Hepatic portal system

Many of the phase 1 enzymes are located in hydrophobic membrane environments. In vertebrates, they are particularly associated with the endoplasmic reticulum of the liver, in keeping with their role in detoxication. Lipophilic xenobiotics are moved to the liver after absorption from the gut, notably in the hepatic portal system of mammals. Once absorbed into hepatocytes, they will diffuse, or be transported, to the hydrophobic endoplasmic reticulum. Within the endoplasmic reticulum, enzymes convert them to more polar metabolites, which tend to diffuse out of the membrane and into the cytosol. Either in the membrane, or more extensively in the cytosol, conjugases convert them into water-soluble conjugates that are ready for excretion. Phase 1 enzymes are located mainly in the endoplasmic reticulum, and phase 2 enzymes mainly in the cytosol. 

Bile is produced continuously by the liver bile salts are secreted by the hepatocytes and the water, sodium bicarbonate, and other inorganic salts are added by the cells of the bile ducts within the liver. The bile is then transported by way of the common bile duct to the duodenum. Bile facilitates fat digestion and absorption throughout the length of the small intestine. In the terminal region of the ileum, the final segment of the small intestine, the bile salts are actively reabsorbed into the blood, returned to the liver by way of the hepatic portal system, and resecreted into the bile. This recycling of the bile salts from the small intestine back to the liver is referred to as enterohepatic circulation. 

Most of any exogenous chemical absorbed from the GI tract must pass through the liver via the hepatic-portal system (leading to the so-called first-pass effect) and, as mixing of the venous blood with arterial blood from the liver occurs, considera-... 

Drug molecules that have traversed the physieal and enzymatic barriers of the colonic mucosa may enter the blood-eapillary bed or the lymphatic sinuses. Intact drug that reaches the venous capillaries from the submucosa is transported to the liver via the hepatic-portal system where they may undergo significant metabolism. On the other hand, uptake into the lymphatie sinuses of the colon results in direct delivery into the systemic circulation that causes less metabolic breakdown of the absorbed drug [3]. 

Wilson, R.A., Coulson, P.S. and McHugh, S.M. (1983) A significant part of the concomitant immunity of mice to Schistosoma mansoni is the consequence of a leaky hepatic portal system, not immune killing. Parasite Immunology 5, 595-601. 

Gastrointestinal Tract Absorption. The structure and function of this tract is varied and complex. The structure of the pesticide may be altered within the G.I. tract due to changes in pH in the stomach and intestine, or due to enzymatic action within the gut before it is absorbed into the lacteals and eventually into the hepatic portal system or lymphatic system. 

Nutrients (and drugs) absorbed pass directiy to the liver in the hepatic portal system before going to other parts of the body. 

Other rectal dosage forms may be used other than fat-based suppositories. One study describes a liquid suppository that immediately after administration forms a gel with strong adhesion to the rectal mucosa [14]. The gelling at body temperature is caused by a poloxamer. Adhesion to the rectal mucosa is provided by carbomers and cellulose derivates. Compared to a fatty suppository, this delivery system is expected to spread less far into rectum and colon, thereby avoiding the hepatic portal system (see also Sect. 11.3). 

The small intestine, which comprises the duodenum, the jejunum and the ileum, is the main absorption site and contains a series of finger-like projections, the vilh, which greatly increase the surface area available for absorption of nutrients. Each villus contains an arteriole and venule, together with a drainage tube of the lymphatic system, a lacteal. The venules ultimately drain into the hepatic portal system, and the lacteals into the thoracic lymphatic duct. The luminal side of each villus is covered with projections, the microvilli, which are often referred to as the brush border. 

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