GIT - 2017 (Pharmacy) Physiology of the Gastrointestinal System PDF

Physiology of the Gastrointestinal System Physiology Unit 1  Outline o Introduction o Histology of the Alimentary Canal o Regulation of the digestive system – Neuronal control of GI activities Extrinsic control sys...

Physiology of the Gastrointestinal System Physiology Unit 1  Outline o Introduction o Histology of the Alimentary Canal o Regulation of the digestive system – Neuronal control of GI activities Extrinsic control system by ANS Intrinsic control system by ENS (enteric NS) – The GIT hormonal control system o Splanchnic circulation o Hepatic Portal System o Enterohepatic Circulation 2  Outline… o General Functions of the GIT o Ingestion of Food o Deglutition (Swallowing) o Motility  Motility in the Small Intestine  Motility in the Large Intestine  Defecation o Secretory Functions of the GIT  Mucus Secretion  Secretion of Saliva  Esophageal Secretion  Gastric Secretion  Pancreatic Secretion  Secretion of Bile by the Liver  Secretions of the Small Intestine  Secretions of the Large Intestine o Digestion in the GI Tract o Digestion of Carbohydrates o Digestion of Proteins o Digestion of Fats o Absorptive function of GIT o Absorption in Stomach o Absorption in Small Intestine o Absorption in the Large Intestine 3  Objectives Discuss the functions and structures of digestive system Describe the regulation of GIT activities Describe the major gastrointestinal secretions, their components and their digestive function Describe mechanisms of absorption 4 Introduction: Gastrointestinal system (GIS) 5  Structure of Digestive System The digestive system consists of the following: A. Principal structures that make up alimentary canal: – Oral cavity – Pharynx – Esophagus – Stomach – Small intestine – Large intestine – Anus B. The accessory organs include: – Salivary glands – Liver – Gallbladder – Pancreas 6  Structure of Digestive System Principal Accessory structures organs 1. Oral cavity 2. Pharynx 1. Salivary glands 3. Esophagus 2. Liver 4. Stomach 3. Gallbladder 5. Small intestine 4. Pancreas 6. Large intestine 7. Rectum (Anus) 7 Organs of the digestive system 8  Introduction… Some of the roles played by GIS include: 1. Its roles in homeostasis 2. In fluid balance, and 3. In microbial defense 9  Introduction…  GIS role in homeostasis: Body cells require nutrients to obtain energy (ATP) and function properly. The food has to be crushed into smaller units and be available for utilization by cells. The overall function of the GIS is to digest, transport, secrete, absorb, and finally eliminate unwanted residues away from the body. So, as one of the homeostatic organs of the body, the GIS maintains the day-to-day balance of food intake and excretion and, thereby, guarantees the perpetuation of life. 10  Introduction…  GIS in fluid balance Secretion: ~ 7 Liters of fluid are secreted (added) from different organs into the tract ~ 2 Liters of fluid is drunk ~ total ~ 9 Liters of fluid are added into the Gut daily. Absorption: ~ 8.5 Lit are absorbed by the SI ~ 400 ml is absorbed by the LI Excretion: only ~ 50-to -100 ml of fluid is excreted daily with feces 11  Introduction…  GIS in microbial defense  The GI-system can protect itself from hazards by some defense mechanisms found in the: A. Mouth: Saliva contains lysozymes that attacks microbes in the mouth B. Stomach: HCl secreted in the stomach has bactericidal actions C. Small intestine: Immuno-competent lymph tissues like Payer's patches attack microbes in the SI D. Macrophages: in SI, developed from Monocytes destroy microbes by Phagocytosis 12 Introduction… 13  Digestive Process Mouth  Food ingestion  Food intake is controlled by Hypothalamus Esophagus  Simple passage of food Stomach  Temporary storage, mixing, digestion, secretion, emptying Small intestine  Digestion, secretion and absorption Large Intestine  Storage, absorption and passage of faecal matter Figure 23.2 14  Generally, there are 2-types of digestion 1. Mechanical Digestion:  Is the physical grinding of food to smaller units without altering their chemical composition.  Mechanical digestion helps to expose and increase the surface area for enzymatic attacks (e.g., inside the mouth) 2. Chemical Digestion:  Is the enzymatic breakdown of nutrients (CHO, fat, protein etc) through different chemical reactions into simpler forms.  