7. Hepatobilliary Function Flashcards
How can liver failure lead to edema
- Liver synthesizes almost all plasma proteins
- Liver failure can result in hypoalbuminemia that can lead to edema
What is liver Cirrhosis
Chronic liver disease in which normal liver cells are damaged and replaced by scar tissue
-alcohol abuse leads to accumulation of fat within hepatocytes
What changes to venous circulation are associated with portal hypertension
Esophageal varices: swollen connection between systemic and portal systems at inferior end of esophagus
Caput Medusae: swollen connections between systemic and portal systems around umbilicus
How can liver dysfunction lead to hepatic encephalopathy
Decreased hepatic urea cycle metabolism in the context of liver cirrhosis or portosystemic shunting leads to accumulation of ammonia in the systemic circulation
(ammonia readily crosses the blood-brain barrier)
What are the relative amounts of the four bile acids
Most to least
Cholic Acid > Chenodeoxycholic Acid > Deoxycholic Acid > Lithocholic Acid
What role does CCK play in bile secretion
CCK-induced gallbladder contraction and sphincter of Oddi relaxation
What happens to bile flow between periods of digestion
Gallbladder fills with bile
- Gallbladder is relaxed
- Sphincter of Oddi is closed
How are bile salts recirculated
Enterohepatic Circulation
- bile salts are transported from the ileum to the portal blood
- bile salts back to liver
- synthesis of bile salts to replace the amount that was lost
Within the enterohepatic circulation what two systems are used to uptake bile salts across the BASOLATERAL membrane of the HEPATOCYTES
- Sodium Dependent (NTCP)
- Sodium Independent (OATPs)
What highly efficient system is responsible for more than 90% of the bile acids returning to the portal blood
Ileal transport process
What is inhibited by bile salts and helps the negative feedback on bile synthesis
Cholesterol 7alpha-hydroxylase
What procedure can reduce bile secretion
Ileal resection
What is Icterus
Jaundice- hyperbilirubinemia
What known hereditary defects cause UNCONJUGATED Jaundice
Gilbert’s Syndrome
Crigler-Najjar Syndrome (1 and 2)
What known hereditary defects cause CONJUGATED Jaundice
Dubin-Johnson
Rotor Syndromes
What effect does Hemolytic Anemia have on bilirubin
Increased production of bilirubin overwhelms liver’s capacity to produce conjugated bilirubin which results in INCREASED UNCONJUGATED BILIRUBIN
What is physiological neonatal jaundice
Increase in Unconjugated Bilirubin in blood during the first week postnatal age
Caused by
- shortened lifespan of fetal erythrocytes
- low activity of UDP glucuronyl transferase
Summarize Gilbert Syndrome
- High levels of UNCONJUGATED Bilirubin in the blood
- Mutation in gene that codes for UDP Glucuronyltransferase
- UGT1A1 activity level is 30% of normal
Summarize Crigler-Najjar Syndromes
- High levels of UNCONJUGATED bilirubin in the blood
- Nonhemolytic jaundice
- Mutations in gene related to UDP Glucuronyltransferase
- Type 1 VERY SEVERE
What is special about Type 1 Crigler-Najjar
No function in UDP glucuronyltransferase
Kernicterus- brain damage caused by accumulation of unconjugated bilirubin in the brain and nerve tissue
What is Kernicterus
Permanent neurologic sequelae of bilirubin-induced neurologic dysfunction
Summarize Dubin-Johnson
- Increase in CONJUGATED Bilirubin
- Mutations for gene that encodes the multidrug resistance-associated protein 2 (MRP2)
- Liver has BLACK pigmentation
Summarize Rotor Syndrome
- Build up of both unconjugated and conjugated bilirubin but MAJORITY IS CONJUGATED
- Gene mutation causing nonfunctional OATP1B1 and OATP1B3 proteins or an absence of these proteins
- Liver cells are not pigmented
What is the primary treatment in neonates with unconjugated hyperbilirubinemia
Phototherapy
What are treatments for Crigler-Najjar Syndrome
- Phototherapy
- Blood Transfusions
- Oral calcium phosphate and carbonate
- Liver transplant (type 1)
- Phenobarbitol (type 2 only)
What biochemical tests are done to test liver function
Liver enzymes- commonly measured in the serum (ALT, AST and aminotransferases)
Bilirubin
Albumin
PT
What do elevated aminotransferases and elevated alkaline phosphatase suggest
Aminotransferase- result of hepatocyte injury
Alkaline phosphatase- result of bile duct injury (cholestasis)
What do bilirubin, albumin and PT test tell us
Bilirubin- measure liver’s ability to detoxify metabolites and transport organic ions into bile
Albumin- severe impairment of hepatocyte function decreases albumin in the plasma
PT- reflects the degree of hepatic synthetic dysfunction
