Chapter 50 Small Intestine
The small intestine is a marvel of complexity and efficiency. The primary role of the small intestine is the digestion and absorption of dietary components after they leave the stomach. This process depends on a multitude of structural, physiologic, endocrine, and chemical factors. Exocrine secretions from the liver and pancreas enable complete digestion of the foodstuffs. The enlarged surface area of the small intestinal mucosa then absorbs these nutrients. In addition to its role in digestion and absorption, the small bowel is the largest endocrine organ in the body and is one of the most important organs of immune function. Given its essential role and complexity, it is amazing that diseases of the small bowel are not more frequent. In this chapter, the normal anatomy and physiology of the small intestine are described, as well as disease processes involving the small bowel, which include obstruction, inflammatory diseases, neoplasms, diverticular disease, and miscellaneous disorders.
The primitive gut is formed during the fourth week of fetal human gestation.1 The endodermal layer gives rise to the epithelial lining of the digestive tract and the splanchnic mesoderm surrounding the endoderm gives rise to the muscular connective tissue and all the other layers of the intestine. Except for the duodenum, which is a primitive foregut structure, the small intestine is derived from the midgut. During the fifth week of fetal development, when the intestinal length is rapidly increasing, herniation of the midgut occurs through the umbilicus (Fig. 50-1). This midgut loop has a cranial and caudal limb, with the cranial limb developing into the distal duodenum, jejunum, and proximal ilium and the caudal limb becoming the distal ilium and proximal two thirds of the transverse colon. The juncture of the cranial and caudal limbs is where the vitelline duct joins to the yolk sac. This duct structure normally becomes obliterated before birth; however, it can persist as a Meckel’s diverticulum in approximately 2% of the population. This midgut herniation persists until about 10 weeks of fetal gestation, when the intestine returns to the abdominal cavity. After completing a 270-degree rotation from its initial starting point, the proximal jejunum reenters the abdomen and occupies the left side of the abdomen, with subsequent loops lying more to the right. The cecum enters last and is located temporarily in the right upper quadrant; however, with time, it descends to its normal position in the right lower quadrant. Congenital anomalies of gut malrotation and fixation can occur during this process.
FIGURE 50-1 Rotation of the intestine. A, The intestine after a 90-degree rotation around the axis of the superior mesenteric artery, the proximal loop on the right and the distal loop on the left. B, The intestinal loop after a further 180-degree rotation. The transverse colon passes in front of the duodenum. C, Position of the intestinal loops after reentry into the abdominal cavity. Note the elongation of the small intestine, with formation of the small intestine loops. D, Final position of the intestines after descent of the cecum into the right iliac fossa.
(From Podolsky DK, Babyatshy MW: Growth and development of the gastrointestinal tract. In Yamada T [ed]: Textbook of gastroenterology, vol 2, Philadelphia, 1995, JB Lippincott.)
The primitive small bowel is lined by a sheet of cuboidal cells until about the ninth week of gestation, when villi begin to form in the proximal intestine and then proceed in a caudal fashion until the entire small bowel, and even the colon, for a period of time, are lined by these finger-like projections. Crypt formation begins in the 10th to 12th weeks of gestation. The crypt layer of the small bowel is the site of continual cell renewal and proliferation. As the cells ascend the crypt-villous axis, proliferation ceases, and cells differentiate into one of the four main cell types: absorptive enterocytes, which compose about 95% of the intestinal cell population; goblet cells; Paneth cells; and enteroendocrine cells. Cells are eventually extruded into the intestinal lumen. Amazingly, this entire process of complete renewal of the intestinal lining occurs in less than 1 week in humans.
The entire small intestine, which extends from the pylorus to the cecum, measures 270 to 290 cm, with duodenal length estimated at approximately 20 cm, jejunal length at 100 to 110 cm, and ileal length at 150 to 160 cm. The jejunum begins at the duodenojejunal angle, which is supported by a peritoneal fold known as the ligament of Treitz. There is no obvious line of demarcation between the jejunum and the ileum; however, the jejunum is commonly considered to make up the proximal two fifths of the small intestine and the ileum makes up the remaining three fifths. The jejunum has a somewhat larger circumference, is thicker than the ileum, and can be identified at surgery by examining mesenteric vessels. In the jejunum, only one or two arcades send out long, straight vasa recta to the mesenteric border, whereas the blood supply to the ileum may have four or five separate arcades with shorter vasa recta (Fig. 50-2). The mucosa of the small bowel is characterized by transverse folds (plicae circulares), which are prominent in the distal duodenum and jejunum.
FIGURE 50-2 The jejunal mucosa is relatively thick with prominent plicae circulares; the mesenteric vessels form only one or two arcades with long vasa recta. The ileum is smaller in circumference and has thinner walls; the mesenteric vessels form multiple vascular arcades with short vasa recta.
