3 Hepatobiliary Function Flashcards
What are the main functions of the liver
Bile production
Metabolism of FA, Carbs, proteins
Bilirubin production
Detoxification
What is cirrhosis
Chronic liver disease in which normal liver cells are damaged and replaced by scar tissue (fibrosis)
What is the most commmon cause of cirrhosis
Excessive alcohol intake
Steatohepatitis is also known as
Fatty liver disease
What is the most common cause of portal hypertension
Cirrhosis
Where are primary bile acids synthesized
Hepatocytes
Secondary bile acids are made where
SI
Where are bile salts conjugated
Liver
What are the two primary bile acids
Cholic acid and chenodeoxycholic acid
What are the two secondary bile acids
Deoxycholic acid from cholic acid
Lithocholic acid from chenodeoxycholic acid
What is the most prevalent bile acids
Cholic > chenodeoxycholic > deoxycholic > lithocholic
What is the function of bile salts
Solubilizes lipids that are naturally insoluble
What is the primary hormonal regulator of bile secretion
Gallbladder contraction directly and relaxation of sphincter of oddi
What is the effect of the vagus on bile secretion
Increases bile flow, induces contraction of gallbladder
What transporters assist with bile salt uptake into hepatocytes
NTCP and OATPs
What are the bile salt transporters that move bile into canaliculi
BSEP and MRP2
What moves bile salts into enterocytes
ASBT
What moves bile salts out of enterocytes
OST α/β
What enzyme makes bile salts
Cholesterol 7α hydroxylase
Interruption of the enterohepatic circulation does what to bile acid synthesis
Can increase it by 10 fold
What makes conjugated bilirubin
UDP glucuronyl transferase (responsible for infant jaundice)
What are the hereditary defects in bilirubin metabolism
Gilbert’s syndrome
Dubin-Johnson syndrome
Rotor syndrome
Crigler-Najjar syndrome (Type 1 and 2)
What is hemolytic anemia
Type of anemia which causes increased unconjugated bilirubin
What are the 2 main causes of neonatal jaundice
Elevated bilirubin production due to breakdown of fetal erythrocytes
Low activity of UDP gluuronyl transferase
What is Gilbert’s syndrome
- increased levels of uncojugated bilirubin in the blood
- usually recognized during adolescence
- episodes are brought on by physiological stress
What causes Gilbert’s syndrome
Mutation in gene that codes fro UDP glucuronyltransferase
What causes Crigler-Najjar syndrome
Mutations in the gene that codes for UDP glucuronyltransferase
CN1 or 2 is more severe
1
What is a major symptom of CN1
Kernicterus (form of brain damage cause by the accumulation of unconjugated bilirubin)
What are the treatments for CN1
- phototherapy
- heme oxygenase inhibitors
- oral calcium phosphate and carbonate
- liver transplantation
- phenobarbitol (no response in CN1)
What are the clinical symptoms of kernicterus
- cerebral palsy
- sensory nerual hearing loss
- gaze abnormalities
What distinguishes CN2
Less than 20% UPD glucuronyltransferase function
Less likely to develop kernicterus
What is found in Dubin-Johnson syndrome
- increased bilirubin w/o liver enzyme elevation
- mutations in MRP2 (unable to secrete conjugated bilirubin)
- liver has black pigmentation
What is Rotor syndrome
Buildup of conjugated and unconjugated bilirubin but the majority is conjugated
What mutation is responsible for Rotor syndrome
OATP1B1 and OATP1B3
How does phototherapy work
Changes trans-bilirubin to cis-bilirubin
What causes gallstones
- too much absorption of water from bile
- too much absorption of bile acids from bile
- too much cholesterol in bile
- inflammation of epithelium
Modification of drugs by liver to their active form
First pass effect
What are the liver enzymes
ALT and AST and alkaline phosphatase
What does elevated aminotransferases suggest
Hepatocyte injury
What does elevated alkaline phosphatase suggest
Cholestasis
Bilirubin can be used to measure
The liver’s ability to detoxify metabolites and transport organic anions
What is albumin used to measure
Severe impairment in liver function
What is prothrombin time used to measure
Reflects the degree of hepatic synthetic dysfunction
PT increases as the liver is unable to synthesize clotting factors
