L10 & L11: Functions of the Liver Flashcards
Major blood supply to liver
Portal venous blood (70-80%)
Macrophages in liver
Kupfer cells
Hepatic stellate cell, when activated over a long period time….
…makes collagen deposition contributing to fibrosis.
Which is NOT in the portal triad? A. Hepatic artery B. Hepatic vein C. Portal vein D. Bile duct
B. Hepatic vein
Which zone contains cells closest to the portal triad?
Zone 1 - Periportal cells; see pathogens first, most active in detoxification
Which zone contains cells furthest from portal triad?
Zone 3 - Pericentral cells; die first in ischemia, most active in bile synthesis
Where are non-essential aa’s synthesized?
liver
What protein maintains plasma oncotic pressure?
albumin from liver
Liver converts ammonia to
Urea.
Note: too much NH3+ can cross BBB and cause mental injury
Drug design should take into account
First pass metabolism
1st pass metabolism consists of what phases?
Phase I: oxidation/hydroxylation of substances via p450
Phase II: solubilize substances via conjugation
What happens to large water-soluble catabolites and molecules bound to plasma proteins, steroid hormones, etc. that can’t be excreted via kidney?
Liver excretes these products in bile, so it can be defecated
Bilirubin is a byproduct of
heme metabolism
Calcified bilirubin produces
gall bladder stones
Composes 65% of bile
bile acids
Bile acids are derived from
cholesterol in hepatocytes
Rate limiting enzyme for bile acid synthesis
7-alpha hydroxylase
under negative feedback of bile acids (the more we recycle back, the more we suppress the synthesis of bile acids. You lose bile acids and thus the feedback regulation when you resect the ileum though.
95% of bile acids recycled back to liver via
ASBT
Is 7-alpha hydroxylase more active when ASBT is lost (eg. during ileal resection), or present (healthy ileum)?
ASBT recycles bile acids. Bile acids negatively regulate 7-alpha hydroxylase. Thus, when ASBT is gone, can’t recycle the bile acids, so 7-alpha hydroxylase needs to make more bile acids
Why does ileal resection promote steatorrhea?
Ileal resection –> no recycled bile –> bile synthesis de novo –> doesn’t ever really catch up –> less bile –> fatty stool
What happens when some of the bile acids enter the colon?
Colonic bacteria can work on them and make 2ndary bile acids. 3 types. Both primary and secondary are conjugated bile acids. These conjugated bile acids are called bile salts (more water soluble) and these are not capable of crossing intestinal membrane. the only way they can come back is through ASBT
Can conjugated bile acids, or unconjugated bile acids, be reabsorbed by intestine?
Unconjugated. If conjugated, need ASBT active transport.
Lithocholic acid is sulfated so…
not transported by ASBT so lost in stool. Method for getting rid of toxic versions of 2ndary bile acid.
Who has the highest bile acid synthesis rate?
Ileum resected people (almost 10x as much)