(Adapted from Thompson JC: Atlas of surgery of the stomach, duodenum, and small bowel, St Louis, 1992, Mosby–Year Book, p 263.)
The small intestine is served by rich vascular, neural, and lymphatic supplies, all traversing through the mesentery. The base of the mesentery attaches to the posterior abdominal wall to the left of the second lumbar vertebra and passes obliquely to the right and inferiorly to the right sacroiliac joint. The blood supply of the small bowel, except for the proximal duodenum, which is supplied by branches of the celiac axis, comes entirely from the superior mesenteric artery (Fig. 50-3). The superior mesenteric artery courses anterior to the uncinate process of the pancreas and the third portion of the duodenum, where it divides to supply the pancreas, distal duodenum, entire small intestine, and ascending and transverse colons. There is an abundant collateral blood supply to the small bowel provided by vascular arcades coursing in the mesentery. Venous drainage of the small bowel parallels the arterial supply, with blood draining into the superior mesenteric vein, which joins the splenic vein behind the neck of the pancreas to form the portal vein.
FIGURE 50-3 Blood supply to the jejunoileum and distal duodenum is entirely from the superior mesenteric artery, which courses anterior to the third portion of the duodenum. The celiac artery supplies the proximal duodenum.
(Adapted from Thompson JC: Atlas of surgery of the stomach, duodenum, and small bowel, St Louis, 1992, Mosby–Year Book, p 265.)
The innervation of the small bowel is provided by parasympathetic and sympathetic divisions of the autonomic nervous system, which in turn provide the efferent nerves to the small intestine. Parasympathetic fibers are derived from the vagus; they traverse the celiac ganglion and affect secretion, motility, and probably all phases of bowel activity. Vagal afferent fibers are present but apparently do not carry pain impulses. The sympathetic fibers come from three sets of splanchnic nerves and have their ganglion cells usually in a plexus around the base of the superior mesenteric artery. Motor impulses affect blood vessel motility and probably gut secretion and motility. Pain from the intestine is mediated through general visceral afferent fibers in the sympathetic system.
The lymphatics of the small intestine are noted in major deposits of lymphatic tissue, particularly in the Peyer patches of the distal small bowel. Lymphatic drainage proceeds from the mucosa through the wall of the bowel to a set of nodes adjacent to the bowel in the mesentery. Drainage continues to a group of regional nodes adjacent to the mesenteric arterial arcades and then to a group at the base of the superior mesentery vessels. From there, lymph flows into the cisterna chyli and then up the thoracic ducts, ultimately to empty into the venous system located in the neck. The lymphatic drainage of the small intestine constitutes a major route for transport of absorbed lipid into the circulation and similarly plays a major role in immune defense and also in the spread of cells arising from cancers of the gut.
FIGURE 50-4 Layers of the small intestine. A large surface is provided by villi for the absorption of required nutriments. The solitary lymph follicles in the lamina propria of the mucous membrane are not labeled. In the stroma of both sectioned villi are shown the central chyle (lacteal) vessels or villous capillaries.
(From Sobotta J, Figge FHJ, Hild WJ: Atlas of human anatomy, New York, 1974, Hafner.)
The serosa is the outermost layer of the small intestine and consists of visceral peritoneum, a single layer of flattened mesoepithelial cells that encircles the jejunoileum, and the anterior surface of the duodenum.
The muscularis propria consists of two muscle layers, a thin outer longitudinal layer and a thicker inner circular layer of smooth muscle. Ganglion cells from the myenteric (Auerbach) plexus are interposed between the muscle layers and send neural fibers into both layers, thus providing electrical continuity between the smooth muscle cells and permitting conduction through the muscle layer.
The submucosa consists of a layer of fibroelastic connective tissue containing blood vessels and nerves. It is the strongest component of the intestinal wall and therefore must be included in anastomotic sutures. It contains elaborate networks of lymphatics, arterioles, and venules and an extensive plexus of nerve fibers and ganglion cells (Meissner plexus). The nerves from the mucosa and submucosa muscle layers are interconnected by small nerve fibers; cross connections between adrenergic and cholinergic elements have been described.
The mucosa can be divided into three layers, the muscularis mucosae, lamina propria, and epithelial layers (Fig. 50-5). The muscularis mucosae is a thin layer of muscle that separates the mucosa from the submucosa. The lamina propria is a connective tissue layer between the epithelial cells and muscularis mucosae that contains a variety of cells, including plasma cells, lymphocytes, mast cells, eosinophils, macrophages, fibroblasts, smooth muscle cells, and noncellular connective tissue. The lamina propria, the base on which the epithelial cells lie, serves a protective role in the intestine to combat microorganisms that penetrate the overlying epithelium, secondary to a rich supply of immune cells. Plasma cells actively synthesize immunoglobulins and other immune cells in the lamina propria and release various mediators (e.g., cytokines, arachidonic acid metabolites, histamines) that can modulate various cellular functions of the overlying epithelium. The epithelial layer is a continual sheet of epithelial cells covering the villi and lining the crypts. The main functions of the crypt epithelium are cell renewal and exocrine, endocrine, water, and ion secretion; the main functions of the villous epithelium are digestion and absorption. Four main cell types are contained in the mucosal layer: (1) goblet cells, which secrete mucus; (2) Paneth cells, which secrete lysozyme, tumor necrosis factor (TNF), and the cryptidins, which are homologues of leukocyte defensins thought to be related to the host mucosal defense system; (3) absorptive enterocytes; and (4) enteroendocrine cells, of which there are more than 10 distinct populations that produce the gastrointestinal hormones.
