Lecture 19: Hepatobiliary Function

Question 1

What are the main functions of the liver?

Answer 1

-bile, billirubin, metabolism of carbs/lipids/proteins, detoxification

Question 2

What are the metabolic functions of the liver?

Answer 2

carbohydrate metabolism (make/release glucose storing clycogen)
protein metabolism (AA and plasma protein synthesis and modification, ammonia conversion)
lipid metabolism (FA oxidation, lipid synthesis)

Question 3

If protein metabolism is impaired due to liver dysfunction, what happens?

Answer 3

Hypoalbuminemia > loss of oncotic pressure in capillary so fluid leaks out > edema/ascites

Question 4

Describe the blood flow system serving the liver

Answer 4

2 capillary beds connected by hepatic portal system:
Abdominal/pelvic bed > hepatic portal vein (all GI blood passes through liver sinusoidal bed

Hepatic artery feeds liver with oxygenated blood

Question 5

How can liver dysfunction cause bruising?

Answer 5

-lack of coagulation factors synthesized by liver

Question 6

What is cirrhosis and how does it happen

Answer 6

-liver cells are damaged & replaced with fibrotic tissue

major cause is alcohol > fat accumulation in hepatocytes > fatty liver > steatohepatitis (fat + inflammation) > scarring

Question 7

What is portal hypertension and what causes it?

Answer 7

-hepatocytes are dysfunctional and can’t drain the venous blood well > turbulence at HPV > blood is shunted to other veins causing them to distend

Question 8

Clinical manifestations of Portal HTN

Answer 8

esophageal varices - swollen vessels at inferior esophagus

caput medusae - swollen vessels by umbilicus

Question 9

What is hepatic encephalopathy and what causes it?

Answer 9

• alteration of brain function due to NH3+ buildup

- impaired urea cycle in liver > NH3+ accumulates and is able to cross the BBB

Question 10

What is the importance of bile?

Answer 10

basically “opens” lipid cluster so enzymes can digest it

Question 11

Be able to draw the synthesis of bile (also from Zaidi’s lecture)

Answer 11

Ok

Question 12

Where are primary bile acids synthesized?
Where are secondary bile acids generated?
Where is bile conjugated?

Answer 12

liver
Small intestine
liver

Question 13

What are the relative amounts of the four bile acids in the body?

Answer 13

cholic > chenodeoxycholic > deoxycholic > lithocholic

Question 14

What happens to bile at these locations?
duodenum
jejunum
ileum

Answer 14

• bile emulsifies
• bile aggregates and forms micelles and recruit lipases to break down lipids
• bile and b12 reabsorbed/recycled

Question 15

What is the mechanism of bile secretion and absorption?

Answer 15

1. canalicular bile formed @ liver (isotonic to plasma)
2. some of the final bile formed from secretions of HCO3, Na and H2O by secretin
3. storage @ gallbladder and release in bile duct
4. Sphincter of Oddi opens in response to CKK > bile released to duodenum
5. bile salts and b12 reabsorbed in ileum
6. return to canaliculi via portal circulation

Question 16

How much bile does the liver produce?

Answer 16

As much as it lost/excreted

Question 17

What happens at the biliary system during these periods of digestion?
Interdigestive
Eating

Answer 17

1. ) Bile fills gallbladder (relaxed), sphincter of Oddi is closed contracted
2. ) CCK stimulates = signals food, gallbladder contracts, Sphincter of Oddi opens and relaxes to release the bile

Question 18

What are two transport mechanisms for recycled bile to return to the hepatocyte?

Answer 18

Na dependent: Na taurocholate cotransporting polypeptide
Na independent: organic anion transport proteins

-both located on the basolateral side of the hepatocyte

Question 19

What transporters allow bile to enter the canaliculi from the hepatocyte?

Answer 19

BSEP and MRP2 (active transport)

*located on the canalicular membrane

Question 20

What transporters allow bile to be reabsorbed at the ileum?

