HAP1 L04_ Gastrointestinal Secretions_N.pdf

Human Anatomy and Physiology I Lecture 4 Digestive System (Part Two): Gastrointestinal Secretions Dr. George Chow [email protected] 1  Lecture outline The production, secretion, composition, and actions of the following sec...

Human Anatomy and Physiology I Lecture 4 Digestive System (Part Two): Gastrointestinal Secretions Dr. George Chow [email protected] 1  Lecture outline The production, secretion, composition, and actions of the following secretions: Salivary glands – consisting of parotid ( 腮 腺 ), sublingual ( 舌 下 腺 ), and submandibular (下頜下腺) glands Saliva – composition, functions Stomach juice (gastric juice) – HCl, regulation of HCl secretion, pepsinogen (active form: pepsin), gastric lipase Pancreatic juice – has enzymes including pancreatic amylase, trypsin, chymotrypsin, carboxypeptidase, elastase, pancreatic lipase, ribonuclease, deoxyribonuclease. Physical breakdown Bile – contains bile salts, cholesterol, lecithin, bile pigments, bilirubin. Intestinal juice – contains bicarbonate ions, brush border enzymes, four carbohydrate-digesting enzymes (α-dextrinase, maltase, sucrase, and lactase); protein-digesting enzymes (aminopeptidase and dipeptidase); and nucleotide- digesting enzymes (nucleosidases and phosphatases). 不是完全分開, 有灰色地帶, 大約咁分 Phases of digestion and regulation: communication with brain Cephalic phase nerve Gastric phase stomach Intestinal phase intestine  The buccal (oral) cavity Salivary glands Ordinarily, just enough saliva is secreted to keep the mucous membranes of the mouth and pharynx moist and to cleanse the mouth and teeth. When food enters the mouth, however, secretion of saliva increases, and it lubricates, dissolves, and begins the chemical breakdown of the food. salivary amylase The mucous membrane of the mouth and tongue contains many small salivary glands that open directly, or indirectly via short ducts, to the oral cavity. These glands include: Labial (唇的)glands in the lips, Buccal (面頰的) glands in the cheeks, Palatal (顎的) glands in the palate, Lingual (舌的) glands in the tongue 3  3 Major salivary glands exocrine The parotid glands 下 & 前 Located inferior and anterior to the ears. Each secretes saliva into the oral cavity via a parotid duct. The submandibular glands On the floor of the mouth The submandibular ducts, run under the mucosa on either side of the midline of the floor of the mouth. The sublingual glands 上 Beneath the tongue and superior to the submandibular glands. The lesser sublingual ducts open into the floor of the mouth in the oral cavity proper. 4  Composition and functions of saliva Composition Overall 99.5% water and 0.5% solutes. The solutes are ions, including sodium, potassium, chloride, bicarbonate, and phosphate. IgA Some dissolved gases and various organic substances, 免疫球蛋白 including urea and uric acid, mucus, immunoglobulin A, the bacteriolytic enzyme lysozyme, and salivary amylase. The parotid glands secrete a watery (serous) liquid containing salivary amylase. The submandibular glands contain cells similar to those found in the parotid glands, plus some mucous cells. They secrete a fluid that contains amylase but is thickened with mucus. antigen抗原 The sublingual glands contain mostly mucous cells, so they secrete a much thicker fluid that contributes only a small amount of salivary amylase. 5  Composition and functions of saliva Functions The water in saliva provides a medium for dissolving foods so that they can be tasted by gustatory receptors and so that digestive reactions can begin. taste bud Salivary amylase breaks down starch in the mouth into maltose, maltotriose, and α-dextrin. rice is sweet Bicarbonate and phosphate ions buffer acidic foods that enter the mouth, so saliva is only slightly acidic (pH 6.35-6.85), ~6.7 being the average pH. 尿素, major secrete in kidney & sweat, metabolic waste when breaking down protein Salivary glands (like the sweat glands of the skin) help remove waste molecules from the body, which accounts for the presence of urea and uric acid in saliva. Mucus lubricates food so it can be moved around easily in the mouth, formed into a ball, and swallowed. Immunoglobulin A (IgA) prevents attachment of microbes so they cannot penetrate the epithelium, and the enzyme. lysozyme kills bacteria, but NOT in large enough quantities to eliminate all oral bacteria. 