GI Regulation of Gastrointestinal Secretions PDF

REGULATION OF GASTROINTESTINAL SECRETIONS In this lecture we will discuss the digestive hormones, their sites of origin, appropriate triggers for secretion, their target cells and their functions. We will also look at the roles played by the autonomic and enteric nervous systems in controlling ga...

REGULATION OF GASTROINTESTINAL SECRETIONS In this lecture we will discuss the digestive hormones, their sites of origin, appropriate triggers for secretion, their target cells and their functions. We will also look at the roles played by the autonomic and enteric nervous systems in controlling gastrointestinal secretions, as well as the secretions of the different components of the gastrointestinal tract. Digestive hormones: We have already discussed several hormones linked to regulation of feeding behavior (Ghrelin, Leptin, Cholecystokinin, Peptide YY, Insulin and Glucagon). In this lecture we will focus on the following hormones: Gastrin Somatostatin Secretin Cholecystokinin Vasoactive Intestinal Polypeptide (VIP)  Gastrin: Gastrin is actually several related short-chain polypeptide hormones secreted by G cells of the stomach and duodenum. Secretion is stimulated by the presence of food in the stomach and/or duodenum. Gastrin stimulates gastric release of hydrochloric acid and, to a lesser extent, also pepsinogen (an inactive precursor of the proteolytic enzyme pepsin).  Somatostatin: Also a mixture of several related polypeptides, somatostatin is released by cells in gastric glands and also by cells of the pancreas (as well as hypothalamic cells). It’s primary function is to inhibit secretions of the stomach (Gastrin and hydrochloric acid), duodenum (Secretin and Cholecystokinin) and pancreas (Glucagon). Therefore, the release of Somatostatin tends to reduce the rate of nutrient absorption from the digestive tract (it slows down digestion).  Secretin: Another polypeptide, Secretin is released by cells of the duodenum in response to the presence of low pH (an increase in acidity in the duodenum means that the stomach has begun to empty its contents – “chyme” - into the duodenum). The secretin then has several effects, primarily to stimulate the pancreas to release bicarbonate (to neutralize the chyme and thereby allow activation of digestive enzymes). It also starts to inhibit further acid secretion by the stomach and slows peristalsis (allowing the duodenum time to digest the food entering from the stomach).  Cholecystokinin: A group of similar small polypeptides which are secreted by cells of the duodenum and jejunum (primarily in response to the presence of lipids and their catabolites). Therefore, associate CCK secretion in particular with fatty meals. CCK stimulates gall bladder contraction (thereby releasing bile into the duodenum for emulsification of lipids, allowing fats to be digested efficiently), stimulates the pancreas to secrete digestive enzymes, slows the rate of gastric emptying (because it takes quite a while to digest fat compared to protein or carbohydrate), and also stimulates the satiety center (as mentioned previously).  Vasactive Intestinal Polypeptide (VIP): VIP is a polypeptide hormone (Duh!) that is more of a neurotransmitter, but is released at “loose” synapses and can also be called a hormone. VIP produces vasodilation in vessels of the gastrointestinal tract during digestion (in response to increased parasympathetic input to the enteric nervous system – see below). The vasodilation produces increased blood flow to those areas, assuring that the active cells receive sufficient oxygen for working and also sufficient plasma as the precursor for enterocytes (small intestine cells) to produce mucous secretions. Finally, the increased blood flow also assures that nutrients can be efficiently absorbed from the gut. Neural Regulation of Gastrointestinal Secretions: The central nervous system plays an important role in regulating gastrointestinal function. The outflow for this regulation is carried by way of the autonomic nervous system, with the parasympathetic portion being more active than the sympathetic during periods of digestion. However, much of the autonomic outflow does not directly innervate gastrointestinal cells, but instead moderates the activity of the Enteric Nervous System (ENS).  The ENS runs much of the length of the digestive tract (from part way down the esophagus until the external anal sphincter) and consists of about as many neurons as are present in the spinal cord. The ENS is divided into two layers (plexuses): The Myenteric (Auerbach’s) Plexus primarily regulates contractions of smooth muscle that result in peristalsis and sphincter control. The Submucosal (Meissner’s) Plexus neurons are associated with regulation of secretions and blood flow along the length of the digestive tract.  Both plexuses contain not only motor neurons (for producing secretions and muscle contraction), but also interneurons for coordinating functions (local control) and sensory neurons (to provide information from the gut back to the CNS). There are a variety of different sensory receptors of the ENS, and they respond to mechanical (stretch and tension), thermal (heat and cold), osmotic and chemical (glucose and amino acids) stimuli. The sensory information is conveyed to the CNS primarily along afferent fibers of the Vagus. Parasympathetic outflow to the gut includes the Glossopharyngeal (IX) and Facial (VII) nerves innervating salivary glands, the vagus innervating much of the length of the digestive tract, and sacral nerves innervating the colon.  Sympathetic innervation of the salivary glands travels through the superior cervical ganglion, while the splanchnic nerves conduct impulses to much of the rest of the GI tract. The ability to send sensory information toward the CNS and receive motor information as a result sets up the potential for reflex loops, and there are a number of notable digestive reflexes (e.g. gastrocolic or enterogastric reflexes). The digestive reflexes are named for the site of initiation followed by the site affected. Therefore, the gastrocolic reflex refers to how food entering the stomach (“gastro”) results in increased motility of the colon (“colic”) – something that happens to millions of people every day just after eating breakfast! Secretions by components of the gastrointestinal tract: Mouth: Saliva is pretty much the whole story here. Of course there are many significant components to saliva, and these are covered in a separate lecture. Esophagus: Another simple one. The esophagus secretes mucous throughout the length of the esophagus. This mucous is thicker and contains a higher level of bicarbonate (for acid neutralization) at the gastric end of the esophagus. The function of the mucous is lubrication (to facilitate the movement of food from the mouth to the stomach) and also protection against excoriation (scraping) and acidic erosion of the lower portion of the esophagus.  Stomach: Besides releasing the hormone Gastrin into the blood, the stomach also secretes the following into the lumen of the digestive tract: Hydrochloric acid, pepsinogen, mucous, gastroferrin (for facilitating iron absorption) and Intrinsic Factor (essential for vitamin B12 absorption). Small Intestine (Duodenum, Jejunum, Ileum): Secretin and Cholecystokinin are hormones that are released into the blood, while the following are secreted into the lumen of the small intestine: serous mucous and bicarbonate-enriched mucous, lysozyme, and defensins (the later two serving antibacterial functions). Colon: Mucin-rich mucous is pretty much the whole story for secretions by the colon.  Pancreas: The pancreas secretes the hormones insulin, glucagon and somatostatin into the blood (as mentioned earlier). The pancreas also plays a key role in secreted digestive enzymes into the lumen of the gastrointestinal tract. These enzymes include: Trypsinogen, Chymotrypsinogen, Procarboxypeptidase A and B, Pro-elastase (all of the preceding are inactive precursors of proteolytic enzymes), Pancreatic Lipase, Pancreatic Amylase, and Ribonucleases. In addition, the pancreas also secretes about 2 liters per day of bicarbonate-rich fluid (used to neutralize the acidic chime coming from the stomach). Liver: The liver synthesizes and releases plasma proteins, VLDLs (very low density lipoproteins) and HDLs (high density lipoproteins) into the blood. The liver also secretes bile into the lumen of the digestive tract. The bile, which is then concentrated in the gall bladder, contains bile salts and bile acids for lipid emulsification, and also serves as an avenue for excretion of bilirubin from heme breakdown.