Search

We have demonstrated previously that ethanol causes alterations in jejunal morphology and fluid secretion, and that these changes are accompanied by an increase in mucosal arteriolar blood flow, shunting of blood through noncapillary microvessels, hyperemia, hemoconcentration, and an enhanced loss of plasma protein into the gut lumen. All the microcirculatory changes are compatible with an ethanol-induced mucosal microvascular stasis. The present study was undertaken to examine whether these changes are accompanied by an enhanced mucosal microvascular permeability. Using a colloidal carbon vascular labeling technique, we demonstrated that 6% wt/vol intraluminal ethanol caused marked accumulation of carbon particles in the walls of the capillaries and microvenules of the villus tips. The effect of 3% ethanol was much less pronounced, and the extent of carbon entrapment did not significantly differ from microvessels in villi perfused with Krebs-Ringer solution without ethanol. Electron microscopy indicated that the carbon was localized between the endothelial cell and the basal lamina of the microvessels. Because the carbon accumulation was always localized at the vicinity of endothelial cell junctions, the escape of carbon particles from the lumen probably occurred through these cell junctions. This could have been the result of a transient retraction of endothelial cells. Electron microscopic examination also demonstrated that the lumina of some capillaries and venules of the villus tip of jejunal segments perfused with 6% ethanol were clogged with carbon particles. This latter finding indicates that there was stasis in these vessels at the time of carbon injection. Similar intraluminal carbon accumulation was never seen in control jejunum or jejunum perfused with 3% ethanol. Thus the results of this study indicate that 6% (wt/vol) ethanol causes microvascular injury and stasis. The findings with 6% ethanol are reminiscent of those described by others in the early phases of acute inflammation, and thus it is possible that the microvascular changes caused by ethanol may be related to the liberation of some of the chemical mediators of the immediate response to acute injury.

The basal blood flow of the proximal and distal body of the esophagus, and that of the lower esophageal sphincter, and the vascular response of these sites to intravenous infusion of nifedipine (1.0 microgram/kg.min) and isoproterenol (0.1 microgram/kg.min) were studied. The basal blood flow of the mucosa plus submucosa, muscularis propria, and the whole wall was significantly higher in the lower esophageal sphincter than in the proximal or the distal body. Intravenous nifedipine caused a similar decrease in vascular tone of the mucosa and the muscularis propria in all sites of the esophagus. Isoproterenol infusion significantly decreased the vascular tone of the mucosa with columnar epithelium (i.e., mucosa overlying the lower esophageal sphincter), but not of the mucosa with squamous epithelium (i.e., mucosa overlying the body). In the muscularis propria the vasodilatory effect of isoproterenol and nifedipine was significant at all sites, but this effect was greater in the striated muscle of the body than in the smooth muscle of the lower esophageal sphincter (p less than 0.05). Thus, not only do different vasodilators have different effects on the vasculature of the esophagus, but also a single agent may have differing effects on the various sites and layers of this organ.

The effects of intraluminal ethanol perfusion (3.0% and 6.0% vt/vol) on mucosal morphology, water transport, and regional blood flow were examined in in vivo jejunal segments of pentobarbital-anesthetized rabbits. Compared with control segments, ethanol-perfused segments exhibited morphological alterations of the mucosa consisting of subepithelial fluid accumulation (bleb formation), exfoliation of enterocytes, and vascular congestion. The prevalence of epithelial damage was significantly increased in the segments perfused with 6% ethanol. Net water transport was significant (p less than 0.025) depressed in segments perfused with 3.0% and 6.0% wt/vol ethanol. In animals in which the control segment was absorbing water, ethanol led to a depression in net water absorption or to the reversal of absorption to net secretion. In animals in which the control segment exhibited secretion, ethanol led to an enhanced net secretion. Blood flow through the total jejunal wall and through the luminal layer (consisting of mucosa plus submucosa) was significantly (p less than 0.05) increased by the presence of 3.0% and 6.0% wt/vol ethanol in the intestinal lumen. Blood flow in the external layer of the jejunum (consisting of muscularis plus serosa) did not change significantly. It therefore appears that the ethanol-induced alterations in jejunal mucosal morphology and water transport are accompanied by a localized mucosal or submucosal hyperemia, or both. However, a direct cause and effect relationship between these remains to be established.

