Biliary Secretion: Liver And Gallbladder Function-1/25/16

Question 1

___ is a chronic liver disease in which normal liver cells are damaged and replaced by scar tissue

Answer 1

Cirrhosis–> excessive ETOH intake is most common cause; Alcohol abuse leads to accumulation of fat within hepatocytes

Question 2

____ is fatty liver accompanied by inflammation, which leads to scarring of liver and cirrhosis

Answer 2

Steatohepatitis

Question 3

List the primary bile acids

List the secondary bile acids

Answer 3

Primary=Cholic acid and Chenodeoxycholic acid

Secondary=Deoxycholic acid and Lithocholic acid

Question 4

The liver converts cholesterol into primary bile acids (cholic and chenodeoxycholic acid) by this enzyme:

Answer 4

7-alpha-hydroxylase

Question 5

Primary bile acids are converted to secondary bile acids (deoxycholic and lithocholic acid) by intestinal bacteria by this enzyme:

Answer 5

7-alpha-dehydroxylase

Question 6

Deoxycholic acid (secondary bile acid) is conjugated in the liver to these bile salts:

Lithocholic acid (secondary bile acid) is conjugated in the liver to these bile salts:

Answer 6

Glycodeoxycholic and Taurodeoxycholic acid

Glycolithocholic and Taurolithocholic acid

Question 7

Which bile acid is the most abundant?

Answer 7

Cholic > Chenodeoxycholic > Deoxycholic > Lithocholic

Question 8

___ are amphipathic molecules whose role is to emulsify lipids and form micelles

Answer 8

Bile salts-Primary are more effective at solubilizing lipids than secondary

Question 9

____ are amphipathic molecules, but are not soluble in H2O. They are solubilized by bile salts and form micelles

Answer 9

Phospholipids

Question 10

Where do you find cholesterol relative to the micelle?

Answer 10

Interior

Question 11

Bilirubin is the most important ____ and does not take part in micellar formation

Answer 11

Bile pigment

Question 12

Micelle formation tends to take place at ___ concentrations of bile salts

Answer 12

Increased

At decreased concentrations, no aggregation among bile acid molecules

Question 13

___ stimulates contraction of the gallbladder to release bile into the bile duct

___ stimulates relaxation of sphincter of oddi to allow passage of bile into the duodenum

___ stimulates the secretion of ions and water into the common hepatic duct with bile to go to the gallbladder

Answer 13

Ach and CCK

CCK

Secretin

Question 14

List the steps for how bile salts are recirculated to the liver via enterohepatic circulation

Answer 14

1-Bile salts transported from ileum to portal blood
2-Bile salts back to the liver
3-Synthesis of bile salts to replace amount that was lost

Question 15

The uptake of Bile salts across the basolateral membrane of the hepatocytes is mediated by what 2 systems?

Answer 15

• Na-dependent transport protein, sodium taurocholate cotransporting polypeptide (NTCP)
• Na-independent transport protein, organic anion transport proteins (OATPs)

Question 16

What transporter allows for bile salts to be taken up by hepatocytes from the portal circulation?

Answer 16

Na-Bile acid NTCP (Na Taurocholate cotransporting polypeptide)

Question 17

Bile acids are transported within the hepatocyte into the bile canaliculi via these transporters:

Answer 17

MRP2 (Multidrug resistance protein 2)

BSEP (Bile salt excretory pump)

Question 18

Bile acids and Na are taken up on the apical region of the enterocyte from biliary secretion via this transporter:

Answer 18

Na-Bile acid ASBT (Apical Na dependent bile acid transporter)

Question 19

____ bile is primarily an ultrafiltrate of plasma

___ stimulates the secretion of HCO3 and water from the ductile cells, resulting in a significant increase in bile volume, HCO3 concentration, and pH and a decrease in [bile salts]

Answer 19

Canalicular

Secretin

Question 20

Describe the gallbladder and sphincter of oddi during:
A) Interdigestive period
B) On eating

Answer 20

A) Gallbladder fills with bile–> Gallbladder is relaxed, sphincter of oddi is closed

B) CCK-mediated –> Gallbladder contract, sphincter of oddi relaxes

Question 21

Hemoglobin –> Biliverdin –> Bilirubin occurs where?

