interesting case rounds july 31, 2008 sean caine ccfp-em resident
TRANSCRIPT
Interesting Case Rounds
July 31, 2008
Sean CaineCCFP-EM Resident
The Case
90 d F referred from urgent care for FTT and prolonged jaundice
History
History
Pregnancy 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 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
Followed by GP qweekly x 6 wks
Jaundiced noted again at 6wk follow up with maternity care clinic
1 oz wt loss in past month
Exclusively breast fed. Feeds well.
~6-8 BM/day. Stools are typically yellow. Recently have become more pale.
~6-8 wet diapers/day. Urine is brown.
ROS otherwise unremarkable for sleep, appetite, activity, or symptoms indicative of focus for infection etc
On exam
VS: 36.6 119 88/47 36
No apparent distress. Awake. Alert. Interactive and pleasant
++scleral icterus. +jaundice
Firm liver edge. Palpable spleen tip.
CV, Resp, CNS, Abdo exam otherwise unremarkable
Labs/Investigations
Labs/Investigations
CBC Hb 110 (90-140) WBC 21.5 H (5-19.5) Plt 569 H (150-400) Neut 9.2 H (1-9)
Lytes, Cr, Urea – NORMAL
Urinalysis/R&M LARGE Leuks, SMALL blood 20-30 WBC/hpf 0-5 RBC Few bacteria
LFT/enzymes 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
Review features of physiologic and pathologic jaundice
Review approach to neonatal cholestasis
Highlight some common pitfalls
Return to the case to review the work up and diagnosis
Hyperbilirubinemia
Has increasingly become a presenting complaint to ER due to early postpartum discharge
However, still rare to encounter in Calgary ER
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
Unconjugated hyperbilirubinmia
60% term & >80% preterm neonates in first week
Rises at rate <85 umol/L/day
Appears on 2nd or 3rd day of life
Typically peaks btwn days 2-4
Begins to decline on days 5-7 at rate of 34 umol/L/day
Pathologic
Appears <24 hrs
Excessive for infant’s age (Tbili > 205 umol/L)
Elevated direct bilirubin
Jaundice present at or beyond 3 wks
Sick infant
Tbili rising >85 umol/L/day
Unexplained jaundice following phototherapy
Jaundice in the presence of risk factors
Ddx Conjugated vs. Unconjugated Hyperbilirubinemia
UNCONJUGATED CONJUGATED
Physiologic Pathologic
Non-hemolyticCephalohematomaPolycythemiaSepsisHypothyrodismGilbert’sCrigler- Najjar
Hemolytic Intrinsic
Membrane Spherocytosis ElliptocytosisEnzyme G6PD PK deficiencyHemoglobin Alpha thal
Hemolytic Extrinsic
Immune ABO-incompatibility Rh-incompatibility Kelly-Duffy etcNon immune Splenomegaly Sepsis AV malformation
HepaticInfectious Sepsis Hep B, TORCHMetabolic Galactosemia Tyrosinemia Alpha-1-antitrypsin Hypothyroidism CFDrugsTPNIdiopathic neonatal CholestasisBile duct paucityAbN Bile acid metabolism
Extra HepaticBiliary atresiaCholedocal cyst
Ddx of Hyperbilirubinemia According to Time of Onset
First 24 hours 24-72 hours 72-96 hours > 1 week
Often pathologic•Hemolysis (Rh or ABO)
•Sepsis (GBS, TORCH)
•Cephalohematoma
•Spherocytosis
•Hemorrhagic disease of thenewborn
•Physiologic
•Polycythemia
•Dehydration
•Hemolysis•G6PD•PK def
•Cephalohematoma
•Spherocytosis
•Sepsis/TORCH
•Physiologic
•Dehydration
•Sepsis
•Gilbert’s
•Crigler-Najjar
•Hypoxia/resp distress/hypoG
Often pathologic
•Breast milk jaundice
•Prolonged Physiologic
•Hypothyroidism
•Neonatal Hepatitis
•Galactosemia
•Familial Cholestasis
•Biliary atresia•Paucity of bile ducts
Neonatal Cholestasis
Defined as the impaired canalicular biliary flow resulting in acumulation of biliary substances (bilirubin, bile acids, and cholesterol)2
Estimated incidence of 1/2500 live births