(Adapted from Keljo DJ, Gariepy CE: Anatomy, histology, embryology, and developmental anomalies of the small and large intestine. In Feldman M, Scharschmidt BF, Sleisenger MH [eds]: Sleisenger & Fordtran’s gastrointestinal and liver disease: Pathology, diagnosis, management, Philadelphia, 2002, WB Saunders, p 1646.)
Microscopically, the mucosa is designed for maximal absorptive surface area, with villi protruding into the lumen. Villi are tallest in the distal duodenum and proximal jejunum and shortest in the distal ileum. Absorptive enterocytes represent the main cell type in the mucosa and are responsible for digestion and absorption. Their luminal surface is covered by microvilli that rest on a terminal web. The microvilli increase the absorptive capacity by 30-fold. To increase absorption further, the microvilli are covered by a fuzzy coat of glycoprotein, the glycocalyx.
The complex process of digestion and eventual absorption of nutrients, water, electrolytes, and minerals is the main role of the small intestine. Liters of water and hundreds of grams of food are delivered to the small intestine daily and, with remarkable efficiency, almost all food is absorbed, except for indigestible cellulose. The stomach initiates the process of digestion with the breakdown of solids to particles 1 mm or smaller, which are then delivered to the duodenum, where pancreatic enzymes, bile, and brush border enzymes continue the process of digestion and eventual absorption through the small intestinal wall.2 The small bowel is primarily responsible for the absorption of the dietary components (carbohydrates, proteins, and fats), as well as ions, vitamins, and water.
An adult consuming a normal Western diet will ingest 300 to 350 g of carbohydrates a day, with about 50% consumed as starch, 30% as sucrose, 6% as lactose, and the remainder as maltose, trehalose, glucose, fructose, sorbitol, cellulose, and pectins.2 Dietary starch is a polysaccharide consisting of long chains of glucose molecules (Fig. 50-6). Amylose makes up about 20% of starch in the diet and is broken down at the α-1,4 bonds by salivary (i.e., ptyalin) and pancreatic amylases that convert amylose to maltotriose and maltose. Amylopectin, making up about 80% of dietary starch, has branching points every 25 molecules along the straight glucose chains; the α-1,6 glucose linkages in amylopectin produce the end products of amylase digestion—maltose, maltotriose, and the residual branch saccharides, the dextrins. In general, the starches are almost totally converted into maltose and other small glucose polymers before they have passed beyond the duodenum or upper jejunum. The remainder of carbohydrate digestion occurs as a result of brush border enzymes of the luminal surface.
(Adapted from Alpers DH: Digestion and absorption of carbohydrates and proteins. In Johnson LR, Alpers DH, Christensen J, et al [eds]: Physiology of the gastrointestinal tract, ed 3, vol 2, New York, 1994, Raven Press, p 1727.)
The brush border of the small intestine contains the enzymes lactase, maltase, sucrase-isomaltase, and trehalase, which split the disaccharides, as well as other small glucose polymers, into their constituent monosaccharides (Table 50-1). Lactase hydrolyzes lactose into glucose and galactose. Maltase hydrolyzes maltose to produce glucose monomers. Sucrase-isomaltase is a complex of two subunits; sucrase hydrolyzes sucrose to yield glucose and fructose, and isomaltase hydrolyzes the α-1,6 bonds in α-limit dextrins to yield glucose. Glucose represents more than 80% of the final products of carbohydrate digestion, with galactose and fructose usually representing no more than 10% of the products of carbohydrate digestion.
|α-1,4-linked oligosaccharides, up to nine residues
|Sucrase-isomaltase (sucrose-α -dextrinase)
|α-1,4-link at nonreducing end
From Marsh MN, Riley SA: Digestion and absorption of nutrients and vitamins. In Feldman M, Sleisenger MH, Scharschmidt BF (eds): Sleisenger and Fordtran’s gastrointestinal and liver disease: Pathophysiology, diagnosis, management, vol 2, Philadelphia, 1998, WB Saunders, p 1480.
