Structure and permeability of goblet cell tight junctions in rat small intestine

Summary Two major cell types, goblet and absorptive cells, dominate the epithelial lining of small intestinal villi. We used freezefracture replicas of rat ileal mucosa to examine the possibility that tight junction structure, known to relate to transepithelial resistance, might vary with cell type. Tight junctions between absorptive cells were uniform in structure while those associated with villus goblet cells displayed structural variability. In 23% of villus goblet cell tight junctions the strand count was less than 4 and in 30% the depth was less than 200 nm. In contrast, only 4% of absorptive cell tight junctions had less than 4 strands and only 9% had depth measurements less than 200 nm. Other structural features commonly associated with villus goblet cell tight junctions but less commonly with absorptive cell tight junctions were: deficient strand cross-linking, free-ending abluminal strands, and highly fragmented strands. Bothin vivo ileal segments and everted loops were exposed to ionic lanthanum. Dense lanthanum precipitates in tight junctions and paracellular spaces were restricted to a subpopulation of villus goblet cells and were not found between villus absorptive cells. After exposure of prefixed ileal loops to lanthanum for 1 hour, faint precipitates of lanthanum were found in 14% of tight junctions and paracellular spaces between absorptive cells compared to 42% of tight junctions and paracellular spaces adjacent to villus goblet cells. When tested in Ussing chambers, the methods used for lanthanum exposure did not lower transepithelial resistance. Everted loops exposed to ionic barium and examined by light microscopy showed dense barium precipitates in the junctional zone and region of the paracellular space of villus goblet cells but not in these regions between absorptive cells. However, the macromolecular tracers, microperoxidase, cytochromec and horseradish peroxidase, were excluded from both villus goblet cell and absorptive cell paracellular spaces inin vivo segments. These findings suggest that a subpopulation of villus goblet cells may serve as focal sites of high ionic permeability and contribute to the relatively low resistance to ionic flow which characterizes the small intestinal epithelium.     

The permeability coefficient of the wall of a villous membrane

Summary The equations hitherto used to correct the permeability coefficient for the unstirred layer influence are valid only for flat membranes. Therefore, appropriate equations for membranes with a villous surface (e.g., small intestine) have been derived. They take into account the non-linear concentration gradient in the intervillous part of the unstirred layer. Quantitative information about the geometry of the villous surface and the unstirred layer thickness are needed to calculate the permeability coefficient of the membrane wall (e.g., intestinal epithelium). The concentration of highly permeable substances drops sharply already in the upper part of the intervillous space, so that the tips of the villi function as effective absorbing area. The intervillous concentration gradient of a substance with a low permeability coefficient is so small, that such a substance is absorbed by the total surface area of the villous membrane. The effective absorbing area of substances with intermediate permeability coefficient lies between the described limits.     

Evaluation of two-way protein fluxes across the alveolo-capillary membrane by scintigraphy in rats: effect of lung inflation.

Pulmonary microvascular and alveolar epithelial permeability were evaluated in vivo by scintigraphic imaging during lung distension. A zone of alveolar flooding was made by instilling a solution containing 99mTc-albumin in a bronchus. Alveolar epithelial permeability was estimated from the rate at which this tracer left the lungs. Microvascular permeability was simultaneously estimated measuring the accumulation of (111)In-transferrin in lungs. Four levels of lung distension (corresponding to 15, 20, 25, and 30 cmH2O end-inspiratory airway pressure) were studied during mechanical ventilation. Computed tomography scans showed that the zone of alveolar flooding underwent the same distension as the contralateral lung during inflation with gas. Increasing lung tissue stretch by ventilation at high airway pressure immediately increased microvascular, but also alveolar epithelial, permeability to proteins. The same end-inspiratory pressure threshold (between 20 and 25 cmH2O) was observed for epithelial and endothelial permeability changes, which corresponded to a tidal volume between 13.7 +/- 4.69 and 22.2 +/- 2.12 ml/kg body wt. Whereas protein flux from plasma to alveolar space ((111)In-transferrin lung-to-heart ratio slope) was constant over 120 min, the rate at which 99mTc-albumin left air spaces decreased with time. This pattern can be explained by changes in alveolar permeability with time or by a compartment model including an intermediate interstitial space.     

