Physiology, Small Bowel

Article Author:
Elizabeth Fish
Article Editor:
Bracken Burns
2/1/2019 2:30:31 PM
PubMed Link:
Physiology, Small Bowel


The small intestine is a 6- to 7-meter-long tubular organ, beginning at the pylorus of the stomach and ending at the ileocecal valve. From more proximal to distal, the small bowel is divided into the duodenum, jejunum, and ileum. Whereas the large intestine is primarily responsible for the absorption and transport of water and electrolytes, the small intestine’s main job is digestion and absorption of nutrients. Digestion involves the mechanical and chemical breakdown of substances/nutrients, while absorption involves the uptake of these substances. The mucosa of the small intestine lines the lumen, and the cells of the mucosa responsible for absorption are termed enterocytes. Enterocytes have about 3000 microvilli on their surfaces, helping to increase the surface area to facilitate effective absorption. Each region of the small bowel can absorb and digest a variety of nutrients, including carbohydrates, proteins, fats, water, and fat-soluble vitamins, minerals, and micronutrients.[1]


Enterocytes, gastrointestinal cells responsible for absorption, have villi and microvilli that increase absorption by 30- to 600-fold. These villi are covered by columnar epithelial cells. This region is collectively called the brush border. Crypt cells are also found in the small intestine, yet they are primarily secretory. Many transport proteins are responsible for solute transport across the gastrointestinal tract, whereas fluid movement across the epithelium happens due to active transport of mainly sodium, chloride, and bicarbonate.[2]


Development of the small bowel begins at week 3 with gastrulation. Gastrulation involves early tubular and digestive gland formation. It is composed of all three germ cell layers, including ectoderm, mesoderm, and endoderm. The small intestine epithelium is made from the endoderm. Tube formation is facilitated by many genes, including SOX9, GATA4, and FOXA2. The Hox signalizing pathway, involving interplay between the endoderm and mesoderm, determines the different features of the small intestine. Around week 4, the premature midgut is open to the yolk sac, which grows more slowly than the developing embryo. Eventually, the edges of the embryonic disc come together with the midgut. This forms the small intestinal lumen and the yolk sac becomes the vitelline duct. By week 5, the midgut has grown to the point that it must begin folding onto itself, and during the 6 week, the loops herniate through the umbilicus. This herniation allows more room for the developing bowel, liver, and kidneys to grow. By weeks 9 to 10, the small bowel may return to the abdomen. Counterclockwise rotation 90 degrees during herniation (week 6) allows for the ileum to reach the right upper quadrant, and another counterclockwise rotation of 180 degrees happens as the intestinal loops return to the abdomen. Around week 11, the process is complete, and the small intestinal components are in their final arrangement. The villi and microvilli form during week 11. Throughout early development, the epithelium of the small intestine goes through recurrent turnover via stem cells. The cells are then able to migrate upward and reach lumen. The enteric nervous system (ENS) is completed by week 13 of development, and it originates from neural crest cells, and the vagal nerve thus supplies the small intestine.[1]

Organ Systems Involved

Although digestion and absorption of nutrients primarily happens in the small bowel, other areas of the body provide additional enzymes involved. The salivary glands, stomach, pancreas, and small intestine interact with each other to facilitate digestion and absorption. Due to the involvement of these other organs, malabsorption issues and clinical diagnoses may stem from regions other than the small intestine. For example, pancreatic insufficiency, pernicious anemia, and cystic fibrosis are all diseases involving malabsorption, yet they do not originate in the small intestine.


Carbohydrates, proteins, and lipids are digested and absorbed by the small intestine. Dietary carbohydrates begin as polysaccharides, such as amylose, or disaccharides, such as lactose, sucrose, maltose, or trehalose. Each disaccharide is made up of 2 monosaccharides. The monosaccharides are glucose, fructose, and galactose. For the small bowel enterocytes to absorb carbohydrates, they must be broken down into monosaccharides. The enzyme responsible for carb digestion is amylase, which is found in the saliva and pancreas. Alpha-amylase is found in the mouth and begins the digestion of carbohydrates, but the pancreatic amylase is primarily responsible for hydrolyzing starches. Along with amylase, the small intestine brush border contains enzymes that digest carbohydrates, including maltase, isomaltase, sucrase, beta-galactosidase, and trehalase complex. The monosaccharides are absorbed on the apical membrane via carrier-mediated transporters, SGLT1 and GLUT5. Glucose and galactose use SGLT1 (fueled by sodium), while GLUT5 transports fructose.[1]

Protein digestion occurs via the breaking of peptide bonds through hydrolysis by proteolytic enzymes. Proteins are broken down into their amino acids. Pepsin is a proteolytic enzyme in the stomach, which is where protein digestion is started. Chief cells secrete pepsinogen, an inactive precursor of pepsin, which can activate itself. Although pepsin helps digestion in the stomach, it is not completely necessary for protein digestion and must have an environment with a pH of 1 to 3 to work properly. Pepsin is not found in the small intestine, as the pancreatic fluids cause the duodenum to be a more basic environment. The pancreas secretes trypsin, chymotrypsin, elastase, and carboxypeptidase A and B. These proteases from the pancreas are released once the duodenum releases cholecystokinin (CCK) in the presence of proteins. The inactive forms of these pancreatic proteases are released first, and enteropeptidase (also called enterokinase) turns them into their active forms. Once Trypsin is activated, it can activate more of itself to hasten digestion. Protein digestion yields free amino acids, dipeptides, tripeptides, and oligopeptides. Dipeptides and tripeptides are transported via Pept-1, which requires a hydrogen ion gradient. Amino acid absorption involves many carrier-mediated active and facilitated transport proteins.[1]