The carbohydrates are absorbed in the form of monosaccharides. Transport of the released hexoses (glucose, galactose, and fructose) is by specific mechanisms involved in active transport. The major routes of absorption are by three membrane carrier systems—sodium glucose transporter 1 (SGLT-1), glucose transporter 5 (GLUT-5), and glucose transporter 2 (GLUT-2)2 (Fig. 50-7). Glucose and galactose are absorbed by a carrier-mediated active transport mechanism, which involves the cotransport of Na+ (SGLT-1 transporter). As Na+ diffuses into the inside of the cell, it pulls the glucose or galactose along with it, thus providing the energy for transport of the monosaccharide. The exit of glucose from the cytosol into the intracellular space is predominantly by a Na+-independent carrier (GLUT-2 transporter) located at the basolateral membrane. Fructose, the other significant monosaccharide, is absorbed from the intestinal lumen through a process of facilitated diffusion. The carrier involved in fructose absorption is GLUT-5, which is located in the apical membrane of the enterocyte. This transport process does not depend on Na+ or energy. Fructose exits the basolateral membrane by another facilitated diffusion process involving the GLUT-2 transporter.
FIGURE 50-7 Model for glucose, galactose, and fructose transport across the intestinal epithelium. Glucose and galactose are transported into the enterocyte across the brush border membrane by the Na+ glucose cotransporter (SGLT-1) and then transported out across the basolateral membrane down their concentration gradients by GLUT-2. The low intracellular Na+ driving uphill sugar transport across the brush border is maintained by the Na+,K+ pump on the basolateral membrane. Glucose and galactose therefore stimulate Na+ absorption across the epithelium. Fructose is transported across the cell down the concentration gradient across the brush border and basolateral membranes. GLUT-5 is the brush border fructose transporter, whereas GLUT-2 handles fructose transport across the basolateral membrane.
(From Wright EM, Hirayama BA, Loo DDF, et al: Intestinal sugar transport. In Johnson LR, Alpers DH, Christensen J, et al [eds]: Physiology of the gastrointestinal tract, ed 3, vol 2, New York, 1994, Raven Press, p 1752.)
Protein digestion is initiated in the stomach, where gastric acid denatures proteins.2 Digestion is continued in the small intestine, where the protein comes into contact with pancreatic proteases. Pancreatic trypsinogen is secreted in the intestine by the pancreas in an inactive form but becomes activated by the enzyme enterokinase, a brush border enzyme in the duodenum. Activated trypsin then activates the other pancreatic proteolytic enzyme precursors. The endopeptidases, which include trypsin, chymotrypsin, and elastase, act on peptide bonds at the interior of the protein molecule, producing peptides that are substrates for the exopeptidases (carboxypeptidases), which serially remove a single amino acid from the carboxyl end of the peptide (Table 50-2). This results in splitting the complex proteins into dipeptides, tripeptides, and some larger proteins, which are absorbed from the intestinal lumen by an Na+-mediated active transport mechanism and digested further by enzymes in the brush border and in the cytoplasm of the enterocytes (Fig. 50-8). These peptidase enzymes include aminopeptidases and several dipeptidases, which split the remaining larger polypeptides into tripeptides and dipeptides and some amino acids. The amino acids, dipeptides, and tripeptides are easily transported through the microvilli into the epithelial cells where, in the cytosol, additional peptidases hydrolyze the dipeptides and tripeptides into single amino acids; these then pass through the epithelial cell membrane into the portal venous system. In normal humans, digestion and absorption of protein are usually 80% to 90% completed in the jejunum.
|Hydrolyze interior peptide bonds of polypeptides and proteins
|Attacks peptide bonds involving basic amino acids; yields products with basic amino acids at carboxyl-terminal end
|Attacks peptide bonds involving aromatic amino acids, leucine, glutamine, and methionine; yields peptide products with these amino acids at carboxyl-terminal end
|Attacks peptide bonds involving neutral aliphatic amino acids; yields products with neutral amino acids at carboxyl-terminal end
|Hydrolyze external peptide bonds of polypeptides and protein
|Attacks peptides with aromatic and neutral aliphatic amino acids at carboxyl-terminal end
|Attacks peptides with basic amino acids at carboxyl-terminal end
From Castro GA: Digestion and absorption. In Johnson LR (ed): Gastrointestinal physiology, St Louis, 1991, Mosby, pp 108-130.
Most adults in North America consume 60 to 100 g/day of fat. Triglycerides, the most abundant fats, are composed of a glycerol nucleus and three fatty acids; small quantities of phospholipids, cholesterol, and cholesterol esters also are found in the normal diet. Essentially all fat digestion occurs in the small intestine, where the first step is the breakdown of fat globules into smaller sizes to facilitate further breakdown by water-soluble digestive enzymes, a process termed emulsification.2 This process is facilitated by bile from the liver, which contains bile salts and the phospholipid lecithin. The polar parts of the bile salts and lecithin molecules are soluble in water, whereas the remaining portions are soluble in fat. Therefore, the fat-soluble portions dissolve in the surface layer of the fat globules and the polar portions, projecting outward, are soluble in the surrounding aqueous fluids. This arrangement renders the fat globules more accessible to fragmentation by agitation in the small intestine. Therefore, a major function of bile salts, and especially lecithin in the bile, is to allow the fat globules to be readily fragmented by agitation in the intestinal lumen. With the increase in surface area of the fat globules resulting from the action of the bile salts and lecithin, the fats can now be readily attacked by pancreatic lipase, the most crucial enzyme in the digestion of triglycerides, which splits triglycerides into free fatty acids and 2-monoglycerides.
