Lecture 10 and 11: Functions of the Liver

Question 1

What are the 3 major functions of the liver?

Answer 1

1) Metabolism
2) Detoxification
3) Excretion

Question 2

How are hepatocytes arranged in the liver?

Answer 2

in anastomosing cords that form plates

Question 3

What it the main benefit of the high blood flow received by hepatocytes?

Answer 3

high quantities of O2 and nutrients

Question 4

What are sinusoids?

Answer 4

low-resistance cavities that supply the plates of hepatocytes

(sinusoids are supplied by branches of portal vein and hepatic artery)

Question 5

What comprises the hepatic triad?

Answer 5

hepatic artery, portal vein, and bile duct

Question 6

Which cells are closest to the triad?

Answer 6

zone 1/periportal cells

Question 7

Where are the pericentral cells?

Answer 7

Zone 3 (furthest from the triad)

Question 8

Which cells receive the largest supply of nutrients and O2?

Answer 8

periportal cells (nearest to the triad)

Question 9

Which cells are most sensitive to oxidative damage?

Answer 9

periportal cells (require the most O2)

Question 10

Which cells are most active in detoxification?

Answer 10

periportal cells

Question 11

True or false: zone 2 and 3 cells can function as zone 1 cells in liver disease

Answer 11

true

Question 12

What are Kupffer cells?

Answer 12

resident liver macrophages

Question 13

apical membranes of adjacent hepatocytes form channels called ____________

Answer 13

canaliculus

Question 14

What is the function of the cancaliculi?

Answer 14

drain bile

Question 15

Name the cell type that lines the biliary ductules

Answer 15

cholangiocytes

Question 16

trace the path of bile from formation to storage

Answer 16

hepatocyte –> canaliculus –> biliary ductules –> hepatic ducts –> common hepatic ducts –> gall bladder or intestine

Question 17

What roles do the liver play in carb metabolism?

Answer 17

1) Gluconeogenesis

2) Glycogen storage, buffering excess glucose

Question 18

What roles do the liver play in lipid metabolism?

Answer 18

1) fatty acid oxidation (rich store of enzymes)
2) convert products of carb metabolism into lipids (make lipoproteins, cholesterol, phosphlipids)
3) Convert cholesterol to bile acids

Question 19

What roles do the liver play in protein metabolism?

Answer 19

1) makes all non-essential amino acids
2) makes all plasma proteins (albumin, clotting factors)
3) converts ammonia to urea

Question 20

What are the 2 steps of first pass metabolism?

Answer 20

1) Phase 1 reactions (oxidation, hydroxylation)

2) Phase 2 reactions (conjugate substances with glucuronide, sulfate, amino acids, glutathion)

Question 21

What enzymes catalyze Phase 1 reactions of detoxification? (oxidation)

Answer 21

Cytochrome P-450

Question 22

What role does the liver play in excretion?

Answer 22

gets rid of large water-soluble catabolites and molecules bound to plasma proteins, steroid hormones, etc that cannot fit through the kidney

Question 23

Name the components of bile

Answer 23

bile acids
phospholipids
proteins
cholesterol
bile pigments
electrolytes

Question 24

What are the 2 primary bile acids produced by the hepatocytes?

Answer 24

1) cholic acid

2) chenodeoxycholic acid

Question 25

What produces secondary bile acids?

Answer 25

colonic bacterial enzymes

Question 26

What are the 3 secondary bile acids?

Answer 26

1) ursodeoxycholic acid 2) deoxycholic acid 3) lithocholic acid

Question 27

What are bile acids conjugated with?

Answer 27

glycine or taurine

Question 28

What is the benefit of conjugated bile acids?

Answer 28

more water solube

Question 29

Where are conjugated bile acids ACTIVELY absorbed?

Answer 29

terminal ileum

Question 30

What transporter absorbs bile acids?

Answer 30

asbt (Na+ dependent bile salt transporter)

Question 31

If bile acids are not absorbed in the terminal ileum, what happens to them?

Answer 31

they are deconjugated by colonic bacterial enzymes then passively reabsorbed in colonic epithelium

Question 32

What does bile acid synthesis depend on?

Answer 32

the body's needs | ex: ileal resection requires increased bile synthesis since it is not getting absorbed

Question 33

What is the avenue for bile acid recycling?

Answer 33

enterohepatic circulation

Question 34

True or false: conjugated bile acids are able to passively cross the intestinal epithelial lining?

