Gastrointestinal Physiology 1 PDF

GASTROINTESTINAL PHYSIOLOGY 1 Prof.Dr. Haluk KELEŞTİMUR Istanbul Okan University Medical School Department of Physiology For Contact Tlf: 5054120697 [email protected] 1st Floor Room Number: 139 General Features of Gastrointestinal System The digestive system consists of the digestive trac...

GASTROINTESTINAL PHYSIOLOGY 1 Prof.Dr. Haluk KELEŞTİMUR Istanbul Okan University Medical School Department of Physiology For Contact Tlf: 5054120697 [email protected] 1st Floor Room Number: 139 General Features of Gastrointestinal System The digestive system consists of the digestive tract plus the accessory digestive organs Transit times of nutrients in digestive organs The Functions of the Gastrointestinal System The features of digestive canal  The pH of the stomach contents falls as low as 2 as a result of gastric secretion of hydrochloric acid (HCl), yet in the body fluids the range of pH compatible with life is 6.8 to 8.0.  The digestive enzymes that hydrolyze the protein in food could also destroy the body tissues that produce them. Therefore, once these enzymes are synthesized in inactive form, they are not activated until they reach the lumen, where they actually attack the food outside the body (that is, within the lumen), thereby protecting the body tissues against self-digestion.  In the lower part of the intestine exist quadrillions of living microorganisms that are normally harmless and even beneficial, yet if these same microorganisms enter the body proper (as may happen with a ruptured appendix), they may be extremely harmful or even lethal.  Foodstuffs are complex foreign particles that would be attacked by the immune system if they were in contact with the body proper. However, the foodstuffs are digested within the lumen into absorbable units such as glucose, amino acids, and fatty acids that are indistinguishable from these simple energy rich molecules already present in the body. Motility Types in Gastrointestinal Tract Peristalsis For the peristaltic contraction, behind the bolus (orad) circular muscle contracts and longitudinal muscle relaxes; in front of the bolus (caudad), circular muscle relaxes and longitudinal muscle contracts Peristalsis moves the chyme in the caudad direction. Segmentation contractions mix the chyme Energy-rich nutrients and hydrolysis Fluid intake and output in GI tract Gastrointestinal tract is separated by sphincters (cont’d) The upper esophageal sphincter separates the pharynx and the upper esophagus; The lower esophageal sphincter separates the esophagus and the stomach; The pyloric sphincter separates the stomach and the duodenum; The ileocecal sphincter separates the ileum and the cecum; The internal and external anal sphincters maintain fecal continence. (cont’d) At rest, the sphincters maintain a positive pressure that is higher than the pressures in the adjacent organs; thus at rest, both anterograde (forward) and retrograde (backward) flow is prevented. For example, at rest, the positive pressure of the lower esophageal sphincter prevents the gastric contents from refluxing into the esophagus. For gastrointestinal tract contents to move through the sphincter, it must relax and transiently lower its pressure. Changes in sphincter pressure are coordinated with contractions of the smooth muscle of the adjacent organs via reflexes (e.g., the swallowing reflex). Layers of the digestive tract wall Control of digestive system activities Slow waves of the gastrointestinal tract superimposed by action potentials and contraction The Phases of slow waves Phase 0: Resting membrane potential; outward potassium current. Phase 1: Rising phase (depolarization); activation of voltage-gated calcium channels Phase 2: Activation of voltage-gated potassium channels. Phase 3: Plaeau phase; balance of inward calcium current and outward potassium current. Phase 4: Falling phase (repolarization); inactivation of voltage-gated calcium channels and activation of calcium-gated potassium channels. Electrical slow waves with similar waveforms occur at different frequencies in the stomach, small intestine, and colon Electrical slow waves in the circular muscle occur at 3 waves/min in the human antrum, 11 to 12 waves/min in the duodenum, and 2 to 13 waves/min in the colon. Action potentials are not always associated with slow waves (A) No action potentials appear at the crests of the slow waves and the muscle contractions associated with each slow wave are small. (B) Muscle action potentials appear as sharp upward–downward deflections at the crests of the slow waves. Large-amplitude muscle contractions are associated with each slow wave when action potentials are present. Arrangement of Neurons of Enteric Nervous System  The submucosal plexus (Meissner plexus) lies between the submucosa and the circular muscle.  