KIDS G.I. CENTER RUBEN GONZALEZ-VALLINA, MD, FAAP - PowerPoint Presentation

Slide1

KIDS

G.I. CENTER

RUBEN GONZALEZ-VALLINA, MD, FAAPDirector, Gastroenterology OutPatient Initiativesrubengidoc@aol.com

Neonatal Cholestasis(Ictericia Neonatal) Abordaje y manejo

Slide2

BREAST MILK JAUNDICE

Early Onset

Very common – 12 percent of breast-fed babies affected.Onset during the first three days of life.May be related to caloric deprivation and dehydration.

Slide3

Late Onset

Occurs in approximately 0.5 to 3 percent of healthy newborn.Serum bilirubin rises rapidly after the fourth day of life.Serum bilirubin peaks at the end of the second week of life.Severe jaundice (bilirubin

15 mg per deciliter) occurs in 2 percent of breast-fed babies and 0.3 percent of formula-fed babies. BREAST MILK JAUNDICE

Slide4

Not associated with

kernicterus.Cessation of breast-feeding for 24 to 48 hours results in a significant drop in serum bilirubin.BREAST MILK JAUNDICE

etiology [?]abnormal progesterone metabolite

Inhibition of conjugating mechanism↑ levels of nonesterfied FA

↑ absorption of bile from the GI tract

Slide5

JAUNDICE – BREAST FEEDING

Bilirubin may to 20mg/dl = in term infantsNeed to interrupt feeding = extremely rareResolves spontaneously = without interruptionIf bilirubin is too high = interrupt for up to 3 days / bilirubin will Minimal rebound

= after reinstitution of breast feeding

Slide6

A breast-fed infant is found to have an

indirect bilirubinlevel of 15 mg/dL on day 15 of life. Of the following, thestatement which most correctly describes hyperbilirubinemia

as aresult of ingestion of breast milk is: (A) Excess bilirubin production is the primary etiologic factor. (B) A bilirubin level >10 mg-dL on the first day of life is typical

(C) The condition will resolve spontaneously (D) Affected infants are at risk of kernicterus (E) The bilirubin is transmitted in the breast milk.

Slide7

Early Signs:

Poor suckingLethargy Late Signs:SeizuresFeverDirect bilirubin does not give kernicterusKERNICTERUS

Slide8

JAUNDICE

BREAST FEEDINGVITAMIN K DEFICIENCYVitamin K Content

Commercial formulas = 50 mcg/LHuman milk = <1mcg/L

Slide9

JAUNDICE – BREAST FEEDING

HEMORRHAGIC DISEASE -NEWBORNClassification

Classic = 2-5 days of life infant=not receive prophylaxis of Vit K Late= 2-12 wks of age

Slide10

Prolongation of

2nd to (II, VII, IX, X)

In contrast congenital defects: PTT PT normalDIC (disseminated intravascular coagulation): platelets fibrinogen BREAST FEEDING VITAMIN K DEFICIENCY

PT

PTT

In the absence of vitamin K, these factors do not bind Ca

2+ normally and their coagulation activity is greatly reduced

Slide11

Breast Feeding Vitamin K Deficiency

Sample Questions1 month born at home = with subdural hematoma PT, PTT =

Platelets, fibrinogen = normal3 day old born at home = bloody stools6 week old born at home = diarrhea bloody stools skin bruises

Deficiency of Factors II, VII, IX, and X

Slide12

CONJUGATED

HYPERBILIRUBINEMIAALWAYS: PATHOLOGIC IN NEONATESEVALUATION

: MANDATORYGOALS:IDENTIFYINFECTIOUSMETABOLICCONGENITALGENETICOBSTRUCTION

Slide13

DIFFERENTIAL DIAGNOSIS

OFCONJUGATED HYPERBILIRUBINEMIA

Extrahepatic ObstructionInfantile Obstructive CholangiopathyBiliary atresiaNeonatal hepatitisCholedochal cystOther causesBile plug syndromeCholedocholithiasis

Spontaneous bile duct perforationExtrinsic bile duct compressionGenetic and Metabolic DisordersDisorders of carbohydrate metabolismGalactosemiaFructosemiaGlycogen storage disease type IVDisorders of amino acid

metabolism

Tyrosinemia

Disorders of lipid metabolism

Niemann

-Pick disease

Gaucher

disease

Wolman disease

Cholesterol ester storage disease Chromosomal disordersTrisomy 18Down syndromeMiscellaneous genetic & metabolic disorders α1-Antitrypsin deficiencyNeonatal hypopituitarismCystic fibrosisZellweger cerebrohepatorenal syndrome

Familial hepatosteatosis

Persistent Intrahepatic Cholestasis

Paucity of intrahepatic bile ductsArteriohepatic

dysplasiaBenign recurrent intrahepatic cholestasisByler diseaseHereditary cholestasis with lymphedema

Trihydroxycoprostanic

academia

Acquired Intrahepatic Cholestasis

Infections

Hepatitis B (non-A, non-B?)

