1、Gastrointestinal Physiology (Part 2)Outlines 1. Pregastric digestionnMastication nSwallowing nSecretion of salivaryo Saliva：secretion，composition and functionso Nervous regulation of salivary secretion2. Gastric digestionnGastric secretiono Gastric juice：source，composition and functionso HCl secreti
2、on：cellular mechanism and regulationo Control of gastric secretion during digestive periodnGastric motilityo Receptive relaxation，tonic contraction and Peristaltic contractiono Gastric emptying：mechanism and control胃前消化o 咀嚼Mastication (chewing)n 将大颗粒块状食物研磨成小块，增加唾液淀粉酶作用面积n 与唾液混合，形成食团n刺激口腔内感受器，参与胃、小肠消
3、化功能调节 Pregastric digestionPregastric digestiono 吞咽Deglutitionn分期及特点U UPregastric digestionn蠕动蠕动Peristalsiso 蠕动的机械消化功能蠕动的机械消化功能o 蠕动过程中平滑肌的收缩特征蠕动过程中平滑肌的收缩特征o 介导蠕动的主要是内在神经系统介导蠕动的主要是内在神经系统Pregastric digestionn 食管下括约肌 lower esophageal sphincter (LES)的功能o 未进食期间o 吞咽时Pregastric digestionn吞咽时介导LES 张力下降的物质：NO
4、和VIP（由迷走神经末梢释放）n其它体液因素/ / NONOAchAch返流性食管炎In humans, common disorders involving the esophagus include heartburn and gastroesophageal reflux disease (GERD). In both cases, the lower sphincter does not close properly, allowing acid from the stomach to reflux back into the esophagus, causes a burning s
5、ensation in the chest or throat (heartburn) or additional signs such as coughing or a sensation of choking. Pregastric digestiono 唾液腺n腮腺n下颌下腺n舌下腺Pregastric digestiono 唾液 n来源：Secreted from serous and mucous cells of salivary glandsn理化特性：A 97-99.5% water, 低渗hypo-osmotic, pH6-7，containingo 电解质 Na+, K+,
6、 Cl, PO42, HCO3o 唾液淀粉酶o 蛋白质 mucin, lysozyme, defensins, and IgAo 代谢产物 urea and uric acidPregastric digestionn导管上皮细胞：主动吸收Na+，被动吸收Cl-，主动分泌K+和HCO3- o 分泌速率改变对唾液渗透压的影响o 分泌速率改变对唾液pH值的影响Pregastric digestionn 唾液的功能o 形成可以吞咽的食团 o 开始对淀粉的化学性消化（唾液淀粉酶）o 杀菌和参与机体防御作用 o 对牙齿的保护作用 Pregastric digestiono 唾液分泌的神经调节 n主要由副
7、交感神经调节n交感神经兴奋时也能引起唾液分泌增加n刺激和抑制唾液分泌的因素 胃内消化o 胃的主要消化功能:n 接纳和暂时贮存n 胃内的机械性和化学性消化n 将食糜送入小肠（排空）n 分泌内因子，帮助 vitamin B12 在小肠吸收Gastric digestiono 胃液的来源o贲门腺贲门腺 ：mucous o幽门腺：幽门腺：mucouso泌酸腺泌酸腺nSurface Epithelium - insoluble mucousnNeck Cells - soluble mucous nParietal (or oxyntic) Cells - HCl & Intrinsic Factorn
8、Chief Cells - pepsinogen Gastric digestiono 胃液的成分n Salt, water, HCl, pepsin, intrinsic factor, and mucus.（pH1.0-3.5, 1.5-2.5L/Day）n 胃液中胃液中HCl有哪些生理功能有哪些生理功能? n 分泌速率改变对胃液成分的影响o pHo K+-呕吐引起的低血钾症TEM of resting parietal cell from piglet stomach, showing canaliculus (C C) surrounded by numerous tubulovesi
9、cles (TVTV) and mitochondria. Bar = 1m TEM of maximally stimulated parietal cell (piglet), showing greatly enlarged canaliculi with elongated microvilli. Remaining space has densely packed mitochondria and very few tubulovesicles. Bar = 1m 壁细胞分泌盐酸的机制o细胞内H2O 分解为H+和 OH- ，OH- 与 CO2反应生成HCO3-;碳酸酐酶（CA）催化这
10、一过程oHCO3- 在基底膜与Cl-交换. HCO3- 随后进入毛细血管，导致血液pH轻微升高 (餐后碱潮，餐后碱潮，postprandial alkaline tide） oCl- 和K+从管腔膜上的特异通道进入胃腔o管腔膜上的质子泵（proton pump ，H+-K+ ATPase )主动将 H+ 泵出细胞，同时交换一个K+ 进入细胞o管腔内，H+与Cl-生成HClGastric digestiono质子泵抑制剂Proton pump inhibitors, PPIs抑酸机制nDrugs have been developed that non-competively bind and
11、inactivate the ATPase, resulting in strong inhibition of acid secretion. nOmeprazole奥美拉唑 is an acid-activated prodrug that binds covalently to two cysteines on the ATPase, resulting in its irreversible inactivation. .nOther inhibitors, including lansoprazole兰索拉唑, esomeprazole艾美拉唑, rabeprazole雷贝拉唑 an
12、d pantoprazole泮托拉唑 have similar modes of action. PPIs盐酸分泌的调节n 内源性刺激物：Ach，组织胺和胃泌素通过壁细胞上的各自受体（M3-R，H2-R和G/CCK-B-R）刺激HCl分泌o 迷走神经末梢：Acho G细胞：胃泌素（血液循环途径）o ECL细胞：组织胺（旁分泌途径）n ECL细胞是重要调节细胞，其上分布Ach和胃泌素受体n G细胞释放胃泌素的调节因素o 对胃窦的机械牵张刺激和化学刺激促进G细胞分泌o 迷走神经兴奋末梢释放GRP激活GRP受体促进G细胞分泌o 来源于D细胞的生长抑素激活生长抑素受体抑制G细胞分泌o 迷走神经末梢释放