What transporters allow bile to travel from the enterocyte in the ileum back to portal circulation?

Answer 20

ASBT (with reabsorbed Na)

OSTa/B

Question 21

What type of transport is utilized by bile at these regions?
Jejunum
Ileum
Colon

Answer 21

• passive
• active and passive, absorbs most bile
• passive

Question 22

Is the bile that makes it to the ileum conjugated or unconjugated?

Answer 22

Conjugated, so needs to be actively reabsorbed at the ileum

-unconjugated bile passively diffuses proximal to the ileum

Question 23

What happens to bile synthesis during ….
ileal resection
bile acid feeding

Answer 23

• ileum gone so most bile isn’t reabsorbed > increase in bile synthesis
• lots of bile secreted so lots of bile coming back from the ileum > decrease in bile synthesis

Question 24

How is bile synthesis inhibited?

Answer 24

returning bile feedbacks and inhibits 7a hydroxylase > inhibits bile synthesis, not secretion

*secretion is triggered by food

Question 25

Draw the pathway of bilirubin excretion including locations in the GI tract

Answer 25

Ok

Question 26

Jaundice | How would you determine if jaundice is unconjugated or conjugated?

Answer 26

defect @ pathway up to liver > unconjugated jaundice | after liver > conjugated jaundice

Question 27

Hemolytic anemia Physiological neonatal jaundice

Answer 27

- RBC destruction > unconjugated bili buildup - UDPGT activity not up to speed at birth > unconjugated bili from fetal Hgb breakdown builds up, treat with phototherapy to avoid brain damage

Question 28

Crigler Najjar syndrome Cause Clinical

Answer 28

-UDPGT enzyme mutations, Type 1 (complete absence) more sever than Type 2 (decreased activity) -Type 1: manifests in infancy, leads to kernicterus Type 2: later onset, less likely to lead to kernicterus, less than 20% activity of UDPGT

Question 29

Gilbert syndrome:

Answer 29

- UDPGT mutation > UGT1A1 activity 30% of normal | - usually asymptomatic

Question 30

Kernicterus Cause clinical

Answer 30

- unconjugated bilirubin buildup in brain (yellow brain | - cerebral palsy, gaze abnormalities, sensorineural hearing loss

Question 31

Treatment for Crigler-Najjar syndrome

Answer 31

``` phototherapy blood transfusion phenobarbitol (type 2 only) liver transplant (type 1) oral phosphate and carbonate ```

Question 32

Dubin Johnson syndrome cause clinical

Answer 32

- MRP2 transporter mutation > can't transport conjugated bilirubin into bile - black liver (due to melanin buildup), mild jaundice

Question 33

Rotor syndrome cause clinical

Answer 33

- OSTPB1/B3 mutations that transport bilirubin from ileum to portal circulation - conjugated bilirubin buildup, non-pigmented liver

Question 34

How does phototherapy work?

Answer 34

- converts trans bilirubin to soluble cis bilirubin | - used to treat infants with > 21 mg//dL bilirubin

Question 35

Cholelithiasis:

Answer 35

-caused by cholesterol buildup in bile, too much absorption of bile acids from bile or epithelium inflammation

Question 36

Cholecystitis Choledocholithiasis Cholangitis

Answer 36

- cystic duct obstruction by stone > gallbladder inflammation - common bile duct occlusion > jaundice or conjugated hyperbilirubinemia - bile duct infection

Question 37

What do biochemical tests evaluate? | Examples?

Answer 37

test liver enzyme function -ALT, AST: elevated in hepatocyte injury Alkalinephosphatase: elevated in bile duct injury

Question 38

If albumin is reduced, what does this mean about liver function? If PT is elevated, what does this mean about liver function?

Answer 38

- albumin is made in the liver, so if it is reduced there is something wrong with hepatic function - longer clotting time means liver isn't producing enough clotting proteins, synthetic ability is impaired