6  Regulation of saliva secretion Salivation On average 1000-1500 mL/day. Normally, parasympathetic stimulation promotes continuous secretion of a moderate amount of saliva, which keeps the mucous membranes moist and lubricates the movements of the tongue and lips during speech. The saliva is then swallowed and helps moisten the oesophagus. Eventually, most components of saliva are reabsorbed, which prevents fluid loss. Sympathetic stimulation dominates during stress, resulting in dryness of the mouth. If the body becomes dehydrated, the salivary glands stop secreting saliva to conserve water. The resulting dryness in the mouth contributes to the sensation of thirst. Drinking not only restores the homeostasis of body water but also moistens the mouth. nerve 7  Regulation of saliva secretion Salivation The feel and taste of food also are potent stimulators of salivary gland secretions. 望到食物流口水 Chemicals in the food stimulate receptors in taste buds on the tongue, and impulses are conveyed from the taste buds to two salivary nuclei in the brain stem (superior and inferior salivatory nuclei). Returning parasympathetic impulses in fibres of the facial (VII) and glossopharyngeal (IX) nerves stimulate the secretion of saliva. Saliva continues to be secreted heavily for some time after food is swallowed. trigeminal nerve 三叉神經 This flow of saliva washes out the mouth and dilutes and vestibulocochlear nerve 前庭蝸神經 buffers the remnants of irritating chemicals such as hot ---> listen, blalance 殘餘物 spinal nerve (from spinal cord) pepper. The smell, sight, sound, or thought of food may also stimulate secretion of saliva. 8  chewing 內壁 moved 粉碎 9  The Stomach The mucosa Surface mucous cells Mucous neck cells Parietal cells Chief cells Gastric glands Gastric pits G cells Lamina propria Muscularis mucosae 10 The Stomach 11  For溫書! 攪拌 12 lower esophageal sphincter The Stomach Parietal cells secrete hydrogen ions (H+) and chloride ions (Cl−) separately into the stomach lumen, the net effect is secretion of hydrochloric acid (HCl). carbonic acid Proton pumps powered by H+–K+ ATPases actively transport H+ ions into the lumen while enzyme 起點 bringing potassium ions (K+) into the cell. At the same time, Cl− and K+ ions diffuse out into the lumen through Cl− and K+ channels in the apical membrane. 13 channel (一出一入)  The enzyme carbonic anhydrase, which is especially plentiful in parietal cells, catalyses the formation of carbonic acid (H2CO3) from water (H2O) and carbon dioxide (CO2). As carbonic acid dissociates, it provides a ready source of H+ for the proton pumps but also generates bicarbonate ions (HCO3−). As HCO3− ions build up in the cytosol, they exit from the parietal cell in exchange for Cl − ionsvia HCO3− – Cl − antiporters in the basolateral membrane (next to the lamina propria). HCO3− ions diffuse into nearby blood capillaries. This ‘alkaline tide’ of bicarbonate ions entering the bloodstream after a meal may be large enough to elevate blood pH slightly and make urine more alkaline. 14  Regulation of HCl secretion HCl secretion by parietal cells are stimulated by: Acetylcholine (ACh) released by parasympathetic (副交感神經)neurons, Gastrin secreted by G cells, 組織胺 Histamine, a paracrine substance released by mast cells in the nearby lamina propria. 神經傳導物質 & 荷爾蒙 Acetylcholine and gastrin stimulate parietal cells to secrete more HCl in the presence of histamine. 1+1>2 In other words, histamine acts synergistically, enhancing the effects of acetylcholine and gastrin. Receptors for all three substances are present in the plasma membrane of parietal cells. The histamine receptors on parietal cells are autocrine 自己吉大脾起身 called H2 receptors. paracrine 拍隔離同學起身 They mediate different responses than do the endocrine H1 receptors involved in allergic responses. 抗組織胺(antihistamine) 是一般民眾常常使用的藥品，用途很廣泛，可分為H1 和H2 二大類， 其中能有效緩解過敏相關症狀的是H1 抗組織胺。目前H1 抗組織胺 藥品可分為兩代，第一代抗組織胺能有效改善過敏症狀，但有嗜睡、甚至腸胃不適或口乾舌燥的現象，第二代抗組織胺改善了此類的副作用，因此可應用在副 作用明顯或特殊族群的病人。不過第一代抗組織胺也有它們的角色，除了抗過敏的藥效外，部分藥品還具有抗暈、止吐的效果，臨床上也具不可取代性。 