The gastrointestinal circulation is the largest systemic regional vasculature and nearly one third of the cardiac output flows through the gastrointestinal viscera, with 10% (500 ml min-1) supplying the small intestine. Each anatomical region (salivary glands, pharynx, oesophagus, stomach, liver and intestine) possesses separate blood vessels. The blood vessels of the jejunum and ileum are derived from the superior mesenteric artery. Arterioles branch off and supply the muscular coat and form plexuses in the submucosal layer. From each plexus, tiny vessels direct blood to the villi and the glands in the mucosa.
The distribution of the blood flow varies according to the metabolic demands of the cells within each region. The highly metabolic villi receive 60% of the blood flow to the mucous layer, while the muscle layer with it's lower demand for oxygen receives only 20% of the blood flow. During periods of enhanced absorption or electrolyte secretion, the blood flow is preferentially distributed to the mucosa, whilst increased intestinal motility causes diversion of the blood flow to the muscle layers. After a meal, blood flow increases by 30 to 130% of basal flow and the hyperaemia is confined to the segment of the intestine exposed to the chyme. Long chain fatty acids and glucose are the major stimuli for hyperaemia, which is probably mediated by hormones such as cholecystokinin released from mucosal endocrine cells2.
The blood from the small intestine flows into the large hepatic portal vein which takes the blood directly to the liver. The liver has the highest drug metabolising capacity in the body and, in a single pass, can remove a large proportion of the absorbed drug before it reaches the systemic circulation. This process, termed first-pass metabolism, may have a significant effect on drug bioavailability when formulations are given by the oral route. The blood supply from the buccal cavity and the anal sphincter do not drain to the portal vein, and a greater proportion of a drug with a high hepatic extraction may be absorbed from these regions.
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