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Liver function tests: Biliary

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Title: Liver function tests: Biliary


1
Liver function testsBiliary
  • Megan Chan, PGY-1
  • UHCMC 2015

2
Guess the LFTs
3
cholelithiasis
  • If Asymptomatic
  • AST
  • Normal
  • ALT
  • Normal
  • Alk Phos
  • Normal
  • T bili
  • Normal
  • If Pass a Stone
  • AST
  • Elevated
  • ALT
  • Elevated
  • Alk Phos
  • Elevated
  • T bili
  • Normal

http//radiopaedia.org/articles/cholelithiasis
4
Acute cholecystitis
  • AST
  • Normal
  • ALT
  • Normal
  • Alk Phos
  • Elevated
  • T bili
  • Normal

http//radiopaedia.org/images/1780983
http//radiopaedia.org/cases/acute-cholecystitis-4
5
choledocholithiasis
  • AST
  • Normal ? Elevated
  • ALT
  • Normal ? Elevated
  • Alk Phos
  • Elevated
  • T bili
  • Elevated

http//radiopaedia.org/articles/choledocholithiasi
s
6
Practice cases
7
Case 1
  • 46 y/o female presents with intermittent RUQ pain
    and heartburn to your clinic. Vitals are stable
    and exam is unremarkable. CT abdomen from an OSH
    is shown on the right.
  • What is the diagnosis?

http//radiopaedia.org/articles/cholelithiasis
8
Case 1
  • 46 y/o female presents with intermittent RUQ pain
    and heartburn to your clinic. Vitals are stable
    and exam is unremarkable. CT abdomen from on OSH
    is shown on the right.
  • What is the diagnosis?
  • Cholelithiasis

http//radiopaedia.org/articles/cholelithiasis
9
cholelithiasis
  • Gallstones or sludge in the gallbladder
  • 10 population, symptomatic in only 25 of cases
  • 3 types of stones
  • Cholesterol stonesassociated with obesity, DM,
    HLD, OCP use, multiple pregnancies, advanced age,
    Crohns disease, ileal resection, cirrhosis, CF
  • Pigment stones
  • Black stoneshemolysis, alcoholic cirrhosis
  • Brown stonesbiliary tract infection
  • Mixed stones 80
  • Pathophysiology
  • Cholesterol supersaturation from reduced bile
    secretion (age, TI disease, liver dz) or
    hypersecretion of cholesterol (e.g. estrogen,
    obesity liver dz)
  • Crystal nucleation
  • Gallbladder hypomotility (e.g. pregnancy,
    prolonged TPN, somatostatin)
  • Other Decreased bile transit time, bacteria
    presence

10
Cholelithiasis
  • Clinical features
  • Biliary colic, esp after eating at night, lasts
    30 min to 3 hrs
  • Boas sign referred right subscapular pain of
    biliary colic
  • Diagnosis RUQ ultrasound has sensitivity and
    specificity gt 95 for stones gt 2mm, best if
    fasting 8 hrs
  • Tx Elective cholecystectomy for pts with
    recurrent biliary colic
  • DDx Gallbladder polyp/carcinoma

11
Case 2
  • 55 y/o male with PMHx of recurrent pancreatitis
    presents to the ED with RUQ abdominal pain and
    vomiting. Pt is found to be febrile and
    hypotensive. IV fluids are initiated and the
    following labs are obtained
  • WBC 13,000, AST 25, ALT 30, Alk Phos 450, T bili
    1.0, Lipase 20
  • What is the most likely diagnosis and what is the
    next best diagnostic step?

12
Case 2
  • 55 y/o male with PMHx of recurrent pancreatitis
    presents to the ED with RUQ abdominal pain and
    vomiting. Pt is found to be febrile and
    hypotensive. IV fluids are initiated and the
    following labs are obtained
  • WBC 13,000, AST 25, ALT 30, Alk Phos 450, T bili
    1.0, Lipase 20
  • What is the most likely diagnosis and what is the
    next best diagnostic step?
  • Acute Cholecystitis, RUQ ultrasound

13
acute cholecystitis
  • Inflammation of gallbladder 2/2 obstruction of
    cystic duct
  • Develops in 10 of those with cholelithiasis
  • Clinical features
  • RUQ tenderness gt4-6 hrs rebound
  • Murphys sign inspiratory arrest during deep
    palpation of RUQ
  • Low grade fever, leukocytosis, nausea, vomiting,
    hypoactive bs

