Population Dynamics of Intestinal Epithelia in the Rat Two Months After Partial Resection of the Ileum

Abstract

Sprague-Dawley rats that had been subjected 2 months previously to partial resection (10 per cent) of thc small intestine and an equal number of control rats were injected with tritiated thymidine and sacrificcd at intervals during the subsequent 16 hours. Segments of duodenum, jejunum and ileum were prestained by the Feulgen technique and radioautographed. ~fhe proportion of crypt cells bearing labeled nuclei, the perccntage of labeled crypt cells in mitosis and the appearance of labeled crypt ceils on the villi were determined. Comparison of control and resected rats showed that (a) the proportion of intestinal crypt cells incorporating thymidine was considerably greater and uniformly high throughout the shortened intestinc, (b) the life cycle of crypt cells was slightly reduced, and was uniform throughout the shortened intestine, and (c) the time during which cells wcre retained in crypts was markedly reduced. On the basis of persistent, generalized increase in the production of crypt cells, and on prior evidence that the epithelial cells of shortened intestine continue to have a brief life span and evidence of metabolic immaturity, the existence of a humoral factor, tentatively called "intestinal epithelial growth hormone," is postulated.As reported previously (1), resection of I0 per cent of the small intestine (removal of 10 cm of ileum) in rats was followed by a pronounced increase in the rate of migration of the epithelial cells covering the villi in the remaining portion of small intestine. Two months after resection, the distance traveled by mucosal cells examined 2 and 24 hours after labeling with tritiated thymidine was increased by approximately 23 per cent in the duodenum, 114 per cent in the jejunum, and 141 per cent in the ileum. The "life span" of epithelial cells in the intestinal mucosa, as estimated from the rate of migration and the height of villi, was decreased to 82, 46, and 42 per cent of normal for duodenum, jejunum, and ileum, respectively.The present study demonstrates that the rate of appearance of new ceils on the intestinal villi is accelerated in proportion to the increased rate of cell migration. Proliferation in intestinal crypts is also increased throughout the small intestine, but this increase is not proportional to the increase in the rate of migration. It is proposed that a growth factor, provisionally called intestinal epithelial growth hormone (IEGH), is released in response to intestinal resection and that this factor accelerates the rate of epithelial proliferation throughout the small bowel. M A T E R I A L S AND M E T H O D SIn a first experiment, the experimental animals consisted of 16 male Sprague-Dawley rats, weighing 300 to 350 gin. A 10 cm portion of the lower ileum, representing 10 per cent of the length of the small intestine, was removed from each at a point about 20 cm 285 on

Changes in Sucrase, Enterokinase, and Peptide Hydrolase after Intestinal Resection THE ASSOCIATION OF CELLULAR HYPERPLASIA AND ADAPTATION

“…Similarly, others have shown that postoperatively increases in the heights of ileal villi greatly exceed those of jejunal villi (13). By contrast, studies of crypt cell kinetics after resection show almost identical responses proximally and distally (11,12). This suggests that cell turnover in the crypts is controlled by mechanisms different from those regulating the villi.…”

“…Regional variations in mucosal enzymne concentrations also highlight the need for careful standardization of the segments being studied. In the present experiments all of these factors were matched in control and resected animals and therefore it seems reasonable to attribute the observed effects to the resection per se; however the possibility remains that endogenously synthesized steroid or other hormones played a part in the production of the observed effects (11,36,37), especially since the known changes in cell kinetics also occur in the unresected members of paired parabiotic rats (36).…”

“…But since enzyme activity per milligram DNA falls in resected rats there must also be a marked increase in cells devoid of or low in enzyme activity. these appearing either as crypt cells (11,12) or immature cells on villi (43). The increase in villus height is only of the order of 40% at maximum (14) and frequently much less, but a large increase in the crypt cell population has also been described in several studies (2,11,12,47): one of these (47) reported that the crypt cell layer had increased by 70% at 4 wk postresection.…”

“…Resection of the proximal two-thirds of the small intestine causes the greatest morphological change or "compensatory hypertrophy," with little or no nutritional disturbance to the animal (3,4) while distal resection is associated more with weight loss and malabsorption (4,5), gastric hypersecretion (6), enhanced gastric emptying (7), and reduced intestinal transit time (5,7). Whether proximal or distal factors underlie the reported disturbances in ileal blood flow (8), vitamin A transport (9), or mucosal cell kinetics (10)(11)(12) is still uncertain.…”

Patterns, Mechanisms and Signals for Intestinal Adaptation

“…There is a dissociation between the mor phological, enzymatic and transport changes following resection [64,65]. Why might changes in intestinal structure and function occur independently rather than in concert?…”