Fat digestion is further accelerated by bile salts, which, secondary to their amphipathic nature, can form micelles. Micelles are small spherical globules composed of 20 to 40 molecules of bile salts with a sterol nucleus that is highly fat-soluble and a hydrophilic polar group that projects outward. The mixed micelles thus formed are arrayed so that the insoluble lipid is surrounded by the bile salts oriented with their hydrophilic ends facing outward. Therefore, as quickly as the monoglycerides and free fatty acids are formed by lipolysis, they become dissolved in the central hydrophobic portion of the micelles, which then act to carry these products of fat hydrolysis to the brush borders of the epithelial cells, where absorption occurs.
The monoglycerides and free fatty acids, which are dissolved in the central lipid portion of the bile acid micelles, are absorbed through the brush border because of their highly lipid-soluble nature and simply diffuse into the interior of the cell.2 After disaggregation of the micelle, bile salts remain within the intestinal lumen to enter into the formation of new micelles and act to carry more monoglycerides and fatty acids to the epithelial cells. The released fatty acids and monoglycerides in the cell re-form into new triglycerides. This re-formation of a triglyceride occurs in the cell through the interactions of intracellular enzymes that are associated with the endoplasmic reticulum.
The major pathway for resynthesis involves synthesis of triglycerides from 2-monoglycerides and coenzyme A (CoA)–activated fatty acids. Microsomal acyl-CoA lipase is necessary to synthesize acyl-CoA from the fatty acid before esterification. These reconstituted triglycerides then combine with cholesterol, phospholipids, and apoproteins to form chylomicrons, which consist of an inner core containing triglycerides and a membranous outer core of phospholipids and apoproteins. The chylomicrons pass from the epithelial cells into the lacteals, where they pass through the lymphatics into the venous system. From 80% to 90% of all fat absorbed from the gut is absorbed in this manner and transported to the blood by way of the thoracic lymph in the form of chylomicrons. Small quantities of short- to medium-chain fatty acids may be absorbed directly into the portal blood rather than being converted into triglycerides and absorbed into the lymphatics. These shorter chain fatty acids are more water-soluble, which allows for the direct diffusion into the bloodstream.
The proximal intestine absorbs most of the dietary fat. Although the unconjugated bile acids are absorbed into the jejunum by passive diffusion, the conjugated bile acids that form micelles are absorbed in the ileum by active transport and are reabsorbed from the distal ileum. The bile acids then pass through the portal venous system to the liver for secretion as bile. The total bile salt pool in humans is 2 to 3 g; it recirculates about six times every 24 hours (the enterohepatic circulation of bile salts).2 Almost all the bile salts are absorbed, with only about 0.5 g lost in the stool every day; this is replaced by resynthesis from cholesterol.
Eight to 10 liters of water/day enter the small intestine. Much of this is absorbed, with only approximately 500 mL or less leaving the ileum and entering the colon2 (Fig. 50-9). Water may be absorbed by the process of simple diffusion. In addition, water may be drawn in and out of the cell through a process of osmotic pressure, resulting from active transport of sodium, glucose, or amino acids into cells.
(Adapted from Westergaard H: Short bowel syndrome. In Feldman M, Scharschmidt BF, Sleisenger MH [eds]: Sleisenger & Fordtran’s gastrointestinal and liver disease: Pathology, diagnosis, management, Philadelphia, 2002, WB Saunders, p 1549.)
Electrolytes can be absorbed in the small bowel by active transport or by coupling to organic solute.2 Na+ is absorbed by active transport through the basolateral membranes. Cl− is absorbed in the upper part of the small intestine by a process of passive diffusion. Large quantities of HCO3− must be reabsorbed, which is accomplished in an indirect fashion. As the Na+ is absorbed, H+ is secreted into the lumen of the intestine. It then combines with HCO3− to form carbonic acid, which then dissociates to form water and carbon dioxide. The water remains in the chyme, but the carbon dioxide is readily absorbed in the blood and is subsequently expired. Calcium is absorbed, particularly in the proximal intestine (duodenum and jejunum), by a process of active transport; absorption appears to be facilitated by an acid environment and is enhanced by vitamin D and parathyroid hormone. Iron is absorbed as a heme or nonheme component in the duodenum by an active process. Iron is then deposited within the cell as ferritin or transferred to the plasma bound to transferrin. The total absorption of iron is dependent on body stores of iron and the rate of erythropoiesis; any increase in erythropoiesis increases iron absorption. Potassium, magnesium, phosphate, and other ions also can be actively absorbed throughout the mucosa.
