Source of net water and electrolyte loss following intestinal ischaemia

Abstract

Ischaemia of the dog intestine lasting 1 h causes desquamation of the epithelium at the villus tips and congestion in the villus capillaries. The crypt cells are relatively undamaged. These changes are associated with a loss of active transport of organic solutes, determined in vitro, a reduction in mucosal sucrase activity and an abolition of glucose absorption in vivo. A profuse net loss of water and electrolytes into the lumen in vivo develops. The net sodium loss is due primarily to an inhibition of the lumen-blood flux of this ion, the blood-lumen flux being relatively unchanged. In uraemic dogs, the loss of urea into the lumen is the same in control and ischaemic loops, testifying to the lack of change in the unidirectional water flow from blood to lumen. Perfusion of the dog intestine with 1% Triton X-100 leads to morphological changes that have certain similarities with those provoked by ischaemia. Damage was restricted to the villus tips, protection from further alterations apparently being provided by a mucus layer that forms on the mucosal surface; the crypt region remained unchanged. After 10 min exposure, organic solute transport in vitro and glucose absorption in vivo were both reduced by not abolished; sodium and water absorption in vivo were suppressed, but no net secretion occurred. To account for these observations, we have suggested that the normal crypt cell is a secretory element with respect to sodium and water. During maturation, its absorptive properties develop such that the mature enterocyte, possessing both absorptive and secretory mechanisms, is capable of net absorption of sodium. After destruction of the villus tips, net secretion continues in the crypts; if there are insufficient villus cells remaining to ensure reabsorption, a net secretory capacity is observed.

Activation of Cl secretion during chemical hypoxia by endogenous release of adenosine in intestinal epithelial monolayers.

“…Flasks were passaged weekly, and monolayers for experiments were fed every 2-3 d. Over 400 monolayers (7-14 days postplating) composed of cells from passages 59 through 90 were used for these experiments. Monolayers were bathed in a Hepes-phosphate buffered Ringer's solution (HPBR) containing 135 mM NaCl, 5 mM KC1, 3.33 mM NaH2PO4, 0.83 mM Na2HPO4, 1 mM CaCl2, 1 mM MgCl2, and 5 mM Hepes, pH 7.4 (Fig. 3).…”

“…Curiously, despite the sudden deprivation of oxygen and nutrients, secretion from the intestinal crypts persists and may, in fact, be stimulated (1)(2)(3)(4)(5)(6)(7). Net intestinal absorption is replaced by secretion, resulting in significant intraluminal fluid sequestration and occasionally diarrhea as an initial manifestation (8).…”

“…The basis for the differential sensitivity of intestinal transport functions to ischemia is not immediately apparent, and the mechanism for the activation of secretion in the face of a mucosal energy deficit remains a matter of speculation. In animal models, the appearance of net secretion precedes the development of histologic evidence of intestinal infarction or gross increases in intestinal permeability and is associated with submucosal vascular stasis (1)(2)(3)5). Thus, one cannot explain the massive fluid losses solely by increased filtration of plasma through damaged mucosa (5).…”

Functional Alterations in the Dog Colon Mucosa following Temporary Ischaemia

“…As in the small intestine ------------------------------------------------------ [12,19], the net absorption of water and elec trolytes across the normal mucosa is trans formed after this trauma into net loss across the ischaemic bowel. However, detailed ex amination of the functional characteristics of the two canine intestines gives rise to inter esting questions concerning the source of this fluid.…”

“…Net absorption can be transformed into net secretion by inhibition of the absorptive flux or stimulation of the secretory one [5], There is much circumstan tial evidence in favour of the idea that the mature cells on the villus tips are absorptive elements, whereas the crypt cells are the site of net secretion [6. 19], We have argued in an earlier study [19] that following brief, tempo rary ischaemia the absorptive cells on the vil lus tips are damaged and therefore no longer capable of active absorption, whereas the crypt cells are unaffected and continue to secrete water and electrolytes, the overall re sult being net loss into the perfusate.…”