This processes changes the original composition of the nutrient or food. For example, alpha amylase is catalytic enzyme that acts on starches in mouth and changes it into maltose (a disaccharide) 15  Histology of the Alimentary Canal From esophagus to the anal canal the walls of the GIT have the same four layers: 1. Mucosa, 2. Submucosa, 3. Muscularis externa, and 4. Serosa 16  Histology of the Alimentary Canal… Fig. General organization of the layers of the gastrointestinal tract 17  Mucosa Moist epithelial layer that lines the lumen of the alimentary canal It has three major functions: – Secretion of mucus – Absorption of the end products of digestion – Protection against infectious disease Consists of three layers: – A lining epithelium, – Lamina propria, and – Muscularis mucosae 18  Mucosa: Epithelial Lining Covers the mucosa Two types of epithelial cells along the GIT 1. Non-keratinized stratified squamous epithelium lining the mouth, pharynx, esophagus and anal canal. Function: protection 2. Simple columnar epithelium: through out the rest of the tract Function: absorption and secretion The mucus secretions: – Protect digestive organs from digesting themselves – Ease food rolling along the tract 19  Mucosa: Lamina Propria and Muscularis Mucosae Lamina Propria is areolar connective tissue under the epithelium containing: –Blood vessels and lymph vessels. –Nourishes the epithelium and absorbs nutrients. –Contains lymph nodes important in defense against bacteria (e.g., Payers patches that produce B-lymphocytes). Muscularis Mucosae –Located underneath the lamina. –It is a thin layer of smooth muscle and its contraction and relaxation changes the degree of folding of the luminal diameter –Throws the mucous membrane of the stomach and small intestine into many small folds. –The folds increase the surface area for digestion and absorption. 20  Submucosal layer  Loose connective tissues consists of: Blood and lymphatic vessels Secretary glands, Lymph nodes The Submucosal Plexus (Plexus of Meissner), which is the enteric nerve plexus. – This plexus controls secretions by the GIT 21  Muscularis Externa The muscularis of the mouth, pharynx, and upper esophagus consists of skeletal muscles that produces voluntary swallowing. The skeletal muscle also forms the external anal sphincter, which permits voluntary control of defecation. Through out the rest of the tract, the muscularis consists of smooth muscles that is generally found in two sheets: Inner sheet of circular fibers and Outer sheet of longitudinal fibers 22  Muscularis Externa… The circular layer (inner luminal side)  Their contractions decrease the diameter of the lumen.  At some regions, the circular SM thicken and forms a sphincter that prevents backflow of food contents. The outer longitudinal layer  When it contracts, it decreases the length of the tract and cause shortening and lengthening of the tract.  The effect of both contractions help mix and propel the chyme in aboral direction (i.e., towards the anus). 23  Muscularis Externa… Involuntary contraction of both smooth muscles help: – Breakdown of food physically, – Mix it with digestive secretions, and – Propel it along the tract Between muscularis layer there are second plexus of neurons, the Myenteric Plexus (Plexus of Auerbach). This plexus mostly controls GIT motility. 24  Serosa The serosa is the outer most layer of the GIT It is a serous membrane composed of connective tissue lined by epithelium (mesothelium). Its squamous epithelial cells secrete serous fluid that helps in moistening & lubricating the tubes outer surface. This helps the abdominal cavity to slide freely against one another, there by decreasing friction. – Below the diaphragm, this layer is also called the visceral peritoneum. – Above the diaphragm it is adventitia 25  Regulation of GIT Regulation of GI activities involve: 1. Neuronal control of GI activities Gastrointestinal reflexes are initiated by luminal stimuli. The sensory neurons of the ENS supply the mucosal epithelium Receptors in the mucosal epithelium include:  Mechanoreceptors: respond to distension  Chemoreceptors: respond to osmolarity, irritation, pH, presence of fat and protein food.  