14
acute cholecystitis
  • Diagnosis
  • US is test of choice
  • Distended gallbladder with thickened wall gt 5mm,
    pericholecystic fluid, stones
  • HIDA radionuclide scan if US inconclusive
  • If gallbladder not visualized 4 hours after
    injection, diagnosis is confirmed.(97 sensitive,
    96 specific)
  • Treatment
  • Supportive IV fluids, NPO, IV abx (Zosyn,
    Unasyn, 3rd gen cephalasporin Flagyl),
    analgesics, electrolyte replacement
  • Semiurgent Cholecystectomy w/in 72 hrs to avoid
    gangrenous/emphysematous cholecystitis

http//www.stritch.luc.edu/lumen/MedEd/Radio/curri
culum/Procedures/HIDA_scan1.htm
15
Case 3
  • 52 y/o male transferred from an OSH for
    intermittent abdominal pain and progressive
    jaundice over the past 2 days. Further history
    reveals symptoms consistent with biliary colic.
    Exam shows a patient in mild distress with
    tenderness in the RUQ and jaundice. Labs are
    significant for AST 450, ALT 520, Alk Phos
    630, T Bili 4.2
  • What is the most likely diagnosis and what is
    your next step in management?

16
Case 3
  • 52 y/o male transferred from an OSH for
    intermittent abdominal pain and progressive
    jaundice over the past 2 days. Further history
    reveals symptoms consistent with biliary colic.
    Exam shows a patient in mild distress with
    tenderness in the RUQ and jaundice. Labs are
    significant for AST 450, ALT 520, Alk Phos
    630, T Bili 4.2
  • What is the most likely diagnosis and what is
    your next step in management?
  • Choledocholithiasis, ERCPdiagnostic and
    therapeutic

17
choledocholithiasis
  • Gallstones within the common bile duct or common
    hepatic duct, formed in situ or passed from
    gallbladder
  • Presentation asymptomatic (50)? biliary colic
    ? ascending cholangitis, obstructive jaundice,
    acute pancreatitis
  • Definitions of dilated bile duct
  • gt6mm 1mm per decade above 60 y/o
  • gt10 post-cholecystectomy
  • Dilated intrahepatic biliary tree

18
Choledocholithiasis
  • Diagnostic studies
  • Transabdominal US 13-55 sensitivity1,
    Endoscopic US higher sensitivity and specificity
    for intraductal stones
  • CT w/ contrast 65-88 sensitive2, CT
    cholangiography 93 sensitive, 100 specific but
    difficult to perform3
  • MRCP and ERCP both have sensitivities and
    specificities approaching 1004
  • Treatment
  • ERCP with sphincterotomy, stone extraction, stent
    placement
  • Successful in 90 of patients
  • Complication rates 6-245, including pancreatitis
  • DDx cholangiocarcinoma, pancreatic adenocarcinoma

19
choledocholithiasis
  • ERCP

MRCP
http//www.jcdr.net/article_fulltext.asp?issn0973
-709xyear2013volume7issue9page1941issn09
73-709xid3365
http//radiopaedia.org/images/2413474
20
Case 4
  • 50 y/o female admitted to the MICU for AMS.
    Vitals include temp 39, HR 110, BP 90/60, RR 20,
    sat 96 on RA. Exam reveals a somnolent female
    with jaundice, scleral icterus, and guarding upon
    palpation of the RUQ. Labs reveal WBC 16,000,
    AST 160, ALT 200, Alk Phos 650, T bili 8.0. Blood
    cultures are pending.
  • What is the most likely diagnosis?

21
Case 4
  • 50 y/o female admitted to the MICU for AMS.
    Vitals include temp 39, HR 110, BP 90/60, RR 20,
    sat 96 on RA. Exam reveals a somnolent female
    with jaundice, scleral icterus, and guarding upon
    palpation of the RUQ. Labs reveal WBC 16,000,
    AST 160, ALT 200, Alk Phos 650, T bili 8.0. Blood
    cultures are pending.
  • What is the most likely diagnosis?
  • Septic shock 2/2 Acute Cholangitis

