The Gastrointestinal Physiology
The gastrointestinal (GI) system is a complex system for processing food, extracting nutrients and passing wastes. The alimentary canal begins in the mouth and ends at the anus. The processes chewing, swallowing, digestion, absorption, defecation are controlled by autonomic, nervous and hormonal mechanisms. Digestive glands act to provide moisture, lubrication, emulsification and enzymes for digestion of proteins, carbohydrates and fats. Dysfunction and disease of the gastrointestinal system are covered in the companion web site Gastrointestinal.net.
Anatomy & Physiology
Anatomically the GI tract is a tube that from the exterior to the lumen is composed of connective tissue, smooth muscle layers with embedded nervous plexus, connective tissue, and an inner epithelial layer. The epithelial type, muscle thickness, gladular elements and nervous supply differ in the various functional regions, as does the diameter and shape of the tube.
The features of the oral cavity participate in digestion by reducing the food to smaller pieces, moistening and lubricating the food and by the addtion of amylase for the breakdown of carbohydrates. The teeth are specialized for cutting and grinding the food to small pieces so that there is more surface area for digestive enzymes to work on and to ease swallowing. The tongue moves the food around within the mouth and has taste receptors for sweet, salt, sour, and bitter. Salivary glands add saliva which contains water, ions, salivary amylase and mucous. When the food bolus is of the proper consistency, the tongue moves it to the back of the mouth where swallowing is initiated. The epiglottis covers the trachea as the bolus is passed into the esophagus. The bolus stretches the esophagus initiating smooth muscle contractions that push the bolus along toward the stomach in peristaltic waves.
The esophagus joins the stomach near the diaphragm which normally pinches the esophagus closed due to its muscular tone. Stomach movement also helps to keep the esophagus closed. The net effect is that the esophageal-gastric junction can withstand 10-20 mmHg pressure from the stomach. The stomach is a muscular pear-shaped organ where serious digestion begins. Three layers of smooth muscle act to mix the incoming food bolus with gastric fluids. Glands within the stomach lining produce hydrochloric acid (pH<1) and the enzyme precursor pepsinogen. Pepsin becomes active in the acidic environment of the stomach. The stomach is separated into three functional areas: the cardiac, fundic and pyloric regions. The cardiac region is closest to the heart and contains the esophageal junction and only a few glands. The fundic region contains complex glands secreting hydrochloric acid, mucous, intrinsic factor, pepsinogen and other proteases. The pyloric region contains very few glandular elements, other than mucous producing cells, but rather serves as a muscular gatekeeper to the duodenum, the first portion of the small intestine.
The gastric contents are emptied into the small intestine as long as the paticle sizes are not too large or the duodenal pressure is not too high. Other factors involved in gastric emptying include the temperature of the chyme, duodenal pH, and osmolarity of chyme. The duodenum accepts material from the stomach at a relatively constant caloric rate such that highly caloric chyme enters the duodenum at a slower rate. Emulsifying bile enters the duodenum from the gall bladder and pancreatic secretions water, enzymes and sodium bicarbonate) are added here as well. Most digestion and absorption occurs in the upper two thirds (duodenum and jejunum) of the almost nine foot long small intestine and removal of water and bile salts occurs in the lower one third (ileum). Cells lining the lumen of the small intestine are called enterocytes. These cells are replaced every 3-5 days by new cells arising from deep within simple tubular glands (crypts of Lieberkuhn). The interior lining of the small intestine has numerous projections into the lumen called villi. The villi function to increase the surface area available for digestion and absorption. Enterocytes also have adaptations to increase absorptive surface area on their luminal border called microvilli.
In the colon, ions are secreted for elimination or recovered along with water from the chyme. Colonic bacteria modify the contents such that biogenic amines like histamine or serotonin may be formed, the yellowish bile pigments are altered causing a brown color, and fermentation produces the odor causing chemicals in feces. Bacteria also make vitamin K and some B-complex vitamins that are absorbed in the colon. The bacterial flora vary with individuals and can change with diet, medication, or environmental changes. Such changes may cause diarrhea, gas or constipation . The colon is separated into three anatomic regions; the ascending, transverse and descending. The ascending and transverse sections absorb water and electrolytes and excrete metal ions. The descending colon removes water from the feces and controls the delivery of feces to the rectum. Wastes are removed by defecation as initiated by stretching of the rectal walls.