Jaundice at 2-3 weeks of age increases suspicion2
2.4-15% of newborns are jaundice at 2 weeks of age6
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
Breast feeding jaundice Exaggeration of physiologic jaundice Day 2 7 Premature babies: can last up to 10 days
Breast milk jaundice 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
Prolonged jaundice
Pale stools
Dark urine
Coagulopathy
Hepatomegaly
Splenomegaly
RUQ mass
FTT
Less specific suggestive of underlyingmetabolic, CNS, or infectious aetiology:
Fever Irritability Lethargy, Seizures Poor feeding Dysmorphic features
Ddx Neonatal CholestasisObstruction
Biliary Atresia
Choledochol cyst
Tumor
Inspissated bile/plug sybdrome
Gallstone
Biliary Sludge
Infectious
Bacterial
Protozoal
TORCH
Echovirus
Adenovirus
Parvovirus B18
Metabolic/Genetic
Alagille Syndrome
α-1-Antitrypsin
Galactosemia
Tyrisonemia
Lipid metabolism disorders
Bilae acid metabolism disorders
Mitochondrial Disease
Citrin deficiancy
Approach to Neonatal Cholestasis
1. Initial investigations: Establish cholestasis and determine severity of disease
Detailed hx, exam Fractioned serum bili Tests for liver injury (AST, ALT, ALP, GGT) LFT (Albumin, INR, PTT, serum ammonia, glucose)
2. Detect conditions that require immediate treatment 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
3. Differentiate extrahepatic disorders from intrahepatic causes of cholestasis
U/S Hepatobiliary scintigraphy Perc liver bx, Exploratory laparotomy with intraoperative
4. Establish other specific diagnosis α-1-antitrypsin, CF, Alagille, PFIC, storage
disorders
Back to the Case
1. Initial investigation: establish cholestasis
2. Detect conditions that require treatment
3. Differentiate extrahepatic disorders from intrahepatic causes of cholestasis
4. Investigate for the rare diagnosis
BiliaryAtresia
Inflammation of bile ducts leading to progressive obliteration of the extrahepatic biliary tract
Most common cause of cholestasis in the first few weeks of life
Incidence of 1/10,000 to 1/20,000 births
Cause remains unknown though various infectious (CMV, reovirus, rotavirus) and genetic causes have been proposed
Biliary Atresia
Jaundice typically develops in weeks 3-6
Uncommon for jaundice to be present at birth
10-15% association with congenital malformations (polysplenia, malrotation, etc)
Biliary Atresia
Diagnosis U/S can be suggestive Liver biopsy is the most useful test HIDA useful
Specificity improved with phenobarb 5d before scan
Duodenal aspirate Exploratory laparotomy & intraoperative
cholangiogram ERC and MRC likely to have future
Ultrasound
Main utility is to r/o other extrahepatic causes (ie choledochol cyst)
Findings suggestive of biliary atresia Absence of gallbladder Abnormal gallbladder size and shape “Triangular cord” sign Absence of a common bile duct
Ultrasound
Ultrasound
Abnormally small and contracted gallbladder and irregular contour and septations in the gallbladder neck.
Common bile duct not visualized
Consistent with biliary atresia
Biliary Atresia
Treatment Primary treatment is Kasai procedure Early diagnosis and surgery is critical
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 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
Recognize pathologic features of jaundice
Obtain fractioned serum bili level (ie total and direct) on all 2-3 week old jaundiced infants
Infants with biliary atresia will often appear to be well in the first 1-2 weeks of life
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;28:348-355.
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