Effects of partial hepatectomy on the distal ileum in rats

M. B. Rodríguez Sanz, J. Alarcón García, F. J. del Riego Tomás and C. Vaquero Puerta

Laboratory of Experimental Surgery. Department of Otorhinolaryngology, Ophthalmology and Surgery. School of
Medicine. University of Valladolid. Spain

 

ABSTRACT

Introduction: hepatectomy, both partial resection and transplant, has greatly developed and advanced during the last years as a result of a better understanding of surgical anatomy and the progress of technological means; it has also allowed a widening of surgical indications, including living-donor liver transplantation. The aims of our study was to assess the morphological impact of partial hepatectomy on the distal ileum, since the liver and intestine behave as a unit from an anatomical, functional, and metabolic point of view.
Material and methods: twenty-four Wistar rats were used; they were divided into two groups, a control and an experimental group (30, 90, and 180 days). We studied changes occurred in the distal ileum after a 70% liver resection, taking 4 parameters into account.
Results: an important drop in total thickness occurred at the ileum wall in the experimental group (p < 0.001). There were no important differences in villus height with regard to the control group. Thickness at the villi fell significantly (p < 0.01), as did the depth of the crypts, which diminished significantly in relation to the control group (p < 0.001).
Conclusions: a 70% hepatectomy induces trophic changes on the distal ileum that remain in both the short and longer term, and causes atrophy of the ileum wall and a drop in villus thickness.

Key words: Partial hepatectomy. Distal ileum.

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Rodríguez Sanz MB, Alarcón García J, del Riego Tomás FJ, Vaquero Puerta C. Effects of partial hepatectomy on the distal ileum in rats. Rev Esp Enferm Dig 2004; 96: 185-190.

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Recibido:22-07-03.
Aceptado:07-10-03.

Correspondencia: Mª Belén Rodríguez Sanz. C/ esteban García Chico,10-6º- L. 47003 Valladolid. Tels.: 983355828. 646874565. e-mail: brodriguez@hrcr.sacyl.es

 

INTRODUCTION

Partial hepatectomy is a surgical technique that thrived during the last decades due to tumor resections (both primary and metastatic tumors) and in the last few years due to living-donor liver transplantation.

The functions of the liver are numerous. With hepatic resection a number of changes occur in these functions, as well as specific pathophysiologic events.

Some experimental studies proved that a redistribution of the liver's phagocytic capacity and an overactivation of extrahepatic macrophagocytes occurred after a loss of hepatic volume (1), which caused failures at the intestinal barrier and a deficiency against infection. These changes depended on the kind of resection, duration of operation, and intraoperative hemorrhage (2), and implied an increase in the intestinal endothelial permeability, tissue edema, epithelial dysfunction, and bacterial invasion. On the other hand, some factors may modify the intestinal mucosa. These factors include: type of feeding, bilio-pancreatic secretion, gastrointestinal hormones, different surgical operations, autonomic nervous system, conditions such as hemorrhagic shock, thermal lesions, etc.

For all these reasons, we attempted to study the changes that develop in the distal ileum in the short, medium and long term after a 70% hepatectomy.

MATERIAL AND METHODS

This study was performed in 24 Wistar rats with an approximate weight of 200-240 grams. These rats were obtained from the Experimental Animal Facility (School of Medicine at the University of Valladolid. Spain). This Facility has standard conditions of inhabitability in accordance with the current animal care guidelines issued by the European Directive (November 1986) and the Spanish Legislation (March 1988).

Animals were distributed into a control group (n = 6), whose rats underwent a resection of the distal ileum, and an experimental group (n = 18), whose rats underwent a 70% hepatectomy and then a resection of the distal ileum 30 (n = 6), 90 (n = 6) and 180 (n = 6) days after hepatectomy.

The partial hepatectomy was performed under general anesthesia with ketamine hydrochloride. A mid laparotomy was performed with removal of the left lateral hepatic lobe and mid lobe; blood vessels were identified and cut, and both lobes were ligated and resected, thus making up the classically so-called 70% hepatectomy. Then the laparotomy was stitched up and rats were placed in recovery cupboards with appropriate temperature and humidity conditions. They returned to their standard feeding.

After 30, 90 and 180 days, respectively, rats underwent -again under general anesthesia with ketamine hydro-chloride- mid relaparotomy with identification of the ileum-cecum valve, and measurement of 10 centimetres, seven of which were resected. Finally, animals were sacrificed.

In the control group, only the cutting of 7 centimeters of distal ileum was carried out, using the same technique as in the experimental group.

Immediately afterwards, a macroscopic study of samples obtained was undertaken. The histologic study was done by using 10% formaldehyde fixation, paraffin inclusion, and hematoxylin-eosin staining.

A morphometric study of ileal villi was carried out to assess the parameters of total wall thickness, height of villi, depth of the crypts, and villi thickness.

Data obtained were submitted to statistical analysis for a descriptive study including mean and standard deviation values. An adjustment to normality analysis was done by using the Shapiro-Wilks test. When variable distribution was normal, an analysis of variance with a post-hoc Sheffe test was performed; a Kruskall-Wallis test was used when distribution of variables was not normal.

RESULTS

Macroscopically, no alteration was found in the ileum of the experimental group as compared with the control group.