22
cholangitis
  • Infection of biliary tract 2/2 obstruction ?
    biliary stasis bacterial overgrowth
  • Ecoli Klebsiella 70, Enterococcus Anaerobes
    (15)
  • Choledocholithiasis accounts for 60 of cases
  • Other causes pancreatic/biliary neoplasm,
    strictures, s/p ERCP, choledochal cysts
  • Clinical features
  • Charcots Triad RUQ pain Jaundice Fever
  • Present in 60-79
  • Reynolds Pentad Charcots triad Septic shock
    AMS
  • Present in 15
  • Medical emergency if fever gt40ºC, septic shock,
    peritoneal signs, or bilirubin gt 10

23
cholangitis
  • Diagnosis/Treatment
  • IV abx (Zosyn, Unasyn, 3rd gen cephalasporin), IV
    fluids
  • RUQ ultrasound as initial study
  • When pt stable and afebrile for 48 hrs perform
    either
  • PTC (percutaneous transhepatic cholangiography)
    decompression via catheter placement
  • ERCP sphincterotomy
  • T-tube insertion via laparotomy
  • May need emergent procedures if pt doesnt
    respond to IV abx (15)

24
Summary
Cholelithiasis Cholecystitis Choledocho-lithiasis Cholangitis
Stones in gallbladder Obstruction of cystic duct ? Inflammation Gallstones in CBD Infection of biliary tract
Biliary colic Murphys sign Fever, ? WBC Biliary colic, jaundice Charcots triad
25
Case 5
  • You are asked to consult on a 62 y/o Caucasian
    female with pruritis for 4 months. She has also
    noticed progressive fatigue and a 5-lb wt loss.
    She has intermittent nausea but no vomiting
    denies changes in her bowel habits. She denies
    any history of alcohol use, blood transfusions or
    illicit drugs. She is widowed and had 2
    heterosexual partners in her lifetime. PMHx if
    significant only for hypothyroidism, for which
    she takes levothyroxine. Her mother has Sjogrens
    but there is no family hx of liver disease.
  • On exam, she is mildly icteric, has spider
    angiomata on her torso, and the following skin
    findings

26
Case 5 exam
What is this?
http//www.hxbenefit.com/wp-content/uploads/2011/1
2/Xanthelasma.jpg
27
Case 5 exam
Xanthelasma
http//www.hxbenefit.com/wp-content/uploads/2011/1
2/Xanthelasma.jpg
28
Case 5 cont
  • Furthermore, you palpate a nodular liver edge 2cm
    below the right costal margin. The remainder of
    the exam is unremarkable.
  • A RUQ ultrasound confirms your suspicion of
    cirrhosis. CBC and CMP are pending.
  • What is the most appropriate next step?
  • 24-h urine copper
  • Antimitochondrial antibioties (AMA)
  • ERCP
  • Hepatitis B serologies
  • Serum ferritin

29
Case 5
  • What is the most appropriate next step?
  • 24-h urine copper
  • Antimitochondrial antibioties (AMA)
  • ERCP
  • Hepatitis B serologies
  • Serum ferritin
  • The presence of cirrhosis in an elderly woman
    with no prior risk factors for viral or alcoholic
    cirrhosis should raise the possibility of primary
    biliary cirrhosis (PBC). AMA is in 95 with low
    false positives. Liver biopsy showing chronic
    inflammation and fibrous obliteration of
    intrahepatic ducts can confirm the diagnosis.

30
Primary biliary Cirrhosis
  • Autoimmune destruction of intrahepatic bile ducts
  • Associated with other autoimmune dz often
    presents with fatigue and pruritus
  • Clinical jaundice when total bilirubin gt2 mg/dL
  • Labs
  • Increased alk phos, bilirubin, and cholesterol
    (but no ? risk for CAD)
  • antimitochondrial Ab (AMA) in 95
  • Tx
  • Ursodeoxycholic acid (13-15 mg/kg/d)reduces the
    overall toxicity of bile salt pool, ? survival
  • Cholestyramine for puritis--? serum bile levels
    by binding preventing gut absorption
  • Fat soluble vitamins Vit A, E, D, K
  • Screen for osteoporosis (independent risk factor
    for Vit D deficiency)
  • Liver transplant 20 recur
  • However without liver transplant, medial survival
    is 10-12 yrs after dx

31
Case 6
  • 24 y/o patient is admitted to the MICU with
    obtundation and jaundice over 1-2 days. No
    further history is available. The following labs
    are obtained
  • Total Bili 7.2, Direct Bili 4.0, AST 1478, ALT
    1056, Alk Phos 132, INR 3.1, Albumin 3.6.
  • All of the following tests are indicated except?
  • Antinuclear Ab (ANA)
  • Ceruloplasmin
  • Hepatitis B surface Ag
  • ERCP
  • Toxicology screen