Thermoreceptors: respond to warm food/drinks  Pain receptors: respond to tissue injury  They initiate GI-reflexes that: 1. Activate or inhibit digestive glands 2. Mix lumen contents and move them along the GIT 26  Regulation of GIT… Neuronal control of GI activity include: – Intrinsic control system by ENS (enteric NS)  Submucosal plexus (plexus of Meissner)  Myenteric plexus (plexus of auerbach) – Extrinsic control system by ANS  Sympathetic NS = ↓GI function  Parasympathetic NS = ↑GI function 2. The GIT hormonal control system 27  Neuronal control of GI activities A. Intrinsic control system involves the enteric nerve plexuses present with in the GIT. – The plexuses of the ENS consist of sensory, inter, and motor neurons. – Nerve plexuses in the GI tract initiate short reflexes – Myenteric plexus (plexus of auerbach): mainly controls motility of the gut – Submucosal plexus (plexus of Meissner): controls GI secretary activities 28  Enteric Nervous System (ENS)  Enteric nervous system (ENS), the “brain of the gut”.  It consists of about 100 million neurons that extend from the esophagus to the anus.  The neurons of the ENS are arranged into two plexuses: – The myenteric plexus (plexus of Auerbach), is located between the longitudinal and circular smooth muscle layers of the muscularis. – The submucosal plexus (plexus of Meissner), is found within the submucosa. 1. The plexuses of the ENS consist of motor neurons, interneurons, and sensory neurons 29  Enteric Nervous System (ENS)…  ENS possesses multiple preprogrammed responses.  For example, both mechanical distention of the jejunum and the presence of a bacterial enterotoxin in the jejunum can elicit identical responses: stimulation of profuse fluid and electrolyte secretion, together with propagated, propulsive, coordinated smooth muscle contractions.  Such preprogrammed efferent responses are probably initiated by sensory input to the enteric interneuronal connections.  However, efferent responses controlled by the ENS may also be modified by input from autonomic ganglia, which are, in turn, under the influence of the spinal cord and brain. In addition, the ENS receives input directly from the brain through parasympathetic nerves (i.e., the vagus nerve). 30  ENS neurotransmitters  Neurotransmitters secreted by the enteric neurons  Acetylcholine - excitatory  Norepinephrine - inhibitory  Adenosine triphosphate  Peptides:  Vasoactive intestinal peptide (VIP)  Enkephalins/Leu-enkephalin, Met-enkephalin/  Somatostatin and  substance P  Amines such as  Serotonin (5-hydroxytryptamine [5-HT]); and  Nitric oxide (NO).  Bombasin, Cholecystokinin, Dopamine  More than one neurotransmitter has been identified within single neurons. 31  Neuronal control of GI activities… B. Extrinsic controls Involve CNS centers and extrinsic autonomic nerves – CNS centers –Satiety & hunger center in the hypothalamus. Extrinsic autonomic nerves – Sympathetic NS –GI function; ↓Motility, ↓Secretions – Parasympathetic NS –GI function; ↑Motility, ↑Secretions 32  Autonomic control of the GIT Parasympathetic innervation to the gut Parasympathetic innervation to the gut is divided into cranial and sacral division. The cranial parasympathetic are transmitted almost entirely in the vagus nerves, providing extensive innervation to the: – Esophagus, – Stomach, – Pancreas Parasympathetic innervation of the GI tract from the pharynx to the distal colon is through the vagus nerve; the distal third of the colon receives its parasympathetic innervation from the pelvic nerves. 33 Parasympathetic Division 34 35  Autonomic control of the GIT (cont’d) The sacral parasympathetic originate in the 2nd, 3rd and 4th sacral segments of spinal cord and pass through the pelvic nerves to: – The distal half of the large intestine, – The sigmoidal, – Rectal and – Anal regions. These fibers function in the defecation reflexes. The preganglionic fibers of the parasympathetic nerves use ACh as their neurotransmitter and synapse on some neurons of the ENS. These ENS neurons are thus postganglionic parasympathetic fibers, and their cell bodies are, in a sense, the parasympathetic ganglion. The post gonglionic neurons of the PNS are located in the myenteric and submucosal plexuses. Stimulation of PNS causes a general increase in activity of the entire enteric NS, enhancing GI function. 