human anatomy - Circulation through the liver in light of drug metabolism

I have a lingering question which stems from an answer that I gave to What hydrolyses aspirin within the digestive tract and blood stream?

When a drug or any other substance is absorbed into the bloodstream in the stomach or small intestine, it ultimately passes through the hepatic portal vein and into the liver sinusoids, where it is processed by hepatocytes and introduced into the general circulation via the vena cava. In terms of metabolism, this is what causes a "first-pass" effect for drugs that are ingested.

For drugs that are delivered either by intravenous, intramuscular, or sub-lingually (as in the other Biology.SE question), this first-pass effect is avoided, and the drug is introduced into the general circulation without being metabolized by the liver first.

Even though the first pass is avoided, the blood in the body still makes its way back through the liver eventually via the hepatic artery, which is a branch off of the celiac artery.

The issue I still have is, does the incoming blood from the hepatic artery merge with the blood from the hepatic portal vein? If not, does the blood from the hepatic artery still interact with the hepatocytes in some way? (it makes sense that it does, and I have also read that one of the main functions of the hepatic artery was to deliver blood supply for the liver's metabolic needs) If this is not the case, where in the body would these drugs that were introduced via IV, etc., be metabolized?

Answer

Yes, the blood from the hepatic artery (proper) and the portal vein mix in the sinusoids of the liver. The hepatic vein supplies about 75% of the blood to the liver, and the hepatic artery the remaining 25%. Because the portal vein provides such a large part of the blood supply to the liver, then any disease that causes the blood to build up can cause portal hypertension.

The hepatic artery carries oxygen-rich blood from the heart. The portal vein is part of the portal system and connects the capillary beds of the gastrointestinal tract to those of the liver. Because of the larger volume through the portal vein, I think that each vessel carries about half the oxygen supply to the liver.

For drugs introduced through an injection, for example, metabolism occurs throughout the circulatory system and in the liver. Remember that it's all the same blood supply, but the first-pass effect just refers to the blood that goes to the liver before entering the systemic circulation (by which it can travel to its target).