Embryology
A. Origin
The small intestine forms during the fourth week of fetal development. The duodenum arises from the foregut, and the jejunum and ileum derive from the fetal midgut. The endoderm forms the absorptive epithelium and the secretory glands. The splanchnic mesoderm gives rise to the rest of the intestinal wall, including the musculature and the serosa.
B. Rotation
During the fifth week of fetal development, the intestine herniates through the umbilicus, rotating 90 degrees around the axis of the vitelline duct and the superior mesenteric artery. By the 10th week, the intestine returns to the abdominal cavity and rotates another 180 degrees. This rotation places the ligament of Treitz in the left upper quadrant and the cecum into the right upper quadrant. Around the fourth month, the cecum descends to the right lower quadrant.
C. Lumen formation
Between the fourth and seventh weeks, the small intestine is lined by cuboidal cells. Rapid proliferation occasionally occludes the lumen, particularly in the duodenum. Through apoptosis, the lumen regains patency by the 10th week.
II. Anatomy
A. Gross anatomy
The small intestine begins at the pylorus and extends approximately 3 m to the ileocecal valve. The duodenum measures 20 cm. The first portion, the bulb, is intraperitoneal, with the remaining second, third, and fourth portions retroperitoneal. The second portion is particularly important because biliary and pancreatic secretions enter at the ampulla of Vater. The jejunum measures approximately 100 cm, and the ileum measures 150 cm. The jejunum and ileum can be differentiated by closely examining the mesenteric blood supply. Jejunal arcades are fewer and larger than ileal arcades, with longer vessels between the arcades and the bowel wall. Furthermore, the jejunum has many circumferential mucosal folds called plicae circularis.
B. Vascular supply
The pancreaticoduodenal arteries supply the duodenum, connecting the gastroduodenal and superior mesenteric arteries. The superior mesenteric artery (SMA) supplies the jejunum and ileum. The superior mesenteric vein runs parallel to the SMA and provides the venous drainage of the small bowel, joining with the splenic vein to form the portal vein.
C. Lymphatic drainage
The submucosal Peyer patches feed small lymphatics extending to the mesenteric lymph nodes. From there, drainage parallels the course of the named blood vessels and eventually accumulates at the subdiaphragmatic cysterni chyli before entering the thoracic duct.
D. Innervation
The vagus nerve is the origin for all abdominal parasympathetic fibers and plays an important role in regulating intestinal secretions and motility. These fibers cross mesenteric ganglia, particularly the celiac ganglion, and innervate the myenteric ganglion cells within the walls of the small intestine. Three sets of sympathetic nerves innervate the gut. They form a plexus around the superior mesenteric artery and modulate intestinal blood supply, secretion, and motility. Sympathetic nerves carry all pain signals from the intestine.
E. Anatomy of the intestinal wall
Anatomy of the intestinal wall is uniform from the duodenum to the ileocecal valve, consisting of four distinct tissue layers.Mucosa. The epithelium, lamina propria, and muscularis mucosae compose the mucosa that lines the lumen of the gut.
The epithelium has both villi and crypts. The villi are protrusions of the epithelial layer into the lumen that act to dramatically increase absorptive capacity. The crypts are the sites of pluripotent cells that give rise to the absorptive enterocytes (over 95% of the epithelial layer), Paneth cells secrete lysozyme, tumor necrosis factor, and cryptidins, which function in nonspecific immunity. Goblet cells secrete mucus. There are more than ten different subpopulations of enteroendocrine cells, which secrete a variety of hormones. Of note, the entire intestinal lining is replaced every 3 to 5 days.
The lamina propria is a layer of loose connective tissue between the epithelial lining and the muscularis mucosae. Peyer patches, collections of lymphocytes that span the lamina propria and submucosa, are crucial for mucosal immunity.
The muscularis mucosa is a layer of muscle separating the mucosa from the submucosa.
Submucosa. This layer of connective tissue adjacent to the mucosa is the strongest layer of the intestinal wall. Blood vessels and nerves run within this layer, including Meissner ganglion cells.
Muscularis propria consists of a thicker, inner circular layer and an outer longitudinal layer of smooth muscle cells. The Auerbach (myenteric) ganglion cells are located between those layers.
Serosa is a single layer of flat mesothelial cells composing the outermost layer of the small bowel. Serosa lines the extraluminal surface of the anterior duodenum and the entire jejunum and ileum.
F. Enterocyte histology
Two particular structures enhance the absorptive area of an enterocyte. Microvilli (tiny apical protrusions or folds projecting into the lumen) and a glycocalyx coating outside the cell membrane both increase absorptive capacity. Digestive enzymes, such as disaccharidases, and sodium-nutrient cotransporters are located in the apical membrane. In the lateral membrane, tight junctions prevent crossing of intraluminal contents across the epithelial layer. Intermediate junctions and desmosomes also help to maintain the barrier function of the intestinal epithelium. Na-K ATPases and passive nutrient transporters are located in the basal membrane.
III. Physiology
Physiology of the small intestine involves a complex balance between absorption and secretion. The gut is also the largest endocrine organ in the human body.
A. Absorption
Absorption is the principal function of the gastrointestinal (GI) tract.
