Biliary Secretion: liver and Gallbladder function Flashcards
What is bile made up of?
Mixture of salts (50%), pigments (i.g. bilirubin 2%) and cholesterol (4%), phospholipids (ie.g. lecithin 40%); ions; water.
True or false: alcohol abuse can lead to accumulation of fat within the hepatocytes (steatohepatitis)
True. Steatohepatitis is fatty liver with inflammation which leads to scarring of liver and cirrhosis.
What are some complications of cirrhosis?
- jaundice
- ascites,
- loss of albumin leading to edema
- problems with blood flow ( lack of clotting factor)
- Coma
- Death
What are the two primary bile acids?
- Cholic acid
2. Chenodeoxycholic acid
What are the two secondary bile acids?
- Deoxycholic acid
2. Lithocholic acid
Which of the bile acids are the most common and which one is least common?
Cholic acid is most common. Lithocholic acid is least common.
What enzyme adds the OH groups to cholesterol to produce primary bile acids?
7a-hydroxylase
Where is primary bile acids produced?
Hepatocytes.
where are secondary bile acids produced?
lumen of small intestine via bacteria.
Which form of bile salts are more effective at solubilizing lipids (primary or secondary)
Primary.
What is the primarily cation and anion of bile?
Cation = Na Anion = Cl and HCO3-
What is meant by critical micellar concentration?
It is the concentration of bile at which micelle formation begins.
True or False. Only newly formed bile is dumped into the bile canaliculi.
False. Both new and the returning bile are dumped in the canaliculi.
What are three components of enterohepatic circulation?
- bile salts are transported from the ileum to the portal blood
- bile salts goes back to the liver
- synthesis of new bile salts to replace amount that was lost.
Once bile returns back to the liver, how is it taken up into the hepatocytes?
It’s taken up across the the basolateral membrane of the hepatocytes which is mediated by two types of system:
- Na-dependent transport protein called sodium taurocholate cotransporting polypeptide (NTCP)
- Na-independent transport protein, organic anion transport protein (OATPs)
In the enterohepatic circulation of bile acids, both active and passive transport processes occur. what’s involved in each.
Active: Ileum
Passive: ileum, jejunum, and colon
Via negative feedback, bile salts inhibits what enzyme?
Cholesterol 7a-hyroxylase
How is bile synthesis affected after an ileal resection?
Ileal resection interrupts the enterohepatic circulation and so bile synthesis is increased up to 10-fold higher than normal.
What cells do secretin stimulate which adds volume to the bile?
Secretin sitmulates ducile cells which adds H20 and HCO3- increasing the volume of bile.
The content of the bile in the canaliculi resembles what?
Canalicular bile is primarily ultrafiltrate of plasma. electrolyte and water is added to the in the ducts.
In what cell/system is bilirubin formed?
In reticuloendothelial system. RBC is taken up the macrophages and broken down releasing Hg which then is converted to biliverdin and then to bilirubin.
Once inside the liver, bilirubin is conjugated to what via what enzyme?
UDP glycoronyl transferase adds glucoronic acid to bilirubin = conjugated.
What compounds give feces it’s dark color?
Urobilin and stercobilin
Why do infants usualy have increased level of unconjugated bilirubin in the blood during the first week of life.
- UDP glucoronyl transferase, the enzyme that is needed to conjugate bilirubin, is synthesized slowly after birth. bilirubin remains unconjugated until that enzyme is made.
- Fetal erythrocytes have shorter life span and so that increased breakdown of feltal erythrocytes elevates bilirubin.
What are the diseases associated with hereditary defects in bilirubin metabolism.
Crigler-Najjar, Gilbert’s, Dubin-Johnson, Rotar syndomes.
WHat kind of jaundice is seen in hemolytic anemia and what is the cause?
Unconjugated jaundice. It’s due to increased breakdown of RBC, and the increased bilirubin level overswhelms the liver’s capacity to produce conjugated bilirubin resulting in elevated unconjugated bilirubin.
In Gilbert’s Syndrome, what kind of jaundice is produced and what is the cause?
Increased in unconjugated bilirubin. It’s due to mutation in gene that code for UDP glucoronyltransferase.
In Crigler Najjar syndrome, what kind of jaundice is seen? and what is the cause?
INcreased levels of UNconjugated bilirubin. Also due to mutation in gene that code for UDP glucoronyltrransferase just like in Gilbert’s syndrome.
Kernicterus is a condition seen in which kind of Jaundice?
Crigler-Najjar syndrome. where unconjugated bilirubin is elevated and it accumulates in the brain and nerve tissues producing kernicterus. Babies will have neurological problems.
Phototherapy is a treatment used in what type of Jaundice?
Used in Gilberts and Crigler-Najjar
Phenobarbitol is used in patients with what kind of juandice?
Type Crigler-Najjar syndrome
In patients with Dubin-Johnson, would you expect to see elevated liver enzymes?
No.
What is the cause of Dubin-Johnson syndrome?
Defect in the ability of hepatocytes to secrete conjugated bilirubin into the bile. The mutation is on multidrug resistance protein 2 (MRP2) which is responsible fro transporting bilirubin out of liver cells into bile.
Black pigmentation on liver, and mild jaundice throughout life that which may not present until puberty or adulthood, is what kind of jaundice?
Dubin-johnson
THis type of jaundie is common in iranian and moraccan jews
Dubin-Johnson
What kind of jaundice is Rotor syndrome?
Build up of both unconjugated and conjugated bilirubin in the blodd but majority is conjugated.
In Rotor syndrome, gene mutation affects proteins that normally transports bilirubin and other compounds from the blood into the liver to be cleared from the body. What proteins are these?
OATP1b1 and OATP1b3.
would you expect to find a pigmented or unpigmented liver in Rotor syndrome?
Liver cells are NOT pigmented in rotor.
Explain how phototherapy works. isomers.
Phototherapy works through a process of isomerization that changes trans-bilirubin into the water-soluble cis bilirubin
Gallstones occur when there is excess in either 1 and 2.
- access pigment of bilirubin breakdown or
2. cholesterol
In patients with Mirizzi’s syndrome, the gallstones are located where?
Stones in the cystic duct compressing or fistulizing into the commone hepatic duct.
Obstruction of which anatomical position with stones will cause acute cholecystitis and is about 10% of all gallstones cases?
stones imparted in cystic duct.
One would not expect to see pancreatitis until gallstones block what structure?
Stones at the entrance at diodnum and obstruct pancreatic duct.