32
Case 6
  • All of the following tests are indicated except?
  • Antinuclear Ab (ANA)
  • Ceruloplasmin
  • Hepatitis B surface Ag
  • ERCP
  • Toxicology screen
  • When evaluating a patient with jaundice, initial
    steps include determining whether the
    hyperbilirubinemia is predominantly unconjugated
    or conjugated and whether there is any other
    evidence for hepatobiliary dysfxn. Next is to
    discriminate into a predominantly cholestatic or
    hepatocellular pattern. In this case, the pt has
    a hepatocellular pattern with AST/ALT elevated
    out of proportion to Alk Phos.

33
Harrisons Internal Medicine
34
Case 7
  • 41 y/o male who presents to your clinic with a
    week of jaundice. He notes pruritus, icterus,
    and dark urine. He denies fever or abdominal
    pain. Exam is unremarkable except for jaundice.
  • Labs Total bili 6.0 , direct bili 5.1, AST 84 ,
    ALT 92, Alk phos 662.
  • CT scan of abdomen is unremarkable. RUQ
    ultrasound shows a normal bile duct but does not
    visualize the common bile duct.
  • What is the most appropriate next management
    step?
  • Antibiotics and observation
  • ERCP
  • Hepatic serologies
  • HIDA scan
  • Serologies for antimitochondrial Ab

35
Case 7
  • What is the most appropriate next management
    step?
  • Antibiotics and observation
  • ERCP
  • Hepatic serologies
  • HIDA scan
  • Serologies for antimitochondrial Ab
  • Anatomic abnormalities are more common when there
    is a cholestatic pattern of injury (Alk Phos
    elevated out of proportion to AST/ALT). Painless
    jaundice always requires extensive workup with
    concern for malignant causes (e.g.
    cholangiocarcinoma, tumor of ampulla of vater) vs
    nonmalignant causes (e.g. primary sclerosing
    cholangitis), which may only be detected by
    direct visualization with ERCP. Negative CT does
    not rule out source of cholestatis in biliary
    tree. Furthermore, ERCP is useful therapeutically
    with stenting to alleviate the obstruction.

36
Harrisons Internal Medicine
37
Case 8
  • 44 y/o woman is evaluated for complaints of
    abdominal pain. She describes the pain as
    postprandial burning pain. It is worse with spicy
    or fatty foods and is relieved with antacids. She
    is diagnosed with a gastric ulcer and treated
    appropriately for H. pylori. Following treatment
    of H. pylori, her symptoms have resolved. During
    the course of her evaluation for her abdominal
    pain, the patient has a RUQ ultrasound that
    demonstrates the presence of numerous gallstones,
    including in the neck of the gallbladder. The
    largest stone measures 2.8cm. She is requesting
    your opinion regarding whether treatment is
    required for her gallstone disease.

38
Case 8
  • What is your advice to the patient regarding the
    risk of complications and the need for definitive
    treatment?
  • Given the size and number of stones, prophylactic
    cholecystectomy is recommended.
  • No treatment is necessary unless the patient
    develops symptoms of biliary colic frequently and
    severely enough to interfere with the patients
    life.
  • The only reason to proceed with cholecystectomy
    is the development of gallstone pancreatitis or
    cholangitis.
  • The risk of developing acute cholecystitis is
    about 5-10 per year.
  • Ursodeoxycholic acid should be given at a dose of
    10-15 mg/kg for a minimum of 6 months to dissolve
    the stones.

39
Case 8
  • What is your advice to the patient regarding the
    risk of complications and the need for definitive
    treatment?
  • Given the size and number of stones, prophylactic
    cholecystectomy is recommended.
  • No treatment is necessary unless the patient
    develops symptoms of biliary colic frequently and
    severely enough to interfere with the patients
    life.
  • The only reason to proceed with cholecystectomy
    is the development of gallstone pancreatitis or
    cholangitis.
  • The risk of developing acute cholecystitis is
    about 5-10 per year.
  • Ursodeoxycholic acid should be given at a dose of
    10-15 mg/kg for a minimum of 6 months to dissolve
    the stones.
  • Only 1-2 of patients with asymptomatic
    gallstone disease will develop compliations that
    will require surgery yearly. 4 factors should be
    considered in evaluation for surgery
  • Symptoms that are severe and frequent enough to
    necessitate surgery.
  • Hx of prior complications of gallstone disease
    (e..g pancreatitis, acute cholecystitis)
  • Presence of anatomic factors that increase the
    likelihood of complications (e.g. porcelain
    gallbladder, congenital biliary tract
    abnormalities)
  • Large stones gt3cm
  • Ursodeoxycholic acid can be used in some
    instances to dissolve gallstones. It acts to
    decrease the cholesterol saturation of bile
    allows the dispersion of cholesterol from
    stones. It is only effective, however, for
    radiolucent stones lt10mm.