Vitamins are fat-soluble (e.g., vitamins A, D, E, and K) or water-soluble (e.g., ascorbic acid [vitamin C], biotin, nicotinic acid, folic acid, riboflavin, thiamine, pyridoxine [vitamin B6], and cobalamin [vitamin B12]).2 The fat-soluble vitamins are carried in mixed micelles and transported in chylomicrons of lymph to the thoracic duct and into the venous system. The absorption of water-soluble vitamins appears to be more complex than originally thought. Vitamin C is absorbed by an active transport process that incorporates a sodium-coupled mechanism as well as a specific carrier system. Vitamin B6 appears to be rapidly absorbed by simple diffusion into the proximal intestine. Thiamine (vitamin B1) is rapidly absorbed in the jejunum by an active process similar to the sodium-coupled transport system for vitamin C. Riboflavin (vitamin B2) is absorbed in the upper intestine by facilitated transport. The absorption of vitamin B12 occurs primarily in the terminal ileum. Vitamin B12 is derived from cobalamin, which is freed in the duodenum by pancreatic proteases. The cobalamin binds to intrinsic factor, which is secreted by the stomach, and is protected from proteolytic digestion. Specific receptors in the terminal ileum take up the cobalamin–intrinsic factor complex, probably by translocation. In the ileal enterocyte, free vitamin B12 is bound to an ileal pool of transcobalamin II, which transports it into the portal circulation.
Food particles are propelled through the small bowel by a complex series of muscular contractions.2 Peristalsis consists of intestinal contractions passing aborally at a rate of 1 to 2 cm/second. The major function of peristalsis is the movement of intestinal chyme through the intestine. Motility patterns in the small bowel vary greatly between the fed and fasted states. Pacesetter potentials, which are thought to originate in the duodenum, initiate a series of contractions in the fed state that propel food through the small bowel.
During the interdigestive (fasting) period between meals, the bowel is regularly swept by cyclical contractions that move aborally along the intestine every 75 to 90 minutes. These contractions are initiated by the migrating myoelectric complex (MMC), which is under the control of neural and humoral pathways. Extrinsic nerves to the small bowel are vagal and sympathetic. The vagal fibers have two functionally different effects; one is cholinergic and excitatory and the other is peptidergic and probably inhibitory. Sympathetic activity inhibits motor function, whereas parasympathetic activity stimulates it. Although intestinal hormones are known to affect small intestinal motility, the one peptide that has been clearly shown to function in this regard is motilin, which is found at its peak plasma level during phase III (intense bursts of myoelectrical activities resulting in regular, high-amplitude contractions) of MMCs.
The gastrointestinal hormones are distributed along the length of the small bowel in a spatially specific pattern. In fact, the small bowel is the largest endocrine organ in the body. Although often classified as hormones, these agents do not always function in a truly endocrine fashion (i.e., discharged into the bloodstream, where an action is produced at some distant site; Fig. 50-10). Sometimes, these peptides are discharged and act locally in a paracrine or autocrine manner. In addition, these peptides may serve as neurotransmitters (e.g., vasoactive intestinal peptide). The gastrointestinal hormones play a major role in pancreaticobiliary and intestinal secretion and motility. In addition, certain gastrointestinal hormones exert a trophic effect on normal and neoplastic intestinal mucosa and pancreas. The location, major stimulants of release, and primary effects of the more important gastrointestinal hormones are summarized in Table 50-3. In addition, the diagnostic and therapeutic uses of gastrointestinal hormones are listed in Table 50-4. Dockray3 and Gariepy and Dickinson4 have presented a more in-depth discussion of the structure, molecular biology, physiologic functions, and uses of these hormones.
(Adapted from Miller LJ: Gastrointestinal hormones and receptors. In Yamada T, Alpers DH, Laine L, et al [eds]: Textbook of gastroenterology, ed 3, vol 1, Philadelphia, 1999, Lippincott Williams & Wilkins, p 37.)
|DIAGNOSTIC AND THERAPEUTIC USES
|Pentagastrin (gastrin analogue) used to measure maximal gastric acid secretion
|Biliary imaging of gallbladder contraction
|Provocative test for gastrinoma
|Measurement of maximal pancreatic secretion
|Suppresses bowel motility for endocrine spasm
|Relieves sphincter of Oddi spasm
|Provocative test for insulin, catecholamine, and growth hormone release
|Treat carcinoid diarrhea and flushing
|Decrease secretion from pancreatic and intestinal fistulas
|Ameliorate symptoms associated with hormone-overproducing endocrine tumors
|Treat esophageal variceal bleeding
The gastrointestinal hormones interact with their cell surface receptors to initiate a cascade of signaling events that eventually culminate in their physiologic effects. These hormones primarily signal through G protein–coupled receptors that traverse the plasma membrane seven times and represent the largest group of receptors found in the body. The heterotrimeric G proteins, which are composed of α, β, and γ subunits, are the molecular switches for signal transduction. Agonist binding to the seven-transmembrane domain receptor is thought to cause a conformational change in the receptor that allows it to interact with the G proteins. Intracellular second messengers that can then be activated include cyclic adenosine monophosphate (cAMP), Ca2+ cyclic guanosine monophosphate (cGMP), and inositol phosphate.
