Intestine secretory disorders

Cells throughout the gastrointestinal tract release somatostatin. Somatostatin inhibits acid secretion in the stomach and it promotes absorption of sodium, chloride and water in the small intestine and colon (Krejs 1986). The somatostatin analogs octreotide and lanreotide have been shown to decrease intestinal secretion in animal models (Botella et al 1993) and in humans with specific metabolic intestinal secretory disorders however, these drugs are not used widely in human medicine. In one study in horses, octreotide was shown to decrease gastric acidity (Sojka et al 1992) but its effects on intestinal or colonic secretion in horses have not been reported. 

Disorders that cause increased secretion of fluid and electrolytes into the small intestine of the horse are characterized by abdominal discomfort, distension of the small intestine and enterogastric reflux. In young foals with small intestinal secretory disorders, diarrhea may occur. Increased intestinal secretion can result from the active secretion of electrolytes and water, for example the cyclic nucleotide-stimulated secretion that results from exposure to bacterial enterotoxins. Passive secretion of water can result from increased permeability of the intestine, such as in enteritis, distension or ischemia, or decreased absorption of osmoti-caUy active substances, such as with lactose intolerance in foals. Disorders in which there is decreased secretion of fluid into the small intestine are not appreciated, although impactions of ingesta in segments of the small intestine can occur. 

True antisecretory agents, those that block a biochemical process that promotes intestinal fluid secretion, are not available for clinical use in horses. Loperamide can reduce the volume of diarrhea in foals with a primarily small intestinal secretory disorder. However, treated foals may become colicky as a result of fluid distention in the intestines because the mechanism of action is primarily retention of fluid within the intestine. Also, retention of intestinal content may promote the proliferation of enteropathogens. The enkephalinase inhibitor racecadotril appears to have true antisecretory effect in animal models and in humans with diarrhea (Izzo et al 1998). Its safety or effectiveness in foals and horses has not been reported. 

In chylomicron retention disease (Anderson s disease) the secretory defect is restricted to intestinal apoB-containing lipoproteins (i.e., chylomicrons). This very rare recessively inherited disorder results from defects in a GTPase, Sarlb, which plays a critical role in the intracellular assembly and trafficking of chylomicrons. The affected patients present with fat malabsorption resulting in steatorrhea and deficiency of fat-soluble vitamins [46, 52, 54]. 

Q2 Constipation is a condition in which faecal material moves too slowly through the large intestine. As a result too much water is reabsorbed hard, dry faeces which are difficult to move and very abrasive are produced. Infrequent or difficult defecation is a common problem in the elderly as ageing is associated with a decline in both secretory activity and motility in the gut. Constipation could develop because of emotional problems, inactive or sedentary lifestyle, lack of fibre and fluid in the diet, intestinal muscle weakness, a neurogenic disorder or an iatrogenic effect. Iatrogenic conditions are those caused by drugs or other medical treatments. 

Diarrhoea results from an imbalance between secretion and reabsorption of fluid and electrolytes it has numerous causes, including infections with enteric organisms (which may stimulate secretion or damage absorption), inflammatory bowel disease and nutrient malabsorption due to disease. It also commonly occurs as a manifestation of disordered gut motility in the absence of demonstrable disease (see below). Rarely it is due to secretory tumours of the alimentary tract, e.g. carcinoid tumour or vipoma (a tumour which secretes VIP, vasoactive intestinal peptide). 

In vivo, 5-HT4 agonists are clearly prokinetic [44,133] and display a wide range of therapeutic applications in gastrointestinal motility disorders. ether or not their therapeutic actions are entirely mediated by 5-HT4-RS is not clear. In isolated human stomach, renzapride has been shown to potentiate electrically-evoked contractions [84]. This effect was antagonized by mM concentrations of tropisetron, suggesting that 5-HT4-RS are involved [85]. 5-HT4-RS are also present in human small intestinal mucosa [86] where the non neuronal electrogenic secretory effect of 5-HT appears to be mediated by 5-HT4-RS. 

---