The myenteric plexus (Aurback plexus) lies between the circular muscle and the longitudinal muscle. The intrinsic nervous system of the gastrointestinal tract The motor neuron pool of the ENS consists of both excitatory and inhibitory neurons Neurotransmitters and Neuromodulators in the Enteric Nervous System The extrinsic nervous system of the gastrointestinal tract Parasympathetic system innervating GI tract Parasympathetic innervation is supplied by the vagus nerve (cranial nerve X) and the pelvic nerve. The vagus nerve innervates the upper gastrointestinal tract including the striated muscle of the upper third of the esophagus, the wall of the stomach, the small intestine, the ascending colon, and a portion of the transverse colon. The pelvic nerve innervates the lower gastrointestinal tract including the walls of the transverse, descending, and sigmoid colons. Sympathetic system innervating GI tract Four sympathetic ganglia serve the gastrointestinal tract: celiac, superior mesenteric, inferior mesenteric, and hypogastric. Postganglionic nerve fibers, which are adrenergic (i.e., release norepinephrine), leave these sympathetic ganglia and synapse on ganglia in the myenteric and submucosal plexuses, or they directly innervate smooth muscle, endocrine, or secretory cells. GASTROINTESTINAL REGULATORY SUBSTANCES Gastrointestinal Hormones Gastrin Protein in the stomach stimulates the release of gastrin, 2. It acts in multiple ways to increase secretion of HCl and pepsinogen, two substances of primary importance in initiating 1. 3. 4. 5. digestion of the protein that promoted their secretion. It enhances gastric motility, stimulates ileal motility, relaxes the ileocecal sphincter, and induces mass movements in the colon—all functions aimed at keeping the contents moving through the tract on arrival of a new meal. It also is trophic to both the stomach mucosa and the small-intestine mucosa, helping maintain a well-developed, functionally viable digestive tract lining. Gastrin secretion is inhibited by an accumulation of acid in the stomach (negative feedback effect) and by the presence in the duodenal lumen of acid and other constituents that necessitate a delay in gastric secretion. Cholecystokinin 1. 2. 3. 4. 5. As chyme empties from the stomach, fat and other nutrients enter the duodenum. These nutrients—especially fat and, to a lesser extent, protein products—cause the release of CCK. It inhibits gastric motility and secretion, thereby allowing adequate time for the nutrients already in the duodenum to be digested and absorbed. It stimulates the pancreatic acinar cells to increase secretion of pancreatic enzymes, which continue the digestion of these nutrients in the duodenal lumen (this action is especially important for fat digestion because pancreatic lipase is the only enzyme that digests fat). It causes contraction of the gallbladder and relaxation of the sphincter of Oddi so that bile is emptied into the duodenum. CCK is an important regulator of food intake. It plays a key role in satiety, the sensation of having had enough to eat. Secretin 1. 2. 3. 4. 5. As the stomach empties into the duodenum, the presence of acid in the duodenum stimulates the release of secretin. It inhibits gastric emptying to prevent further acid from entering the duodenum until the acid already present is neutralized. It inhibits gastric secretion to reduce the amount of acid being produced. It stimulates the pancreatic duct cells to produce a large volume of aqueous NaHCO3 secretion, which is emptied into the duodenum to neutralize the acid. Neutralization of the acidic chyme in the duodenum helps prevent damage to the duodenal walls and provides a suitable environment for optimal functioning of the pancreatic digestive enzymes, which are inhibited by acid. Secretin and CCK are both trophic to the exocrine pancreas. GIP (gastric inhibitory peptide, glucose-dependent insulinotropic peptide) 1. 2. 3. This hormone was originally named gastric inhibitory peptide (GIP) for its presumed role as an enterogastrone. It was believed to inhibit gastric motility and secretion, similar to secretin and CCK. Its contribution in this regard is now considered minimal. Instead, this hormone stimulates insulin release by the pancreas, so it is now called glucose-dependent insulinotropic peptide. Stimulated by the presence of a meal, especially glucose, in the digestive tract, GIP initiates the release of insulin in anticipation of absorption of the meal, in a feedforward fashion. Insulin is especially important in promoting the uptake and storage of glucose. Candidate Hormones Motilin is secreted from the upper duodenum during fasting states. Motilin is believed to increase gastrointestinal motility and, specifically, to initiate the interdigestive myoelectric complexes that occur at 90minute intervals. Pancreatic polypeptide is secreted by the pancreas in response to ingestion of carbohydrates, proteins, or lipids. Pancreatic polypeptide inhibits pancreatic secretion of HCO3 − and enzymes, although its physiologic role is uncertain. Enteroglucagon is released from intestinal cells in response