In addition to the gastrointestinal hormones, a number of other peptides and growth factors are located in the gastrointestinal mucosa, including epidermal growth factor, transforming growth factor-α and -β, insulin-like growth factor, fibroblast growth factor, and platelet-derived growth factor. These peptides play a role in cell growth and differentiation and act through tyrosine kinase receptors, which have a single membrane-spanning domain.
A third class of surface receptors, the ion channel–linked receptors, are found most commonly in cells of neuronal lineage and usually bind specific neurotransmitters. Examples include receptors for excitatory (acetylcholine and serotonin) and inhibitory (γ-aminobutyric acid, glycine) neurotransmitters. These receptors undergo a conformational change on binding of the mediator, which allows passage of ions across the cell membrane and results in changes in voltage potential.
During the course of a normal day, we ingest a number of bacteria, parasites, and viruses. The large surface area of the small bowel mucosa represents a potential major portal of entry for these pathogens; the small intestine serves as a major immunologic barrier in addition to its important role in digestion and endocrine function. As a result of constant antigenic exposure, the intestine possesses abundant lymphoid cells (e.g., B and T lymphocytes) and myeloid cells (e.g., macrophages, neutrophils, eosinophils, mast cells). To deal with the constant barrage of potential toxins and antigens, the gut has evolved into a highly organized and efficient mechanism for antigen processing, humoral immunity, and cellular immunity. The gut-associated lymphoid tissue is localized in three areas—Peyer patches, lamina propria lymphoid cells, and intraepithelial lymphocytes.
Peyer patches are unencapsulated lymphoid nodules that constitute an afferent limb of the gut-associated lymphoid tissue, which recognizes antigens through the specialized sampling mechanism of the microfold (M) cells contained within the follicle-associated epithelium (Fig. 50-11). Antigens that gain access to the Peyer patches activate and prime B and T cells in that site. The M cells cover the lymphoid follicles in the gastrointestinal tract and provide a site for the selective sampling of intraluminal antigens. Activated lymphocytes from intestinal lymphoid follicles then leave the intestinal tract and migrate into afferent lymphatics that drain into mesenteric lymph nodes. Furthermore, these cells migrate into the lamina propria. The B lymphocytes become surface immunoglobulin A (IgA)–bearing lymphoblasts, which serve a critically important role in mucosal immunity.
FIGURE 50-11 Mucosal barrier of the gut. Antigens contact specialized microfold (M) cells overlying Peyer patches, which then process and present the antigen to the immune system. When B lymphocytes are stimulated by antigenic material, the cells develop into antibody-forming cells that secrete various types of immunoglobulins, the most important of which is IgA.
(Adapted from Duerr RH, Shanahan F: Food allergy. In Targan SR, Shanahan F [eds]: Immunology and immunopathology of the liver and gastrointestinal tract, New York, 1990, Igaku-Shoin, p 510.)
B lymphocytes and plasma cells, T lymphocytes, macrophages, dendritic cells, eosinophils, and mast cells are scattered throughout the connective tissue of the lamina propria. Approximately 60% of the lymphoid cells are T cells. These T lymphocytes are a heterogeneous group of cells and can differentiate into one of several types of T effector cells. Cytotoxic T effector cells damage the target cells directly. Helper T cells are effector cells that help mediate induction of other T cells or the induction of B cells to produce humoral antibodies. T suppressor cells perform just the opposite function. Approximately 40% of the lymphoid cells in the lamina propria are B cells, which are primarily derived from precursors in Peyer patches. These B cells and their progeny, plasma cells, are predominantly focused on IgA synthesis and, to a lesser extent, on IgM, IgG, and IgE synthesis.
The intraepithelial lymphocytes are located in the space between the epithelial cells that line the mucosal surface and lie close to the basement membrane. It is thought that most of the intraepithelial lymphocytes are T cells. On activation, the intraepithelial lymphocytes may acquire cytolytic functions that can contribute to epithelial cell death through apoptosis. These cells may be important in the immunosurveillance against abnormal epithelial cells.
