Transcript 2008_07_31-Caine-Biliary_atresia

Interesting Case Rounds
July 31, 2008
Sean Caine
CCFP-EM Resident
The Case
90 d F referred from urgent care for FTT
and prolonged jaundice
History
History
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Pregnancy
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Mother was 23 yo Caucasian female G1P0 O neg
Routine serology was normal
GBS negative
Nonsmoker. No EtOH
Uncomplicated pregnancy (no PIH or GDM)
Delivery
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SVD @ 39wks GA
ROM x 3 hrs
BW=3220
Apgar 91,95
DAT negative
Newborn metabolic screen was normal
Tbili at discharge =190
d/c home 24hrs postpartum
History
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Followed by GP qweekly x 6 wks
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Jaundiced noted again at 6wk follow up with maternity care clinic
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1 oz wt loss in past month
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Exclusively breast fed. Feeds well.
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~6-8 BM/day. Stools are typically yellow. Recently have become
more pale.
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~6-8 wet diapers/day. Urine is brown.
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ROS otherwise unremarkable for sleep, appetite, activity, or
symptoms indicative of focus for infection etc
On exam
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VS: 36.6 119 88/47 36
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No apparent distress. Awake. Alert. Interactive and
pleasant
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++scleral icterus. +jaundice
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Firm liver edge. Palpable spleen tip.
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CV, Resp, CNS, Abdo exam otherwise
unremarkable
Labs/Investigations
Labs/Investigations
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CBC
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Hb 110 (90-140)
WBC 21.5 H (5-19.5)
Plt 569 H (150-400)
Neut 9.2 H (1-9)
LFT/enzymes
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Lytes, Cr, Urea – NORMAL
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Urinalysis/R&M
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LARGE Leuks,
SMALL blood
20-30 WBC/hpf
0-5 RBC
Few bacteria
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Tbili 178 H (0-23)
Direct bili 118 H (0-7)
ALT 199 H (1-35)
AST 262 H (10-65)
ALP 461 H (40-390)
GGT 796 H (8-35)
Albumin 38
INR 1.1
PTT 40.5 H (27-36)
Ammonia 61 H (12-47)
Objectives
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Review features of physiologic and
pathologic jaundice
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Review approach to neonatal cholestasis
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Highlight some common pitfalls
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Return to the case to review the work up
and diagnosis
Hyperbilirubinemia
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Has increasingly become a presenting
complaint to ER due to early postpartum
discharge
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However, still rare to encounter in Calgary
ER
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Screened by PHN/GP in first 3-5 days postpartum
Direct admit to PLC Unit 31 for assessment +/phototherapy
Hyperbilirubinemia
Physiologic vs. Pathologic Jaundice in
the Newborn
Physiologic vs. Pathologic Jaundice in
the Newborn1
Physiologic
Pathologic
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Unconjugated hyperbilirubinmia
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Appears <24 hrs
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60% term & >80% preterm neonates in
first week
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Excessive for infant’s age (Tbili > 205
umol/L)
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Rises at rate <85 umol/L/day
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Elevated direct bilirubin
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Appears on 2nd or 3rd day of life
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Jaundice present at or beyond 3 wks
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Typically peaks btwn days 2-4
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Sick infant
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Begins to decline on days 5-7 at rate of
34 umol/L/day
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Tbili rising >85 umol/L/day
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Unexplained jaundice following
phototherapy
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Jaundice in the presence of risk factors
Ddx Conjugated vs. Unconjugated
Hyperbilirubinemia
UNCONJUGATED
Physiologic
CONJUGATED
Pathologic
Hepatic
Non-hemolytic
Cephalohematoma
Polycythemia
Sepsis
Hypothyrodism
Gilbert’s
Crigler- Najjar
Hemolytic
Extrinsic
Hemolytic
Intrinsic
Membrane
Spherocytosis
Elliptocytosis
Enzyme
G6PD
PK deficiency
Hemoglobin
Alpha thal
Immune
ABO-incompatibility
Rh-incompatibility
Kelly-Duffy etc
Non immune
Splenomegaly
Sepsis
AV malformation
Infectious
Sepsis
Hep B, TORCH
Metabolic
Galactosemia
Tyrosinemia
Alpha-1-antitrypsin
Hypothyroidism
CF
Drugs
TPN
Idiopathic neonatal
Cholestasis
Bile duct paucity
AbN Bile acid metabolism
Extra Hepatic
Biliary atresia
Choledocal cyst
Ddx of Hyperbilirubinemia
According to Time of Onset
First 24 hours
24-72 hours
72-96 hours
Often pathologic
•Hemolysis (Rh
or ABO)
•Physiologic
•Physiologic
•Sepsis (GBS,
TORCH)
•Cephalohematoma
•Spherocytosis
•Hemorrhagic
disease of the
newborn
> 1 week
Often pathologic
•Breast milk jaundice
•Polycythemia
•Dehydration
•Dehydration
•Sepsis
•Prolonged
Physiologic
•Hemolysis
•G6PD
•PK def
•Gilbert’s
•Hypothyroidism
•Crigler-Najjar
•Neonatal
Hepatitis
•Cephalohematoma
•Hypoxia/resp
distress/hypoG
•Galactosemia
•Spherocytosis
•Sepsis/TORCH
•Familial
Cholestasis
•Biliary atresia
•Paucity of bile
ducts
Neonatal Cholestasis
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Defined as the impaired canalicular biliary flow resulting in
acumulation of biliary substances (bilirubin, bile acids, and
cholesterol)2
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Estimated incidence of 1/2500 live births
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Jaundice at 2-3 weeks of age increases suspicion2
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2.4-15% of newborns are jaundice at 2 weeks of age6
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Estimated that 60-375 jaundiced infants at 2 weeks of age
would need to be tested to detect one case of cholestasis 26
Common Pitfalls