15  The Stomach search圖 Pepsin for protein Secreted in an inactive precursor form called pepsinogen. Pepsinogen is converted into active pepsin only in the presence of hydrochloric acid secreted by parietal cells or by active pepsin molecules. pepsin=scissors The stomach epithelial cells are protected from gastric juices by a layer 1-3 mm thick of alkaline mucous secreted by surface mucous cells and mucous neck cells. Gastric lipase for lipid It splits triglycerides (fats and oils) in fat molecules into fatty acids and monoglycerides. It has a limited role in the adult stomach, operates best at a pH of 5-6. More important than either lingual lipase or gastric lipase is the pancreatic lipase, an enzyme secreted by the pancreas into the small intestine. pancreatic amylase for starch 16  The Pancreas Head, body and tail Common bile duct Pancreatic duct (duct of Wirsung) Hepatopancreatic ampula (ampula of Vater) Sphincter of the hepatopancreatic ampula (sphincter of Oddi) Accessory duct (duct of Santorini) Pancreatic juice 1.2 to 1.5 L/day Contains some salts, Sodium bicarbonate, Pancreatic amylase, Trypsin, Chymotrypsin, Carboxypeptidase, Elastase, Pancreatic Lipase, Ribonuclease, and Deoxyribonuclease. 17  The Pancreas Common bile duct ampulla Pancreatic duct (duct of Wirsung) Hepatopancreatic ampula (ampula of Vater) Sphincter of the hepatopancreatic ampula (sphincter of Oddi) Accessory duct (duct of Santorini) 有機會唔經 因為切咗 18  The Pancreas Pancreatic juice 1.2 to 1.5 L/day Slightly alkaline (pH 7.1 - 8.2) Buffers acidic gastric juice in chyme. Stops the action of pepsin from the stomach. Creates the proper pH for the action of digestive enzymes in the small intestine. Some salts, Sodium bicarbonate. Contains the following enzymes: Pancreatic amylase, Trypsin, Chymotrypsin, Carboxypeptidase, Elastase, Pancreatic Lipase, Ribonuclease, and Deoxyribonuclease. Protein Trypsin is secreted in an inactive form called trypsinogen. Pro-enzyme (Stomach : Pepsin & pepsinogen) Pancreatic acinar cells also secrete a protein called trypsin inhibitor that combines with any trypsin formed accidentally in the pancreas or in pancreatic juice and blocks its enzymatic activity. 防止enzyme 趙返自己 When trypsinogen reaches the lumen of the small intestine, it will encounter an activating brush- border enzyme called enterokinase, which splits off part of the trypsinogen molecule to form trypsin. like HCL squeeze pepsinogen into In turn, trypsin acts on chymotrypsinogen, procarboxypeptidase, and proelastase to produce pepsin protein enzyme in chymotrypsin, carboxypeptidase, and elastase, respectively. pro-enzyme 19 active form  Liver and Gall Bladder Bile 800 - 1000 mL bile produced per day. pH 7.6 - 8.6 乳化作用 emulsifier 乳化劑 Contains water, bile salts, cholesterol, lecithin (a phospholipid) , bile pigments, and several ions. Bilirubin broken down into stercobilin and eliminated through defecation. yellow to brown Emulsification of large lipid globules by bile salts into a suspension of small lipid globules. product=emulsion The small lipid globules present a very large surface area that allows pancreatic lipase to more rapidly accomplish digestion of triglycerides. Bile salts also aid in the absorption of lipids following their digestion. When digestion and absorption continue in the small intestine, bile release increases. Between meals, after most absorption has occurred, bile flows into the gall bladder for storage temporarily because the sphincter of the hepatopancreatic ampulla closes off the entrance to the duodenum. 20  Small Intestine The mucosa Composed of epithelium, lamina propria, and muscularis mucosae. The epithelial layer 縫隙 Many deep crevices lined with glandular epithelium. Cells lining the crevices form the intestinal glands, or crypts of Lieberkü hn, and secrete intestinal juice. Absorptive cells Release enzymes that digest food and contain microvilli that absorb nutrients in small intestinal chyme. Goblet cells Secrete mucus. Paneth cells Secrete lysozyme, a bactericidal enzyme. Capable of phagocytosis. 吞噬作用 May have a role in regulating the microbial population in the small intestine. Enteroendocrine cells 腸道內分泌細胞, 要識3種 : pepsin (stomach), S cells & CCK cells (Small intestine) S cells secrete secretin. CCK cells secrete cholecystokinin(CCK). K cells secrete glucose-dependent insulinotropic peptide (GIP). 