The total height of the ileum's wall dropped by 40.09, 47.03, and 22.86% after 30, 90 and 180 days, respectively. This fall was significant (p < 0.001) with regard to the control group, and remained stable over time (Table I).

The height of villi decreased by 8.44%, and 11.8% after 30 and 90 days, respectively, and increased by 4.22% after 180 days. Statistically, these differences were not significant in relation to the rats not having undergone partial hepatectomy (Table II).

The thickness of villi fell by 53.08, 19.73 and 27.94% after 30, 90 and 180 days of partial hepatectomy, respect-ively. Differences with regard to the control group were statistically significant (p < 0.001) (Table III).

In rats that underwent hepatectomy, the depth of crypts decreased by 95.91% after 30 days, 102.03% after 90 days, and 83.49% after 180 days. Differences were statistically significant in relation to the rats not having undergone partial hepatectomy (p < 0.001) (Table IV).

DISCUSSION

Many experimental studies about the alterations brought about by partial hepatectomy on the large intestine have been carried out. These alterations include enzymatic changes, bacterial overgrowth, bacterial translocation, etc., and also hepatic regeneration in the remaining liver, pathophysiologic facts that are specific for hepatic resection or enzymatic and metabolic modifications.

Ponfick was first to observe hepatic regeneration in dogs back in 1894. This concept implies a restoration of the original anatomical structure after partial hepatectomy. It involves two phenomena: one is hypertrophy and the other is cellular hyperplasia, which are defined as an increase in the number and size of cells. Rabes HM et al. (3) carried out studies that established that rat hepato-cytes proliferated at least once within 24-36 hours follow-ing partial hepatic resection, and complete regeneration was finished in about 20 days. This regeneration is regulated by a strict homeostatic control, and depends on hormonal changes.

Partial hepatectomy in the rat is an easy surgical technique, although not free from difficulties. These difficulties depend on a series of factors described by Andersson and Yanaga (5,6). These include: duration of operation, intraoperative hemorrhage, kind of resection, and surgical procedure; in our research, duration of operation varied from 10 to 15 minutes, and intraoperative hemorrhage was minimal with 10 to 20 milliliters. The mortality rate is 1-4% and the morbidity rate is 25% (7). In our study, mortality was 0% and no morbidity was apparent.

This surgery predisposes to bacterial infections, sepsis, overgrowth, and bacterial translocation at the intestinal level, which depend on the amount of liver resected (8). The latter factor results in mucosal alterations at the intestinal wall.

Hepatic resection results in failing intestinal barrier. The most important factors responsible for this failure include: a fall of blood flow in the intestinal mucosa, mainly on the distal ileum; excessive activation of intestinal macrophagocytes, and changes in intestinal permeability, which cause tissue edema, epithelial dysfunction and bacterial invasion (9).

A series of factors that may modify the intestinal mucosa have been described. They include type of nutrition, biliopancreatic secretion, enteric hormones, surgical operations, hemorrhagic shock, burns, autonomic nervous system, etc. It has been proved that enteral nutrition has trophic effects on the intestinal mucosa and reduces the disturbance of the intestinal flora and septic complications, while parenteral feeding and fasting enhance lesions that develop on the large intestinal mucosa. Biliopancreatic secretion and enteric hormones have a trophic action.

Once hepatic resection was completed, our animals were placed in recovery cages under appropriate conditions of temperature and humidity, since preventing hypothermia and hypoglycemia has been shown to improve survival in rats. Likewise, enteral nutrition and standard food were introduced because of the trophic effects these factors have on the intestinal mucosa, as Qui et al. (10) demonstrated in their study on sepsis prevention. Thus, in our work we obtained an overall survival rate of 100%. In their studies, Alverdy et al. (11) and Illig et al. (12) report-ed that parenteral feeding caused intestinal atrophy, which favored overgrowth and bacterial translocation.

In the rat, the size of intestinal villi falls gradually from the duodenum to the ileum. In the ileum the height of villi is less than half their size in the duodenum (13).

Authors like Navaratnam et al. (14) proved that hepatic resection caused an alteration and failure of the intestinal barrier due to hypovolemia, and also a drop in flow through the intestinal mucosa mainly in the distal ileum, which in turn results in diminished height of intestinal villi. In 1993, Wang XD et al. (1) showed the effect of hepatic resection on the intestinal structure and metabolism; he observed a drop in villus height, mainly at the distal ileum, which developed 2 hours after hepatic surgery; this factor may explain bacterial overgrowth and translocation. However, other authors like Jones WG et al. (15) concluded that intestinal barrier atrophy may be a mechanism of bacterial translocation. In our research, we found evidence that atrophy developed at the intestinal wall with no significant modification of villus height, but a drop in crypt depth and villus thickness.

We conclude that partial hepatectomy (about 70%) results in atrophy of the small intestinal wall without inducing significant changes in the height of distal ileal villi. We also observed that enteral nutrition given early in the postoperative period has little trophic effect on distal small bowel mucosa. Similarly, wide hepatic resection generated alterations in the intestinal mucosal barrier that may give rise to bacterial translocation, which leads to wall atrophy as Navaratnam et al. and Wong et al. demonstrated in their studies. These morphologic changes that become apparent in the distal ileum wall may have a functional impact that falls outside the scope of the present study.

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