7. Hepatobiliary Function Flashcards
What is the cause of Gilbert’s syndrome?
Mutation in UDP glucuronyl transferase.
Usually results in UDP glucuronyl transferase activity to about 30% of normal.
What is usually indicated by elevated serum aminotransferases (ALT/AST)?
Damage to hepatocytes.
What is the effect of liver damage on prothrombin time?
Prothrombin time increases due to a lack of hepatic coagulation factors.
What five things, discussed in class, can lead to pigment or cholesterol gallstones?
Too much absorption of water from bile.
Too much absorption of bile acids from bile.
Too much cholesterol in bile.
Too much bilirubin in bile (hemolytic anemia).
Inflammation of epithelium.
What are the sodium dependent and sodium independent transporters for bile salts on the basolateral side of hepatocytes?
Sodium dependent: sodium taurocholate cotransporting polypeptide (NTCP).
Sodium independent: organic anionic transport proteins (OATPs)
Which two transporters of the enterohepatic circulation are sodium dependent, and what spaces do they move bile acids between?
Sodium dependent taurocholate cotransporting polypeptide (NTCP) – from the portal circulation into the hepatocytes.
Apical sodium dependent bile acid transporter (ASBT) – from the intestinal lumen into the enterocytes.
What serum aminotransferases are tested as liver function enzymes?
Alanine aminotransferase.
Aspartate aminotransferase.
When bilirubin is produced by the reticular endothelial system, it is not water soluble. How does it get to the liver?
Through attachment to albumin.
What is the main issue in Dubin-Johnson syndrome?
Increase in serum conjugated bilirubin due to a malfunctioning multidrug-resistant protein 2 (MRP2).
This prevents hepatocytes from being able to secrete bilirubin into the bile canaliculi.
What is the primary issue in Rotor syndrome?
Defective OATPs, resulting in an inability to transfer conjugated bilirubin into the hepatocytes from the blood
What are the five given treatments for Crigler-Najjar syndrome?
Phototherapy.
Blood transfusions.
Oral calcium phosphate and carbonate.
Liver transplant (some type I patients).
Phenobarbital (type II patients only).
How is unconjugated bilirubin neurotoxic?
It upregulates apoptotic events in the neurons, astrocytes, microglia, and oligodendrocytes.
How does the amount of bile acid in the portal system regulate the amount of bile acid produced by the liver?
Bile acids inhibit the action of cholesterol 7alpha-hydroxylase – the rate limiting step in bile acid synthesis.
What four things, discussed in class, can occur as sequelae to cirrhosis of the liver?
What dysfunction of the liver causes the symptoms?
Ascites – lack of albumin, decreased oncotic pressure.
Hepatic encephalopathy – lack of urea processing.
Bruising – lack of coagulation factors.
Portal hypertension – due to the fibrotic liver.
(Portal hypertension causes caput medusae and esophageal varices)
How does conjugated bilirubin get to the small intestine?
Via the common bile duct with the bile.