36  Autonomic control of the GIT (cont’d) Sympathetic Innervation The sympathetic fibers to the GIT originate in the spinal cord between segments T5 and L-2. The preganglionic sympathetic fibers to the GI tract synapse on postganglionic neurons in the sympathetic ganglia/ prevertebral ganglia; the neurotransmitter at this synapse is ACh. The postganglionic sympathetic fibers either synapse in the ENS plexuses or directly innervate effector cells 37  Autonomic control of the GIT (cont’d) Sympathetic fibers innervate all portion of the GIT but more extensive in the oral and anal areas. Sympathetic nerve endings secret norepinephrine. – Norepinephrine has inhibitory effect on the neurons of the enteric nervous system. – In general, stimulation of SNS inhibits activities of GIT. 38 Sympathetic Division… 39 Sympathetic Division… 40 Neuronal control of GI activities… 41 42  Autonomic control of the GIT (cont’d) In addition to the control that is entirely within the ENS, as well as control by autonomic centers in the medulla, the GI tract is also under the control of higher CNS centers. – Examples of cerebral function that affects GI behavior include the flight-or-fight response, which reduces blood flow to the GI tract, and the sight and smell of food, which increase gastric acid secretion. – It is common to experience gastrointestinal (GI) symptoms such as diarrhea, dyspepsia, and abdominal discomfort in response to alterations in emotional state. The brain-gut axis is a bidirectional system that controls gastrointestinal function 43  GIT reflexes  Basic Principles Gastrointestinal reflexes are initiated by a relatively small number of luminal stimuli: – Distension of the wall by the volume of the luminal contents; – Chyme osmolarity (total solute concentration); – Chyme acidity; and – Chyme concentrations of specific digestion products like monosaccharides, fatty acids, peptides, and amino acids. These stimuli act on mechanoreceptors, osmoreceptors, and chemoreceptors located in the wall of the tract and trigger reflexes that influence the effectors—the muscle layers in the wall of the tract and the exocrine glands that secrete substances into its lumen. 44  GIT reflexes 1. Reflexes that occur entirely within the ENS. These include reflexes that control GI-secretion, peristalsis, mixing contractions, local inhibitory effects. 2. Reflexes that arise from the gut go to the sympathetic ganglia and then back to the GI-tract. Examples: a) The gastro-colic reflex: signals send from the stomach to cause evacuation of the colon. b) The entero-gastric reflexes: signals from the colon and small intestine to inhibit stomach motility and secretion. c) The colono-ileal reflex: reflexes from the colon to inhibit emptying of ileal contents into the colon. 3. Reflexes from the gut to the spinal cord or brain stem and then back to GIT: Example: Defecation reflex Defecation reflexes that travel from the colon and rectum to the spinal cord and back again to produce the powerful colonic, rectal, and abdominal contractions required for defecation. 45 Nervous Control of the GI Tract 46  Hormonal control of GI function Entero-endocrine cells produce several GIT- hormones, capable of regulating motility and secretary activities. Cholecystokinin (CCK) Secreted by “I” cells in the mucosa of the duodenum and jejunum in response to the presence of fatty food. Function – Has a very potent effect on gallbladder contractility for expelling bile into the intestine. – Relaxation of the sphincter of Oddi. – CCK inhibits stomach motility in order to give adequate time for fat digestion. It augments the contraction of the pyloric sphincter inhibits gastric emptying. 47 48  Hormonal control… Secretin Secreted by the “S” cells in the mucosa of the duodenum in response to: – Acidic gastric juice from the stomach. Secretin increases the secretion of bicarbonate by the duct cells of the pancreas, which in turn helps to neutralize the acid in the small intestine. It decreases gastric acid secretion. 49  Hormonal control… GIP: Gastric inhibitory peptide Produced by “K” cells in the mucosa of the duodenum and jejunum in response to fat and amino acids in the intestine. It inhibits the motor activity of the stomach. Gastrin Gastrin is produced by “G” cells in the antral portion of the gastric mucosa. Gastrin secretion is increased by the presence of the products of protein digestion in the stomach. – Particularly amino acids, which act directly on the G cells – Phenylalanine and tryptophan are particularly effective. 