Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Intrahepatic Cholestasis of Pregnancy Rare Cholestasis: What Does it Mean? Pathology: Histological demonstration of bile in liver tissue Physiology: Measurable reduction in hepatic secretion of solutes and water Biochemical: Demonstrable accumulation in blood of substances normally excreted in bile (bilirubin, cholesterol, bile acids) 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 Pathophysiology Liver is an estrogen sensitive organ – Estrogen affects organic anion transport (bilirubin, bile acids) Bilirubin excretion very mildly impaired during normal pregnancy Biliary phospholipids secretion may be impaired (gene mutation, estrogen effect) Pregnancy is associated w/ decreases in GI motility, including gall bladder motility Physiological Consequences: The Liver in Pregnancy Pregnant women more likely to become jaundiced if cholestatic or hepatocellular injury occur Spider angiomata and palmar erythema develop in up to 2/3 pregnancies due to effects of estrogen and progesterone Cholecystectomy generally safe 3rd Trimester see increased alk phos 2/2 developing placenta (not liver) Intrahepatic Cholestasis of Pregnancy (IHCP) Incidence 0.1% - 1% of pregnancies Recurrence in subsequent pregnancies Pruritis develops in late 2nd and 3rd trimester High transaminases - 40% > 10 x (Hay) Bilirubin < 5mg/dL Total bile acids increase 100 fold Intrahepatic Cholestasis of Pregnancy (IHCP) Pathogenesis: genetic, hormonal – Women who develop clinical cholestasis during pregnancy or with oral contraceptives likely have genetic polymorphisms in the genes responsible for bile formation and flow – Familial - 10% occurrence in 1st degree relatives – Hormonal – timing in pregnancy, twins ICHP Clinical Features Pruritis is the defining characteristic About 50% develop jaundice Disappears rapidly after delivery Severity is variable Rarely see a familial, progressive course to cirrhosis IHCP Therapy Ursodeoxycholic acid 10mg- 10mg/Kg/day Cholestyramine Vitamin K p.r.n. Reassurance and support Consider early delivery in severe cases – Unbearable maternal pruritis or risk of fetal distress/death – Deliver at 38 weeks if mild, at 36 weeks for severe cases – if jaundice Summary Normal pregnancy is associated w/ characteristic, benign changes in liver physiology Several unique diseases occur during pregnancy and all resolve following delivery Implications are disorder specific Case Study What is the Problem Abnormal LFTs Jaundice, pruritis, abdominal pain, and vomiting Ultrasound R/O Gallstones Family Hx Co-morbidities Case study (Hay) 32 year old Para 1 @ 24 weeks – two weeks of severe pruritis – Pruritis and abnormal LFTs in last pregnancy – Known gallstones – no biliary dilatation on ultrasound – No abdominal pain, fever, rash – Exam normal apart from pregnancy – AST 277 ALT 655 Bili 2.1 Alk Phos 286 Case Study Hepatitis A, B, C serologies non reactive 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 Questions? Inherited and Pediatric Liver Disease A Brief Overview Inherited and Pediatric Liver Diseases Wilson Disease Hereditary hemochromatosis Alpha 1 Antitrypsin Deficiency Inborn errors of metabolism Fibrocystic diseases Pediatric cholestatic diseases Porphyria 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 Wilson Disease Variable Presentation Liver, brain damage due to oxidative stress Age of onset between 6 to 45 May present as chronic liver disease or acute liver failure, progressive neurological disorder without liver involvement or as a psychiatric illness Wilson Disease Variable Presentation Neurological decade: sequelae occur 2nd – 3rd – Increased or abnormal motor disorder w/ tremor/dystonia – Loss of movement w/ rigidity Psychiatric sequelae – Depression – Phobias – Psychosis Wilson Disease Ocular Features Classic finding: Kayser-Fleisher ring, a golden-brown deposit at the outer rim of the cornea Sunflower cataract, less frequent. Copper deposition in the lens Wilson Disease Involves Other Organs Hemolytic anemia 2/2 sporadic release of copper into the blood Renal involvement w/ Fanconi syndrome, microscopic hematuria, stones Arthritis 2/2 copper deposit in synovial joints Osteoporosis, Vitamin D resistant rickets 2/2 renal damage Wilson Disease Involves Other Organs Cardiomyopathy Muscles: Rhabdomyolysis Pancreatitis Endocrine disorders Wilson Disease Diagnosis and Treatment Lab findings: Decreased ceruloplasmin and serum copper, excess urinary copper 24 hour urine x 3 to confirm diagnosis Histology: Hepatic copper deposition Treatment is chelation: – penicillamine, which increases urinary copper excretion – ammonium tetrathiomolybdate Wilson Disease Treatment Zinc interferes w/ copper binding, decreasing absorption Elimination of copper-rich foods from the diet: – Organ meats, shellfish, nuts, chocolate, mushrooms – Check drinking water supply Liver transplantation if ALF Wilson Disease Prognosis is good on chelation therapy if diagnosed promptly Affected sibling diagnosed and treated prior to symptom onset has the best prognosis Pediatric Cholestatic Syndromes Neonatal jaundice is common, transient, usually due to immature glucouronosyl transferase or to breast feeding If jaundice persists after 14 days, investigate Extrahepatic biliary atresia requires urgent surgical repair of abnormal hepatic or common bile ducts 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, skeletal abnormalities – Autosomal dominant, Incidence: 1:70,000 Pediatric Cholestatic Syndromes Progressive Familial Intrahepatic Cholestasis, another group of autosomal recessive disorders involved w/ errors in bile acid synthesis and bile acid transport – Byler Disease now called PFIC1 – Byler Syndrome now called PFIC 2 Case Study