Weak acid permeability of a villous membrane: Formic acid transport across rat proximal tubule

Chloride/formate exchange, in parallel with Na⁺/H⁺ exchange and nonionic diffusion of H₂CO₂, has been proposed as a mechanism of electroneutral transcellular Cl⁻ reabsorption by the proximal tubule. However, the measured brush border H₂CO₂ permeability of the rat proximal tubule is at least an order of magnitude too low to support sufficient H₂CO₂ recycling. To investigate the possibility that an unstirred layer within the brush border might depress the measured H₂CO₂ permeability, we constructed a mathematical model of a villous membrane. Axial fluxes along villous and intervillous spaces were specified by Nernst-Planck diffusion equations. Model parameters were set to achieve agreement with ion and water fluxes measured in the rat proximal tubule. The equations were solved numerically to generate steady-state concentration profiles in the villous and intervillous spaces. An apparent brush border H₂CO₂ permeability was determined by perturbing luminal [H₂CO₂] and calculating the change in H₂CO₂ flux. Overall, the ratio of apparent brush border H₂CO₂ permeability to cell membrane H₂CO₂ permeability was greater than 90%. Contributing to the small decrease in apparent permeability are finite diffusion coefficients, folding of the membrane, and acidification of the luminal solution. An approximate analysis of this system shows the critical parameters of brush border formate transport to be the actual membrane H₂CO₂ permeability, and the diffusion coefficients of HCO ₃ ⁻ and HCO ₃ ⁻ . Nevertheless, decreasing the diffusion coefficients by one order of magnitude failed to depress apparent brush border H₂CO₂ permeability by more than an additional 25%. We conclude that although permeability is systematically underestimated across a villous membrane, unstirred layer effects in the brush border are still too small to resolve the discrepancy between the measured value of H₂CO₂ permeability and the value needed to allow recycling.     

Effect of aldosterone and insulin on mannitol, Na+ and Cl- fluxes in cultured epithelia of renal origin (A6): evidence for increased permeability in the paracellular pathway

Transepithelial fluxes of mannitol, Na+ and Cl- were measured under open circuit conditions in cultured epithelia derived from toad kidney (A6). Both aldosterone and aldosterone plus insulin produced significant increases in the apparent permeability to mannitol (40 and 83%, respectively). Na+ permeabilities calculated from basolateral to apical Na+ fluxes showed approximately the same percentage increases in response to aldosterone and aldosterone plus insulin. Cl- permeabilities calculated from basolateral to apical Cl- fluxes did not show the same percentage increases. The flux ratios for Cl- were significantly lower than would be predicted for simple electrochemical diffusion in both control and hormone-treated epithelia. In aldosterone-treated epithelia, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) caused Cl- flux ratios to approach predicted values. The unidirectional Cl- fluxes may have significant contributions from both the transcellular and paracellular pathways, with the direction of departure from predicted values being consistent with the presence of Cl- exchange diffusion. In aldosterone plus insulin-treated epithelia, amiloride significantly reduced both the mannitol and Na+ permeabilities. These findings are consistent with aldosterone- and aldosterone plus insulin-induced increases in paracellular pathway permeability which may be secondary to the change in active Na+ transport rather than a primary effect.     

Simultaneous minute by minute determination of unidirectional and net water fluxes in frog urinary bladder. A reexamination of the two barriers in series hypothesis.

Unidirectional and net water fluxes were simultaneously estimated in frog urinary bladder. The minute by minute tritiated water (3HOH) transepithelial flux and the net volume of fluid traversing the tissue were employed. It was observed that: (1) the time course of the increase in the 3HOH flux induced by antidiuretic hormone had a very similar pattern to that reported for the increase in the net movement. (2) Unstirred layers strongly affected the magnitude of the antidiuretic hormone-induced increase in 3HOH fluxes while the time course of the response was almost non-affected. In non-stimulated bladders 3HOH fluxes were poorly modified by medium stirring. New steady-state conditions for 3HOH fluxes were established 1 min after stirring rate modifications. (3) The simultaneously determined net water flux was not affected by a modification in the unstirred layers, indicating that the variations in the measured net water fluxes are a good estimation of the changes in the mucosal border permeability. (4) The presence of an osmotic gradient during hormonal challenge (implying net water fluxes, cell swelling and dilation of the intracellular spaces) did not modify the time course of 3HOH movements. These results suggest that the time course of the increase in water permeability is an intrinsic characteristic of the experimental system that could result from the addition of permeability units that increase in number during the development of the hormonal action.     

