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Bowel obstruction (Text).doc (173 KB) Pobierz 12 BOWEL OBSTRUCTION Small Intestine Anatomy and Physiology GENERAL CONSIDERATIONS The small bowel measures 12 to 20 feet in length from pylorus to ileocecal valve. The duodenum is mostly retroperitoneal and wraps in a C-shape around the head of the pancreas. Its first and second portions lie adjacent to the gallbladder and liver, and thus duodenal pathology may extend to involve these organs and vice versa. Pathology at the ampulla of Vater may produce obstructive jaundice or pancreatitis. The jejunum begins at the ligament of Treitz. The jejunum and ileum are suspended on a mobile mesentery covered by a visceral peritoneal lining that extends onto the external surface of the bowel to form the serosa. Adhesions caused by surgery or inflammation may limit the mobility of the loops and lead to obstruction or internal hernia. The jejunum and ileum comprise about two-fifths and three-fifths of the mobile portion of the small intestine, respectively. Circumferential mucosal folds (plicae circularis) are abundant in the jejunum but absent in proximal duodenum and distal ileum. BLOOD SUPPLY AND LYMPHATIC DRAINAGE The proximal duodenum receives its blood supply from the celiac axis, but the remainder of the small intestine is supplied by the superior mesenteric artery (SMA). Although mesenteric arcades form a rich collateral network, occlusion of a major branch of the SMA may result in segmental intestinal infarction. Venous drainage is via the superior mesenteric vein, which then joins the splenic vein behind the neck of the pancreas to form the portal vein. Elliptical, approximately 2 cm, lymphoid aggregates (Peyer’s patches) are present on the antimesenteric border along the distal ileum, and smaller follicles are evident throughout the remainder of the small intestine. Lymphatic drainage of the intestine is abundant. Regional lymph nodes follow vascular arcades and drain toward the cysterna chyli. LAYERS OF THE BOWEL WALL The small bowel wall consists of the outermost serosa, followed by the muscularis, submucosa, and, innermost, the mucosa. The serosa is a single layer of flattened mesothelial cells that covers the jejunum and ileum but only the anterior surface of the duodenum. The muscularis consists of two layers of smooth muscle, a thicker inner circular layer and a thinner outer longitudinal layer. Specialized intercellular junctional structures called gap junctions electrically couple adjacent smooth muscle cells and allow efficient propagation of peristaltic signals. Ganglion cells and nerve fibers of Auerbach’s myenteric plexus interdigitate between layers and communicate with smaller neural elements between cells. The submucosa is a dense connective tissue layer populated by diverse cell types, including fibroblasts, mast cells, lymphocytes, macrophages, eosinophils, and plasma cells. The submucosa is the strongest layer of the bowel wall, which should be taken into account when performing sutured anastomoses. Networks of arterioles, lymphatic and venous plexuses, and nerves crisscross through the submucosa. Meissner’s submucosal neural plexus interconnects with neural elements from Auerbach’s plexus in this region. The mucosa is characterized by a villus architecture that, combined with circular folds, amplifies potential absorptive surface area 20-fold. The mucosa is subdivided into three layers. The muscularis mucosae consists of a thin sheet of smooth muscle cells. The lamina propria consists of connective tissue that extends from the base of the crypts up into the core of the intestinal villi. The innermost layer is made up of a continuous sheet of columnar epithelial cells composed of multiple cell types. The Intestinal Epithelium and Its Functions GENERAL CONSIDERATIONS The intestinal epithelium is extraordinarily complex, composed of heterogenous cell types that reside within a highly organized supporting tissue structure containing multiple regulatory elements. Intestinal epithelial cells rest on a thin basement membrane overlying the lamina propria. A central arteriole within the villus core is surrounded by a fenestrated capillary network that optimizes countercurrent exchange of oxygen and plasma solutes while providing an efficient pathway for absorption of nutrients. Mononuclear cells and neutrophils reside in or traffic into the lamina propria during normal or disease states. There are two major compartments to the intestinal