lecture 13/14: bile + bilirubin Flashcards Preview

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Flashcards in lecture 13/14: bile + bilirubin Deck (40):
1

what are functions of bile?

digestive secretion: essential for lipid absorption
excretion fluid

2

what is hepatic bile mostly made up of?

majority = H2O
most of solutes = bile acids

3

what are bile acids synthesized from primarily?

cholesterol

4

what contributes to bile flow?

increased bile acid secretion

5

what are the functions of bile ducts?

conduits for bile
osmotic equilibration of bile (regulate permeability)
bicarbonate secretion
absorption of bile acids, AA's, glucose
secretion of mucus
hydrolysis of oxidized glutathione

6

why do bile acids need the gallbladder?

bile acids =
potent solubilizers of dietary lipids
toxic to enterocytes
subject to loss with rapid intestinal transit
subject to modification by intestinal bacteria

7

how did nature keep the gallbladder "bag" small?

develop mechanism for concentration of bile

8

how is the gallbladder "bag" protected?

secretion of mucin

9

what are determinants of gallbladder pressure and filling?

(1) pressure of hepatic bile
(2) Sphincter of Oddi pressure
(3) gallbladder with receptive relaxation at rest; postprandial gallbladder contraction

10

what is the role of bile acids in digestion?

solubilize fat soluble vitamins
denature dietary protein promoting proteolysis
promote intestinal motility
bacteriostatic
induce water + electrolyte secretion into colon
function as hormones to regulate enterohepatic circulation as well as fat, glucose, energy homeostasis

11

what is the order of enterohepatic circulation of bile acids?

1. liver
2. duodenum
3. terminal ileum
4. portal vein
(back to liver)

12

why are there minimal bile acids in urine?

+ low concentration of bile acids in systemic plasma
+ bile acids mainly albumin bound in plasma - limiting quantities in glomerular filtrate
+ efficiently absorbed in proximal tubule by sodium-dependent transporter called ASBT

13

what is bilirubin?

breakdown product of heme

14

what is jaundice?

widespread tissue deposition of bilirubin, leading to yellow skin and eye discoloration

15

what are causes of jaundice?

(1) increased unconjugated bilirubin (over production of bilirubin; dec. hepatic uptake; or impaired conjugation)

(2) increased conjugated bilirubin (genetic disorder of impaired excretion; blockade such as tumor or gallstone)

16

describe neonatal jaundice

due to immaturity of conjugation enzyme function

unconjugated hyperbilirubinemia

17

what is the treatment for neonatal jaundice?

phototherapy

18

are bile acids conjugated or unconjugated at lower pH (~2 or 4)?

conjugated with amino acids

19

describe the overall enterohepatic circulation (EHC) pattern for bile acids

majority taken up by ASBT and into portal vein blood
some taken up by colonic bacteria to be converted to secondary BAs
some taken up passively to portal vein blood and then excreted in feces

20

describe transport of bile acids into hepatocytes

transported on basolateral end:
conjugated go into cell by NTCP (sodium-bile acid cotransporter)
unconjugated to into cell by OATP uniporters

21

what is the effect of bile acid conjugation?

decreases passive absorption from biliary tract, gallbladder or intestine
decreased binding to albumin in blood (which allows some filtration into urine)

22

describe apical transport of bile acids out of cell into canaliculus

BSEP secretes conjugated BAs into canaliculus; this activity stimulates cholesterol and PC transport into canaliculus along with water and ions => form bile

23

what do colonic bacteria do to the bile acids?

will de-conjugate them or convert them to secondary bile acids

24

what happens if there is excess bile acids in colon?

water secretion + diarrhea

25

what is the composition of bile acids in serum?

conjugated that has been actively absorbed from ileum

26

what are the urine constituents of bile acids?

almost none because only a little is filtered and whatever does get filtered ends up absorbed by ASBT

27

what is cholestasis?

gall stone or tumor blocking bile duct

28

what are clinical correlations associated with cholestasis?

increased serum BA becomes enough that renal ASBT can't re-absorb bile acids and THEN you wind up with some in the urine

29

distinguish solubilities of bilirubin depending on whether it is conjugated

un-conjugated = low water solubility
conjugated = greater water solubility

30

how is bilirubin (BR) made?

liver macrophages will convert heme from old RBCs into BR

31

Describe the enterohepatic circulation pattern of BR?

macrophage bilirubin => portal blood, where it is taken up by hepatocytes and conjugated so that it has greater solubility to go into bile

Travels into duodenum until it reaches the colon - bacteria there will de-conjugate the BR and convert it to urobilinogen

32

how is bilirubin brought into hepatocyte?

OAT

33

what transports bilirubin out of hepatocyte and into canaliculus?

MRP2

34

is bilirubin absorbed by small intestine?

no! that's why it all passes to colon

35

what is most of the BR in serum?

that made by spleen macrophages

36

why does urine never contain bilirubin?

almost all of BR is bound to albumin in the blood

37

what happens to urine with high BR levels?

conjugated BR will get filtered into urine and turn it brown

38

how can jaundice come about?

result of:
excess BR (indirect) or
excess conjugated BR (direct)
in blood

39

how does indirect jaundice occur?

results from decreased UGT activity, resulting in risk of BRAIN DAMAGE at high BR levels, but no brown urine

examples:
Crigler-Najar
Gilbert's

40

How does jaundice occur directly?

reflux of hepatic conjugated BR into blood
this leads to jaundice and brown urine

examples:
cholestasis = light, clay-colored feces
MRP2 deficiency
neonatal