Hemolytic disease of the newborn (erythroblastosis fetalis) results in the accumulation of _________ bilirubin in the brain and can lead to _______.
Hemolytic disease of the newborn (erythroblastosis fetalis) results in the accumulation of unconjugated bilirubin in the brain and can lead to kernicterus.
Deficiency of canalicular membrane transporters (i.e., Dubin-Johnson syndrome, or Rotor syndrome) results in which form of hyperbilirubinemia (unconjugated or conjugated)?
Impaired bile flow from a duct obstruction or autoimmune cholangiopathies result in what type of hyperbilirubinemia (uncojugated or conjugated)?
What is the inheritance pattern of Crigler-Najjar syndrome type I?
What is defective and how seriously?
- Autosomal Recessive
- Complete absence of UGT1A1 activity
What is the inheritance pattern of Crigler-Najjar syndrome type 2?
What is defective and how seriously?
- Autosomal Dominant w/ variable penetrance
- Decreased activity of UGT1A1
What is the inheritance pattern of Gilbert Syndrome?
What is the inheritance pattern of the Conjugated-Hyperbilirubinemias, Dubin-Johnson and Rotor Syndrome?
Which hereditary hyperbilirubinemia is associated w/ pigmented cytoplasmic globules in the liver?
What are the 2 characteristic lab findings of Cholestasis?
- Increased Alkaline Phosphatase
- Increased GGT (gamma-glutamyl transpeptidase)
What are 2 morphological features common to both obstructive and nonobstructive cholestasis?
I.e., seen in bile canaliculi and hepatocytes
1) Elongated green-brown plugs of bile visible in dilated bile canaliculi
2) Bile pigment in hepatocytes = fine, foamy appearance, with so called "feathery degeneration"
A secondary bacterial infection of the biliary tree that aggravates the inflammatory injury produced by subtotal or intermittent obstruction is known as?
What is the most severe form of cholangitis and what is seen?
Why is prompt diagnostic evaluation and intervention imperative?
- Suppurative cholangitis = purulent bile fills and distends bile ducts
- Sepsis rather than cholestasis tends to dominate, requiring prompt intervention!
What is the histologic hallmark of ascending cholangitis?
Influx of periductular neutrophils directly into the bile duct epithelium and lumen
Surgical intervention is warranted and imperative for which type of biliary obstruction causing cholestasis (extraheptic or intrahepatic or defects in hepatocyte bile secretion)?
- NOT indicated for intrahepatic or hepatocellular secretory failure because the patients condition may actually worsen
What can sometimes become superimposed on the pathogenesis of untreated chronic biliary obstruction and the damage accruing in the liver (i.e., ductular rxns, periportal fibrosis, and hepatic scarrin)?
Can trigger what?
- Ascending cholangitis
- Triggering acute-on-chronic liver failure
Response by the liver to circulating microbial products of which kind of organisms is most likely to lead to cholestasis of sepsis?
What is the most common form?
- Gram-negative organisms
- Canalicular cholestasis = MOST COMMON = bile plugs in centrilobular canaliculi + mild portal inflammation + NO hepatocyte necrosis
Unlike other forms of cirrhosis, nodules of liver cells in biliary cirrhosis often take on what characteristic shape?
Not round, but IRREGULAR, like jigsaw puzzle pieces
Where does Primary Hepatolithiasis (aka recurrent pyogenic cholangitis) have a very high prevalence?
What is the typical presentation of someone with Primary Hepatolithiasis?
- Repeated episodes of ascending cholangitis
- Fever and abdominal pain 2' to infection of ducts
- Sometimes a mass-like lesions may be present and mistaken for malignancy
Primary Hepatolithiasis is caused by a gallstone where and what does this lead to?
Increased risk of which malignancy?
- INTRAhepatic gallstone --> repeat bouts of ascending cholangitis --> progressive inflammatory destruction of hepatic parenchyma
- Increased risk of invasive cholangiocarcinoma
Pigmented calcium bilirubinate stones in distented intrahepatic bile ducts, with chronic inflammation, mural fibrosis, and peribiliary gland hyperplasia, ALL in the absence of extrahepatic duct obstruction is characteristic of which disease?
Which infants should be evaluated for neonatal cholestasis?
Infants w/ jaundice BEYOND 14-21 days after birth
Why is the differentiation of biliary atresia from nonobstructive neonatal cholestasis very important in regards to treatment?
- Definitive treatment of biliary atresia requires surgical intervention (Kasai procedure)
- Surgery may adversely affect clincal course of child w/ other disorders
Neonatal infeciton by which virus is a common cause of Neonatal Cholestasis?
What is a characteristic feature of hepatocytes associated with Neonatal Hepatitis?
Panlobular giant-cell transformation of hepatocytes
Biliary atresia is defined as what?
Complete or partial obstruction of the lumen of the extrahepatic biliary tree within the first 3 months of life
What is the single most frequent cause of death from liver disease in early childhood and accounts for 50-60% of children referred for liver transplantation?
What are the 2 major forms of Biliary Atresia and how do they differ?
Which is most common?
1. Fetal form: due to ineffective formation of laterality of thoracic and abdominal organs during development ---> aberrant intrauterine development of the biliary tree
2. Perinatal form: normally developed biliary tree is destroyed AFTER birth (CMV, Reovirus, Rotavirus) = MOST COMMON form
Which 3 viruses have been implicated in the development of the perinatal form of biliary atresia?
Morphologically what are the characteristic features seen in the hepatic or common bile ducts of biliary atresia?
Inflammation and/or fibrosing strictures