4.10 Liver Physio, Biochem, Pharm

Question 1

Why is circulation to the liver unique?

Answer 1

Dual blood supply: hepatic artery (25%) & portal vein (75%)

Question 2

Normal liver vascular pressures? HA, PV and HV?

Answer 2

ENTER
HA - 100 mmHg
PV - 5-10 mmHg

EXIT
HV - 4-6 mmHg

Question 3

How to calculate portal hypertension pressures?What is normal?

Answer 3

PPG = PVP - HVP

Pressure gradient = portal vein - hepatic vein

(N) =1-5

Question 4

At what PPG or HVPG is at risk of variceal bleeding risk?

Answer 4

> 12 mmHg

Question 5

At what PPG or HVPG is clinically significant (varies, ascites)?

Answer 5

> 10 mmHg

Question 6

> 16 mmHg PPG would be a sign of?

Answer 6

Very severe portal hypertension

Question 7

Blood flow crossing over what causes the liver venous blood pressure to drop (no matter if healthy or not)?

Answer 7

Sinusoids

Question 8

What produces the compensatory flow changes at the pre-sinusoidal level in response to changesin the portal blood flow?

Answer 8

Hepatic artery
Hepatic Artery Buffer Response

Question 9

What causes the hepatic artery to dilate in response to decreased portal flow?

Answer 9

Adenosine

Question 10

What causes the hepatic artery to constrict in response to increased portal flow to reduce the sinusoid blood flow?

Answer 10

NE

Question 11

What zone of the hepatocytes are does the cholesterol responsible for bile synthesis emerge from?

Answer 11

Zone 3

Question 12

Where is primary bile synthesis?

Answer 12

Within hepatocytes

Question 13

Classic pathways to make primary bile acid (choline acid) is catalyzed by what enzyme (rate limiting step)*?

Answer 13

CYP7A1 (cholesterol 7a-hydroxylase)

Question 14

What is the alternative pathway to primary bile acid (chenodeoxycholic acid) catalyzed by (Rate Limiting Step)?

Answer 14

CYP7B1 oxysterol 7a-hydroxylase

Question 15

What primary bile acid synthesis pathways is predominant in adults and can reduce bile up to 90% if mutated?

Answer 15

Classic Pathway - CYP7A1 mut.

Question 16

What primary bile acid synthesis pathway is importation in neonates that can lead to severe/fatal cholestatic liver Dx or spastic paraplegia?

Answer 16

Alternative Pathway - CYP7B1

Question 17

Where does SECONDARY bile acid synthesis occur?

Answer 17

Intestine

Question 18

What enzyme is used by intestinal bacterial to deconjugate primary bile acids to secondary bile acids?

Answer 18

7a-dehydroxylase

Question 19

Deoxycholic acid and lithocholic acids are what kind of bile acids?

Answer 19

Secondary

Question 20

Where does conjugation of bile acids take place?

Answer 20

Within the liver

Question 21

Secondary bile acids return to the liver to undergo conjugations into what AA before being secreted into bile?

Answer 21

Glycine and Taurine

Question 22

What does conjugation of secondary bile acids do?

Answer 22

Improve water solubility and enhance micelles absorption at intestine

Question 23

What is responsible for maintaining high intraluminal concentrations of bile acid in biliary tract?

Answer 23

Conjugation of bile acids

Question 24

What inherited defect can lead to impaired bile acid conjugation = impaired fat absorption (vitamins + steatorrhea) ?

Answer 24

BACD1 bile acid conjugation defect 1

Question 25

In what forms can bile acids be passively transported via diffusion?

Answer 25

Unconjugated bile salts and bile acid

Question 26

In what form do bile acids need to be actively transported via membrane carriers?

Answer 26

Conjugated bile salt (BA Z-)