50  Hormonal control… Function Stimulation of gastric acid and pepsinogen secretion. Increase acid secretion through activation of: – Enterochromaffin-like cells to release histamine – Direct stimulation of parietal cells 51  Hormonal control… Motilin Secreted by enterochromaffin cells in the stomach, small intestine, and colon. Produces rhythmic contraction of smooth muscle in the stomach and intestines between meals. When a meal is ingested, secretion of motilin is suppressed until digestion and absorption are complete. Ghrelin - secreted primarily by the stomach and play an important role in the central control of food intake. – Increases food intake – Increase during periods of fasting – Ghrelin levels are low after eating and in obesity 52  Hormonal control… Somatostatin Secreted by “D” cells in the gastrointestinal mucosa in response to acid in the lumen. Somatostatin has broad inhibitory actions: – Reduces GI secretion & motility – Inhibits the secretion of gastrin – Pepsinogen secretion – Inhibits pancreatic enzyme, fluid and bicarbonate secretion – Reduces bile flow – Reduces intestinal transport of nutrients and fluid 53  Hormonal control… Gastrin-releasing peptide (secreted by vagal nerve endings); – ↑ Gastrin release/G cells in antrum of stomach/ Guanylin (secreted by ileum and colon); – ↑ Fluid absorption/Small and large intestine/ Neurotensin (secreted by endocrine cells, widespread in GI tract); – Vasoactive stimulation of histamine release/Intestinal smooth muscle/ Peptide YY (secreted by endocrine cells in ileum and colon); – Stomach: ↓ Vagally mediated acid secretion – Pancreas: ↓ Enzyme and fluid secretion 54  Blood Supply to Digestive System The blood vessels of the GI-system are part of a more extensive system called the splanchnic circulation. Splanchnic BF Includes blood flow through the GIT plus through the spleen, pancreas and the liver. All of the blood that flows through the gut, spleen and pancreas then passes into the liver by way of the portal vein. In the liver, blood passes through millions of liver sinusoids and finally leaves the liver by way of the hepatic veins that empty into the inferior vena cava of the general circulation. The advantage of sinusoidal passage of blood is that the reticuloendothelial cells in the liver remove bacteria and other particles entering the blood from the GIT. 55  Splanchnic circulation… Splanchnic is used to describe organs in the abdominal cavity (visceral organs). The term ‘splanchnic circulation’ describes the blood flow to the abdominal gastrointestinal organs including the stomach, liver, spleen, pancreas, small intestine, and large intestine. It comprises three major branches of the abdominal aorta; the celiac artery, superior mesenteric artery and inferior mesenteric artery. Portal circulatory system + arterial blood flow into the liver 56 Splanchnic circulation… 57 Splanchnic BF… Venous blood collected from these regions pass through the portal circulation and end in the liver > liver sinusoids > hepatic vein> inferior vena cava Advantage of portal circulation: Potentially harmful agents that come with the blood are destroyed by macrophages of the liver (Reticuloendothelial cells) 58  Splanchnic circulation… The superior mesenteric and inferior mesenteric arteries supply blood to the wall of small and large intestine. The celiac artery supplies blood to the stomach. Big arteries are branched and re-branched to encircle and penetrate deep into the mucosal, villi, layers of the gut wall. Blood flow to the GIT is increased during meal but then decreases back to the resting level over another 2 to 4 hours. Possible causes – The release of vasodilator GI hormones during digestive processes. – These include CCk, VIP, gastrin, secretin, bradykinin, nitric oxide. 59  Factors that control blood flow to the GIT include: Metabolic: Increase in metabolism during or after a meal increases releases vasoactive substances that increases blood flow by 8-fold. Decreased O2-tension: Increases blood flow (local metabolites like adenosine) Neural : PNS , increases gut blood flow SNS, decreases gut blood flow Counter-current: Arterial and venous blood vessels arranged in opposite direction, so shunt may occur that may cause ischemia of the villi 60 Microvasculature of the villus, showing a countercurrent arrangement of blood flow in the arterioles and venules 61  Splanchnic circulation… Gastrointestinal blood flow is decreased when other parts of the body need extra blood flow: – In heavy exercise, when the skeletal muscle and heart need increased flow – In circulatory shock, when all the body’s vital tissues are in danger of cellular death for lack of blood flow—especially the brain and the heart 62 Blood Supply to GIT… 63 64  Hepatic Portal System The products of