Transepithelial organic anion transport by shark choroid plexus

Spiny dogfish shark (Squalus acanthias) lateral and IV choroid plexuses (CPs) are ultrastructurally similar to the corresponding tissues of rat. However, shark IV CP is proportionally larger and easily accessible. Moreover, this epithelial sheet can be halved and studied in Ussing flux chambers. We have used confocal fluorescence microscopy and radiotracer techniques to characterize transepithelial transport of the organic anions (OAs) fluorescein (FL) and 2,4-dichlorophenoxyacetic acid (2,4-D), respectively, by shark CP. Lateral and IV CP accumulated 1 microM FL, with highest levels in the underlying extracellular spaces, intermediate levels in epithelial cells, and lowest levels in the medium. 2,4-D and probenecid inhibited FL accumulation in cells and extracellular spaces, suggesting that these substrates compete for common carriers. Unidirectional absorptive [cerebrospinal fluid (CSF)-to-blood] and secretory (blood-to-CSF) fluxes of 10 microM [(14)C]2,4-D were measured under short-circuited conditions in IV CP mounted in Ussing chambers. 2,4-D underwent net absorption, with an average flux ratio of 7. Probenecid, 2,4,5-trichlorophenoxyacetic acid, and 5-hydroxyindolacetic acid reduced net absorption, reversibly inhibiting unidirectional absorption, with no effect on secretion. Ouabain irreversibly reduced net 2,4-D absorption and cellular and extracellular accumulation of FL, suggesting energetic coupling of OA absorption to Na(+) transport. Collectively, these data indicate that shark CP actively removes OAs from CSF by a process that is specific and active.     

Studies on the Movement of Water through the Isolated Toad Bladder and Its Modification by Vasopressin

Measurements of diffusion permeability and of net transfer of water have been made across the isolated urinary bladder of the toad, Bufo marinus, and the effects thereon of mammalian neurohypophyseal hormone have been examined. In the absence of a transmembrane osmotic gradient, vasopressin increases the unidirectional flux of water from a mean of 340 to a mean of 570 µl per cm² per hour but the net water movement remains essentially zero. In the presence of an osmotic gradient but without hormone net transfer of water remains very small. On addition of hormone large net fluxes of water occur; the magnitude of which is linearly proportional to the osmotic gradient. The action of the hormone on movement of water is not dependent on the presence of sodium or on active transport of sodium. Comparison of the net transport of water and of unidirectional diffusion permeability of the membrane to water indicates that non-diffusional transport must predominate as the means by which net movement occurs in the presence of an osmotic gradient. An action of the hormone on the mucosal surface of the bladder wall is demonstrated. The effects of the hormone on water movement are most simply explained as an action to increase the permeability and porosity of the mucosal surface of the membrane.     

Simultaneous minute by minute determination of unidirectional and net water fluxes in frog urinary bladder A reexamination of the two barriers in series hypothesis

Unidirectional and net water fluxes were simultaneously estimated in frog urinary bladder. The minute by minute tritiated water (³HOH) transepithelial flux and the net volume of fluid traversing the tissue were employed. It was observed that: (1) the time course of the increase in the ³HOH flux induced by antidiuretic hormone had a very similar pattern to that reported for the increase in the net movement. (2) Unstirred layers strongly affected the magnitude of the antidiuretic hormone-induced increase in ³HOH fluxes while the time course of the response was almost non-affected. In non-stimulated bladders ³HOH fluxes were poorly modified by medium stirring. New steadystate conditions for ³HOH fluxes were established 1 min after stirring rate modifications. (3) The simultaneously determined net water flux was not affected by a modification in the unstirred layers, indicating that the variations in the measured net water fluxes are a good estimation of the changes in the mucosal border permeability. (4) The presence of an osmotic gradient during hormonal challenge (implying net water fluxes, cell swelling and dilation of the intracellular spaces) did not modify the time course of ³HOH movements. These results suggest that the time course of the increase in water permeability is an intrinsic characteristic of the experimental system that could result from the addition of permeability units that increase in number during the development of the harmonal action.     

