with edema and thickening of the GB wall) High intensity echo and post sonic shadowing (PSS) Treatment Cholecystectomy Specific Treatment for Complication Acute Cholecystitis most common complication of gallstone disease Associated with gallstone in 95% of cases Due to obstruction of cystic duct by stone Etiology: E. Coli, Klebsiella, Streptococci Emphysematous Cholecystitis gas in the wall of GB Spectrum of acute cholecystitis Clinical Manifestations are more pronounced Due to gas-forming microorganisms Diabetics are more prone to develop Can lead to gangrene or perforation (40-60%) Diagnosis is based on radiologic findings of gasfilled shadow and/or intraluminal gas Emergent cholecystectomy is needed Acalculous Cholecystitis Inflammation without stones

PANCREATIC HEAD CARCINOMA

Derived from ductal cells of exocrine pancreas Worst prognosis- 5 years survival of all GI malignancy (5%) Most common site in pancreatic CA- head (70%) Other sites: body, tail Common Presenting Features Obstructive jaundice (75%); often painless (50%) Substantial weight loss (60%) Abdominal pain (dull and deep seated) Less Common Features Cholangitis Gastric Outlet Obstruction- post prandial vomiting Acute Pancreatitis Diabetes Mellitus Physical Examination Suggesting Advance Disease Palpable Mass Ascites Courvoisiers Sign (Enlarged/palpable Gall Bladder) In gall stones-GB wall is thickened and fibrotic

 In carcinoma- gradual distention of gall bladder->marked obstruction of GB; no fibrosis; painless jaundice Courvoisiers sign

PERIAMPULLARY TUMORS Can be in the ampulla, distal CBD, or duodenum(uncommon) Clinical feature similar to pancreatic head CA Better prognosis than pancreatic CA Treatment: Whipples procedure

Diagnosis Ultrasound- mass is detected ERCP CT Scan/ MRCP-FNAB PTC- rat-tailing sign- intrinsic obstruction Endoscopic UTZ- mass in the periampullary area Treatment A. Mostly Palliative most die within 7-8 months and only 20% is resectable; treatment is for: relief of obstructive jaundice (cholecystectomy or stenting) relief of pain (block of celiac ganglia) relief of gastric outlet obstruction (gastrojejunostomy) B. Resection (Whipples Operation) offers the only chance for cure 5-year survival rate (21-35%) Duration- 9-12 hours Whipples Operation- 3-4 anastomosis

BILE DUCT STRICTURES Iatrogenic (injury sustained during cholecystectomy and other operations) Patients with prior biliary enteric anastomosis Clinical features: development of jaundice anytime following cholecystectomy Diagnosis: ERCP/PTC Treatment: Reconstruction with Hepaticojejunostomy HEPATOBILIARY TUBERCULOSIS Rarely mentioned in western literature May occur without pulmonary lesions

Pathophysiology TB from the primary site enters the blood stream and is disseminated into different parts of the body; can be from: - Tuberculous peritonitis - Gastrointestinal tuberculosis - Hepatobiliary tuberculosis Clinical Features Jaundice Weight Loss Abdominal Pain Splenomegaly/Ascites Mechanism of Obstructive Jaundice Extrinsic compression of CBD by periportal lymphadenopathies Direct involvement of bile duct by TB bacilli 7

Tuberculosis of the pancreatic head compressing the CBD

Diagnosis History and PE Plain abdominal X-ray shows confluent hepatic calcification ERCP/PTC UTZ/CT identify:liver parenchymal disease, abscess, tumor-like lesion in the liver, periportal abscess, segmental dilatation of the intra and extrahepatic ducts) Treatment Medical- Prolonged Anti-Kochs Medication (12 months) Surgical (Biliary-Enteric bypass or U-Tube hepatostomy) Cholangiocarcinoma Classified based on the location: 1. Hilar or proximal (50%) also known as Klatskins tumor 2. Midduct 3. Distal bile ducts (periampullary) 4. Diffuse Treatment Palliative (Operative or endoscopic stenting) Surgical Resection (Roux-en-Y) or Whipples op Biliary Ascariasis Erratic ascrais Colicky pain of ascaritic biliary pain/maniacal pain History of vomiting or passing out of adult worms in stool railroad tract sign in ultrasound or cholangiogram Treatment Endoscopic Extraction Cholecystectomy, choledochotomy, T-Tube Insertion Choledochal Cyst Idiopathic cystic dilatation of the bile duct May degenerate to malignancy Alonso-Lej classification: Type IA- marked cystic dilation of the entire extrahepatic biliary tree, with sparing of the

intrahepatic ducts. The cystic duct and the gallbladder arise from the CBD Type IB- focal, segmental dilation of the extrahepatic bile duct, the cyst can arise from anywhere within the extrahepatic biliary tree, it is most commonly distal, with the cystic duct branching off a normal CBD. The biliary tree proximal to the gallbladder is usually normal Type-IC-smooth fusiform dilations of the entire extrahepatic bile duct, usually extending from the pancreaticobiliary junction to the intrahepatic biliary tree Type-II cysts are discrete diverticuli of the extrahepatic duct with a narrow stalk connection to the CBD. Type-III- choledochocele, dilation of the distal CBD that is confined to the wall of the duodenum, and often bulge into the duo denal lumen TypeIVA- multiple intrahepatic and extrahepatic dilations. Type-IVB- multiple dilations of the extrahepatic biliary tree only, described radiographically as either a string of beads or bunch of grapes appearance Type-V CCs refer to Caroli disease, also known as communicating cavernous ectasia, which is multiple saccular or cystic dilations of the intrahepatic bile ducts.

Shallows Traid: Jaundice(45-65%) 8

 abdominal pain(37-58%) abdominal mass(51-55%) Treatment Excision of cyst, roux-en-Y hepaticojejunostomy Excise cyst because they might develop malignancy later on Complications Cholangitis Cholecycstolithiasis/choledocholithiasis Pancreatitis Malignancy (cholangiocarcinoma) Biliary Atresia Portal Hypertension Billiary Cirrhosis References: -Dr. Francos lecture and ppt -JAX notes - Gastrointestinal and Liver Disease- Sleissenger and Fordtrans, 9th edition http://www.cma.ca/multimedia/staticContent/HTML/N 0/l2/cjs/vol-52/issue-5/pdf/pg434.pdf

By: Mary Arnie Dolendo=)