Syphilis

Toxoplasmosis

Rubella

Cytomegalovirus

Herpes

Varicella

Echovirus

Coxsackievirus

Leptospirosis

Tuberculosis

Bacterial sepsis

Drug-induced cholestasis

Cholestasis associated with parenteral nutrition

Slide14

Slide15

Neonatal

CHOLESTASISPhysiologic definition: Decreased bile flowIncreased in premature infants Cholestatic

Jaundice indicates hepatobiliary dysfunction.Conjugated hyperbilirubinemia developing within the first 90 days of life.Conjugated bilirubin > 1.0 mg/dl Incidence: 1 in 2500 live births US

Slide16

Slide17

IDIOPATHIC NEONATAL

HEPATITISMOST COMMON DX: IN CHOLESTATIC NEONATES

ETIOLOGY: UNKNOWNDX: OF EXCLUSIONCLASSIFICATION:SPORADICFAMILIAL (10%

POOR PROGNOSIS) ?HEREDITARY VS. METABOLIC FACTORSINCIDENCE (1:4800/ 1:9000) LIVE BIRTHS

Slide18

NEONATAL HEPATITIS

CLINICAL PRESENTATIONS↑ MALESLOW BIRTH WEIGHT

50% = JAUNDICE 1ST WEEK OF LIFELFT’S: ↑ MILD TO MODERATE (2-10x

)1/3 = FTT, MORE COMPLICATED COURSE, LOOKS ILL, DECREASED APPETITE, AND DECREASED

ACTIVITY

ACHOLIC STOOLS

=

NOT COMMON

LIVER

:

ENLARGED

FIRM

Slide19

TREATMENT

CONSERVATIVEPROGNOSIS :

GOOD

Slide20

NEONATAL HEPATITIS

SAMPLE QUESTION4 week old maleMild

jaundice since birthPoor weight gainPale yellow – green color stoolsNext step: fractionate bilirubin (direct or indirect)DX: Neonatal HepatitisRSV is not associated with Neonatal HepatitisTorch

Titers should be done

Slide21

BILIARY ATRESIA

1/3 OF CASES OF NEONATAL CHOLESTASISINCIDENCE:

1: 15000 (400-500 INFANTS PER YEAR)FEMALES: (4 x) MORE FREQUENT

FAMILIAL INCIDENCE: RARE

Slide22

BILIARY ATRESIA

IS A DYNAMIC AND PROGRESSIVE

PANDUCTULAR SCLEROTIC PROCESSETIOLOGY UNKNOWN REOVIRUS TYPE 3 (?)

Slide23

TYPES OF

BILIARY ATRESIA

Slide24

BILIARY ATRESIA

CLINICAL PRESENTATIONSHINT

OBSTRUCTIVE JAUNDICEPATIENT LOOKS WELLPARENCHYMAL OR METABOLIC DISEASEPATIENT LOOKS ILL

Slide25

BILIARY ATRESIA

CLINICAL PRESENTATIONSJAUNDICE: 3-5 WEEKS AFTER BIRTH

LFT’S: MILD ELEVATION UP TO 5x (USUALLY IN THE 200 RANGE, 150-300).BILIRUBIN: 14-15 RANGE, MOSTLY DIRECT

ALK PHOSPHATASE: MARKEDLY ELEVATEDHEPATOSPLENOMEGALYACHOLIC STOOLS: COMMON

Slide26

Slide27

BILIARY ATRESIA

ASSOCIATED ANOMALIES(10-15%)PREDUODENAL PORTAL VEIN

MALROTATIONPOLYSPLENISM OR HYPOSPLENISMABSENT INFERIOR VENA CAVABILOBED RT LUNGTEFESOPHAGEAL ATRESIA

Slide28

EVALUATION OF THE INFANT WITH CHOLESTASIS

Slide29

Slide30

INTRAOPERATIVE CHOLANGIOGRAM

Intraoperative cholangiogram shows no evidence of cystic duct or gallbladder. No common bile duct stone is present.

