Biliary System

    .

    PSC vs. PBC

     

      Primary Sclerosing Cholangitis Primary Biliary Cirrhosis
    Affected Ducts

    BOTH Intra- and extra-hepatic

    LARGER DUCTS

    Intra-hepatic Ducts

    SMALLER DUCTS

    Predominant Gender Male Female
    Assd. comorbidities IBD (esp UC)

    Autoimmune

    (Sjogren's, CREST, RA, etc.)

    Investigations

    ECRP/MRCP:

    narrowing and dilatations of ducts

    Anti-mt Ab (AMA), IgM, Incr. Lipids

    Liver bx (ERCP: no duct narrowing)

    Primary Biliary Cirrhosis (PBC)

    • Introduction
      • Chronic cholestatic liver disease of unknown cause.
      • Incidence: 2-24 / 1million; Prevalence: 19-400/1million.
      • Most asymptomatic, but most develop symptoms within 10 years.
      • Mainly middle-aged women (M:F  is 1:9), median onset: 50yo.
    • Pathobiology:
      • Chronic inflammation and fibrous obliteration of intrahepatic bile ducts.
    • Etiology:
      • Likely autoimmune
      • Associations:
        • Sjogren's Syndrome
        • Scleroderma
        • CREST syndrome
        • RA
        • Thyroiditis
      •  
    • Signs/Symptoms:
      • Often asymptomatic (most develop symptoms in 10y)
      • Initial: pruritis, fatigue, dry eyes, dry mouth.
      • Chronic: Jaundice, Melanosis (skin darkening), hepatosplenomegaly, xanthelasmas (cholestasis signs).
        • (Rarely observed at diagnosis.)
    • Investigations:
      • ↑ ALP >1.5x ULN, 
      • ↑ GGT
      • Total Bilirubin usually normal, but  in late disease
      • ALT, AST can rise, but <5x ULN
      • Positive anti-mitochondrial ab. (AMA) 90-95% sensitivity at titres >1:40
      • Liver biopsy (if AMA negative, and still suspect)
        • Histology: Focal duct obliteration with granuloma formation
          (known as "florid duct lesion" pathognomonic)
      • Lipids: Increased LDL and larger increase in HDL
        • May have xanthelasmas and xanthomas
    • Treatment:
      • Can be fatal, but not all pts show progression.
      • Symptoms:
        • Pruritis:
          • Antihistamines and phenobarbital = marginal benefit
          • Cholestyramine, sertraline, rifampin effective for mod-to-severe
        • Xerostomia (dry mouth) & Keratoconjunctivitis sicca:
          • oral sialagogues, artificial tears.
          • oral pilocarpine and cevimeline can be effective
      • Complications:
        • Malabsorption: supplement fat soluble vitamins if levels are low ADEK (not empirically)
        • Hyperlipidemia: statins often used (but no direct link to CAD) (ok even if enzymes are up)
        • Metabolic Bone Disease: weight bearing ex, vitamin D, Ca++.  IV bisphosphonate if esophageal varices.
      • Ursodeoxycholicacid (UDCA)
        • Survival benefit!
        • But 50-60% of pts do not achieve biochemical response (defined as ALP or AST >1.5x normal)
      • Liver Transplant
        • If end-stage liver disease.  
        • Very effective
        • 30% recurrence in new liver.