Water. Under normal circumstances, approximately 7 to 10 L of fluid enter the small intestine each day, but only 1 L reaches the colon. Of this fluid, 2 L are derived from oral intake, 1 L from saliva, 2 L from gastric secretion, 2 L from pancreatic secretion, 1 L from bile, and 1 L from small-intestinal secretion. Alterations in small-bowel permeability, tonicity of enteric substances, or rate of transit can result in diarrhea and large volume losses.
The majority of electrolyte absorption occurs in the small intestine. The most important electrolytes absorbed are sodium, chloride, and calcium. Sodium absorption occurs through passive diffusion, countertransport with hydrogen, and cotransport with chloride, glucose, and amino acids. Chloride is absorbed in exchange for bicarbonate, which accounts for the alkalinity of the luminal contents. Calcium is actively absorbed in the proximal small intestine by a process that is stimulated by vitamin D. Emesis, diarrhea, obstruction, and small-bowel ostomy effluent can result in impaired small-bowel electrolyte absorption.
Bile salts and vitamin B12–intrinsic factor complexes are absorbed in the terminal ileum. Resection that leaves less than 100 cm of the ileum can result in bile acid deficiencies that limit absorption of the fat-soluble vitamins A, D, E, and K. Vitamin B12 deficiency can result in chronic megaloblastic anemia (pernicious anemia).
Nutrients. The absorption of carbohydrates, proteins, and fat is discussed in Chapter 2 and in the next section.
B. Digestion
Macronutrient digestion by salivary, gastric, biliary, and pancreatic secretions is covered in Chapter 2. This section discusses digestion at the level of the enterocyte.
Brush border peptidases and disaccharidases break down peptides and disaccharides into simple amino acids and monosaccharides.
Active transport via Na-K ATPases in the basolateral membrane of enterocytes keeps the intracellular Na concentration very low. This sodium gradient enables Na-nutrient cotransporters to move amino acids and monosaccharides into enterocytes.
Passive transport. After digestion by pancreatic lipases, triglycerides and fatty acids form micelles with bile salts. These micelles diffuse across the apical membrane and are reconstituted into chylomicrons, which subsequently enter submucosal lymphatics.
C. Motility
Types of contractions
Circular muscle contractions can temporarily segment the intestine for improved mixing of contents or they can propel food toward the colon if they progress caudad.
When the longitudinal muscle contracts, sleeve contractions shorten the intestinal length, helping to propel food forward.
Neurohumoral effects. Vagal cholinergic input and hormones such as motilin and cholecystokinin (CCK) stimulate contractions. Conversely, sympathetic neurons inhibit peristalsis.
During the fasting state, the migrating motor complex (MMC) performs the housekeeping function of clearing the lumen of debris. After a period of rest, random contractions of moderate strength are followed by several very strong contractions.
During the fed state, contractions occur more frequently and last longer. Of interest, multiple areas of the small bowel may contract at the same time. From each site of contraction, peristalsis proceeds caudally for a varying distance.
D. Immunity
Tight junctions between the enterocyte apical membranes provide a barrier function and prevent pathogens from crossing the epithelium. Mucosal plasma cells secrete immunoglobulin A (IgA), which binds intraluminal pathogens and targets them for destruction.
M cells are located in the epithelial layer over the Peyer patches. They facilitate the conveying of antigens directly to macrophages and lymphocytes and help to initiate acquired immunity to luminal pathogens.
γδ T cells can be located within vacuoles of M cells and seem to have immunosuppressive effects. This may explain nonreactivity to ingested food.
E. Endocrine
Endocrine function is regulated by neural, hormonal (both autocrine and paracrine), and anatomic mechanisms.
Cholecystokinin is produced by duodenal and jejunal I cells and enteric nerves in response to intraluminal amino acids and fats. CCK induces gallbladder contraction, pancreatic enzyme secretion, and relaxation of the sphincter of Oddi.
Enteroglucagon from ileal and colonic L cells is produced in response to intraluminal fat and bile acids. Of note, inflammatory processes, such as Crohn disease and celiac sprue, can dramatically increase enteroglucagon secretion.
Gastric inhibitory peptide (GIP), secreted by duodenal and jejunal K cells in response to active transport of monosaccharides, long-chain fatty acids, and amino acids, inhibits gastric acid and pepsinogen secretion and gastric emptying but stimulates insulin release.
Duodenal G cells secrete gastrin in response to vagal stimulation and intraluminal peptides. Gastrin stimulates acid secretion by the gastric fundus and body and increases gastric mucosal blood flow.
Motilin is produced by duodenal and jejunal M cells in response to duodenal acid, vagal stimulation, and gastrin-releasing peptide. Motilin initiates phase III of the MMC during the fasting state. Erythromycin is useful as a promotility agent due to its action as a motilin agonist.
Duodenal and jejunal S cells release secretin in response to acid, bile salts, and fatty acids in the duodenum. Secretin increases bicarbonate and water secretion from pancreatic ducts. It inhibits gastric acid secretion and gastric motility.
Somatostatin broadly inhibits gut exocrine and endocrine function. Somatostatin and its analog, octreotide, are often used to decrease the volume of intestinal secretions in patients with enterocutaneous fistulas. Intestinal D cells and enteric neurons secrete somatostatin in response to intraluminal fat, protein, and acid.
Vasoactive intestinal peptide (VIP) is secreted throughout the small intestine in response to vagal stimulation. VIP increases