Slide31

BILIARY

ATRESIA PROGNOSISUNTREATED < 2 YEARS

KASAI: 33% 10 YR SURVIVAL RATE75% < 2 MONTHS10%

>3 MONTHS

Slide32

Slide33

Slide34

BILIARY ATRESIA

SAMPLE QUESTIONS4 week old = female, male

Looks well except that appear yellowMild hepatosplenomegalyTB = 10, LFTS = 200 rangeNext Step: URGENT to differentiate between

intra/extrahepatic obstruction and fractionate bilirubin (direct or indirect)

Slide35

BILIARY ATRESIA

SAMPLE QUESTIONSFT female infant

5th day of life jaundiceAppears healthy otherwiseThe best study to evaluate bile excretion = PIPIDA (hida) = no excretion

Next step = liver biopsy

Slide36

ALPHA1-ANTITRYPSIN

IS A GLYCOPROTEINPRODUCED BY HEPATOCYTES (2 GRAMS PER DAY)SERINE – PROTEINASE INHIBITOR

INHIBITOR OF: NEUTROPHIL ELASTASE ACID PROTEASES OF ALVEOLAR MACROPHAGES

Slide37

Slide38

ALPHA 1 ANTITRYPSIN DEFICIENCY

Pi PhenotypeMMZZNullMmalton

NduharteMZSZMSRiskO10-20%0?

RISK FOR LIVER DISEASE

25%

= LIVER DISEASE

25% = LUNG DISEASE25%

= LIVER AND LUNG DISEASE

25%

= NO DISEASE

Slide39

ALPHA1-ANTITRYPSIN

INCIDENCEARMOST COMMON GENETIC CAUSE OF LIVER

DISEASE IN CHILDRENCOMMON IN WHITESNORTHERN EUROPEAN AND SCANDINAVIANIN THE U.S. 1/2000

IS HOMOZYGOUS 1/30 IS HETEROZYGOUS

Slide40

ALPHA1-ANTITRYPSIN

CLINICAL FEATURES10% OF PATIENTS ZZLACK OF SPECIFIC CLINICAL FEATURES

IN NEONATES: PROBABLY DAMAGE BEGAN IN UTERUS45% SGACOMMON: POOR FEEDING, IRRITABILITY, FIT LETHARGYJAUNDICE = 3-12 WEEKS

RESOLUTION IN 50% BY 6-8 MONTHSREMEMBER, THE PATIENT IN METABOLIC DISEASE OR PARENCHYMAL DISEASE LOOKS SICK.

Slide41

ALPHA1-ANTITRYPSIN

PHYSICAL EXAMINATIONNOT SPECIFICPATIENT UNDERNOURISHED

HEPATOMEGALYSMOOTHFIRMSPLENOMEGALYFREQUENT BRONCHITIS OR PNEUMONIA

REMEMBER TO ASK IF SOMEONE IN THE FAMILY HAS DIED OF EMPHYSEMA AT A YOUNG AGE

Slide42

25% = LIVER DISEASE

25% = LUNG DISEASE25% = LIVER AND LUNG DISEASE25% = NO DISEASE

Slide43

ALPHA 1

ANTITRYPSIN DEFICIENCYSAMPLE QUESTIONS

Alpha 1-antitrypsin level and phenotypeAlways remember to get a phenotype because level could be normal, or in infections. It is an acute phase reactant.

10 year old with no PMH; presents with UGI bleedingHepatosplenomegalyAscites plateletsMild in

LFTs, GGTP

PT

Test of diagnosis?

Slide44

9 month old with

FH = + emphysema

Hepatomegaly+ icterusLooks illTest for diagnosis?Alpha 1-antitrypsin level and phenotypeAlways remember to get a phenotype because level could be normal in infections.

