Morning Report May 25, 2010

Morning Report
December 22, 2010
**Welcome Applicants!**
Geoffrey Smith, MD
Andrew Aronson, MD
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Session ID #A700

MKSAP
A 55-year-old woman is evaluated for a 4-month history of progressive
fatigue and pruritus. She is otherwise healthy and takes no medications.
On physical examination, vital signs are normal; BMI is 25. Examination
reveals mild hepatomegaly and excoriations of the skin. There is no
jaundice, rash, or skin eruption.
Laboratory studies:
• Bilirubin (total) 1.5 mg/dL (25.6 µmol/L)
• Aspartate aminotransferase 60 U/L
• Alanine aminotransferase 75 U/L
• Alkaline phosphatase 470 U/L
• Albumin 4.0 g/dL (40 g/L)
• Hepatitis C virus antibody Negative
• Hepatitis B surface antigen Negative
Ultrasonography of the abdomen is normal with no bile duct dilatation.

Which of the following is the most appropriate
next step in the diagnosis of this patient?
A. α 1-Antitrypsin phenotype
B. Liver biopsy
C. Measurement of serum antimitochondrial
antibody
D. Serum protein electrophoresis

Which of the following is the most appropriate
next step in the diagnosis of this patient?
A. α 1-Antitrypsin phenotype
B. Liver biopsy
C. Measurement of serum
antimitochondrial antibody
D. Serum protein
electrophoresis
25% 25% 25% 25%
A. B. C. D.

• This patient likely has primary biliary cirrhosis, and measurement of
antimitochondrial antibody is a highly sensitive and specific test for the
disorder; more than 95% of patients with primary biliary cirrhosis have
antimitochondrial antibodies and the false positive rate is approximately
2%.
• Fatigue, pruritus, an elevated alkaline phosphatase concentration, and the
presence of these antibodies strongly suggest this diagnosis.
• Although fatigue and pruritus used to be the most common presenting
symptoms of primary biliary cirrhosis, the disease is now more widely
recognized and many patients are diagnosed at earlier stages when they are
asymptomatic.
• If the antimitochondrial antibody is positive, liver biopsy is useful to
provide evidence that would stage the disease and other liver disorders that
may cause cholestasis similar to that associated with primary biliary
cirrhosis.
• α1-Antitrypsin deficiency would present with abnormal aminotransferase
concentrations, not with a cholestatic picture.
• A serum protein electrophoresis may demonstrate elevation in serum IgM,
but would not be diagnostic of primary biliary cirrhosis.

34 y/o M with abdominal pain

• In USOH until yesterday.
• Right upper quadrant and epigastric abdominal pain,
radiating to back.
• Pain constant, 10/10, began at 8pm yesterday.
• Last PO intake pizza at 4:30pm yesterday. Still feels
hungry, no loss of appetite.
• No fevers, chills, nausea, vomiting, constipation,
diarrhea, hematochezia, or melena.
• Notes darker urine, but mildly decreased in quantity

Medical History
• PMH: choledocholithiasis s/p cholecystectomy and ERCP, OSA
not using CPAP
• PSH: cholecystectomy and ERCP 2007
• SH: Lives with wife. Smokes 2-3 cigarettes daily since 1995.
Drinks approximately 40 oz of beer daily, but last drink was 1
week PTA. Occasional marijuana, last 1 week PTA.
• FH: Mother with cervical Ca; father died of unknown causes.
• MEDS: None
• Allergies: IV contrast, ciprofloxacin, clindamycin

Differential Diagnosis?

• Right upper quadrant
– Hepatitis
– Cholecystitis
– Cholangitis
– Pancreatitis
Abdominal pain differential
– Budd-Chiari syndrome
– Pneumonia/empyema pleurisy
– Sub-diaphragmatic abscess
• Right lower quadrant
– Appendicitis
– Salpingitis
– Ectopic pregnancy
– Inguinal hernia
– Nephrolithiasis
– Inflammatory bowel disease
– Mesenteric adenitis (yersina)
• Epigastric
– Peptic ulcer disease
– GERD
– Gastritis
– Pancreatitis
– Myocardial infarction
– Pericarditis
– Ruptured aortic aneurysm
• Periumbilical
– Early appendicitis
– Gastroenteritis
– Bowel obstruction
– Ruptured aortic aneurysm
• Left upper quadrant
– Splenic abscess
– Splenic infarct
– Gastritis
– Gastric ulcer
– Pancreatitis
• Left lower quadrant
• Diverticulitis
• Salpingitis
• Ectopic pregnancy
• Inguinal hernia
• Nephrolithiasis
• Irritable bowel syndrome
• Inflammatory bowel disease
• Diffuse Gastroenteritis
• Mesenteric ischemia
• Metabolic (eg, DKA, porphyria)
• Malaria
• Familial Mediterranean fever
• Bowel obstruction
• Peritonitis
• Irritable bowel syndrome