The various salivary glands add water, electrolytes, mucous and salivary amylase to the food as it is chewed. Secretory cells filter and modify the blood to produce saliva. In humans these secretions are mostly water. Parotid, submaxillary, sublingual glands add saliva to the food during mastication. Salivary amylase begins the breakdown of carbohydrates while the food is still in the mouth. Salivary lysozyme lyses bacterial cell walls. Mucopolysaccharides act as lubricants and the water acts to extract flavors from food. Salivary secretion is controlled by the nervous system.
Gastric glands are present throughout the mucosa of the stomach. These deep tubular glands secrete electrolytes and produce pepsinogen and other proteases at the bottom (chief cells), hydrochloric acid in the neck and body of the gland (parietal cells), and mucous at the neck and opening of the gland. The mucous acts to protect the gastric lining from the acid and enzymes present. Parietal cells also produce a protein called intrinsic factor that is necessary for the absorption of vitamin B12 in the ileum. Pepsinogen is activated by the removal of a small fragment. Pepsin works optimally to digest proteins at a pH of 1.5-2.5. The enzyme rennin is most active in infants where it causes milk proteins to curdle.
The pancreas has two gladular portions; the endocrine portion and the exocrine protein. Cells of the pancreatic islet make up the endocrine portion and secrete insulin and glucagon into the blood stream as needed. The exocrine portion participates in digestion by the secretion of the natural antacid , bicarbonate, electrolytes, fluid and digestive enzymes that are added to the contents of the duodenum. Secretion by the exocrine pancreas is regulated mostly by GI hormones with some minor influence of the nervous system. The secretions of the pancreas are rich in bicarbonate and other electrolytes. The bicarbonate and electrolytes help to buffer the incoming acidic chyme from the stomach.
Pancreatic enzymes are made by the acinar cells and packaged as inactive precursors into granules prior to release. The enzymes are activated by cleavage of small fragments when acted upon by other pancreatic or intestinal enzymes. Pancreatic trypsinogen, chymotrypsinogen, carboxypeptidase, aminopeptidase, lipase, amylase, ribonucleases, deoxyribonucleases, elastase, alkaline phosphatase, cholesterol esterase and other enzymes reduce food stuffs to absorbable elements.
The liver is an important metabolic, digestive, and excretory organ. It participates in digestive function by the production of bile which when added to the duodenal contents emulsifies fats enabling them to be broken down. Bile is produced in the liver but is stored in the gall bladder until it is needed. In the gall bladder the bile is concentrated by the removal of water and the addition of bicarbonate. Bile salts are steroid or cholesterol derivatives synthesized or recovered from the blood by liver cells. Liver cells also make and secrete lecithin that emulsifies dietary fats. Products of hemoglobin metabolism are excreted in bile salts. In an enterohepatic circulation process bile salts and other substances enter the lumen of the GI tract in the duodenum and are reabsorbed further down the intestine into the blood. The substances are removed from the blood again by liver cells.
Intestinal secretions participate in digestion by adding fluid, electrolytes, and enzymes. Enzymes include intestinal amylase, enterokinase, disaccharidases, peptidases, lipases, nucleotidases and nucleosidases. Some of these enzymes are free in the lumen due to the digestion of sloughed mucosal cells. Intestinal secretion is both passive, due to the concentration of lumen contents, and active. Active secretion is usually directed at a specific ion with others following for electrical neutrality. Water follows because of osmotic pressure. Cholera toxin and E.coli enterotoxins simulate active intestinal secretion and therefore cause diarrhea.
The GI tract is the largest endocrine gland in the body with the endocrine cells being diffusely scattered in the mucosa over the length of the alimentary canal. Food in the lumen of the gut is the normal stimulus for secretion of GI hormones but nervous system activity, stretch, or chemical stimulation may also cause the release of GI hormones. The hormones enter the blood stream to effect tissues distant from the releasing cells. GI hormones regulate the digestive process, motility and blood flow of the GI tract and influence the growth of the pancreas and GI tract. Many of the GI hormones are also found in the central nervous system where they may play a role in appetite control, satiety or nerve transmission to the GI tract. About a dozen agents acting as hormones have been identified in the gut mucosa but only a few are discussed here.
Secretin is a 27 amino acid peptide hormone produced in the crypts of Lieberkuhn of the duodenum and released in response to a luminal pH of less than 4.5. It stimulates fluid and bicarbonate release from the pancreas and stimulates pepsinogen secretion.
