Flashcards in Why am I Yellow? Deck (24):
What is the basic metabolism of bilirubin in the liver?
import across basolateral membrane, conjugation, secretion across apical membrane
What are the basic mechanisms behind unconjugated hyperbilirubinemia?
increased input (hemolysis) or decreased output into bile (conjugation defect)
What are the basic mechanisms behind unconjugated + conjugated hyperbilirubinemia?
normal input and decreased output (transporter/excretion defect) or increased back flux of bilirubin
What is the pre-hepatic mechanism of isolated hyperbilirubinemia?
normal reserve capacity of liver for bilirubin is 7-fold
unconjugated increases and conjugated does not
isolated if no associated liver disease
What is the hepatic mechanism of hepatic hyperbilirubinemia?
no associated liver or biliary disease
decreased hepatic conjugation
mild genetic defects (gilberts) are common
What are more severe conditions associated with hepatic isolated hyperbilirubinemia?
excretion defects (Crigler Najjar and Dubin-Johnson) - rare
What happens in sepsis that causes hyperbilirubinemia?
cytokines alter expression of organic anion transporters for conjugated bilirubin - increase in conjugated transported into circulation with little or no liver inflammation
What tests can help determine if hyperbilirubinemia is unconjugated or mixed?
bilirubin in urine - positive if conjugated elevated and kidney function normal
What is the treatment for isolated hyperbilirubinemia?
UV light for newborns
transplant for rare patient with severe conjugation defect
How can Gilbert's be recognized?
serum bilirubin <3-5 mg/dL, increases with fasting and stress
What are some exogenous agents causing hepatocyte injury and which have highest aminotransferases (>500)?
viruses*, bacteria, protozoa, helminths
*prescription and non-Rx remedies
metals (iron and copper)
What are some endogenous agents causing hepatocyte injury and which have the highest aminotransferases (>500)?
bile and *biliary obstruction
abnormal misfolded proteins
*Host T lymphocytes
How do the measured enzymes differ between necrosis and apoptosis?
aminotransferases raised preferentially in apoptosis
all enzymes released in necrosis
What signs and symptoms suggest ischemia induced hepatitis?
dyspnea, edema, cocaine use, summer
heart failure, hypotension, hyperthermia
What signs and symptoms suggest obstruction induced hepatitis?
RUQ pain and tenderness
When is LD elevated in hepatitis?
elevated when necrosis from ischemia, choledocholithiasis, or acetaminophen toxicity
only modestly elevated in acute viral or autoimmune hepatitis
What is the relationship between jaundice and cholestasis?
usually occur together but can have one w/o other
only cholestasis if obstruction not complete or only affects part of liver
Which enzymes specifically indicate jaundice vs. cholestasis?
elevated bilirubin vs. elevated alk phos
What signs and symptoms suggest cholestasis?
steatorrhea (foul smelling, bulky stools)
night blindness, easy bleeding (fat soluble vitamin deficiency)
increased serum bile acids and lipids (lipoprotein x)
What is the mechanism and examples of intra-cellular disorders leading to cholestasis?
interference with secretion of bile contents into cannaliculus
drugs and hormones
What is the mechanism and examples of intra-hepatic disorders leading to cholestasis?
obstruction to bile flow by portal infiltration - fibrosis
destruction of bile ducts - PBC (primary biliary cirrhosis), sarcoid granuloma
What is the mechanism and examples of extra-hepatic disorders leading to cholestasis?
mechanical obstruction to bile flow
benign stricture, tumors
What imaging studies are indicated with cholestasis?
precise nature might need cholangiography, ERCP or MRC
extra hepatic causes excluded - biopsy