Referred Pain Areas

Physical Exam
• General: Obese man sitting in bed, NAD, A+Ox3
• VS: Ht 172.7cm (5’8”) Wt 140kg T 36.7 P 99 R 18 BP
165/109 SaO2 98% on RA
• HEENT: EOMI, scleral icterus, dry MM
• Neck: no lymphadenopathy, no thyromegaly
• Lungs: Clear to auscultation
• CV: regular, nl S1 and S2, no m/g/r, no JVD, periphery warm
and well perfused, 2+ radial and d.p. pulses
• Abdomen: soft, distended, RUQ tenderness (+Murphy’s
sign)
• GU: no CVA tenderness, no suprapubic tenderness
• Neuro: CN II-XII intact, strength and sensation intact,
• Skin: no rashes but several tattoos, no edema

Work up?
• Which tests would you like to order?

7.5
141
3.7 25
100 10
17.0
48.3
Laboratory Studies
0.9
184
145
Ca 9.3
8.7 4.7
4.9
3.0/1.9
534 421
Lipase 39
U/A: yellow, clear, s.g. 1.035, pH 6.0, Neg LE, Neg
nitrites, trace Protein, Neg blood, Neg glucose,
Neg ketones, Bilirubin 1+, Urobilinogen 1.0,
occasional RBC, no casts, no bacteria,
126
Urine:
Na 87
Cr 111
FENa 0.5%

Management at this point?
• Diagnostic tests?
• Additional Labs?
HAV IgM NR
HBV sAg NR
HBV cAb IgM NR
HCV Ab NR
US technician not available for RUQ US

Biliary Tree

Abdominal CT w

Abdominal CT read
• Probable fatty liver. Cholecystectomy clips with mild central
biliary prominence. No radio-opaque foci in course of cystic
duct remnant, common hepatic, or common bile duct. No
focal liver lesions. Hepatic vasculature enhances normally. No
other significant abnormality noted.
• Impression: post cholecystectomy with mild central biliary
prominence. No CT evidence of choledocholithiasis. Possible
fatty liver.

Accuracy of Imaging Modalities
for Detection of Biliary stones
• Ultrasound
– Sens 20%, Spec 83.3%
• Computerized tomography
– Sens 40%, Spec 91.7%
• MRCP
– Sens 80%, Spec 83.3%
• ERCP
– Sens 90%, Spec 91.7%
• Endoscopic ultrasound
– Sens 95%, Spec 91.7%
– Moon et al., Am J Gastroenterology 2005.

Status change
• ER calls to inform you patient has become
drowsy/altered, spiked a fever, decreasing
oxygen saturation, and is beginning to rigor.
• New vitals 4h after initial exam:
• T38.5 P 102 R 20 BP 141/77 Sat 92%/RA

3.3
138
2.7 17
105 10
12.2
48.3
N 92 L 6 M 2
(+ left shift)
Laboratory Studies
1.0
117
93
Ca 7.0
Mg 1.0
Ph 1.5
INR 2.2
PTT 41
6.2 3.4
5.7
231 315
Lipase 30
Amylase 33
Lactate 4.1
274

Focused differential

Initial management?
• What are we treating?

50-75% of cases

Acute Cholangitis Manifestation
• Charcot triad (fever, RUQ pain, jaundice) occurs in
50-75% of cases.
• Reynold’s pentad (Charcot triad, hypotension,
altered mental status) can occur in suppurative
cholangitis.
• Labs: elevated WBC with neutrophils, cholestatic
liver test abnormalities, amylase can be elevated.
• In the case of microabscess formation in the liver,
acute hepatocyte necrosis can occur, leading to
elevated aminotransferases as well.