21 Small Intestine S cells (Secretin) CCK cells (Cholecystokinin) 22  Small Intestine The submucosa The submucosa of duodenum contains duodenal glands (Brunner’s glands). Secrete an alkaline mucus that neutralizes the gastric acid in the chyme. The microvilli The brush border contains several brush-border enzymes that have the local digestive functions. Transmission Electron Microscopy (TEM) 23  Small Intestine Intestinal juice A clear yellow fluid. About 1-2 liters secreted each day. Contains water and mucus and is slightly alkaline (pH 7.6). The alkaline pH of intestinal juice is due to its high concentration of bicarbonate ions (HCO3−). Together, pancreatic and intestinal juices provide a liquid medium that aids the absorption of substances from chyme in the small intestine. Brush border enzymes Synthesized by the absorptive cells and inserted in the plasma membrane of the microvilli. Thus, some enzymatic digestion also occurs on the absorptive cell surface. 望下就得,記最common 4 carbohydrate-digesting enzymes: α-dextrinase, maltase, sucrase, and lactase. 2 protein-digesting enzymes: aminopeptidase and dipeptidase. 2 types of nucleotide-digesting enzymes, nucleosidases and phosphatases. As absorptive cells slough off into the lumen of the small intestine, they break apart and release enzymes that help digest nutrients in the chyme. 去additional slide 24 Brief summary of digestion of macronutrients 25 Brief summary of digestion of macronutrients 26  Large Intestine Overview of the large intestine 1. Haustral churning, peristalsis, and mass peristalsis drive contents of colon into rectum. 2. Bacteria in large intestine convert proteins to amino acids, break down amino acids, and produce some B vitamins and vitamin K. 3. Absorption of some water, ions, and vitamins (majority of water and other solutes are absorbed in the small intestine). 4. Formation of faeces. 5. Defecation (emptying rectum). 27  Large Intestine - Histology Mucosa same as small intestine Epithelium Tubular intestinal glands (crypts of Lieberkü hn) Absorptive cells – water absorption, microvilli. Goblet cells – mucus secretion to lubricate the passage. 28 Large Intestine - Summary 29 Summary 30  The three phases of digestion Digestive activities occur in three overlapping phases: The cephalic phase, The gastric phase, The intestinal phase. brain Cephalic phase The smell, sight, thought, or initial taste of food activates neural centers in the cerebral cortex, hypothalamus, and brain stem. The brain stem then activates the facial (VII), glossopharyngeal (IX), and vagus (X) nerves. The facial and glossopharyngeal nerves stimulate the salivary glands to secrete saliva, while the vagus nerves stimulate the gastric glands to secrete gastric juice. The purpose of the cephalic phase of digestion is to prepare the mouth and stomach for food that is about to be eaten. 31  The three phases of digestion Gastric phase Once food reaches the stomach, the gastric phase of digestion begins. Neural and hormonal mechanisms regulate the gastric phase of digestion to promote gastric secretion and gastric motility. Neural regulation physcial Food distends the stomach and stimulates stretch receptors in its walls. Chemoreceptors in the stomach detect the pH increase (proteins in the stomach buffered some of the stomach acid). chemical from submucosa layer Nerve impulses from the stretch receptors and chemoreceptors propagate to the submucosal plexus, and activate parasympathetic and enteric neurons. The resulting nerve impulses cause waves of peristalsis and continue to stimulate the flow of gastric juice from gastric glands. The peristaltic waves mix the food with gastric juice. When the waves become strong enough, a small quantity of chyme undergoes gastric emptying into the duodenum. Decrease in pH of the stomach chyme and the less distended stomach walls then suppress secretion of gastric juice. 32 Gastric phase - Neural regulation Neural negative feedback regulation of the pH of gastric juice and gastric motility during the gastric phase of digestion. 