The portal venous system is responsible for directing blood from parts of the gastrointestinal tract to the liver.

[2][3] The benefit of first-pass metabolism, whereby substances absorbed from food in the gut pass through the liver before entering the systemic circulation, is to use the liver as a shield (a first line of defense) between (a) the food, its toxins (whatever they may be), and its metabolic intermediates/metabolites (such as ammonia) and (b) the rest of the body's tissues, including the brain.

Blood passes from branches of the portal vein through cavities between "plates" of hepatocytes called sinusoids.

Blood also flows from branches of the hepatic artery and mixes in the sinusoids to supply the hepatocytes with oxygen.

[4] Color Doppler Ultrasound is the most useful imaging tool used to identify aneurysms, thrombosis, and branching patterns of the portal venous system, and to determine if treatment or surgery will be necessary.

For example, nitroglycerin cannot be swallowed because the liver would deactivate the medication, but it can be taken under the tongue or transdermally (through the skin) and thus is absorbed in a way that bypasses the portal venous system.

Inversely, dextromethorphan, a cough suppressor, is best taken orally because it needs to be metabolised by the liver into dextrorphan in order to be effective.