epithelium, the crypt and the villus, each with distinct function and cellular composition. The majority of crypt cells are undifferentiated; some mature into mucus-secreting goblet cells and enteroendocrine cells, but most take on functional characteristics of absorptive enterocytes.1,2 The lifespan of the enterocyte is 3 to 5 days. The villus compartment is nonproliferative, and senescent enterocytes undergo apoptosis and are extruded. BARRIER FUNCTION The intestinal epithelium selectively limits the permeation of potentially harmful luminal substances. The anatomical locus of this “barrier” is the intercellul ar junctional complex, 4,5 a three-level structure that forms a circumferential seal between adjacent cells. The tight junction (zonula occludens) faces the lumen and is the site of membrane-tomembrane “kisses”. The intermediate or adherens junction (zonula adherens) lies deep to the tight junction, at which site the transmembrane protein E-cadherin interacts with cytoskeletally linked signaling elements. The desmosome is the innermost element of the junctional complex. DIGESTION AND ABSORPTION The small intestine receives about 1 to 1.5 l/day of ingested fluid plus about 8 l of salivary, gastric, and pancreaticobiliary secretions. Most of this fluid is reabsorbed before reaching the colon. Water movement is driven by the active transcellular absorption of Na_ and Cl_ and by the absorption of nutrients such as glucose and amino acids. The energy for many of these transport processes derives from the activity of a basolateral Na_-K_ ATPase, which maintains the low Na_ internal environment that drives uptake via coupled ion exchangers (Na_/H_ and Cl_/HCO3 _) and Na_coupled nutrient transporters. Digestion begins in the stomach with the action of gastric acid and pepsin. In the proximal duodenum, ingested foodstuffs are broken down by pancreatic proteases such as trypsin, elastase, chymotrypsin, and carboxypeptidases. The activity of brush border hydrolases and oligopeptidases then accomplishes terminal protein and carbohydrate digestion, and the resulting monosaccharides, amino acids, or di- and tripeptides then serve as substrates for Na_- or H_-coupled transporters in the apical membrane of absorptive enterocytes. The apical membrane of these cells is well suited to the task of absorption by virtue of a microvillus brush border that amplifies absorptive area 30-fold. Fat digestion and absorption occur in the proximal small intestine, where pancreatic lipase partially hydrolyzes triglycerides into two fatty acids plus a central fatty acid linked to glycerol (monoglyceride). These substances are solubilized by bile salts to form micelles or mixed micelles (which additionally contain phospholipids, cholesterol, and fatsoluble vitamins). Micelles diffuse into enterocytes through the overlying mucus and apical plasma membrane, releasing fatty acid and monoglyceride into the cell along the way. Triglycerides are reformed intracellularly and are incorporated along with cellular protein, phospholipid, and cholesterol to form chylomicrons. Chylomicrons, which consist of an inner core of triglycerides and an outer coat of phospholipid and apoproteins, then exit the cell to be absorbed by the lymphatic system. Bile salts are resorbed into the enterohepatic circulation in the distal ileum by an ileal Na_-coupled bile acid transporter.6,7 SECRETION Intestinal crypt cells have the capacity to secrete an isotonic fluid through the active transcellular transport of Cl_.8–10 This process lubricates mucosal surfaces and facilitates the luminal extrusion of other secreted substances (e.g., secretory IgA and Paneth cell-derived cryptdins). Clinical diarrhea results when secretion exceeds colonic absorptive capacity. The cellular basis for epithelial Cl_ secretion involves Cl_ uptake across the basolateral membrane via a Na_-K_-2Cl_ cotransporter followed by Cl_ extrusion across the apical membrane via Cl_ channels, including the cystic fibrosis transmembrane conductance regulator (CFTR). Intestinal Immune Function GENERAL CONSIDERATIONS The mucosal immune system is critically important in defense against toxic and pathogenic threats from the luminal environment.11,12 The lamina propria contains numerous immune cells including plasma cells, mast cells, and lymphocytes that produce not only immunoglobulins but also cytokine mediators.13 SECRETORY IGA AND EPITHELIAL IMMUNE FUNCTION Lamina propria plasma cells produce IgA in response to food antigens and