SUMMARY The permeability ofthe human small intestine has been studied by measuring the clearance from the plasma into the intestinal lumen of substances with molecular weights ranging from 60 to 80 000. A direct relationship has been demonstrated between intestinal loss and plasma concentration and an inverse one between clearance and molecular size.The permeability of the rabbit small intestine has been studied at various levels by measuring the blood-to-lumen clearance of substances of different molecular size ranging from 60 to 40 000. It has been demonstrated that there is a progressive fall in permeability from the duodenum to the terminal ileum for all the substances studied. Part I Small intestinal permeability in manAlthough the prime function of the small intestine is that of absorption and the transfer of substances from the lumen into the body, a continuous flow in the reverse direction is also known to occur. These substances are derived from the plasma by direct permeation through the mucosa, but also pass out into the lumen in secretions from the gallbladder, pancreas, Paneth and goblet cells, or through desquamation of intestinal epithelial cells.In previous experiments with rabbits (Loehry, Axon, Hilton, Hider, and Creamer, 1970) it has been demonstrated that the transfer of substances passing directly from the blood into the lumen is dependent directly upon their concentration in the plasma and inversely upon their molecular size. The aim of the present experiments was to study the blood-to-lumen flow of substances with different molecular size in man. MethodsTwo methods of study were used.
SUMMARY Various substances containing iron were injected into the lumen of the small intestine in rabbits and into the mesenteric arterial supply. Sections of the mucosa were stained for ferric ions by immersing for 30 minutes into equal parts of 2% HCI and 2% potassium ferrocyanide (Prussian Blue reaction). The ferric ion is bound to various cell structures and its passage through the mucosa could therefore be demonstrated. Iron appeared to pass from the blood into epithelial cells, especially near the tips of the villi, and also between cells as far as the junctional membrane. Studies using 59Fe demonstrated the rapidity of transfer of iron from the blood into the intestinal lumen. After a period of ischaemia epithelial cells in other situations also appeared permeable to iron. The implications of the loss of substances from the blood into the lumen by these routes is discussed.There is a continuous passage of substances from the blood out into the intestinal lumen. It has been demonstrated that mucosal permeation rate both in animals and man depends directly upon the plasma concentration of any substance and inversely upon its molecular size (Loehry, Axon, Hilton, Hider, and Creamer, 1970;Loehry, 1973). How these macromolecular substances actually permeate the intestinal mucosa is not fully understood; theoretically it is possible that they pass through epithelial cells, between them, or through gaps left by extruded cells at the tips of the villi. In order to study this further we injected substances into the arterial supply to the small intestine that could be directly visualized in the mucosa. In the present experiments we have used solutions containing iron as the ferric molecule becomes rapidly fixed to various mucosal and connective tissue constituents and is therefore not removed during fixing and staining procedures. MethodsThe experiments were performed on albino rabbits weighing between 2.5 and 3.5 kg under nembutal anaesthesia. The abdomen was opened by a midline incision and loops of small intestine were gently drawn out. Two-inch segments of intestine were clamped off and 0.25 ml of various iron preparations Received for publication 12 June 1973. injected directly into the mesenteric arterial supply to the segment. A biopsy was taken from the segmmnt at a predetermined time interval and the tissue fixed in 10% formalin. No more than four segments were used in each animal and a control was always taken at the end of the experiments from a portion of bowel not used to ensure that there had not been any significant staining from iron that had leaked into the general circulation. In the experiments where the experimental segment was left for more than one minute after injection, the bulldog clamps isolating the segment were removed to prevent ischaemia. The mucosal biopsies were stained with 2% HCl and 2% potassium ferrocyanide for 30 minutes (Perls' Prussian blue reaction) and equal parts of 20 % potassium ferricyanide and 1 % hydrochloric acid for 15 minutes (Turnbull's stain). Experiments were ...
SUMMARY This autoradiographic study demonstrates the distribution of a range of small solutes and macromolecules in the mucosa of the guinea-pig small intestine after intracardiac injection. The substances investigated were: 14C-urea, 3H-mannose, and 125I polyvinylpyrrolidone (PVP). Small bowel biopsies were taken at intervals from one to 60 minutes after injection and the tissues processed for autoradiography. Light microscopic examination of the autoradiographs showed that the compartmental distribution depended on the molecular size of the substances being studied. Urea and mannose, as small solutes, were uniformly distributed throughout the intravascular, extravascular, and epithelial compartments. Inulin was evenly distributed in the vessel lumen and extravascular space but there was a considerable drop in concentration in the epithelium. PVP exhibited the most marked gradients, the concentration being greatest in the vascular lumina, lower in the extravascular space, least in the epithelium. Thus there appear to be two barriers to macromolecular passage which are freely permeable to small solutes: the capillary wall and the epithelium. At a light microscopical level it is not possible to observe whether the limiting membrane of each of these barriers is the cell plasmalemmal membrane or the basement membrane. The selectivity of the epithelial barrier is greater than that of the capillary barrier.It is widely appreciated that the small intestine represents a semi-permeable barrier between the vascular lumen and the external environment of the intestinal lumen. This is a complex multiple barrier whose anatomical components comprise the vascular endothelium, the vascular basement membrane, the epithelial basement membrane, and the epitlelium of the intestinal mucosa. The small intestine is a relatively impermeable barrier to the solutes whose molecular weight is greater than 180 (Fordtran et al., 1965), but it is well recognised that substances greatly in excess of this size may permeate the mucosa in minor degrees. Plasma proteins up to the size of IgM immunoglobulins certainly pass from the circulation into the intestinal lumen (Barth et al., 1964;Jarnum and Jensen, 1972) and substances as large as ferritin (Bockman and Winborn, 1966) and IgG (Kraehenbuhl and Campiche, 1969) are absorbed from the small intestine by passive sorption. Loehry
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