Inherited Metabolic Liver Disease

Question 1

A blockage of bile flow presents on labs as:

Answer 1

increase in conjugated bilirubin

Question 2

How high must bilirubin be to qualify as conjugated hyperbilirubinemia?

Answer 2

> 2 or >15% of total

Question 3

How is unconjugated bilirubin transported?

Answer 3

by albumin in blood –>potentially toxic

Question 4

At what bilirubin level do we find jaundice?

Answer 4

> 5-7 in newborns, >2 in older children

Question 5

What are some common causes of physiologic jaundice?

Answer 5

decreased albumin, decreased hepatic uptake due to decreased ligandin, decreased conjugation/secretion, infants have enhanced bilirubin production due to large RBC mass, short RBC lifespan, and inefficient erythropoeisis

Question 6

T/F neonatal cholestasis is always pathologic

Answer 6

T –>relative emergency

Question 7

How do we distinguish pathologic from physiologic jaundice in neonates/infants?

Answer 7

conduct fractionated bilirubin: conjugated bilirubin is 0 in physiologic jaundice

Question 8

2 causes of extrahepatic neonatal cholestasis

Answer 8

choledochal cyst, biliary atresia

Question 9

Most common cause of conjugated hyperbilirubinemia

Answer 9

biliary atresia

Question 10

Complete obliteration of the hepatic/common bile ducts

Answer 10

biliary atresia

Question 11

Clinical findings in biliary atreia

Answer 11

acholic stools, dark urine, mild icterus, hepatosplenomegaly, conjugated bilirubin, mildly elevated AST, elevated GGT

Question 12

Imaging of abnormalities in liver/bile ducts

Answer 12

ultrasound + disida scintiscan

Question 13

Histologic findings of biliary atresia

Answer 13

bile duct proliferation, ductal bile plugs, portal fibrosis

Question 14

Bile duct paucity

Answer 14

metabolic disorders, alagille syndrome

Question 15

Gold standard for dx of biliary atresia

Answer 15

operative cholangiogram

Question 16

Tx of biliary atresia

Answer 16

kasai hepatoportoenterostomy

Question 17

Prognostic factors in kasai surgery

Answer 17

age at surgery, experience of surgeon

Question 18

Complications of biliary atresia

Answer 18

persistent jaundice, intractable pruritis, ascending cholangitis, portal hypertension, variceal hemorrhage, vitamin deficiencies, liver failure

Question 19

What gene may be implicated in biliary atresia?

Answer 19

GPC1 –> cell surface heparan sulfate proteoglycan

Question 20

Clinical finding of glycogen storage disease

Answer 20

hypoglycemia + hepatomegaly

Question 21

Clinical finding of Niemann Pick disease

Answer 21

abnormal lipids in reticuloendothelial cells + neurologic involvement in some types

Question 22

Clinical finding of tyrosinemia

Answer 22

early liver failure, cirrhosis, risk of carcinoma, direct toxic metabolic damage

Question 23

alpha1 Antitrypsin deficiency

Answer 23

primary function is to inhibit neutrophil elastase in lung –> deficiency = early emphysema in 3rd/4th decade of life + liver disease due to accumulation of mutant protein

Question 24

Dx of A1AT deficiency

Answer 24

isoelectric focusing of specific protein phenotypes

Question 25

Tx of A1AT deficiency

Answer 25

modify risk factors (smoking), tx of complications, surveillance for cancer, transplants, augmenting autophagy (valproic acid, carbamazepine)

Question 26

Findings in wilson’s disease

Answer 26

aminotransferase elevation, hepatomegaly, hepatitis, cirrhosis, copper ring in eye, dystonia, tremors, choreiform movements, hemolytic anemia, renal disease, cardiomyopathy

Question 27

Wilson’s disease gene

Answer 27

ATP7B –> hepatic biliary excretion of copper

Question 28

Normal copper trafficking pathway

Answer 28

copper enters via Ctr1 channel –> bound to metallothionein or Atox1 –> enters golgi via ATP7B –> transported to bile canaliculus via Murr1

Question 29

Dx of Wilson’s

Answer 29

slit lamp exam, ceruloplasmin (ends up as apocerulosplasmin due to failure of copper binding), 24 hour urine copper –> low ceruloplasmin, +/-rings, high copper –> liver biospy, histology, etc.

• screen family members

Question 30

Tx of Wilson’s

Answer 30

chelating agents like trientene and zinc, liver transplant

Question 31

_____ is the pathologic deposition of excessive iron in parenchymal cells of organs leading to cell damage and functional abnormalities.

Answer 31

hemochromatosis

Question 32

Most common variant of hereditary hemochromatosis.

Answer 32

HFE associated: c282Y or H63D gene

Question 33

Unifying hypothesis for hereditary hemochromatosis

Answer 33

lack/low of hepcidin results in a massive release of iron in body

Question 34

How long does tissue damage take in hemochromatosis?

Answer 34

decades

Question 35

Triad of hemochromatosis

Answer 35

diabetes, hepatomegaly, skin pigmentation –>more in men

Question 36

Tx of hemochromatosis

Answer 36

phlebotomy