Effects of metabolic inhibition on ion transport by dog bronchial epithelium

Mammalian bronchial epithelium absorbs Na+ under basal conditions, but Cl- secretion can be induced. We studied the effects of several modes of metabolic inhibition on the bioelectric properties and solute permeability of dog bronchial epithelium mounted in Ussing chambers. Net Na+ absorption and short-circuit current were inhibited by approximately 75% by hypoxia or by 10(-3) M NaCN. The reduced net Na+ absorption was characterized by a decrease in absorptive flux and an increase in backflux. The latter change was proportional to an increase in permeability to [14C]mannitol, implying that solute flow through a paracellular shunt was increased. In contrast, the reduction of conductance expected from exposure to amiloride (0.94 +/- 0.15 ms/cm2 or 12%) was abolished by NaCN pretreatment. Metabolic inhibition also decreased epithelial conductance and unidirectional Cl- fluxes by approximately 25%. NaCN rapidly and reversibly inhibited the hyperpolarization of potential difference (PD) induced by low luminal bath [Cl-]. This effect was mimicked by the Cl- channel blocker, 5-nitro-2-(3-phenylpropylamino) benzoic acid. Because the transepithelial Cl- diffusion PD reflects, in part, the depolarization of the Cl- -conductive apical cell membrane, metabolic inhibition appears to affect this path. We conclude that metabolic inhibition not only decreased net ion transport by dog bronchial epithelium but also inhibited cellular Na+- and Cl- -conductive pathways and increased paracellular permeability.     

Effects of atropine and guanethidine on canine intestinal absorption and blood flow

The possibility of tonic autonomic control over intestinal Na and H₂O absorption and whether the cardiovascular system was involved was tested by administration of atropine or guanethidine. ³H₂O and ²²Na in saline perfused through the lumen were used to calculate unidirectional fluxes and total and absorptive site blood flow in canine ileum. Both atropine and guanethidine had qualitatively similar effects on absorption and blood flow with atropine being quantitatively greater. Net Na and H₂O absorption were not increased significantly but their absorptive and secretory unidirectional fluxes were increased significantly. Total blood flow was not affected but absorptive site blood flow was increased and resistance decreased. The absorptive site blood flow was correlated with the absorptive Na fluxes similarly in all groups. The secretory fluxes of Na and H₂O were correlated with estimated capillary pressure when all three groups were considered together. It was concluded that there is tonic cholinergic control over intestinal absorption which is mediated, in part, through cardiovascular effects. The findings were consistent with tonic parasympathetic activity having primarily a direct effect on gut absorption and blood flow but tonic sympathetic activity primarily modulating the direct effects of other regulatory mechanisms.     

Passive and active transport properties of a gill model, the cultured branchial epithelium of the freshwater rainbow trout (Oncorhynchus mykiss)

Branchial epithelia of freshwater rainbow trout were cultured on permeable supports, polyethylene terephthalate membranes ("filter inserts"), starting from dispersed gill epithelial cells in primary culture. Leibowitz L-15 media plus foetal bovine serum and glutamine, with an ionic composition similar to trout extracellular fluid, was used. After 6 days of growth on the filter insert with L-15 present on both apical and basolateral surfaces, the cultured preparations exhibited stable transepithelial resistances (generally 1000-5000 ohms cm2) typical of an electrically tight epithelium. Under these symmetrical conditions, transepithelial potential was zero, and unidirectional fluxes of Na+ and Cl- across the epithelium and permeability to the paracellular marker polyethylene glycol-4000 (PEG) were equal in both directions. Na+ and Cl- fluxes were similar to one another and linearly related to conductance (inversely related to resistance) in a manner indicative of fully conductive passive transport. Upon exposure to apical fresh water, transepithelial resistance increased greatly and a basolateral-negative transepithelial potential developed. At the same time, however, PEG permeability and unidirectional effluxes of Na+ and Cl- increased. Thus, total conductance fell, and ionic fluxes and paracellular permeability per unit conductance all increased greatly, consistent with a scenario whereby transcellular conductance decreases but paracellular permeability increases upon dilution of the apical medium. In apical fresh water, there was a net loss of ions from the basolateral to apical surfaces as effluxes greatly exceeded influxes. However, application of the Ussing flux ratio criterion, in two separate series involving different methods for measuring unidirectional fluxes, revealed active influx of Cl- against the electrochemical gradient but passive movement of Na+. The finding is surprising because the cultured epithelium appears to consist entirely of pavement-type cells.     