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Breast feeding jaundice
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Exaggeration of physiologic jaundice
Day 2  7
Premature babies: can last up to 10 days
Breast milk jaundice
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2% of breast fed babies
Starts ~ day 7, persists until week 2-3
May persist for 3-10 weeks at low levels
Unconjugated
Theory: glucuronidase in breast milk 
increased enterohepatic bilirubin re-circulation
Neonatal Cholestasis
Clinical Presentation
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Prolonged jaundice
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Pale stools
Less specific suggestive of underlying
metabolic, CNS, or infectious aetiology:
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Dark urine
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Coagulopathy
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Hepatomegaly
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Splenomegaly
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RUQ mass
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FTT
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Fever
Irritability
Lethargy,
Seizures
Poor feeding
Dysmorphic features
Ddx Neonatal Cholestasis
Obstruction
Infectious
Metabolic/Genetic
Biliary Atresia
Bacterial
Alagille Syndrome
α-1-Antitrypsin
Choledochol cyst
Protozoal
Galactosemia
Tumor
TORCH
Inspissated bile/plug
sybdrome
Tyrisonemia
Echovirus
Lipid metabolism disorders
Adenovirus
Bilae acid metabolism
disorders
Parvovirus B18
Mitochondrial Disease
Gallstone
Biliary Sludge
Citrin deficiancy
Approach to Neonatal
Cholestasis
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Initial investigations: Establish cholestasis and
determine severity of disease
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2.
Detailed hx, exam
Fractioned serum bili
Tests for liver injury (AST, ALT, ALP, GGT)
LFT (Albumin, INR, PTT, serum ammonia, glucose)
Detect conditions that require immediate treatment
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CBC, blood & urine cultures to r/o sepsis
Serum T4 and TSH
Metabolic Screen: lactate, ammonia, iron, ferritin, urinalysis,
urine amino acids and organic acids
Viral serologies, VDRL, and cultures
Approach to Neonatal
Cholestasis
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Differentiate extrahepatic disorders
from intrahepatic causes of
cholestasis
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4.
U/S
Hepatobiliary scintigraphy
Perc liver bx,
Exploratory laparotomy with intraoperative
Establish other specific diagnosis
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α-1-antitrypsin, CF, Alagille, PFIC, storage
disorders
Back to the Case
1.
Initial investigation: establish cholestasis
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Detect conditions that require treatment
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Differentiate extrahepatic disorders from
intrahepatic causes of cholestasis
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Investigate for the rare diagnosis
BiliaryAtresia
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Inflammation of bile ducts leading to progressive
obliteration of the extrahepatic biliary tract
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Most common cause of cholestasis in the first few
weeks of life
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Incidence of 1/10,000 to 1/20,000 births
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Cause remains unknown though various infectious
(CMV, reovirus, rotavirus) and genetic causes have
been proposed
Biliary Atresia
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Jaundice typically develops in weeks 3-6
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Uncommon for jaundice to be present at
birth
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10-15% association with congenital
malformations (polysplenia, malrotation,
etc)
Biliary Atresia
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Diagnosis
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U/S can be suggestive
Liver biopsy is the most useful test
HIDA useful
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Specificity improved with phenobarb 5d before scan
Duodenal aspirate
Exploratory laparotomy & intraoperative
cholangiogram
ERC and MRC likely to have future
Ultrasound
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Main utility is to r/o other extrahepatic
causes (ie choledochol cyst)
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Findings suggestive of biliary atresia
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Absence of gallbladder
Abnormal gallbladder size and shape
“Triangular cord” sign
Absence of a common bile duct
Ultrasound
Ultrasound
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Abnormally small and contracted
gallbladder and irregular contour and
septations in the gallbladder neck.
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Common bile duct not visualized
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Consistent with biliary atresia
Biliary Atresia
Treatment
 Primary treatment is Kasai procedure
 Early diagnosis and surgery is critical
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Narrow window for optimal short and longterm
outcomes
bile drainage achieved in >80% of patients <60 days of
age vs. 20% of infants >90 days
4 yr survival with native liver
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49% with sx <30 days of age
36% with sx at 31-90 days of age
23% with sx at >90 days of age
Kasai
Pearls
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Recognize pathologic features of jaundice
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Obtain fractioned serum bili level (ie total and
direct) on all 2-3 week old jaundiced infants
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Infants with biliary atresia will often appear to be
well in the first 1-2 weeks of life
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Neonatal cholestasis is rare, but timely diagnosis is
crucial!
References
1.
Subcommittee on Hyperbilirubinemia. Management of Hyperbilirubinemia in the
Newborn Infant 35 or More weeks of Gestation. Pediatrics. 2004;114:297-316.
2.
Venigalla S, Gourley GR. Neonatal Cholestasis. Seminars in Perinatology.2004;28:348355.
3.
Suchy F. Neonatal Cholestasis. Pediatrics in Review. 2004;25:388-395.
4.
Schreiber RA, Barker CC, Roberts EA, et al. Biliary Atresia: the Canadian Experience.
Journal of Pediatrics. 2007;151:659
5.
Abrams S, Shulman R. Causes of Neonatal Cholestasis. UpToDate. Last updated June
12, 2008.
6.
Abrams S, Shulman R. Approach to Neonatal Cholestasis. UpToDate. Last updated
September 26, 2006.
The End