33  The three phases of digestion Gastric phase Hormonal regulation Gastric secretion during the gastric phase is also regulated by the hormone gastrin. Gastrin is released from the G cells of the gastric glands in response to several stimuli: distension of the stomach, stimulates stretch receptors, secrete more gastrin partially digested proteins, high pH, neurotransmitter caffeine, and acetylcholine (released from parasympathetic neurons). Once it is released, gastrin enters the bloodstream, makes a round-trip through the body, and finally reaches its target organs in the digestive system. Gastrin stimulates gastric glands to secrete large amounts of gastric juice. 倒流 It also strengthens the contraction of the lower oesophageal sphincter to prevent reflux, increases motility of the stomach, and relaxes the pyloric sphincter, which promotes gastric emptying. Gastrin secretion is inhibited when the pH of gastric juice drops below 2.0 and is stimulated when the pH rises. This negative feedback mechanism helps provide an optimal low pH for the functioning of pepsin, the killing of microbes, and the denaturing of proteins in the stomach. 34  The three phases of digestion Intestinal phase The intestinal phase of digestion begins once food enters the small intestine. Reflexes occurring during the intestinal phase have inhibitory effects that slow gastric emptying. This prevents the duodenum from being overloaded with more chyme than it can handle. In addition, responses occurring during the intestinal phase promote the continued digestion of foods that have reached the small intestine. Neural regulation The enterogastric reflex Communication with stomach Caused by distension of the duodenum by the presence of chyme. Stretch receptors in the duodenal wall send nerve impulses to the medulla oblongata, where they inhibit parasympathetic stimulation and stimulate the sympathetic nerves to the stomach. As a result, gastric motility is inhibited and there is an increase in the contraction of the pyloric sphincter, which decreases gastric emptying. 35  The three phases of digestion Intestinal phase Hormonal regulation Cholecystokinin (CCK) Secreted by the CCK cells of intestinal glands in the small intestine. In response to amino acids from partially digested proteins and fatty acids from partially digested triglycerides in the chyme. Stimulates secretion of pancreatic juice. Causes contraction of the wall of the gall bladder, which squeezes stored bile out of the gall bladder into the cystic duct and through the common bile duct. Causes relaxation of the sphincter of the hepatopancreatic ampulla (sphincter of Oddi), which allows pancreatic juice and bile to flow into the duodenum. Slows gastric emptying by: ◆ Promoting contraction of the pyloric sphincter. ◆ Producing satiety (a feeling of fullness) by acting on the hypothalamus. ◆ Promoting normal growth and maintenance of the pancreas. ◆ Enhancing the effects of secretin. 36  The three phases of digestion Intestinal phase Hormonal regulation Secretin Secreted by the S cells pf the intestinal glands in the small intestine. Stimulated by the acidic chyme entering the duodenum. It stimulates the flow of pancreatic juice (rich in bicarbonate ions) to buffer the acidic chyme. The secretion is alkaline to neutralize the acidic chyme to provide an optimum pH for enzymes in the small intestine. Inhibits secretion of gastric juice. Promotes normal growth and maintenance of the pancreas. Enhances the effects of CCK. 協同效應 Other hormones Vasoactive intestinal polypeptide (VIP) - stimulates secretion of ions and water by the intestines and inhibits gastric acid secretion. Gastrin-releasing peptide - stimulates release of gastrin. Somatostatin (by the delta cells)- inhibits gastrin release. Some of these hormones are thought to act as local hormones (paracrines). Others are secreted into the blood or even into the lumen of the GI tract. 37 The three phases of digestion 38 Partially digested food 39 References Tortora, G. J., & Derrickson B.H. (2017). Principles of anatomy and physiology (15th ed.). Wiley Waugh, A., & Grant, A. (2018). Ross and Wilson anatomy and physiology in health and illness (13th ed.). Churchill Livingstone. Keller, S. M., & Marieb, E. N. (2021). Essentials of human anatomy & physiology. Pearson Education. Additional reference for digestion of nucleic acids Digestion of nucleotide by phosphatase Digestion of nucleoside by nucleosidase 41