As noted, one of the major protective immune mechanisms for the intestinal tract is the synthesis and secretion of IgA. The intestine contains more than 70% of the IgA-producing cells in the body. IgA is produced by plasma cells in the lamina propria and is secreted into the intestine, where it can bind antigens at the mucosal surface. The IgA antibody traverses the epithelial cell to the lumen by means of a protein carrier (the secretory component) that not only transports the IgA, but also protects it against the intracellular lysosomes. IgA does not activate complement and does not enhance cell-mediated opsonization or destruction of infectious organisms or antigens, which is in sharp contrast with the role of other immunoglobulins. Secretory IgA inhibits the adherence of bacteria to epithelial cells and prevents their colonization and multiplication. In addition, secretory IgA neutralizes bacterial toxins and viral activity and blocks the absorption of antigens from the gut.
The description of patients presenting with small bowel obstruction dates back to the third or fourth century BC, when Praxagoras created an enterocutaneous fistula to relieve a bowel obstruction. Despite this success with operative therapy, the nonoperative management of these patients with attempted reduction of hernias, laxatives, ingestion of heavy metals (e.g., lead, mercury), and leeches to remove toxic agents from the blood was the rule until the late 1800s, when antisepsis and aseptic surgical techniques made operative intervention safer and more acceptable. A better understanding of the pathophysiology of bowel obstruction and the use of isotonic fluid resuscitation, intestinal tube decompression, and antibiotics has greatly reduced the mortality rate for patients with a mechanical bowel obstruction. However, patients with a bowel obstruction still represent some of the most difficult and vexing problems that surgeons face with regard to correct diagnosis, optimal timing of therapy, and appropriate treatment. Ultimate clinical decisions regarding the management of these patients dictates a thorough history and workup and heightened awareness of potential complications.
Box 50-1 Adapted from Tito WA, Sarr MG: Intestinal obstruction. In Zuidema GD (ed): Surgery of the alimentary tract, Philadelphia, 1996, WB Saunders, pp 375–416.
Causes of Mechanical Small Intestinal Obstruction in Adults
The causes of small bowel obstruction have changed dramatically since the 1900s.5 At the turn of the 20th century, hernias accounted for more than 50% of mechanical intestinal obstructions. With the routine elective repair of hernias, this cause has dropped to the third most common cause of small bowel obstruction in industrialized countries. Adhesions secondary to previous surgery are now the most common cause of small bowel obstruction (Fig. 50-12).
Adhesions, particularly after pelvic operations (e.g., gynecologic procedures, appendectomy, colorectal resection), are responsible for more than 60% of all causes of bowel obstruction in the United States. This preponderance of lower abdominal procedures to produce adhesions that result in obstruction is thought to be caused by the fact that the bowel is more mobile in the pelvis and more tethered in the upper abdomen.
Malignant tumors account for approximately 20% of the cases of small bowel obstruction. Most of these tumors are metastatic lesions that obstruct the intestine secondary to peritoneal implants that have spread from an intra-abdominal primary tumor, such as ovarian, pancreatic, gastric, or colon cancer. Less often, malignant cells from distant sites, such as breast, lung, and melanoma, may metastasize hematogenously and account for peritoneal implants, resulting in an obstruction. Large intra-abdominal tumors may also cause small bowel obstruction through extrinsic compression of the bowel lumen. Primary colonic cancers, particularly those arising from the cecum and ascending colon, may present as a small bowel obstruction. Primary small bowel tumors can cause obstruction but are exceedingly rare.
Hernias are the third leading cause of intestinal obstruction and account for approximately 10% of all cases. Usually, these represent ventral or inguinal hernias. Internal hernias, generally related to prior abdominal surgery, can also result in small bowel obstruction. Less common hernias can also produce obstruction, such as femoral, obturator, lumbar, and sciatic hernias.
Crohn’s disease is the fourth leading cause of small bowel obstruction and accounts for approximately 5% of all cases. Obstruction can result from acute inflammation and edema, which may resolve with conservative management. In patients with long-standing Crohn’s disease, strictures can develop that may require resection and reanastomosis or strictureplasty.
An important cause of small bowel obstruction that is not routinely considered is obstruction associated with an intra-abdominal abscess, commonly from a ruptured appendix, diverticulum, or dehiscence of an intestinal anastomosis. The obstruction may occur as a result of a local ileus in the small bowel adjacent to the abscess. In addition, the small bowel can form a portion of the wall of the abscess cavity and become obstructed by kinking of the bowel at this point.
Miscellaneous causes of bowel obstruction account for 2% to 3% of all cases but should be considered in the differential diagnosis. These include intussusception of the bowel, which in the adult is usually secondary to a pathologic lead point, such as a polyp or tumor (Fig. 50-13), gallstones, which can enter the intestinal lumen by a cholecystenteric fistula and cause obstruction, enteroliths originating from jejunal diverticula, foreign bodies, and phytobezoars.
FIGURE 50-13 Jejunojenunal intussusception in an adult patient.
(Courtesy Dr. Steven Williams, Nampa, ID.)