It is an acute phase reactant. ALPHA 1ANTITRYPSIN DEFICIENCYSAMPLE QUESTIONS

Appetite

Irritability

lethargy

Slide45

ALPHA

1ANTITRYPSIN DEFICIENCYSAMPLE QUESTIONS

serum alpha 1 antitrypsin level is associated with early cirrhosisMost common manifestation in infancy

Hepatic cirrhosis

Slide46

GALACTOSEMIA

Galactose-1-phosphate uridyl transferase

= deficiencyIncidence >1 : 40,000GalacoseGalactose-1-phosphate accumulates in

Galactitol Lactose  G

lucose and Galactose

Galactose

_galactose-1-phosphate

uridyl

transferase__

G

lucose

LiverKidneyEyesCNS

Slide47

GALACTOSEMIA

SIGNS & SYMPTOMSAnorexiaLethargy

VomitingPoor Weight GainJaundiceHepatomegaly

CataractsAscitiesEarly CirrhosisRisk of sepsis If patient develops Group B Strep sepsis, it is galactosemia until proven otherwise

Symptoms begin within 2 weeks after ingestion of lactose containing

formulas.

Slide48

GALACTOSEMIA - LABS

Mild cirrhosisHypoglycemiaMixed hyperbilirubinemia

LFTs PTRenal FanconiGalactose detected in urine as a non-reducing sugar

AcidosisGlycosuriaProteinuria Aminoaciduria

Slide49

GALACTOSEMIA DIAGNOSIS

Measure in RBC’s = galactose-1- phosphate uridyl activityTreatment =

remove galactose from diet

Slide50

GALACTOSEMIA

SAMPLE QUESTIONS2 week old breast fed

appetiteJaundice, hepatomegalyGlucose oxidate test in urine = (-)Check reducing substance in urine, order a C

linitestGalactose detected in urine as a non-reducing sugar

Slide51

GALACTOSEMIA

SAMPLE QUESTIONS4 week old V + D; multiple cow’s

milk formula changes AppetiteLethargicJaundice, hepatomegalyOrder:Galactose-1-phosphate uridyl transferase activity in RBCs

Diagnosis:GalactosemiaTreatment:Soy formula

Slide52

GALACTOSEMIA

SAMPLE QUESTIONS2-3 month breast fed; prolonged jaundiceV + D

Hepatomegaly, HypotoniaInitial test = check reducing substanceOrder a galactose-1-phosphate uridyl transferase activity in RBCs

Slide53

HEREDITARY FRUCTOSE

INTOLERANCEIncidence: 1:20,000ARDeficiency:

Adolase BLiverKidneySmall BowelFailure to Split Fructose 1 Phosphate

Slide54

SYMPTOMS

Expose to Fructose and SucroseDepends: Age

Fructose loadHINT: Fruits Juices Vegetables

Sucrose

Slide55

SYMPTOMS

AcuteChronicNausea

& vomitingFailure to thriveTremorJaundice-cirrhosisDizzinessVomiting and diarrheaLethargy comaFeeding difficulties

Slide56

DIAGNOSIS

Liver Bx: Fructose 1 Phosphate Aldolase

+ Reducing substance in the urineRemember: Look in the questions if the patient is on fruit juices? FRUCTOSE INTOLERANCE

Slide57

Slide58

THANK YOU

!!!!!!

Slide59

REYES SYNDROME

UncommonIncidence: 3.5 / 100,000After viral infection

EmesisNon-icteric hepatic dysfunction

Slide60

REYES SYNDROME

LABORATORIES ABNORMALITIES LFTs

(3-30 X normal) PT GlucoseIctericia = very rare NH

3 = 2-20 X normalIf >5 X normal = poor prognosis

Slide61

REYES SYNDROME

Diagnosis = Liver BiopsyMicrovesicular steatosis

Mitochondrial alterations

Slide62

REYES SYNDROME TREATMENT

Monitor glucose level ICP

Death usually from encephalopathy

Slide63

Which

best treatment efforts improve prognosis? ICP

6-8 year old, vomiting, lethargic, responds to command LFT’s = 100 NH3 = 150 mg/ml

PT = 2-3 secComa stage IREYES SYNDROMESAMPLE QUESTIONSHINT:

Matching? Look

where

the glucose is the

lowest

and

bilirubin

is almost

normal

.

