Nelson: Liver Flashcards
What is jaundice?
Yellow discoloration of the SKIN d/t retention of bilirubin
When is jaundice clinically evident?
as total serum bilirubin approaches 2-3 mg/dl
What is icterus?
yellow discoloration of the SCLERA d/t retention of bilirubin
What is cholestasis?
impaired secretion of BILE
What are the steps involved in bilirubin metabolism?
Reticuloendothelial cells convert heme (brkdown of old RBC, hepatic heme, marrow RBC precursors) to bilirubin>
bilirubin is transported to the liver complexed w/ ALBUMIN (unconjugated bilirubin)>
cbilirubin is conjugated w/ glucuronic acid in liver cells (conjugated bilirubin)>
conjugated bilirubin is excreted in BILE (brown stools)
What form of bilirubin is toxic to tissues?
Unconjugated (indirect)
- water soluble
- bound to albumin
- not excreted in the urine
Which form of bilirubin is water soluble, not toxic to tissues and is excreted in the urine when present at high serum levels?
conjugated bilirubin
What are some of the causes of unconjugated bilirubinemia?
- Increased bilirubin production
- impaired hepatic bilirubin uptake
- impaired bilirubin conjugation
What increases bilirubin production?
- Extravascular hemolysis
- Extravastation of blood into tissues
- Intravascular hemolysis
- Dyserythropoiesis
What impairs hepatic bilirubin uptake?
- Heart failure
- Portosystemic shunts
- Gilbert’s syndrome
- Drugs
What impairs bilirubin conjugation?
- Crigler-Najjar syndrome (I or II)
- Gilbert’s syndrome
- Neonatal jaundice
- Hyperthyroidism
- Ethyinyl estradiol
- Liver disease
What causes conjugated hyperbilirubinemia?
- extrahepatic cholestasis (biliary obstruction)
2. interhepatic cholestasis
What causes biliary obstruction?
- Choledocholithiasis
- Tumors
- PSC
- AIDS
- Pancreatitis
- Strictures
- Parasitic infxns
What causes intrahepatic cholestasis?
- Hepatitis (many types)
- Drugs & toxins
- Primary biliary cirrhosis
- Sepsis & hypoperfusion
- Infiltrative diseases
- Total parenteral nutrition
- Following organ transplant
- Hepatic crisis in sickle cell
- Pregnancy
- End-stage liver disease
What causes normal neonatal alterations in bilirubin metabolism?
- Increased bilirubin production (neonates have relatively more RBCs with a shorter life span)
- Decreased bilirubin clearance (due to physiologic decrease in UGT1A1 activity)
- Increased enterohepatic circulation*
What are pathological causes of unconjugated hyperbilirubinemia?
- Immune-mediated hemolysis (ABO or Rh(D) incompatibility)
- Inherited RBC membrane or enzyme defect
- Sepsis
- Inherited defects in UGT1A1 activity (e.g. Crigler-Najjar syndrome, Gilbert’s syndrome)
- Breast milk jaundice*
- Intestinal obstruction*
- Breastfeeding failure jaundice*
What are normal TB levels in almost all term and near term newborn inftants?
> 1 mg
If an infant has mild unconjugated hyperbilirubinemia w/ peak TB what can you expect the levels to be?
— 7 to 9 mg/dl in Caucasian & AA infants
— 10 to 14 mg/dl in Asian infanats
A TB >25-30 mg/dl in an infant is indicative of….
How do you treat it?
severe hyperbilirubinemia
Phototherapy
How does severe hyperbilirubinemia affect other organ systems?
- Bilirubin-induced neurologic dysfunction (BIND)
- Acute bilirubin encephalopathy (ABE)
- Long-term neurologic sequelae or kernicterus (if inadequately tx)
What is Gilbert’s syndrome?
AR, BENIGN disorder
What causes Gilbert’s syndrome?
decreased GTF activity (UGT1A1 is 30% of normal)
What lab findings are associated w/ gilbert’s sndrome?
increased unconjugated bilirubin
Morphological findings show:
bile w/in hepatocytes
canalicular bile stasis
feathery degeneration of hepatocytes
intrahepatic cholestasis