Cell turnover in the rat small intestinal mucosa: an appraisal of cell loss.

Abstract

Part I Cell loss in rats with a normal mucosaThe concept of continuous epithelial renewal in the gastrointestinal tract was introduced at the end of the nineteenth century (Patzelt, 1882;Bizzozero, 1888;Schaffer, 1891), and since then labelling experiments with tritium-labelled thymidine have established that epithelial cells are produced in the crypts of the small intestinal mucosa, migrate up onto the villi and are lost at the tips, both in experimental animals (Leblond and Messier, 1958;Quastler and Sherman, 1959;Creamer, Shorter, and Bamforth, 1961) and in man (Shorter, Moertel, Titus, and Reitemeier, 1964;MacDonald, Trier, and Everett, 1964). It has been previously considered that epithelial cells migrate up from the mouth of the crypts directly onto villi on all sides, and it has therefore been assumed that there is an orderly one-to-one relationship of crypts to villi, with one crypt orifice between adjacent villi. In another communication (Loehry and Creamer, 1968) we have established that the crypt-villus relationship in the small intestinal mucosa is more complex than has been assumed, that overall there are many more crypts than villi, that very few of the crypts open out onto villi on all sides, and that, in most cases, much of each crypt opening is adjacent not to villi but to other crypts. The migration therefore of epithelial cells from crypts to villi cannot be a simple direct progression as might be expected from two-dimensional sections. Two possibilities exist: those cells emerging at sites where two crypts are adjacent must either be desquamated here at the crypt mouth or else be channelled round in some way onto villi. Because of this complex crypt-villus relationship it was thought necessary to undertake a reappraisal of cell migration, and, in order to establish whether cells were desquamated at the crypt mouth or channelled onto villi, to study the problem by a consideration of cell loss. METHODS AND TECHNIQUESDesquamated epithelial cells were collected from male 13 albino rats by total small intestinal perfusion. The animals were anaesthetized with intraperitoneal nembutal and the abdomen was opened by a midline incision. A length of 1 mm diameter PVC tubing was passed through the mouth into the rat's stomach, and guided through the pylorus into the fourth part of the duodenum where it was tied by a silk ligature. Another piece of PVC tubing, 4 mm in diameter, was passed through a small incision in the caecum and tied in place in the distal ileum. This cannula passed directly into a collecting bottle. It was found that this method of cannulating the small intestine prevented any significant bleeding into the lumen, and when the tubes were in position the small bowel could be perfused without contamination from the stomach, gallbladder, or pancreas. The small intestine with the cannulae was returned to the peritoneal cavity and normal saline infused via a constant flow pump at a temperature of 37°C. Perfusions were performed at a rate of 250 ml per hour after an initial washout, and hourl...

Changes in Desquamation Rate of Jejunal Epithelium in Cats during Fasting

“…These findings are similar to the observations that the upper small intestines of humans and of rats are relatively free of microorganisms [13,19].…”

“…This method requires relatively long periods of time and specialized knowl edge of histological techniques. In the past few years, Croft et al [5,6], Da Costa et al [7], Lof.hry et al [19], and G oldsmith [9], have introduced a new method for measuring rate of cell loss. In this procedure, the amount of deoxyribonucleic acid (DNA) collecting in a unit of time in the intestinal luminal fluids is equated with desquamation rate.…”

Paneth Cell Secretion

“…Croft et al [9] have estimated that half a million cells each minute are lost from a segment of small intestine 5 cm long, and Loehry el al. [23] have shown that iron is lost into the gut by this route. As yet the only reliable method by which cell loss from the small intestine may be measured is by estimation of desoxyribonucleic acid in small intestinal washings [10].…”

Gastro-Intestinal Cell Loss in Man

“…(c) The epithelial cells must come only from the segment under study. In rat experiments this was ensured by tieing off either end of the small intestine and washing the whole small bowel of the living anaesthetised animal [33]. In man this has been done at the time of surgery [34] with results that com pare well with those obtained by the intestinal perfusion technique described above [18].…”