Group 4 Slides Pm After Break
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Transcript of Group 4 Slides Pm After Break
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Intrahepatic
Cholestasis ofPregnancy
Rare
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Liver Diseases in Pregnancy
High estrogen state: Intrahepatic cholestasis of pregnancy
Gallstones and sludge occur more frequently
Altered fatty acid metabolism: Acute fatty liver of pregnancy
Vascular diseases affect the liver: Pre-eclampsia
HELLP Syndrome
Viral hepatitis: Vertical transmission of hepatitis B and C
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Pathophysiology
Liver is an estrogen sensitive organEstrogen affects organic anion transport
(bilirubin, bile acids)
Bilirubin excretion very mildlyimpaired during normal pregnancy
Biliary phospholipids secretion maybe impaired (gene mutation,
estrogen effect)Pregnancy is associated w/
decreases in GI motility, including
gall bladder motility
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Physiological Consequences:
The Liver in Pregnancy
Pregnant women more likely tobecome jaundiced if cholestatic orhepatocellular injury occur
Spider angiomata and palmarerythema develop in up to 2/3pregnancies due to effects ofestrogen and progesterone
Cholecystectomy generally safe
3rd Trimester see increased alk phos2/2 developing placenta (not liver)
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Intrahepatic Cholestasis of
Pregnancy (IHCP)
Incidence 0.1% - 1% of pregnancies
Recurrence in subsequentpregnancies
Pruritis develops in late 2nd and 3rdtrimester
High transaminases - 40% > 10 x
(Hay)
Bilirubin < 5mg/dL
Total bile acids increase 100 fold
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Intrahepatic Cholestasis of
Pregnancy (IHCP)
Pathogenesis: genetic, hormonal
Women who develop clinical cholestasisduring pregnancy or with oral
contraceptives likely have geneticpolymorphisms in the genes responsiblefor bile formation and flow
Familial - 10% occurrence in 1st
degreerelatives
Hormonal timing in pregnancy, twins
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ICHP Clinical Features
Pruritis is the defining characteristic
About 50% develop jaundice
Disappears rapidly after deliverySeverity is variable
Rarely see a familial, progressive
course to cirrhosis
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IHCP
Therapy
Ursodeoxycholic acid 10mg-10mg/Kg/day
Cholestyramine
Vitamin K p.r.n.Reassurance and support
Consider early delivery in severe
casesUnbearable maternal pruritis or risk of
fetal distress/death
Deliver at 38 weeks if mild, at 36 weeks
for severe cases
if jaundice
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Summary
Normal pregnancy is associated w/characteristic, benign changes inliver physiology
Several unique diseases occur duringpregnancy and all resolve followingdelivery
Implications are disorder specific
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Case Study
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What is the Problem
Abnormal LFTs
Jaundice, pruritis,
abdominal pain,
and vomiting
Ultrasound
R/O GallstonesFamily Hx Co-morbidities
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Case study
(Hay)
32 year old Para 1 @ 24 weeks
two weeks of severe pruritis
Pruritis and abnormal LFTs in lastpregnancy
Known gallstones no biliary dilatationon ultrasound
No abdominal pain, fever, rash
Exam normal apart from pregnancy
AST 277 ALT 655 Bili 2.1 Alk Phos 286
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Case Study
Hepatitis A, B, C serologies nonreactive
Negative autoimmune markers
Urso 300 mg t.i.d. is prescribed
32 weeks - feels well; D/C Urso
33 weeks - pruritis - resume Urso
37 weeks - delivery healthy baby;D/C Urso
2 weeks postpartum - LFTs normal
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Questions?
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Inherited and PediatricLiver Disease
A Brief Overview
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Inherited and Pediatric Liver
Diseases
Wilson Disease
Hereditary hemochromatosis
Alpha 1 Antitrypsin Deficiency Inborn errors of metabolism
Fibrocystic diseases
Pediatric cholestatic diseasesPorphyria
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Wilson Disease
Autosomal recessive pattern of inheritance
Defective gene: ATP7B on chromosome 13
Leads to copper overload in liver, other
organs
World wide distribution
Incidence 1:30,000
Carrier state 1:90 Higher in Sardinians and Chinese,
infrequent in Africa
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Wilson Disease
Variable Presentation
Liver, brain damage due to oxidativestress
Age of onset between 6 to 45
May present as chronic liver diseaseor acute liver failure, progressiveneurological disorder without liverinvolvement or as a psychiatricillness
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Wilson Disease
Variable Presentation
Neurological sequelae occur 2nd 3rddecade: Increased or abnormal motor disorder
w/ tremor/dystoniaLoss of movement w/ rigidity
Psychiatric sequelaeDepression
Phobias
Psychosis
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Wilson Disease
Ocular Features
Classic finding: Kayser-Fleisher ring,a golden-brown deposit at the outerrim of the cornea
Sunflower cataract, less frequent.Copper deposition in the lens
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Wilson Disease
Involves Other Organs
Hemolytic anemia 2/2 sporadicrelease of copper into the blood
Renal involvement w/ Fanconisyndrome, microscopic hematuria,stones
Arthritis 2/2 copper deposit insynovial joints
Osteoporosis, Vitamin D resistantrickets 2/2 renal damage
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Wilson Disease
Involves Other Organs
Cardiomyopathy
Muscles: Rhabdomyolysis
PancreatitisEndocrine disorders
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Wilson Disease
Diagnosis and Treatment
Lab findings: Decreasedceruloplasmin and serum copper,excess urinary copper
24 hour urine x 3 to confirmdiagnosis
Histology: Hepatic copper deposition
Treatment is chelation:penicillamine, which increases urinary
copper excretion
ammonium tetrathiomolybdate
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Wilson Disease
Treatment
Zinc interferes w/ copper binding,decreasing absorption
Elimination of copper-rich foods fromthe diet:
Organ meats, shellfish, nuts, chocolate,mushrooms
Check drinking water supply
Liver transplantation if ALF
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Wilson Disease
Prognosis is good on chelationtherapy if diagnosed promptly
Affected sibling diagnosed andtreated prior to symptom onset hasthe best prognosis
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Pediatric Cholestatic Syndromes
Neonatal jaundice is common,transient, usually due to immatureglucouronosyl transferase or to
breast feeding
If jaundice persists after 14 days,investigate
Extrahepatic biliary atresia requiresurgent surgical repair of abnormalhepatic or common bile ducts
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Pediatric Cholestatic Syndromes
Neonatal hepatitis 2/2 infection,idiopathic
Intrauterine infections i.e., TORCH:
toxoplasmosis, rubella,cytomegalovirus, herpes simplex
Alagille Syndrome few bile ducts,
congenital heart disease, skeletalabnormalities
Autosomal dominant, Incidence:
1:70,000
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Pediatric Cholestatic Syndromes
Progressive Familial IntrahepaticCholestasis, another group ofautosomal recessive disorders
involved w/ errors in bile acidsynthesis and bile acid transport
Byler Disease now called PFIC1
Byler Syndrome now called PFIC 2
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Case Study