Regulation of acid secretion and paracellular permeability by F-actin in the bullfrog, Rana catesbeiana

Many studies have implicated F-actin in the regulation of gastric acid secretion using cytochalasin D (CD) to disrupt apical actin filaments in oxyntic cells. However, it is known that CD also affects mucosal permeability by disrupting tight junction structure. Here we investigated the contribution of F-actin to mucosal permeability and acid secretion in the stomach using CD. Stomachs were mounted in Ussing chambers and acid secretion (stimulated or inhibited), transepithelial resistance (TER), mannitol flux, bicarbonate transport, and dual mannitol/sodium fluxes were determined with or without CD. H(+) back diffusion was predicted from its diffusion coefficient. Incubation with CD resulted in a significant reduction in stimulated acid secretion. TER was unchanged in stimulated tissues but significantly reduced in inhibited tissues. Mannitol flux, bicarbonate transport, and H(+)-back diffusion increased significantly with CD. However, the rates of bicarbonate and H(+) flux were not large enough to account for the inhibition of acid secretion. These findings demonstrate that actin filaments regulate paracellular permeability and play an essential role in the regulation of acid secretion in the stomach.     

Occludin regulates macromolecule flux across the intestinal epithelial tight junction barrier

Defective intestinal epithelial tight junction (TJ) barrier has been shown to be an important pathogenic factor contributing to the development of intestinal inflammation. The expression of occludin is markedly decreased in intestinal permeability disorders, including in Crohn's disease, ulcerative colitis, and celiac disease, suggesting that the decrease in occludin expression may play a role in the increase in intestinal permeability. The purpose of this study was to delineate the involvement of occludin in intestinal epithelial TJ barrier by selective knock down of occludin in in vitro (filter-grown Caco-2 monolayers) and in vivo (recycling perfusion of mouse intestine) intestinal epithelial models. Our results indicated that occludin small-interfering RNA (siRNA) transfection causes an increase in transepithelial flux of various-sized probes, including urea, mannitol, inulin, and dextran, across the Caco-2 monolayers, without affecting the transepithelial resistance. The increase in relative flux rate was progressively greater for larger-sized probes, indicating that occludin depletion has the greatest effect on the flux of large macromolecules. siRNA-induced knock down of occludin in mouse intestine in vivo also caused an increase in intestinal permeability to dextran but did not affect intestinal tissue transepithelial resistance. In conclusion, these results show for the first time that occludin depletion in intestinal epithelial cells in vitro and in vivo leads to a selective or preferential increase in macromolecule flux, suggesting that occludin plays a crucial role in the maintenance of TJ barrier through the large-channel TJ pathway, the pathway responsible for the macromolecule flux.     

The effect of osmotically induced water flows on the permeability and ultrastructure of the rabbit gallbladder

Summary The purpose of these experiments was to determine the effect of osmotic gradients on the permeability of the rabbit gallbladder. Increasing the tonicity of the mucosal solution reduced the permeability of the gallbladder to both ions and nonelectrolytes, whereas there was no significant effect when the serosal solution was made hypertonic. These results cannot be explained by solvent/solute interactions in either the epithelial membranes or the unstirred layers. Associated with the changes in permeability was the appearance of the transport number effect and current induced resistance changes. Morphological studies of the gallbladder under these conditions showed that the extracellular spaces of the epithelium and the rest of the wall dilate in the presence of osmotic flow to the serosa, but that the spaces collapse when the flow is in the opposite direction. Reconstruction of the permeability changes from the dimensions of the tissue show that all the physiological phenomena are accounted for by the changes in morphology, the dominant effect being in the lateral intercellular spaces. These results suggest that the lateral spaces are a common pathway shared by all solutes crossing the epithelium, and that diffusion along these spaces becomes rate limiting as the spaces collapse.     

Mechanisms of glucose absorption at a high carbohydrate level in the rat small intestine in vivo

At low maltose concentations, the rates of maltose hydrolysis and glucose absorption increased with increasing substrate concentration in the infusate. A significant fluid secretion occurred in the isolated intestinal loop perfused with hypertonic maltose solution, but water fluxes were close to zero in case of almost isotonic perfusion solutions. The findings suggest that the active transport remains a main mechanism of glucose absorption at super-high maltose concentration as well. The rates of maltose hydrolysis and released glucose absorption in the isolated intestinal loops perfused with super-high maltose concentration, enhance mainly due to an increase of effective digestive-absorptive surface of the villi and, in part, to substrate diffusion across the intestinal epithelium rather than paracellular solvent drag.     

