How much percentage of substance does liver take in one pass? The portal vein system is to feed the absorbed nutrition and toxin (defined as "substance" here) to liver first for it to take them up as fast as possible, before they reach other organs which may be harmful. For this to be effective, liver should take as much substance as possible in one pass. For example, if the liver only take up 10% of the substance in one pass, then the portal vein system won't make much difference, since most of the substance will circulate to other organs anyway and get taken up by liver in the following circulation passes. On the other hand, it seems to be very difficult for an organ to take up most substance in one pass since this is not a "effective design" (i.e. over designed). How much percentage of substance does liver take in one pass? And if the percentage is low, why is the portal vein architecture important?

It depends entirely on the substance. Substances that are more hydrophobic or quickly metabolized by the liver are absorbed more completely. I think it's worth considering that it isn't as though all the drug must be absorbed quickly in one place, they are passing through a dense capillary bed with lots of distributed opportunity to take substances up throughout the liver.

< has some examples... 75-85% propranolol is metabolized first-pass, 70% of oral morphine.