    Primary Sclerosing Cholangitis

    • PSC is a chronic inflammatory disorder affecting intra- and extra-hepatic bile ducts.
    • Mean age of dx: 40yo,  mostly Men (60%)
    • Annual incidence: 0.9-1.3 / 100,000 ppl.  Point prevalence: 8.5-13.6 / 100,000 ppl.
    • Associations:
      • 70-80% of pts with PSC have IBD  (in Europeans and North Americans).
      • But 2-4% of IBD have PSC
    • Symptoms:
      • 40% asymptomatic at presentation.
      • Pruritis, abdominal pain, jaundice.
    • Diagnosis:
      • ALP 3-10x ULN
      • ALT, AST 2-3x ULN
      • Serum total Bilirubin normal in 60%.
        • If see high TBilli --> advanced disease, superimposed choledocholithiasis, or malignancy.
      • Serum ANA and Anti-Sm (Smooth muscle antibodies) present in 20-50%.
        • Anti-mitochondrial ab (AMA) rare!
      • Cholangiography --> Gold Standard
        • Histology: segmental bile duct fibrosis w/ saccular dilatation of normal intervening areas
          --> "beads on a string" apperance.
      • MRCP: perform if dx is suspected (90% diagnostic accuracy)
        • "beads on a string", upstring intrahepatic bile duct dilatation.
      • ERCP: Only if bile duct obstruction
      • Liver Biopsy: Only for small duct involvement (if cholangiography is normal)
        • Histology: Periductal fibrosis, inflammation, bile duct thickening, ductopenia.
    • Management:
      • Approach is the same as PBC
        • Pruritis
        • Metabolic Bone Disease
      • Complications:
        • Choledocholithiasis (occurs in 10-25%)
        • Dominant strictures (5-10%)
        • Both present with sudden ↑ALP and/or Bilirubin, jaundice, bacterial cholangitis.
          • Treatment endoscopic or percutaneous.
          • If structures -> must do brushings and biopsy to r/o cancer.
        • Cholangiocarcinoma
          • 0.5-1.5% annual risk (prevalence 4-20%)
          • Consider cholangiocarcinoma in all PSC pts and worsening liver tests, symptoms, new dominant stricture (on cholangiography).
      • No medical therapy to change mortality
        • Tried: high-dose UDCA (>25 mg/kg/d) --> fail, no survival benefit.
      • Liver transplant
        • Excellent survival
        • 10-20% recurrence

     

    Gall Stones

    • 90% of gall stones are of cholesterol or mixed type (cholesterol + bilirubin)
      • Black pigmented stones = chronic hemolytic disease / Cirrhosis
      • Brown pigmented stones = biliary tract infection
    • Women (1.5-4%) > Men (0.5%-3%)
    • Risk Factors:
      • Women
      • Obesity
      • Dislipidemia
      • Pregnancy
      • DMII
      • Cirrhosis
      • Crohn's Disease
      • Terminal Ilium Resection
      • Gastric Bypass Surgery
    • Clinical Features:
      • Most asymptomatic (70%)

     

    Asymptomatic Gall Stones

    • Management:
      • If asymptomatic - observation.  (even if Diabetes)
      • Cholecystectomy only in high risk groups for gall bladder carcinoma:
        • Prophylactic cholecystectomy indicated for high risk groups: 

          • Gall bladder polyps >1cm
          • Gall stones >3cm
          • Porcelain gall bladder

     

    Symptomatic Gall Stones

    • Biliary colic / Acute cholecystitis
    • Clinical Features of Biliary Colic
      • Episodic severe abdominal pain in epigastrium or RUQ.
        • Occasionally in RLQ or mid-abdomen.
        • Rapidly intensifies over 15min interval to steady plateau (unlocalized) lasting up to 3h, resolves slowly.
        • Biliary Colic = Unlocalized pain, lasting < 3hrs.
        • Often Nausea/ Vomiting, NO jaundice.
        • (Sometimes radiates to intrascapular region or R shoulder)
      • Not always following large/fatty meal, can occur even with fasting.
    • Clinical Features of Acute Cholecystitis
      • Obstruction of cystic duct by gall stones. (most have prev. attacks)
      • Acute Cholecystitis = Pain lasts >3h and shifts to RUQ causing LOCALIZED tenderness.
        (distension, contraction, infection of gall bladder)
        • Often: Fever, nausea, vomiting.
        • Jaundice is NOT a FEATURE!
      • (Elderly, immunocompromised or diabetes can be asymptomatic)
      • Physical Exam:
        • Murphy's sign (stops inhaling when palpating RUQ) 30-40%.
    • Complications: (preceeded by biliary colic)
      • Cholangitis
      • Pancreatitis
    • Diagnosis:
      • Ultrasound  - perform if biliary colic/cholecystitis suspected.
        • (Sn 84%, Sp 94%) for gallstones, and (Sn 88%, Sp 80%) for cholecytitis
        • See thickening of the gallbladder wall (>2 mm), intramural gas, and pericholecystic fluid.
      • *HIDA Scan* (Hepatobiliary iminodiacetic acid scan) aka "hepatobiliary scintigraphy"
        • Indicated for acute cholecystitis when the ultrasound is indeterminate,
          • High Sn (97%) and Sp (90%)
          • Except in the presence of acalculous cholecystitis, prolonged fasting, and chronic alcoholism (poor biliary flow)
    • Treatment:
      • Asymptomatic:
        • Observe! (benign - except high-risk groups)
      • Symptomatic Biliary Colic:
        • Laparoscopic Cholecystectomy (Mortality rate: <0.7%, complications (laparoscopic = open))
      • Acute cholecystitis:
        • IV fluids, antibiotics,
        • laparoscopic cholecystectomy (within 48-72hrs)
          • (NEW! In the past waited 1 week to settle inflammation)