40
Case 9
  • 62 y/o man has been in the ICU for the past 3
    weeks following an automobile accident results in
    multiple long-bone fractures and ARDS. He has
    been slowly improving, but remains on mechanical
    ventilation. He is now febrile hypotensive,
    requiring vasopressors. He is being treated
    empirically with cefepime and vancomycin.
    Multiple blood cultures are negative. He has no
    new infiltrates on CXR. Labs show a risk in AST,
    ALT, bilirubin, and alk phos. Amylase and lipase
    are normal. A RUQ ultraound shows sludge in the
    gallbladder, but no stones. The bile duct is not
    dilated.
  • What is the next best step in the evaluation and
    treatment of this patient?
  • Discontinue cefepime
  • Initiate clindamycin
  • Initiate metronidazole
  • Perform hepatobiliary scintigraphy (HIDA)
  • Refer for exploratory laparotomy

41
Case 9
  • What is the next best step in the evaluation and
    treatment of this patient?
  • Discontinue cefepime
  • Initiate clindamycin
  • Initiate metronidazole
  • Perform hepatobiliary scintigraphy (HIDA)
  • Refer for exploratory laparotomy
  • Have a high index of suspicion for acalculous
    cholecystitis in critically ill patients who
    develop decompensation during the course of
    treatment with no other apparent source of
    infection. Some predisposing conditions include
    serious trauma or burns, postpartum after
    prolonged labor, prolonged parenteral
    hyperalmentation, post op after orthopedic or
    major surgery. US and CT scan typically only show
    biliary sludge, but may demonstrate large/tense
    gallbladder. HIDA often showed delayed or absent
    gallbladder emptying. In critically ill pts, a
    percutaneous cholecytostomy may be the safest
    immediate procedure to decompress an infected
    gallbladder. Once the pt is stabilized, early
    elective cholecystectomy should be considered.
    Metronidazole to cover anaerobes should be added,
    but would not elucidate the underlying condition.

42
References
  • Adamek HE, Albert J, Weitz M et-al. A prospective
    evaluation of magnetic resonance
    cholangiopancreatography in patients with
    suspected bile duct obstruction. Gut. 199843
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  • Agabegi SS, Agabegi ED. Step Up to Medicine, 3rd
    ed. 2013. Lippincott Williams Wilkins.
    Philadelphia, PA.
  • Caoili EM, Paulson EK, Heyneman LE et-al. Helical
    CT cholangiography with three-dimensional volume
    rendering using an oral biliary contrast agent
    feasibility of a novel technique. AJR Am J
    Roentgenol. 2000174 (2) 487-92.
  • Cronan JJ. US diagnosis of choledocholithiasis a
    reappraisal. Radiology. 1986161 (1) 133-4.
  • Guardino JM. Primo Gastro. 2008. Lippincott
    Williams Wilkins. Philadelphia, PA.
  • Miller FH, Hwang CM, Gabriel H et-al.
    Contrast-enhanced helical CT of
    choledocholithiasis. AJR Am J Roentgenol.
    2003181 (1) 125-30.
  • Sabatine, MS. Pocket Medicine, 4th ed. 2011.
    Lippincott Williams Wilkins. Philadelphia, PA.
  • Sugiyama M, Suzuki Y, Abe N et-al. Endoscopic
    retreatment of recurrent choledocholithiasis
    after sphincterotomy. Gut. 200453 (12) 1856-9.
  • Wiener C, Fauci AS, Braunwald E, et al.
    Harrisons Principles of Internal Medicine
    Self-Assessment Board Review, 17th ed. 2008.
    McGraw Hill. New York, NY.
  • http//medicine.ucsf.edu/education/resed/Chiefs_co
    ver_sheets/SBP,20cirrhosis,20empyema.pdf
  • http//radiopaedia.org
  • Special thanks to Dr. Caroline Soyka for the
    inspiration!
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