to a decrease in blood glucose concentration. It then directs the liver to increase glycogenolysis and gluconeogenesis. (cont.) Glucagon-like peptide-1 (GLP-1) is produced from the selective cleavage of proglucagon. It is synthesized and secreted by the L cells of the small intestine. Like GIP, GLP-1 is classified as an incretin, because it binds to receptors on the pancreatic β cells and stimulates insulin secretion. In complementary actions, it also inhibits glucagon secretion, increases the sensitivity of pancreatic β cells to secretagogues such as glucose, decreases gastric emptying, and inhibits appetite. For these reasons, analogues of GLP-1 have been considered as possible treatments for type II diabetes mellitus. Paracrines Somatostatin is secreted by D cells (both endocrine and paracrine) of the gastrointestinal mucosa in response to decreased luminal pH. In turn, somatostatin inhibits secretion of the other gastrointestinal hormones and inhibits gastric H+ secretion. In addition to these paracrine functions in the gastrointestinal tract, somatostatin is secreted by the hypothalamus and by the delta (δ) cells of the endocrine pancreas. Histamine is secreted by endocrine-type cells of the gastrointestinal mucosa, particularly in the H+ -secreting region of the stomach. Histamine, along with gastrin and ACh, stimulates H+ secretion by the gastric parietal cells. Neurocrines Neurocrines are synthesized in cell bodies of gastrointestinal neurons. An action potential in the neuron causes release of the neurocrine, which diffuses across the synapse and interacts with receptors on the postsynaptic cell. The neurocrines include nonpeptides such as ACh and norepinephrine and peptides such as VIP, GRP, the enkephalins, neuropeptide Y, and substance P. The best-known neurocrines are ACh (released from cholinergic neurons) and norepinephrine (released from adrenergic neurons). The other neurocrines are released from postganglionic noncholinergic parasympathetic neurons (also called peptidergic neurons). GASTROINTESTINAL MOTILITY Chewing and Swallowing Oral Cavity The Functions of Chewing 1. 2. 3. 4. 5. The primary role of chewing is to break down foodstuffs for subsequent digestion. It mixes food with saliva, lubricating it to facilitate swallowing. It reduces the size of food particles, which facilitates swallowing (although the size of the swallowed particles has no effect on the digestive process). It mixes ingested carbohydrates with salivary amylase to begin carbohydrate digestion. It exposes food to the taste buds. Taste bud stimulation not only gives rise to the pleasurable sensation of taste, but also, in feedforward fashion, reflexly increases salivary, gastric, pancreatic and bile secretion to prepare for the arrival of food. The main motor and sensory brainstem nuclei associated with cranial nerves The cranial V motor nucleus contains alfa-motoneurons supplying jawclosing (e.g., masseter) and jaw-opening (e.g., anterior digastric) muscles. The cranial nerve VII nucleus has alfa-motoneurons supplying the muscles of facial expression (e.g., orbicularis oris). The main motor and sensory brainstem nuclei associated with cranial nerves The nucleus ambiguus (IX, X, XI) contains alfa- motoneurons supplying muscles of the palate, pharynx and larynx. The crainal nerve XII nucleus has alfa-motoneurons supplying intrinsic and extrinsic muscles (e.g., genioglossus) of the tongue. Diagram showing the main connections of the orofacial sensorymotor system Mastication or chewing depends on a brainstem center comprising a central neural pattern generator, the chewing center. Chewing has both voluntary and involuntary components. The involuntary component involves reflexes initiated by food in the mouth. Sensory information is relayed from mechanoreceptors in the mouth to the brain stem, which orchestrates a reflex oscillatory pattern of activity to the muscles involved in chewing. Voluntary chewing can override involuntary or reflex chewing at any time. The sensory and motor components of chewing reflex Comparison of orofacial motor system and spinal motor system The trigeminal mesencephalic nucleus is the only site in the body where primary cell bodies are located within the CNS. Many orofacial muscles lack muscle spindles and also Golgi tendon organs. A gamma efferent activation is thus absent due to the lack of muscle spindles in many muscles. The weakness of reciprocal innervation due to the lack of proprioceptors is compensated for by the powerful regulatory influences provided by afferent impulses from facial skin, mucosa, TMJ and teeth. Integrative pathways and processes exist to allow the bilateral activity of orofacial muscles. Requirements of Alimentary Swallow The Neural Control of Phryngeal Phase of Swallowing The Muscles Related to Swallowing and Their Innervations Different Swallow Patterns  Some of the various muscles involved in swallowing are “obligate” swallow muscles, meaning they are always active in swallowing; examples are some of the tongue muscles as well as the palatal, pharyngeal, laryngeal, and esophageal muscles.  