Comparative immunohistolocalization of carbonic anhydrase isozymes I, II and III in the equine and bovine digestive tract

Summary Immunohistochemical localizations of carbonic anhydrase isozymes (CA-I, CA-II and CA-III) in equine and bovine digestive tracts were studied. In the horse, epithelial cells in both the oesophagus and non-glandular part of the stomach lacked all three isozymes. In contrast, surface epithelial and parietal cells in the glandular region of the stomach showed reactivity for CA-II. In the small intestine, absorptive columnar cells covering the villi in the duodenum were positive for CA-II. The epithelium of the jejunum and ileum lacked all three isozymes. In the large intestine, CA-II was detected in the columnar cells in the upper part of the crypt. In cattle, epithelial cells of the oesophagus showed reactions for CA-I and CA-III but not for CA-II. Although the absorptive epithelial cells of the small intestine lacked CA-I, CA-II and CA-III, those of the upper part of large intestine crypts were heavily stained for all three isozymes.     

Stereological studies on the small intestinal epithelium of the rat

Summary Quantitative macroscopic, light-microscopic and electron-microscopic studies were performed on the small intestine of fasted and non-fasted adult, male Sprague-Dawley rats. In non-fasted rats the small intestine was longer than in fasted rats. Due to the presence of villi the surface area in the duodenum and the jejunum was enlarged about six times. The microvilli on the villous crests caused a surface enlargement by 13 times in the duodenum (value corrected for overestimation due to section thickness), and 19 times in the jejunum of the fasted rats. At the base of the villi these values were about 50% lower. It was calculated that, in the fasted rats, the total enlargement of the luminal surface area — due to villi and microvilli — was 63 times in the duodenum and 81 times in the jejunum (corrected for section thickness).Differences between the villous crest epithelium and the villous base epithelium were also found with regard to the mean cell height, and the volume densities of the absorptive cell nuclei, the mitochondria, and the paracellular channels.Supported by grants from the Swedish Medical Research Council (Project No. 12X-2298), from the Swedish Group-Insurance Co. Förenade Liv, from Tore Nilson's Fund for Medical Research and from the Medical Faculty, University of Umeå     

Sodium-dependent lysine flux across bullfrog alveolar epithelium

Amino acid transport across the alveolar epithelial barrier was studied by measuring radiolabeled lysine fluxes across bullfrog lungs in an Ussing chamber. In the absence of a transmural electrical gradient, L-[14C]lysine was instilled into the upstream reservoir and the rate of appearance of the radiolabel in the downstream reservoir was determined. Two lungs from the same animal were used simultaneously to determine tracer fluxes both into and out of the alveolar bath. Results showed that the radiolabel flux measured in the alveolar to the pleural direction was greater than that measured in the opposite direction in the presence of sodium in the bathing fluids. The net flux of L-[14C]lysine was saturable with [Na+], with an apparent transport coefficient (Kt) of 28 mM for Na+. Hill analysis of [14C]lysine flux vs. [Na+] indicated a coupling ratio of 1:1 between sodium and radiolabeled L-lysine. Total L-lysine flux as a function of [L-lysine] was also saturable, with Kt of 7.3 mM for L-lysine. Ouabain significantly decreased absorptive (alveolar-to-pleural) radiolabel flux, while slightly increasing the flux observed in the opposite direction. L-leucine completely inhibited absorptive net flux of L-[14C]lysine. alpha-Methylaminoisobutyric acid (MeAIB), on the other hand, only slightly reduced net flux of L-[14C]lysine from the control value. The presence of a net absorptive, Na+-dependent amino acid flux across the alveolar epithelial barrier indicates that the tissue is capable of removing amino acids and sodium from the alveolar fluid by a coupled cotransport mechanism, which may be important for both protein metabolism and fluid balance by alveolar epithelium.     

Studies on the histogenesis of the tunica mucosa of the small and large intestines of the camel (Camelus dromedarius). I. Histogenesis of the small intestinal mucosa

The histogenesis of the small intestinal mucosa passes through a previllous stage, comprising development until the formation of villi (at a C RL of about 15 cm), and a villous stage, comprising the further development. In the previllous stage, the mucosa consists of a Lamina epithelialis made up of undifferentiated cells with stratified nuclei and a Lamina propria/submucosa made up of homogeneous mesenchyme. The villi appear as luminal epithelial outgrowths associated with vascularized mesenchymal stalks and their growth advances in a cranio-caudal direction. The intestinal glands were firstly observed at the 26 cm-stage as downgrowths of the intervillous epithelium into the underlying mesenchyme.