microbes. IgA and IgM are secreted into the gut lumen by a mechanism that involves transcytosis through epithelial cells.14 Secretory IgA prevents microbial pathogens from penetrating the epithelial layer. IgA– antigen interactions also occur within the intraepithelial and subepithelial compartments. In contrast to IgG, IgM, and IgE, antibodies of the IgA class evoke a much less proinflammatory (indeed, an antiinflammatory) response and thus contribute to the overall immunosuppressive tone of the mucosal immune system. In addition, intestinal epithelial cells themselves may also contribute to the immune function of the gut by transmitting important immunoregulatory signals to the underlying lymphocytic population.15,16 M CELLS AND GUT-ASSOCIATED LYMPHOID TISSUE Specialized cells known as M cells are found overlying Peyer’s patches and serve as the major portal of entry for foreign material.20 Specialized membrane invaginations in M cells create a pocket in which lymphocytes and macrophages gather. Luminal substances are immediately delivered to these professional antigen-processing cells, and this information is then directly conveyed to the underlying follicles. Antigen-specific lymphocyte proliferation occurs within Peyer’s patches, and IgA-producing B cells migrate to regional lymph nodes and into the systemic circulation, from where they migrate back to diffusely populate the mucosa within the lamina propria. Within the lamina propria and submucosa, mature T cells, B cells, and macrophages carry out traditional cell-mediated immune responses including phagocytosis, cell killing, and secretion of cytokines. Intestinal Neuroendocrine Function GENERAL CONSIDERATIONS The intestine is a rich source of regulatory peptides that control various aspects of gut function. These substances, released in response to luminal or neural stimuli, exert their biological actions either at distant sites (by entering the bloodstream in classical hormone fashion) or locally (as paracrine factors or neurotransmitters). SECRETIN AND RELATED PEPTIDES Secretin is a 27-amino-acid peptide released by enteroendocrine cells in the proximal small bowel in response to luminal acidification, bile salts, and fat. Its major function is to stimulate pancreatic ductal bicarbonate secretion. Secretin inhibits gastric release, gastric acid secretion, and gastrointestinal motility. Additionally, it stimulates bile flow by stimulating fluid secretion from cholangiocytes. Paradoxically, secretin stimulates rather than inhibits gastrin release in patients with gastrinoma, and this phenomenon forms the basis for the secretin infusion test in suspected Zollinger–Ellison syndrome. Other members of the secretin family that share substantial sequence homology and interact with similar G-protein-coupled receptors include vasoactive intestinal polypeptide (VIP), pituitary adenylate cyclase-activating polypeptide (PACAP), glucagon, gastric inhibitory polypeptide (GIP), and enteroglucagon.17 Enteroglucagon and glucagon-like peptides (GLP) are secreted by neuroendocrine cells in the colon and small intestine and may be important in gut adaptation and glucose homeostasis.18 CHOLECYSTOKININ Cholecystokinin (CCK) is released by specialized small-bowel enteroendocrine cells in response to luminal amino acids and medium- to long-chain fatty acids.19 CCK release is inhibited by intraluminal trypsin and bile salts. Two major targets of CCK are the gallbladder and the sphincter of Oddi, where it causes coordinated contraction and relaxation, respectively, to enhance luminal mixing of bile with ingested food.20 Additionally, CCK stimulates pancreatic enzyme secretion. CCK stimulates cell growth in intestinal mucosa and pancreas, insulin release, and gut motility. SOMATOSTATIN Somatostatin is a 14-amino-acid peptide that exerts a wide variety of inhibitory functions in the gastrointestinal tract.21 It is released from specialized enteroendocrine cells where it acts in paracrine fashion to inhibit intestinal, gastric, and pancreaticobiliary secretion as well as cell growth. Synthetic forms of somatostatin are used clinically in patients with enterocutaneous and pancreaticobiliary fistulae.22 OTHER PEPTIDES Peptide YY is a 36-amino-acid peptide secreted by the distal small bowel. PYY appears to inhibit gastric acid secretion. It also decreases intestinal motility and inhibits pancreatic secretion and release of various intestinal hormones.23–25 ... 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