Others are “facultative” swallow muscles in that they show a variable participation in swallowing. The facultative muscles are the facial and jaw muscles, and they may be especially sensitive to alterations in the oral environment and to maturational changes. Therefore, their participation can vary depending, for example, on the consistency or volume of a foodstuff being swallowed, or whether the subject is an infant or adult since there can be age-related differences in the involvement during swallowing of facial muscles (particularly noticeable in the infant) versus jaw muscles (noticeable in the adult).  The infantile (visceral or “tooth-apart”) pattern of swallowing, as opposed to the adult (somatic or “tooth-together”) pattern, is often characterized by a pronounced tongue thrust, and retention of this pattern is thought by some clinicians to be of etiologic significance in certain malocclusions such as anterior open bite. However, toothapart swallows are quite normal in adults when a liquid or soft food bolus is being ingested, viz., the teeth may or may not come into occlusion during a normal adult swallow; a major determining factor is the consistency of the bolus. Esophagus Structures of the Upper Gastrointestinal Tract The pharynx, upper esophageal sphincter, and upper third of the esophagus are composed of striated muscle. The middle third of the esophagus contains striated and smooth muscles. The lower third of the esophagus and lower esophageal sphincter are composed of smooth muscle. The propulsive and protective effects of oesophagus and associated sphincters Schematic drawing showing the three major divisions of the stomach The functions of the stomach The stomach’s most important function is to store ingested food until it can be emptied into the small intestine at a rate appropriate for optimal digestion and absorption. The stomach secretes hydrochloric acid (HCl) and enzymes that begin protein digestion. Through the stomach’s mixing movements, the ingested food is pulverized and mixed with gastric secretions to produce a thick liquid mixture known as chyme. Gastric motility has the four aspects Filling Storage Mixing Emptying Gastric filling involves receptive relaxation. The interior of the stomach is thrown into deep folds. During a meal, the folds get smaller and nearly flatten out as the stomach relaxes slightly with each mouthful. This vagally mediated response, called receptive relaxation, allows the stomach to accommodate the meal with little change in intragastric pressure. When empty, the stomach has a volume of about 50 mL, but it can expand up to 20-fold to a capacity of about 1 liter (1000 mL) during a meal. If more than a liter of food is consumed, however, the stomach becomes overdistended, intragastric pressure rises, and the person experiences discomfort. Receptive Relaxation Mechanism of Receptive Relaxation Gastric storage takes place in the body of the stomach A group of pacemaker cells (interstitial cells of Cajal) located in the upper fundus region of the stomach generate slow-wave potentials (Basic electrical rhythm, BER) that sweep down the length of the stomach toward the pyloric sphincter at a rate of three per minute. Once initiated, a peristaltic wave spreads over the fundus and body to the antrum and pyloric sphincter. Because the muscle layers are thin in the fundus and body, the peristaltic contractions in this region are weak. When the waves reach the antrum, they become stronger and more vigorous because the muscle there is thicker. Gastric emptying and mixing Gastric emptying 1. 2. 3. 4. A peristaltic contraction originates in the upper fundus and sweeps down toward the pyloric sphincter. The contraction becomes more vigorous as it reaches the thick-muscled antrum. The strong antral peristaltic contraction propels the chyme forward. A small portion of chyme is pushed through the partially open sphincter into the duodenum. The stronger the antral contraction, the more chyme is emptied with each contractile wave. Gastric mixing 5. 6. When the peristaltic contraction reaches the pyloric sphincter, the sphincter is tightly closed and no further emptying takes place. When chyme that was being propelled forward hits the closed sphincter, it is tossed back into the antrum. Mixing of chyme is accomplished as chyme is propelled forward and tossed back into the antrum with each peristaltic contraction, a process called retropulsion. Factors Regulating Gastric Motility and Emptying There are three types of contractions in the small intestine Segmentation Peristalsis Migrating motility complex (MMC) Segmentation (cont’d) Segmentation consists of ringlike contractions along the length of the small intestine. Within a matter of seconds, the contracted segments relax and the previously relaxed areas contract. These oscillating contractions