Acute Cholangitis Microbiology
• Foreign body (e.g., stone or stent) is nidus for bacterial colonization.
• Bile from patients without obstruction is sterile or nearly sterile. In comparison,
70% of patients with gallstones have bacteria in their bile.
• Common bile duct stones - higher probability of bile culture positivity vs.
gallbladder or cystic duct stones.
• Causative bacteria:
• GNR
– Escherichia coli 25-50%
– Klebsiella 15-20%
– Enterobacter species 5-10%
• GPC
– Enterococcus species 10-20%
• Anaerobes
– Bacteroides, Clostridia usually present as a mixed infection.
– Rarely the sole infecting organisms; not clear if they play a role in acute cholangitis.
– Recovery of anaerobes more common after repeated biliary tree infections or surgery.

Acute Cholangitis
• What’s the next step in management of acute
cholangitis?
• Medical management vs. ERCP vs. surgical
decompression

Management of cholangitis
• Treatment: Antibiotics and Biliary drainage
• 80% of patients will respond to conservative management
and antibiotic therapy. Biliary drainage can then be performed
on an elective basis.
• In 15-20% percent of cases, cholangitis fails to settle over the
first 24 hours with conservative therapy alone, requiring
urgent biliary decompression.
• Indications for urgent biliary decompression include:
– Persistent abdominal pain
– Hypotension despite adequate resuscitation
– Fever greater than 39ºC (102ºF)
– Mental confusion, which is a predictor of poor outcome

Patients with Endoscopic
Biliary drainage:
Spent less time on the
ventilator*
Became afebrile sooner
Had shorter duration of
fasting*
*significant findings
Surgery vs. ERCP
• NEJM 1992 established non-inferiority of ERCP

Surgery vs. ERCP:
Less complications and Deaths with ERCP
• NEJM 1992 established non-inferiority of ERCP

Timing
of
ERCP

• Discussed case with GI Interventional attending on
call.
• Transferred to ICU for closer monitoring
• Aggressive fluids, antibiotics, intubation
• Defervesced with IV Zosyn, ERCP deferred until AM.
• Blood Cx drawn positive for Klebsiella oxytoca
• Bile fluid from ERCP positive for Enterococcus
casselliflavus.

Microbiology
• Klebsiella pneumoniae and oxytoca (named after 19th Century german microbiologist Edwin Klebs), are
both GNR opportunistic pathogens found in the
environment and mammalian mucosal surfaces,
principally GI tract.
• Enterococcus casseliflavus is one of the intrinsically
Vancomycin-resistant enterococcus GPC that is part
of the normal flora of the GI tract of mammals,
occasionally causing disease.

• Impression: -
Choledocholithiasis
with an obstruction
was found.
- Two biliary stents
were placed into the
common hepatic
duct.
- Ascending cholangitis
was found.
ERCP

• How could he have recurrent choledocholithiasis
even after his cholecystectomy?

Pathogenesis of recurrent
choledocholithiasis s/p cholecystectomy
• Bile-duct dysfunction
– Delayed biliary clearance
• Abnormal biliary motility
• Post-ES papillary stenosis
• Altered bile composition
– Biliary cholesterol supersaturation
• MDR3 missense mutations (normally secretes
phosphatidylcholne.

Risk factors for Recurrent biliary stones after
endoscopic sphincterotomy (EST)

Patient follow-up
• Discharged to continue home IV Vanco and Zosyn
• F/U ERCP:
- Choledocholithiasis was found. Complete
removal was accomplished by biliary
sphincterotomy and lithotripsy.

Prevention
• How do we prevent the next episode of
cholangitis? Unclear.
• Options include:
1. Dismiss such patients from follow- up and encourage
return only if symptoms recur.
2. Periodically repeat serum liver chemistries and/or noninvasive
imaging of the ducts.
3. Repeat invasive ductal imaging, usually by ERCP. This
alternative is rarely applied to asymptomatic patients.
4. Prophylactic treatment with antibiotics, cholerrhoeic
agents or stone solubilizing agents, e.g., ursodiol.

Take Home Points
• Recognize ascending cholangitis
• Understand how to triage these patients
• Know the role of ERCP in management of
cholangitis
• Understand the risks for recurrent biliary
stones in the absence of a gallbladder