4.10 Liver Physio, Biochem, Pharm Flashcards
Why is circulation to the liver unique?
Dual blood supply: hepatic artery (25%) & portal vein (75%)
Normal liver vascular pressures? HA, PV and HV?
ENTER
HA - 100 mmHg
PV - 5-10 mmHg
EXIT
HV - 4-6 mmHg
How to calculate portal hypertension pressures?What is normal?
PPG = PVP - HVP
Pressure gradient = portal vein - hepatic vein
(N) =1-5
At what PPG or HVPG is at risk of variceal bleeding risk?
> 12 mmHg
At what PPG or HVPG is clinically significant (varies, ascites)?
> 10 mmHg
> 16 mmHg PPG would be a sign of?
Very severe portal hypertension
Blood flow crossing over what causes the liver venous blood pressure to drop (no matter if healthy or not)?
Sinusoids
What produces the compensatory flow changes at the pre-sinusoidal level in response to changesin the portal blood flow?
Hepatic artery
Hepatic Artery Buffer Response
What causes the hepatic artery to dilate in response to decreased portal flow?
Adenosine
What causes the hepatic artery to constrict in response to increased portal flow to reduce the sinusoid blood flow?
NE
What zone of the hepatocytes are does the cholesterol responsible for bile synthesis emerge from?
Zone 3
Where is primary bile synthesis?
Within hepatocytes
Classic pathways to make primary bile acid (choline acid) is catalyzed by what enzyme (rate limiting step)*?
CYP7A1 (cholesterol 7a-hydroxylase)
What is the alternative pathway to primary bile acid (chenodeoxycholic acid) catalyzed by (Rate Limiting Step)?
CYP7B1 oxysterol 7a-hydroxylase
What primary bile acid synthesis pathways is predominant in adults and can reduce bile up to 90% if mutated?
Classic Pathway - CYP7A1 mut.
What primary bile acid synthesis pathway is importation in neonates that can lead to severe/fatal cholestatic liver Dx or spastic paraplegia?
Alternative Pathway - CYP7B1
Where does SECONDARY bile acid synthesis occur?
Intestine
What enzyme is used by intestinal bacterial to deconjugate primary bile acids to secondary bile acids?
7a-dehydroxylase
Deoxycholic acid and lithocholic acids are what kind of bile acids?
Secondary
Where does conjugation of bile acids take place?
Within the liver
Secondary bile acids return to the liver to undergo conjugations into what AA before being secreted into bile?
Glycine and Taurine
What does conjugation of secondary bile acids do?
Improve water solubility and enhance micelles absorption at intestine
What is responsible for maintaining high intraluminal concentrations of bile acid in biliary tract?
Conjugation of bile acids
What inherited defect can lead to impaired bile acid conjugation = impaired fat absorption (vitamins + steatorrhea) ?
BACD1 bile acid conjugation defect 1
In what forms can bile acids be passively transported via diffusion?
Unconjugated bile salts and bile acid
In what form do bile acids need to be actively transported via membrane carriers?
Conjugated bile salt (BA Z-)
