Mechanisms of fluid losses in small‐bowel obstruction
Authors: Nellgård P. 
Published: February 2011

Abstract: Small‐bowel obstruction (SBO) is a serious condition induced by hindrance of the propagation of intestinal contents. Mortality of 5% is still relatively high, but has decreased since the beginning of this century when it was around 60%. The condition is characterized by severe abdominal pain, accumulation of gas and fluids in the obstructed intestine and dehydration of the patient. The mechanisms responsible for the profuse fluid losses remain unclear. The aim of this thesis was to elucidate some aspects of the pathophysiology by using an experimental in vivo model in rats. In anaesthestized animals jejunum was ***string‐ligated approximately 10 cm distal of the ligament of Treitz. The laparotomy was closed and the animals allowed to recover. Next day the animals were reanaesthetized, tracheostomy was performed and the femoral artery and vein catheterized. Complete obstruction of the jejunum during 18 h resulting in fluid secretion which was subsequently measured using a gravimetric technique allowing continuous registration of intestinal net fluid transport (NFT). After a control period of 30 min with stable net fluid secretion drugs or saline were administered. Mean NFT of the following 2 h was compared to the mean NFT of the control period. In some animals Evans blue dye (20 mg · kg−1) was given as marker of blood vessel permeability. Some aspects of the study were investigated in human gastrointestinal tissue.

Results show that a pronounced inflammation occurs in the obstructed bowel wall, as suggested by extravasation of plasma Evans blue‐albumin visualized by fluorescence microscopy and quantified by spectrophotometry. This was paralleled by net fluid secretion in the obstructed intestine. The importance of inflammation for the mechanisms of fluid losses was illustrated by the actions of the anti‐inflammatory agents, hydrocortisone and indomethacin, which reversed secretion into net fluid absorption. We proposed that the inflammation‐induced secretion of SBO was partly mediated through the enteric nervous system (ENS). This is supported by results showing that lidocaine, a local anaesthetic, with anti‐inflammatory properties, inhibited both inflammation and secretion, and anti‐inflammatory action of lidocaine was also shown in a human model where it reduced release of prostaglandins. The importance of ENS was further supported by results showing that the neurotransmitters vasoactive intestinal peptide (VIP) and somatostatin are involved in the regulation of fluid transport. VIP antiserum significantly reduced the net secretion, while the somatostatin analogue octreotide reversed net secretion into net absorption. Octreotide, which inhibits the release of many peptides including VIP, also reduced the Evans blue‐albumin extravasation. The secretion of SBO was also shown to be under influence of the sympathoadrenal system since clonidine, an α2‐adrenoceptor agonist, and propranolol, a β‐adrenoceptor antagonist, inhibited net fluid secretion. There were no significant effects on NFT after administration of α1‐ or β1‐adrenoceptor agonists or antagonists.

In conclusion, the present work shows that obstruction of the small intestine will induce a pronounced inflammatory reaction in the bowel wall, most prominent in the external muscle layer. This inflammation probably triggers the profuse fluid losses by direct action on the enterocytes and by activation of enteric neurons. The anti‐inflammatory agents hydrocortisone, indomethacin, lidocaine and octreotide significantly reduced both the fluid losses and the increased Evans blue‐albumin extravasation. Neuropeptides of the ENS are also important, and neutralization of VIP using VIP antiserum or inhibiting the release of VIP by octreotide both reduced fluid losses. The fluid transport in obstructed gut seems also to be under tonic control of adrenergic neurons, as stimulation of α2‐adrenoceptors and blockade of β2‐adrenoceptors reduced fluid losses, while blockade of α2‐adrenoceptors and stimulation of β2‐adrenoceptors increased the net fluid secretion. Treatment of patients with small bowel obstruction with anti‐inflammatory drugs may prove beneficial