Slide64

POISONING

CCL4

Causes Severe kidney and liver damageHINT: Matching? Look where the bilirubin and LFT’s are the highest

and High BUNWas used inExposure

Inhalation

Ingestion

Fire extinguisher

As a solvent

Anthelmintic

Slide65

HEPATITIS A

RNA virus, transmitted fecal-orally (food +H

20)No transplacental transmissionNo carrier (occasionally prolonged cholestasis)Incubation is 15-50 daysAcute infection-high anti-HAV

IgMPrevious infection – high anti-HAV IgGSymptoms rare in children1% have a chance of fulminant hepatitis

IG

is good prophylaxis against HAV (

w/in 2 wks of exposure

Give IG

to

household and close

contacts

Slide66

HEPATITIS A

SAMPLE QUESTIONSPre-icteric phase

Milder in children Anicteric infection may occurHINT: Biliary Atresia: Rare LFT’s are higher than 500Hepatitis A: LFT’s are usually higher 500

adults

anorexia

fever

Vomiting

Abdominal pain

Slide67

HEPATITIS B

Hbs Ab = + = vaccinationHbs Ab = + Hbc Ab = +

Had Hepatitis B

Slide68

HEPATITIS B

SAMPLE QUESTIONSInfant born to a mother HbsAg+

Treatment:Hep B immunoglobulin + vaccineBathed immediately after birthInfant risk = 70-90% in HbsAg+ mother 10-25% in HbsAg

- motherReduce vertical transmission by 95%

Slide69

HEPATITIS B

SAMPLE QUESTIONSHepatitis Bs Ag = +No need to be vaccinated

Slide70

CONSTIPATION

Majority is due to functional or behavioral problemSmall percentage

of children present with constipation have an organic causeSome breast-fed babies will stool 1/5-10 daysFunctional fecal retention is the most common nonorganic causeHINT: Rectal examination:

Rectal ampulla is full

Slide71

HIRSCHPRUNG DISEASE

1/5000 birthsAbsence of enteric ganglionic neurons that begin at the anus and then extend proximallyIncreased association with

Down syndromeEvaluate any term infant that does not pass meconium within 48 hours of birthSuction rectal biopsy for diagnosis, full-thickness biopsy needed for unclear casesTreat with surgical resectionHINT: Rectal Ampulla is empty

KUB: No granular appearance or Ca2+ in ABD = CF yes

Slide72

Typical Celiac Disease

Slide73

Gastrointestinal Manifestations

(“Classic”)Most common age of presentation: 6-24 monthsChronic or recurrent diarrheaAbdominal distensionAnorexiaFailure to thrive or weight loss

Rarely: Celiac crisis Abdominal pain Vomiting Constipation Irritability

Slide74

Non Gastrointestinal

ManifestationsDermatitis HerpetiformisDental enamel hypoplasia of permanent teethOsteopenia

/OsteoporosisShort StatureDelayed Puberty Iron-deficient anemia resistant to oral Fe Hepatitis Arthritis Epilepsy with occipital calcifications

Most common age of presentation: older child to adultListed in descending order of strength of evidence

Slide75

Serological Test Comparison

Farrell RJ, and Kelly CP. Am J Gastroenterol 2001;96:3237-46. Sensitivity % Specificity %

AGA-IgG 69 – 85 73 – 90 AGA-IgA 75 – 90 82 – 95 EMA (IgA) 85 – 98 97 – 100 TTG (IgA) 90 – 98 94 – 97

Slide76

HLA Tests

Potential role for DQ2/DQ8 asymptomatic relativesDown, Turner & Williams syndrometype 1 diabetesdiagnostic dilemmas

Slide77

The

Antireflux barrier

Slide78

Question..

Which of the following statements is true regarding reflux ?A. Thickening formula reduces reflux episodesB. Proton pump inhibitors have been found to improve infant irritabilityC. Treatment with PPI’s for three months is indicated in patients with

endoscopically proven reflux esophagitis D.Acute life threatening events have definitely been linked to gastroesophageal reflux diseaseE.Erythromycin has been proven to be beneficial in patients with GERD

Slide79

Munchausen by P

roxy3 yo old female comes to the ER hx of severe constipation. The PE is normal. Mother demands an Xray

of the abdomen to be taken since that’s the way they dx constipation. Xray shows scattered stool around the colon. Mother insists on admission for clean out. The ER MD calls GI for advice for ? Go-Lytely clean out.A. The Abdominal Xray and the HPE are evidence she has constipation, needs a clean out.B. Parental insistence on admission may be reasonable given parents are knowledgeable.C. HPE and Xray do not support a dx of constipation. You will request a Hx of admissions, ER vistis and test results.

D. You recommend no admission: no indication to admit the patient. Refer the patient and mother to a psychiatrist.E. You recommend a CT scan of the abdomen since is more reliable than the Xray.

Slide80

KIDS G.I. CENTER

RUBEN GONZALEZ-VALLINA, MD, FAAP