Normal Pancreas

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Arterial and Venous Supply

As is common in the gastrointestinal tract, numerous anastomoses exist between the intrapancreatic blood vessels. In general the head region of the gland receives its supply from the superior mesenteric artery, whereas the celiac trunk supplies the body and tail of the gland. This is of interest, since this region develops separately from the rest of the pancreas in the embryo. The venous drainage of the pancreas flows into the portal vein from the superior mesenteric and splenic veins. The blood contains high concentrations of the pancreatic hormones, especially insulin and glucagons, which elicit many of their functions directly on the hepato-cytes. Interlobular arteries and veins run in parallel to one another and adjacent to the exocrine ducts. The intralobular arteries run centrally in the lobuli and send tributaries to the exocrine acini, islets and ductules, respectively. However, the latter organization is species dependent [1].


The capillaries derived from the arterioles just mentioned differ markedly between islets and exocrine tissue in that they are wider (approximately 8 to 10 mm versus 4 to 6 mm) in the former. Furthermore, they constitute a much denser network in the islets. The capillary endothelium in the pancreas is fenestrated, but those in the islets possess almost 10 times as many fenestrae as capillaries in the exocrine and ductular compartments [2]. It seems as if vascular endothelial growth factor (VEGF), locally produced within the islets, is responsible for the formation of the fenestrations. Functionally, pancreatic capillaries are very permeable [3], and particularly so those within the islets. Thus, the vascu-lature is unlikely to pose any restrictions to the diffusion of the islet hormones.

The microvasculature of the islets has been described as glomerular-like, since its initial description by Paul Langerhans in 1869. A number of species from various vertebrates have been studied, and species differences exist. A general finding is, however, that all mammals, that is, including humans, have a direct and separate arteriolar flow to the islets. The islet vasculature is otherwise dependent on the size of the islets. Thus, smaller islets are located in the periphery of the lobuli, whereas larger islets (more than 250 mm in diameter) are mainly found at major branches of blood vessels or in association with major ducts. Small islets receive their blood supply from one arteriole and drain through numerous efferent capillaries into a basket-like network around the islets, which subsequently drains into intralobular venules. According to some investigators [4], these efferent capillaries communicate with those around exocrine acini and/or ducts, thereby forming a so called insulo-acinar portal system. Large islets, on the other hand, possess one to three arterioles, and the efferent capillaries drain into postcapillary venules at the edge of the islets, which then empty into intralobular veins. In addition to this, numerous small capillaries and/or venules connect the islets with capillaries in the acini and the ducts. Previously it has been debated to what extent these arrangements are species dependent, and whether all blood in the pancreas passes through the insulo-acinar network. At present this seems unlikely [4].

A summary of microvascular parameters in the endocrine and exocrine pancreas is given in Figure 1.

Lymphatic Capillaries

The exocrine pancreas possesses a network of lymphatic capillaries within the lobules, which drain into larger vessels within interlobular septa, associated with blood vessels and nerves [5]. Their major function is, as expected, to drain interstitial fluid, and they seem to play a minor role in the transportation of exocrine and endocrine secretions. Actually, it is generally agreed upon that the islets of Langerhans do not contain lymphatic capillaries, even though a network in the vicinity of the islet periphery can be seen, especially in rodents.

Blood Perfusion

The blood perfusion of the whole pancreas is in the order of 40 to 100mL/min x 100 g tissue, and it is usually increased in association with increased demands for exocrine secretion. Both metabolic and myogenic mechanisms contribute to the blood flow regulation, and the oxygen uptake remains constant in the flow range of 40 to 100mL/min x 100 g [6]. Administration of secretin and cholecystokinin, for example, increases the blood perfusion,


Flow: 0.4-1.0 ml/min x g Pressure: 6-7 mm Hg pO2:20-25 mm Hg

Figure 1 Summary of microvascular parameters in the endocrine and exocrine pancreas of rodents. (see color insert)

by mechanisms similar to those seen in other salivary glands. That is, nervous signals mediated through parasym-pathetic nerves elicit their effects by using acetylcholine to increase the exocrine secretions and vasoactive intestinal peptide to induce a simultaneous blood flow increase. In contrast, stimulation of adrenergic nerves, or administration of catecholamines, induce an initial vasoconstriction followed by a longer period of vasodilatation (e.g., Ref. [7]). In general, however, the blood flow to the whole gland normally responds to the functional state of the exocrine parenchyma. In addition to nervously mediated signals, this is ascertained by locally produced factors that may either increase (e.g., adenosine and nitric oxide) or decrease (endothelin, angiotensin II) blood flow (see Table I).

The pancreatic islets, on the other hand, have a very complex blood flow regulation, which is totally autonomous from that to the remaining parts of the pancreas [4, 8]. Despite constituting only 1 to 2 percent of the whole pancreas the islets receive from 5-10 percent (mice and rats) to 15 percent (rabbits) of the total pancreatic blood perfusion, representing a single islet blood flow of 10 to 15 nL/minutes. The blood flow is controlled through a series of complex interactions between locally produced factors, nerves and gastrointestinal hormones [8]. A summary of some of the factors affecting the blood perfusion of the total gland as well as the islets is given in Table I. In general there seems to be an association between islet glucose metabolism and blood perfusion, and thereby also a correlation between blood flow and insulin secretion. Thus, in general hyper-glycemia increases islet blood flow, whereas hypoglycemia decreases islet blood perfusion.

Vasculature and Blood Flow during Development

The development of the vasculature in the embryonic pancreas has been studied only to a minor extent. Of interest is the recent observation that signals from the endothe-lium seems to be necessary for induction of endocrine cell development [9]. The vasculature of the islets develop late during gestation and is initially seen as a complex of blood vessels in the vicinity of the developing islets, which then sends tributaries into the clusters of endocrine cells [10]. Furthermore, it seems as if the autonomous blood flow regulation of the islets is initially absent, and matures with time.

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