Cholecystokinin (CCK) is secreted by the endocrine cells of the duodenum and proximal jejunum. CCK exists in a plurality of forms containing 8 to 58 amino acids. It is released by the presence of long chain fatty acids in the chyme. It stimulates pancreatic enzyme synthesis and secretion, increases gall bladder emptying and decreases gastric emptying. A chronic effect of CCK is the stimulation of DNA synthesis in the exocrine pancreas and growth of mucosal tissue.
Gastrin is a 17 amino acid polypeptide hormone made in the duodenum and pyloric antrum. The presence of digested protein in the stomach and duodenum stimulate its release. Gastrin stimulates acid secretion from the parietal cells of the gastric glands and pepsinogen secretion from the chief cells. Histamine is a mediator in the gastrin stimulated release of gastric acid. Gastrin also stimulates nucleic acid and protein synthesis and growth of the exocrine pancreas, mucosa of the small and large intestine and glandular stomach.
Gastric inhibitory peptide (GIP) is a 43 amino acid peptide that causes insulin release from the endocrine pancreas. It also inhibits gastrin release and gastric acid secretion.
Vasoactive intestinal polypeptide (VIP) is a 28 amino acid polypeptide that stimulates bicarbonate release from the pancreas, lipolysis and glycogenolysis in the small intestine and pancreas, decreased GI muscle tone and vasodialation.
Digestion & Absorption
Absorption is the movement of ions and organic molecules from the intestinal lumen into the lymphatic or blood stream. Absorptive capabilities vary over the length of the intestine with the bulk of substances being absorbed in the ileum. The site of absorption varies with nutrient as does the mechanism. Some nutrients are absorbed passively along their concentration gradient while others are actively absorbed using carriers in an energy requiring process.
Lipid or fat digestion begins to some degree in the mouth with a lipase secreted by the sublingual glands. This enzyme remains active in the stomach and is aided by a gastric esterase. Bile added in the duodenum contains emulsifiers, lipases and cholesterol esterase. Fatty acids, glycerol, and multiglycerides are presented to the enterocytes for absorption in the duodenum and jejunum. In the smooth endoplasmic reticulum glycerol and fatty acids are reassembled into fats characteristic of the host. Proteins and glycoproteins are added to the forming fat droplet (chylomicron). The membrane bound chylomicron travels from the Golgi apparatus to the cell membrane where the fat droplet is released to the extracellular space. It then diffuses across the basement membrane to the centrally located lymphatic vessel. Lipoproteins are carried to the general circulation via the lymphatics.
Carbohydrate digestion begins in the mouth due to the action of salivary amylase. Pancreatic amylase completes the job with the aid of other pancreatic enzymes so that mono and disaccharides are available to enterocytes for absorption. Some complex carbohydrates are indigestible in humans and other monogastric species. Pectins, hemicellulose, cellulose, and lignins (all of plant origin) have different chemical linkages for which monogastric species lack enzymes. Ruminants (cattle, sheep) get around this problem by hosting protozoa and bacteria within one of their stomach compartments that digest the plant carbohydrates for them. Termites also host protozoa that digest wood for them.
The intestinal mucosal cells synthesize enzymes like sucrase, lactase, and maltase that are present on the surface of the cells. These enzymes break down disaccharides to monosaccharides like glucose, galactose and fructose that are easily absorbed. Glucose is transported via an active process that exchanges sodium for glucose. Fructose is absorbed via passive diffusion. Monosaccharide absorption is rapid and efficient in all parts of the intestine but absorption is best in the duodenum. A genetic loss of intestinal disaccharidases causes malabsorption. Lactose intolerance is probably the most well known malady caused by the lack of a disaccharidase. Upon the ingestion of milk products, diarrhea results because the lactose remains in the intestinal lumen drawing water with it. Much of the world's adult population is lactose intolerant.
No protein digestion occurs in the mouth. Hydrochloric acid and pepsin in the stomach begin protein digestion. In the duodenum, proteins are digested to amino acids that are rapidly absorbed into the enterocytes. Most amino acids are absorbed in the duodenum and jejunum by carrier mediated processes that exchange sodium ions for the amino acid. Dipeptides and tripeptides are directly absorbed by energy requiring carrier mediated mechanisms. Absorption of intact proteins occurs at all ages to some degree but to a greater extent in infants when the gut is immature. In this way immunoglobulins are transferred from mothers milk to the infant conferring a passive immunity. In the adult, intact proteins that enter enterocytes are digested.
Maladies and Diseases
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