Answer 34

FALSE (they cannot)

Question 35

Bile absorption is __________ in the small intestine (ileum) and _________ in the large (colon).

Answer 35

active; passive

Question 36

How do cholangiocytes modify bile?

Answer 36

1) reclaim glucose and amino acids 2) exchange Cl- for HCO3- (making bile alkaline) 3) Absorb glutathione 4) diluted (secretin stimulates aquaporin water channels)

Question 37

Ejection of bile form the gall bladder begins within ____ _____ of meal injestion

Answer 37

30 minutes

Question 38

What is the stimulus for bile release?

Answer 38

CCK

Question 39

gallstones are composed of ___________ or ____________

Answer 39

cholesterol; Ca++ bilirubinate

Question 40

What normally inhibits the precipitation of cholesterol in bile?

Answer 40

anti-nucleating agents

Question 41

What factors increase chance of bile nucleation?

Answer 41

prolonged storage

Question 42

What is the distinguishing feature of pigment stones?

Answer 42

unconjugated bilirubin

Question 43

What is the first product of heme degradation?

Answer 43

biliverdin (then converted to bilirubin)

Question 44

Bilirubin binds to __________ in the bloodstream to increase solubility

Answer 44

albumin

Question 45

What transporter uptakes bilirubin in hepatocytes?

Answer 45

OATP

Question 46

What enzyme conjugates bilirubin with glucoronic acid?

Answer 46

UDP glucuronyl transferase

Question 47

What deficiency do newborns born with jaundice have?

Answer 47

UDP glucuronyl transferase

Question 48

Walk through the bilirubin formation and excretion pathway

Answer 48

RBCS --> hemoglobin --> biliverdin --> bilirubin --> bilirubin/albumin --> bilirubin --> conjugated bilirubin --> urobilinogen --> urobilin

Question 49

What is the benefit of conjugating bile?

Answer 49

makes it water soluble

Question 50

After bile is deconjugated by bacterial enzymes, it is metabolized into _____________.

Answer 50

urobilinogen

Question 51

Does the enterohepatic circulation absorb urobilinogen?

Answer 51

yes, a portion of it

Question 52

What happens to the urobilinogen that is not absorbed via the enterohepatic system?

Answer 52

converted into urobilin and stercobilin and excreted in feces

Question 53

What form of bilirubin can cross the BBB?

Answer 53

unconjugated

Question 54

What are 2 possibilities that lead to increases in unconjugated bilirubin in the plasma?

Answer 54

1) loss or absense of UGT (enzyme responsible for conjugating bilirubin to glucuronic acid) 2) oversupply of heme

Question 55

Why is high bilirubin in the urine in CONJUGATED bilirubinemia?

Answer 55

1) defect in transporter that secretes conjugated bilirubin in bile 2) blockage of bile flow (gallstone)

Question 56

What is the root cause of jaundice?

Answer 56

accumulation of free and conjugated bilirubin in the blood (hepatic dysfunction)

Question 57

What is pruritus?

Answer 57

itching of skin due to increased bile acids in serum leading to skin deposit

Question 58

What do bilirubin levels need to be at in order for jaundice to be diagnosed? (aka what is the threshold for hyperbilirubinemia?)

Answer 58

>2mg/dL

Question 59

Name a few causes of hyperbilirubinemia?

Answer 59

1) hemolytic anemia (produce too much bilirubin) 2) decreased bilirubin uptake by hepatocytes 3) disturbed intracellular protein binding and conjugation 4) disturbed secretion of conjugated bilirubin into bile canaliculi 5) bile duct obstruction 6) potent antibiotics (no bacteria) 7) lack of UGT in newborns

Question 60

What are the 2 sources of ammonia (NH3) in the body?

Answer 60

1) catabolism of protein | 2) colonic bacteria

Question 61

Which form is membrane permeable, NH3 or NH4?

Answer 61

NH3

Question 62

What is hepatic encephalopathy?

Answer 62

passage of NH3 into brain because liver is damaged and not detoxifying it

Question 63

Can hepatic encephalopathy be fatal?

Answer 63

Yes

Question 64

What causes portal hypertension?

Answer 64

increased bp in the sinusoids

Question 65

Name a few signs of portal hypertension

Answer 65

1) Caput medusae 2) Esophageal varices 3) Spider nevi