    Acalculous Cholecystitis

    • Acute acalculous cholecystitis: gall bladder inflammation in absence of cholelithiasis.
    • Aka "ilius of the gallbladder"
    • Risk Factors:
      • Hospitalization for critical illness, burns, advanced age, atherosclerotic vascular disease, AIDS, infection with Salmonella or cytomegalovirus, polyarteritis nodosa, and systemic lupus erythematosus.
    • Clinical Features:
      • Suspicious if: Unexplained feverhigh amylase in pts with risk factors
    • Diagnosis:
      • Abdominal Ultrasound: Significant gall bladder thickening and/or distension.
      • (HIDA scan will be abnormal, cannot distinguish acalculous from calculous.)
    • Complications:
      • (HIGH RISK)  50% will develop cholangitis, empyema, gangrene, gall bladder perforation
      • 40% risk of gallbladder rupture if treatmen delayed >48hrs.
    • Management:
      • Supportive
      • IV Antibiotics (with anerobic + gram neg coverage).
      • Cholecystectomy is preferred but may be contraindicated if ill.
      • Symptomatic therapy: Image-guided cholecystotomy tube placement.

    Common Bile Duct Stones

    • Choledocholithiasis (CBD stones) is a leading causes of obstructive jaundice.
      • High rate of complications than symptomatic gall stones.
    • Clinical Features:
      • >50% asymptomatic, 20% spontaneously pass stones
      • Symptoms: Jaundice, abdo discomfort, pruritis. (aka Obstructive Jaundice)
        • Dark urine, light-colored stools (acholic stools)
    • Diagnosis:
      • Ultrasound or Non-Contrast CT: Dilatation of intra+extra hepatic bile ducts.
        • Lack sufficient sensitivity to r/o diagnosis
      • MRCP (MR cholangiopancreatography) --> better imaging
        • Sn 95-100%, Sp 75-95%
      • Endoscopic Ultrasound (EUS): similar Sn/Sp as MRCP, but less invasive than ERCP
        • More sensitive for sludge and smaller stones.
    • Complication: Cholangitis!
    • Management:
      • ERCP best way to relieve obstruction.
        • Post-ERCP elective cholecystectomy should be performed in 6 weeks (if eligible).
        • If not surgery candidates: endoscopic sphrincterotomy to allow passage of stones.

    Cholangitis

    • Fever!! --> suggests development of cholangitis.
    • Can be life threatening.
    • Clinical Features:
      • Charcot's Triad: Fever, jaundice, RUQ pain
      • Cholelithiasis, elevated aminotransferases, and high Bilirubin
    • Imaging:
      • Ultrasound: May show dilated bile duct
      • MRCP: more sensitive
    • Causes:
      • E.coli
      • Klebsiella sp.
      • Pseudomonas
      • Enterococcus
    • Complications: Septic shock +/- liver abscess formation.
    • Management:
      • Empiric antibiotics (Immediately if suspected)!
      • ERCP: Urgent biliary decompression
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