Experiments were performed to investigate whether the fluid transported across the small intestine is isoosmotic with the mucosal solution when the active transport of glucose is partially inhibited. Everted hamster mid small intestine was incubated in one of the following four mucosal solutions: (1) Isotonic control, Krebs-Ringer bicarbonate solution containing 10 mM glucose (KRBSG), (2) Isotonic with phlorizin, KRBSG + 5X10-5 M phlorizin, (3) Hypertonic control, KRBSG + 50 mM mannitol, (4) Hypertonic with phlorizin, KRBSG + 50 MM mannitol + 5x10-5 M phlorizin. The serosal surface of the intestine was not bathed. Results indicate that the transported fluid was always isoosmotic with any of the mucosal solutions used. When the mucosal solution was made hypertonic with mannitol, the concentration of glucose and electrolytes in the absorbate increased, and as a result, the absorbate became hypertonic and isoosmotic with the mucosal solution. The presence of phlorizin either in the isotonic or in the hypertonic mucosal solution decreased the glucose concentration of the absorbate, but the transported fluid became isoosmotic with the mucosal solution due to a higher concentration of Na, K, and their associated anions. Phlorizin caused a decrease in the transmural potential difference. In spite of this, the presence of this glucoside in the mucosal solution increased the transport of sodium in relation to glucose transport. It is suggested that, at the concentrations used, phlorizin inhibits sodium movement through the electrogenic pathway, but increases the transport of this ion through the non-electrogenic route. This increase in neutral sodium transport seems to compensate for the low concentration of glucose in the absorbate, so that the absorbate becomes isoosmotic with the mucosal solution whether the latter is isotonic or hypertonic. It is suggested further that isoosmotic transport of fluid is an inherent property of the small intestine and that there may be an osmoregulatory mechanism in the gut which controls this process.

The objective of this study was to investigate the mechanism by which ethanol inhibits intestinal absorption of sugars. In vitro experiments on hamster jejunum have shown that the presence of ethanol in the mucosal solution caused an inhibition of the net transport of water and glucose. There was also a decrease in the intracellular water content and an increase in the intracellular sodium and potassium concentration of the gut tissue. In contrast, the intracellular glucose concentration decreased in the presence of ethanol. These ethanol-induced changes were directly related to the ethanol concentration of the mucosal solution. In the presence of 450 mM (2%) ethanol in the mucosal solution, there was also a significant inhibition of transmural potential difference, estimated glucose metabolism, and both unidirectional fluxes of sodium. The net flux of sodium to the serosal side however did not decrease significantly. These effects of ethanol cannot be fully explained by its osmotic action, and it is suggested that the ethanol-induced reduction in glucose transport could be mainly the result of an interference with the carrier-mediated coupled entrance of glucose and sodium across the brush border. A depression of cellular metabolism could also have played a role in this process.

The purpose of the present study was to investigate the relationship of the gastroesophageal pressure gradient (GEPG) to lower esophageal sphincter pressure (LESP) in normal and in severely obese subjects. Eight lean volunteers with no clinical evidence of gastroesophageal reflux and eight asymptomatic severely obese patients (at least 80% over their ideal weight) underwent esophageal manometric studies with measurements of the LESP and GEPG in both inspiration and expiration. The LESP/GEPG ratio was also calculated in both inspiration and expiration. Acid sensitivity was assessed by means of infusion of 0.1 N HCl subsequent to the baseline motility study. There was no significant difference between the LESP in obese patients (O.P.) and normal subjects (N.Sb.) in either inspiration (mean +/- SEM in mm Hg: N.Sb. = 16.4 +/- 1.6, O.P. = 18.7 +/- 2.5), or expiration (N.Sb. = 16.6 +/- 1.5, O.P. = 20.6 +/- 2.6). However, the GEPG in both inspiration (N.Sb. = 13.3 +/- 1.6, O.P. = 23.1 +/- 2.0; p less than 0.001) and in expiration (N.Sb. = 2.1 +/- 0.5, O.P. = 8.1 +/- 1.1; p less than 0.001) was significantly higher in obese patients than in controls. As a result, the GEPG/LESP ratios were also higher (expiration N.Sb. = 0.15 +/- 0.03, O.P. = 0.46 +/- 0.10; p less than 0.01) in obese patients; and for inspiration (N.Sb. = 0.86 +/- 0.13, O.P. = 1.33 +/- 0.12; p less than 0.01) in the obese patients the ratio was greater than 1. None of the normal subjects exhibited acid sensitivity, but 6 of the 7 obese patients tested developed heartburn during acid infusion. In conclusion, the GEPG/LESP ratio in inspiration was greater than unity for obese patients inspite of normal LESP. Such a change in the ratio could facilitate reflux in obese patients.