Bilirubin is carried through the bloodstream bound to ____

Bilirubin is converted to conjugated bilirubin in the liver via this enzyme ____

Conjugated bilirubin is also called ____ and accounts for bile’s yellow color

Answer 21

Reticuloendothelial cells

Albumin

UDP glucuronyl transferase, conjugated with glucuronic acid

Bilirubin glucuronide

Question 22

___ is when an infant has increased levels of UNCONJUGATED bilirubin in the blood during the 1st week of life and is accompanied by jaundice

Answer 22

Physiological neonatal jaundice

Caused by:
Bilirubin production is elevated b/c of increased breakdown of fetal RBCs
Low activity of UDP glucuronyl transferase, thus making bilirubin water soluble

Question 23

___ can occur due to the breakdown of RBCs leading to jaundice. This leads to increased production of bilirubin.

Answer 23

Hemolytic anemia

Question 24

Increased bilirubin levels due to hemolytic anemia overwhelm the livers capacity to produce conj. Bilirubin, resulting in increased ____

Answer 24

Unconjugated bilirubin

Question 25

____ is known as constitutional hepatic dysfunction and familial nonhemolytic jaunice

Answer 25

Gilbert’s syndrome

Question 26

A mutation in the gene that codes for UDP glucuronyltransferase leads to increased levels of UNCONJUGATED bilirubin in the blood and is characteristic of this disease:

Answer 26

Gilbert’s syndrome

Question 27

___ is a nonhemolytic jaundice that leads to increased levels of unconjugated bilirubin in the blood, is divided into 2 types, and characterized by mutations in the gene that code for UDP glucuronyltransferase

Answer 27

Crigler-Najjar syndrome Type 1 and 2

Question 28

This very severe form of unconjugated hyperbilirubinemia starts earlier in life, has no function of UDP glucuronyltransferase, and leads to kernicterus. It is treated with phototherapy.

Answer 28

Type 1 Crigler-Najjar syndrome

Question 29

This less severe form of unconjugated hyperbilirubinemia starts later in life, less likely to develop kernicterus, and most affected individuals survive into adulthood. Can be treated with phototherapy throughout life, blood transfusions, oral CaPO4 and carbonate to form complexes with bilirubin in the gut, or phenobarbitol

Answer 29

Type 2 Crigler-Najjar syndrome

Question 30

___ results in increased levels of CONJUGATED bilirubin in the serum without elevation of liver enzymes. It leads to a defect in the ability of hepatocytes to secreted conjugated bilirubin into the bile. The liver has a characteristic black pigmentation and is more common among Iranian and Moroccan Jews living in Israel.

Answer 30

Dubin-Johnson

Question 31

___ is a build-up of both unconjugated and conjugated bilirubin in the blood, but the majority is conjugated. The liver cells are not pigmented and there are nonfunctional OATP1B1 and OATP1B3

Answer 31

Rotor syndrome

Question 32

How does phototherapy work?

Answer 32

Isomerization that changes trans-bilirubin into water-soluble cis-bilirubin isomer

Question 33

Gallstones occur when there is an excess in either:

Answer 33

Pigment of bilirubin breakdown or cholesterol

Question 34

Large gallstone that stay in the gallbladder are usually ___

Small stones, if small enough, can pass to the biliary duct getting stuck there which is known as ____

Inflammation of the gallbladder is known as ____

Answer 34

asymptomatic

choledocholithiasis

cholecystitis

Question 35

___ occurs when a gallstone passes into the duodenum and obstructs it

When a gallstone passes all the way to the entrance of the duct at the duodenum and obstruct the pancreatic duct, ___ might develop

If a gallstone passes to the common bile duct and obstructs it, the outflow of both the gallblader and liver is affected and leads to ___

Answer 35

Gallstone ileus

Pancreatitis

Jaundice

Question 36

IV drug administration makes its way to the liver via ___

Oral drug administration makes its way to the liver via ___

Answer 36

Systemic circulation

Hepatic portal vein

Question 37

Drugs are metabolized by the liver via 2 phases. ___ is when drugs are processed via CYP enzymes and ___ is a conjugation step that further detoxifies drugs

Answer 37

Phase 1

Phase 2–> conjugation with glucuronide, sulfate, AAs, glutathione

Question 38

Describe metabolic functions of the liver

Answer 38

Carb metabolism=Gluconeogenesis, storage of glucose as glycogen, release of glucose

Protein metabolism=Synthesize nonessential AAs, modify AAs for use in biosynthetic pathways, synthesis of almost all protein (albumin, clotting factors)–> liver failure can result in hypoalbuminemia; Conversion of ammonia to urea

Lipid metabolism=FA oxidation, synthesis of lipoproteins, cholesterol, and phospholipids