Dietary fats come in the form of triglycerides and are acquired mostly from animal sources. Triglycerides are broken down into 2-monoglycerides and fatty acids. Lipid digestion enzymes come from many areas prior to the duodenum, including lingual, gastric, and pancreatic lipases. CCK release from the duodenum causes sluggish gastric emptying, allowing for more time for lipid digestion by the lingual and gastric lipases. There are also lipases within foods, termed food-bearing lipases, that can begin auto-digesting themselves. Colipase, lipase, phospholipase A2, and cholesterol ester hydrolase are pancreatic enzymes that break down fats. Bile salts cause the inactivation of lipases. Colipase prevents lipase inactivation. Emulsification is important in fat digestion, as it breaks fat globules into smaller droplets, increasing the surface area for pancreatic lipases. Absorption of lipids was thought to be passive, yet discovery of fatty acid binding proteins supports an active course. Fatty acids are relocated to the endoplasmic reticulum of enterocytes and reformed. Free fatty acids are most commonly absorbed in the jejunum of the small intestine.[1]

Vitamins and minerals are also absorbed by the small intestine. Folate goes through hydrolysis, is absorbed in the duodenum and upper part of the jejunum, and is actively transported into portal circulation. Vitamin B12, or Cobalamin, is absorbed in the terminal ileum. B12 must bind to R protein in the stomach. Once the B12-R complex reaches the duodenum, R protein is hydrolyzed, and B12 binds to intrinsic factor (IF), which is secreted by the gastric parietal cells. The B12-IF complex travels to the terminal ileum and enters the enterocyte via ileal receptors. Vitamins A, D, E, and K are fat-soluble and may be passively absorbed in the small bowel. Approximately 9 liters of water travels to the gastrointestinal tract per day, and the small intestine absorbs 7 to 8 liters, while the colon absorbs the remaining 1 to 2 liters. Water absorption is thought to occur via osmotic gradients and aquaporins on intestinal membranes.[1]

Related Testing

Although thorough history-taking can uncover the cause of malabsorption in many cases, classic symptoms may not be present, and diseases can mimic each other. Diagnostic testing can include an array of imaging studies, serology, and stimulation tests; however, workup will be driven by the clinical presentation.

Often, testing begins with routine labs when working up malabsorption. Labs obtained typically include a complete blood count (CBC), complete metabolic panel (CMP), iron studies, urinalysis, and coagulation panel. These blood tests can help support or discard certain diagnoses. Further diagnostic testing for suspected problems with absorption should be individualized based on patient presentation. These tests may include a combination of the following: qualitative and quantitative stool fat assessment, abdominal ultrasound, serologic markers for specific diseases like celiac and Crohn's disease, and colonoscopy, upper endoscopy or sigmoidoscopy when warranted. Additional imaging of the small intestine with barium studies, or magnetic resonance cholangiopancreatography (MRCP) and endoscopic retrograde cholangiopancreatography (ERCP) for suspected pancreatic etiologies of malabsorption, may be necessary in individual cases.[3]

When considering carbohydrate malabsorption, tests such as the lactose tolerance test and D-xylose test (measuring the capacity of small bowel absorption and aiding to mucosal etiologies) may be used.[4] Direct stimulation tests may be used to detect pancreatic insufficiency, along with measuring fecal elastase-1. Lastly, the Schilling test is an extensive method to identify a B12 deficiency, yet it is rarely necessary for the clinical setting.

Clinical Significance

Malabsorption can be classified as either global, involving the entire mucosa, or partial, dealing with malabsorption of specific nutrients. Clinical features of malabsorption are relatively specific to the type of nutrient that is deficient, yet weight loss and fatty, greasy stools are classical findings of global malabsorption. Stools are typically voluminous and pale. Most patients present with nonspecific gastrointestinal symptoms: abdominal pain, flatulence, anorexia, and distension. Patients with malabsorption issues may also be asymptomatic.[5]

During instances of isolated malabsorption, such as celiac disease, specific manifestations such as bone thinning or iron deficiency anemia may be the only presentation.[6] Malabsorption of carbohydrates can cause milk intolerance and watery diarrhea, protein can lead to muscle atrophy, and menstrual irregularities, folic acid, and iron deficiency lead to anemia, vitamin A deficiency causes night blindness, and vitamin K deficiency can cause bleeding disorders. It is also important to note that some causes of malabsorption, such as the malabsorption of fats from celiac disease or pancreatic insufficiency, can cause the malabsorption of other substances such as vitamin D, which needs chylomicrons to be effectively absorbed.

Based on the clinical implications of malabsorption, it is important to recognize that these diseases can cause great hindrances in patients’ lives, altering their ability to go about their daily activities. It is an important topic to continue researching as more pediatric patients are reaching adulthood with diseases such as short bowel syndrome, cystic fibrosis, and inflammatory bowel disease.[7]