Functions of the Liver

Question 1

Differentiate the blood high in nutrients vs the blood high in oxygen running feeding the liver

Answer 1

75% of blood is high in nutrients- comes from portal vein

25% of blood is high in O2- comes from the hepatic artery

Question 2

What makes up the hepatic triad?

Answer 2

Branches of the hepatic artery, portal vein, and bile duct

Question 3

Differentiate the functions of the cells in zone 1 of the hepatic triad from zone 3 of the hepatic triad.

Answer 3

Zone 1: periportal cells are closest to the triad and therefore have the largest supply of O2 and nutrients, and are most active in detoxification

Zone 3: pericentral cells- closest to the hepatic vein- are the most active in bile synthesis

Zone 2: transition between zones 1 and 3

Question 4

Contrast the directionality of blood flow and bile flow in the liver

Answer 4

Blood travels from the periphery towards the central vein, while bile flows from the center towards the periphery

Question 5

Describe the glucose buffer function of the liver

Answer 5

The liver stores excess glucose as glycogen and releases stored glucose in the bloodstream when needed

Question 6

Where does protein metabolism take place?

Answer 6

The liver- the liver synthesizes non-essential amino acids, albumin, clotting factors, and converts ammonia to urea

Question 7

Briefly describe the two steps of detoxification in the liver

Answer 7

1) Oxidation/hydroxylation etc by cytochrome P450

2) Conjugate the substances with glucuronide, sulfate, amino acids and glutathione

Question 8

How is waste from the liver excreted?

Answer 8

Feces (via bile) for larger molecules or protein bound molecules

Kidneys for small water soluble catabolites

Question 9

What are the two main bile acids?

Answer 9

Hepatocytes synthesize Cholic acid and chenodeoxycholic acid

Question 10

How are secondary bile acids produced?

Answer 10

Colonic bacterial enzymes act on the primary acids to produce secondary acids (Ursodeoxycholic acid, deoxycholic acid, and lithocholic acid)

Question 11

What are bile salts?

Answer 11

Conjugated bile acids - acids conjugated to either glycine or taurine.

Conjugation of bile acids makes them more water soluble and therefore better at emulsifying fat

Question 12

What is the scaffold of bile acids?

Answer 12

Cholesterol

Question 13

How are conjugated bile acids in the ileum reabsorbed?

Answer 13

Na+ dependent manner: ASBT symporter

Question 14

How are bile acids in the colon reabsorbed?

Answer 14

They are deconjugated and then reabsorbed passively

Question 15

What is the role of cholangiocytes?

Answer 15

Cholangiocytes line the biliary ductules and can modify bile the same way the the ductal cells of glandular tissue modifies the secretions

Question 16

Why is it important that HCO3- is secreted into the bile (in exchange for Cl-)?

Answer 16

HCO3- makes bile slightly alkaline, which protects against gallstone formation

Question 17

Where is bile diluted?

Answer 17

Bile is diluted in the biliary ductules– where the cholangiocytes modify the bile

Question 18

What happens to bile in the gallbladder?

Answer 18

It is concentrated

Question 19

What is the major stimulus for bile secretion and what happens?

Answer 19

CCK is the major stimulus

• The gallbladder contracts
• The sphincter of Oddi relaxes

Question 20

Describe the neural reflex that leads to contraction of the gallbladder.

Answer 20

CCK is released in response to nutrients in the duodenum. CCK travels through the blood and stimulates the dorsal vagal complex, which relays the signal through vagal efferents to release ACh at the gallbladder. The vagus also synapses at the sphincter of Oddi where VIP and NO are released and causes relaxation of sphincter.

Question 21

What are the two different types of gallstones?

Answer 21

Precipitated cholesterol

Precipitated Ca2+ bilirubinate

Question 22

What normally prevents cholesterol precipitation?

Answer 22

Anti-nucleating proteins

Question 23

Where is heme degraded?

Answer 23

The reticuloendothelial system (RES) –> meaning macrophages.

Question 24

What are the first two breakdown products of hemoglobin?

Answer 24

Hemoglobin –> biliverdin (green) –> bilirubin (yellow)

Question 25

Why is bilirubin bound to albumin?

Answer 25

Conjugation to albumin makes bilirubin soluble such that it can enter the bloodstream and be taken to the liver for further processing in the liver.

Unbound bilirubin is insoluble at neutral pH

Question 26

What is the OATP transporter?

Answer 26

The OATP transported takes up bilirubin-albumin into the hepatocytes

Question 27

Why is bilirubin conjugated with glucuronic acid by UDP glucuronyl transferase?

Answer 27

Conjugated bilirubin is soluble again and can be excreted in urine or secreted in bile.

Question 28

Why are many newborns jaundiced?

Answer 28

UDP glucuronyl transferase is slow to be synthesized after birth - therefore bilirubin is not conjugated to glucuronic acid and cannot be excreted

Question 29

In what forms is hemoglobin excreted in feces?

Answer 29

urobilin and sterocobilin

Question 30

What causes jaundice?

Answer 30

Accumulation of bilirubin

Question 31

WHy is bacteria necessary for the excretion of bilirubin?

Answer 31

In the terminal ileum and colon, bilirubin is deconjugated by bacterial enzymes.

It is metabolized to urobilinogin

Question 32

Why is ammonia produced in the first place, even though it is toxic to the CNS?

Answer 32

Protein catabolism produces urea

Question 33

How is ammonia excreted?

Answer 33

Ammonia is converted into ammonium in the colon by colonic bacteria and excreted in the stool