13、Ach作用于D细胞上的受体抑制其分泌生长抑素，间接促进了G细胞分泌nD细胞介导壁细胞HCl分泌的负反馈调节机制o 胃窦内H+浓度升高，刺激D细胞分泌生长抑素n 阿托品Atropine的抑酸机制：阻断M受体n 西米替丁cimetidine的抑酸机制：阻断H2受体Some other H2 Receptor Antagonists：ranitidine, famotidine and nizatidine Gastric digestiono 胃蛋白酶原和胃蛋白酶 n 胃蛋白酶原的激活o HClo 胃蛋白酶自身激活胃蛋白酶自身激活n pH optima 1.8 - 3.5n Ach and HCl
14、 刺激主细胞分泌胃蛋白酶原o 内因子Intrinsic Factorn 结合Vitamin B12，防止其被消化和破坏n 与VB12生成的复合物 IF-Vit B12 是回肠吸收VB12的形式n 缺乏： 恶性贫血pernicious anemia (PA)Gastric digestiono 粘液-碳酸氢盐屏障Mucus-bicarbonate barriern 物理屏障：厚(500) ，凝胶状n 化学屏障：碳酸氢盐-pH梯度Gastric digestiono Review question How does the stomach protect itself from the gastr
15、ic HCl?1. Gastric barrier2. Tight junctions between the epithelial cells3. Control of HCl secretion4. Trophic effects by GI hormonesAcute gastritisAcute gastritisGastric ulcerGastric ulcerGastric digestiono 消化期胃液分泌的调节Gastric digestiono 头期（神经调节）n头部刺激因素：感觉器官刺激，高级中枢参与的调节反射n支配壁细胞的迷走神经兴奋 (ACh)n支配G细胞的迷走神经
16、兴奋（GRP）n支配ECL的迷走细胞兴奋 （GRP）n支配D细胞的迷走神经兴奋（Ach）Gastric digestiono 胃期Gastric Phasen胃内的机械和化学刺激n经短反射和长反射（迷走-迷走反射）作用于o Parietal cells (ACh)o G cells (release gastrin)o ECL cells (release histamine)n胃酸分泌的正反馈机制 Gastric digestiono 肠期 (pH above 3) n蛋白质消化产物（多肽）在十二指肠刺激G细胞n食糜进入十二指肠机械刺激G细胞n肠泌酸素enterooxyntin的作用Gast
17、ric digestiono 抑制胃酸分泌的因素：n胃内：Gastric pH gastric D cells release somatostatin which inhibits gastrin release n十二指肠：o Acid in duodenum - secretin & CCK- inhibits gastric secretion and motility o Acid, fats, hyper-osmotic solutions in the duodenum - release of enterogastrones -inhibit gastric motility
18、and secretiono Gastric Inhibitory Peptide (GIP) from duodenum - inhibits parietal cell function o Distension and chemical stimulation - 肠胃反射Entero-gastric reflex Gastric digestiono 胃的运动胃的运动n 胃的生理功能分区 EmptyingEmptyingGastric digestionn 紧张性收缩n 头端胃（近端胃）的容受性舒张o 神经反射，NO和VIP介导 VagusVagusNO,VIPNO,VIPEnteri
19、c nervous systemEnteric nervous systemGastric digestiono 远端胃的蠕动Peristaltic contractionn起源于胃中部（3次/min）n向幽门方向推进，一波未平一波又起，蠕动波得以叠加、增强n幽门附件蠕动波最强n食糜o数毫升被挤入十二指肠o大部分返回胃窦进一步研磨和混合 Gastric digestionn胃排空的概念n促进胃排空的因素（反之，抑制）1. Intense peristaltic contractions 2. Decreased pyloric tone3. Relatively decreased duode
20、nal motilityn胃排空的速率由胃内因素和十二指肠内因素共同调节o Gastric factors promote emptyingo Duodenal factors inhibit stomach emptyingGastric digestiono神经和体液因素均参与胃排空速率的调节o维持合适的胃排空速率的生理意义？Gastric digestionoMigrating motor complexes (MMC) 移行性复合运动are waves of activity which sweep through the intestines in a regular cycle d
21、uring fasting state (originates in the stomach roughly every 75-120 minutes).Gastric digestionoThese motor complexes help trigger peristaltic waves which facilitate transportation of indigestible substances such as bone, fiber and foreign bodies from the stomach, through the small intestine past the
22、 ileocecal sphincter into the colon.oIt also serves to transport bacteria from the small intestine to the large, and to inhibit the migration of colonic bacteria into the terminal ileum.oAn increase in gastric, biliary and pancreatic secretion is also seen in conjunction with the motor activity oThe
23、 MMC is thought to be partially regulated by motilin which is initiated in the stomach as a response to vagal stimulation, and does not depend on extrinsic nerves directly. Gastric digestiono VomitingnVomiting is the forceful expulsion of contents of the stomach and often, the proximal small intestine. nIt is a reflex controlled by a center in the medulla（Apomorphine）