thoroughly mix the chyme within the small-intestine lumen. Segmentation is slight or absent between meals but becomes vigorous immediately after a meal. The duodenum starts to segment primarily in response to local distension caused by the presence of chyme. Segmentation of the empty ileum, in contrast, is brought about by gastrin secreted in response to the presence of chyme in the stomach, a mechanism known as the gastroileal reflex. Peristalsis The Migrating motor complex (MMC) (MMC) 1. Phase I: A long period lasting about 40 to 60 minutes of relative quiet with very few contractions 2. Phase II: A 20- to 30-minute period with some peristaltic contractions, with the time varying between contractions 3. Phase III: The shortest phase, where intense peristaltic contractions begin in the upper stomach and propagate (mi grate) through to the end of the small intestine. The contractions rhythmically repeat for 5 to 10 minutes. During this period, the pyloric sphincter relaxes and opens completely. (cont’d)  During periods of short fasting, when most of the meal has been absorbed, the stomach and small intestine exhibit a unique motor activity.  Intestinal segmentation contractions cease and are replaced by the migrating motility complex (MMC), or “intestinal housekeeper” activity. The motor activity of the MMC is thought to sweep any remnants of the preceding meal plus mucosal debris and bacteria forward toward the colon, just like a good “intestinal housekeeper.”  The MMC is regulated between meals by the hormone motilin, which is secreted during the unfed state by endocrine cells of the small-intestine mucosa. When the next meal arrives, the MMC ceases and the motor activity associated with a meal takes over. Motilin release is inhibited by feeding. The Large Intestine The large intestine is primarily a drying and storage organ The colon normally receives about 500 mL of chyme from the small intestine each day. Because most digestion and absorption have been accomplished in the small intestine, the contents delivered to the colon consist of indigestible food residues (such as cellulose), unabsorbed biliary components, and the remaining fluid. The colon extracts more H2O and salt, drying and compacting the contents to form a firm mass known as feces for elimination from the body. The primary function of the large intestine is to store feces before defecation. Cellulose and other indigestible substances in the diet provide bulk and help maintain regular bowel movements by contributing to the volume of the colonic contents. Large Intestinal Motility (Haustral contractions)  Segmentation contractions occur in the cecum and proximal colon. As in the small intestine, these contractions function to mix the contents of the large intestine. In the large intestine, the contractions are associated with characteristic saclike segments called haustra. Haustral contractions slowly shuffle the colonic contents back and forth. These movements are nonpropulsive; they slowly shuffle the contents in a back-and-forth mixing movement that exposes the colonic contents to the absorptive mucosa. Haustral contractions are largely controlled by locally mediated reflexes involving the intrinsic plexuses. Large Intestinal Motility (Mass movements)  Mass movements occur in the colon and function to move the contents of the large intestine over long distances, such as from the transverse colon to the sigmoid colon. These massive contractions drive the colonic contents into the distal part of the large intestine, where material is stored until defecation occurs. Mass movements occur anywhere from 1 to 3 times per day. Water absorption occurs in the distal colon, making the fecal contents of the large intestine semisolid and increasingly difficult to move. Gastrocolic and gastroileal reflexes When food enters the stomach, mass movements are triggered in the colon primarily by the gastrocolic reflex, which is mediated from the stomach to the colon by gastrin and by parasympathetic innervation. In many people, this reflex is most evident after the first meal of the day and is often followed by the urge to defecate. Thus, when a new meal enters the digestive tract, reflexes are initiated to move the existing contents farther along the tract to make way for the incoming food. The gastroileal reflex moves the remaining smallintestine contents into the large intestine, and the gastrocolic reflex pushes the colonic contents into the rectum, triggering the defecation reflex. Defecation reflex  As the rectum fills with feces, the smooth muscle wall of the rectum contracts and the internal anal sphincter relaxes in the rectosphincteric reflex.  When it is appropriate, the external anal sphincter is relaxed voluntarily, the smooth muscle of the rectum contracts to create pressure, and feces are forced out through the anal canal. The intraabdominal pressure created for defecation can be increased by a Valsalva maneuver (expiring against a closed glottis).