Experiments were done for indentification and localization of certain structural changes at different levels of jejunal villus of the hamster during positive and negative water transport across the intestine in vivo and in vitro. Positive transport occurred when the mucosal surface of the intestine was bathed (in vitro experiments) or perfused (in vivo experiments) with isotonic Krebs-Ringer bicarbonate solution containing 10 mM glucose, and negative water transport was achieved by rendering this solution hypertonic with 150 mM mannitol. Results indicate that during positive net water transport the intestine in vivo transported more fluid and exhibited a more conspicuous dilatation of the lateral intercellular spaces (L.I.S.) than did the in vitro preparation. Dilatation of the L.I.S. in both preparations was present only in the apical part of the villus, suggesting that this is the principal site of water absorption. When the mucosal solution was made hypertonic with mannitol, the L.I.S. in the in vivo intestine totally collapsed, whereas in the in vitro intestine these spaces remained open very slightly. These morphological changes correspond well with our finding that in the presence of the hypertonic mucosal solution there was a greater net negative water transport in vivo than in vitro. Incubation of the intestine in the isotonic mucosal solution produced subnuclear swelling of the mid-villus epithelial cells, and this morphological change was associated with an increase in the water content of the tissue. Perfusion of the in vivo intestine with the isotonic solution produced neither the swellings nor the increase in water content of the tissue. In the presence of hypertonic mucosal solution there was a water loss from the tissue both in vivo and in vitro, and these swellings were not observed. These results are discussed in relation to intestinal sugar transport and to the maturity of the epithelial cells, and it is concluded that transport studies on in vitro preparations may provide valid information on a qualitative basis, if not on a strictly quantitative basis.

On the basis of previous studies in our laboratory, we have proposed that ethanol-induced alterations in the mucosal microcirculation, particularly vascular stasis, may be responsible for the genesis of the mucosal morphologic lesions and enhanced fluid secretion observed during acute perfusion of the jejunum with ethanol. In an attempt to substantiate this in the present study, we examined (a) the effects of acute intraluminal alcohol perfusion (3.0% and 6.0% wt/vol) on canine mucosal arteriolar blood flow, mucosal red blood cell volume, and mucosal "plasma volume" (as reflected by total mucosal albumin volume), and (b) whether ethanol induces an enhanced secretory filtration of plasma from the jejunal mucosal microvasculature into the gut lumen. These studies indicate that intraluminal perfusion of the jejunum with 6% ethanol leads to a significant (p less than 0.05) increase in both mucosal arteriolar blood flow and red blood cell volume. Despite these changes, mucosal "plasma volume" (total albumin volume) remained unaltered, indicating that hemoconcentration had occurred in the mucosa of the ethanol-perfused segments. These events could result in congestion or stasis within the blood vessels of the mucosa. Perfusion with 6% ethanol also caused a significant increase (p less than 0.05) in the loss of plasma proteins from the mucosal microvasculature into the gut lumen. These results are consistent with our previous proposal that ethanol leads to mucosal microvascular stasis and plasma transudation and that these conditions may in turn lead to the mucosal morphologic lesions and altered fluid transport induced by ethanol.

Fifteen cases of intractable chronic esophagitis due to gastroesophageal reflux were treated with a continuous intraesophageal antacid drip. A proprietary antacid preparation, Gelusil or monalium hydrate (Riopan), in a concentration of one part of antacid to nine parts of water, was infused into the mid-esophagus through a polyethylene tube with an internal diameter which admits a No. 18 blunted needle. Patients are not confined to bed while the drip is in progress. If the flow is constant and the end of the tube is below the cricopharyngeal sphincter, patients do not experience discomfort even if the drip is administered continuously for several days.Results indicate that remission of symptoms can be achieved in almost every patient, even those who have previously failed to respond to oral antacid therapy.

One of the characteristic motor abnormalities in achalasia of the esophagus is the lack of relaxation of the lower esophageal sphincter during swallowing. In a subject with a clinical history and radiologic evidence of early achalasia all the typical motor abnormalities of the disease were observed in the course of pressure studies, but the sphincter exhibited a fall of pressure in response to a contraction of the body of the esophagus. This relaxation occurred later than would be expected in the normal esophagus and, therefore, this unusual condition was named dyschalasia.The relationship of dyschalasia to classical achalasia is discussed and several theories are advanced. The authors believe that dyschalasia is possibly an early stage of achalasia.