digestion that are absorbed into blood capillaries in the intestine do not directly enter the general circulation. Capillaries in the digestive tract drain into the hepatic portal vein, which carries this blood to capillaries in the liver. It is not until the blood has passed through this second capillary bed that it enters the general circulation through the hepatic vein that drains the liver. The term portal system is used to describe this unique pattern of circulation: capillaries ⇒ vein ⇒ capillaries ⇒ vein The hepatic portal vein drains the capillaries of the intestine, pancreas, gallbladder, and spleen, and accounts for about 70% of the blood flow to the liver. 65  Hepatic Portal System… The hepatic artery supplies the remaining 30% of the liver’s incoming blood flow. Blood flows within sinusoids from a portal vein to the central vein (from the periphery to the center of a lobule). Bile flows within hepatic plates from the center to bile ductules at the periphery of a lobule. 66  Hepatic Portal System… Structure of the Liver Hepatocytes, form hepatic plates that are one to two cells thick. The plates are separated from each other by large capillary spaces called sinusoids The liver sinusoids are lined by endothelial cells with flattened processes and fenestrae This makes the hepatic sinusoids much more permeable than other capillaries, even permitting the passage of plasma proteins with protein-bound nonpolar molecules, such as fat and cholesterol The sinusoids also contain phagocytic Kupffer cells 67 68 Scheme of principal blood vessels of hepatic portal circulation and arterial supply and venous drainage of liver 69 Veins of the Hepatic Portal System and Its Tributaries 70  Enterohepatic Circulation Bile and drugs are secreted by the liver into the bile ducts. The liver can thus “clear” the blood of particular compounds by removing them from the blood and excreting them into the intestine with the bile. Molecules that are cleared from the blood by secretion into the bile are eliminated in the feces. Many compounds that are released with the bile into the intestine are not eliminated with the feces, however. Some of these can be absorbed through the small intestine and enter the hepatic portal blood. These molecules are thus carried back to the liver, where they can be again secreted by hepatocytes into the bile ducts. Compounds that recirculate between the liver and intestine in this way are said to have an enterohepatic circulation. 71  Enterohepatic Circulation The enterohepatic circulation:substances secreted in the bile may be absorbed by the intestinal epithelium and recycled to the liver via the hepatic portal vein. 72 Compounds Excreted by the Liver into the Bile Ducts 73  General Functions of the GIT A. Ingestion: taking food into the mouth. B. Motility : churning and propulsion of food through the GI tract. C. Secretion: release of water, acid, buffers, mucus and enzymes into the lumen of the GI tract. D. Digestion: mechanical and chemical breakdown of food. E. Absorption: passage of digested products from the GI tract into the blood and lymph. F. Elimination: excretion of the fecal matters through the process of defecation from the GI tract. 74 A. Ingestion of Food – taking the food into the mouth The amount of food that a person ingests is determined principally by the intrinsic desire for food (hunger). The type of food that a person preferentially seeks is determined by appetite. Two areas in the hypothalamus are important for controlling appetite: The "satiety center" is located in the ventromedial nucleus (VMN) – Stimulation of this center elicits sensations of satiety – Lesion of the center causes continuous food intake (hyperphagia) The "hunger (feeding) center" is in the lateral nucleus: – That initiate crave for food and – Desire for a particular type of food (appetite) is determined by the feeding center. – Lesion causes a complete and lasting cessation of food intake (aphagia). A Long-term factor that suppresses appetite is Leptin – a protein secreted by adipocytes that binds to hypothalamic receptors 75  Mastication (Chewing) Increases the surfaces of food particles for digestive enzymes The rate of digestion is absolutely dependent on the total surface area exposed to the digestive secretions. Mechanical digestion in the mouth results from chewing or mastication. The food is manipulated by the tongue, ground by the teeth, and mixed with saliva. After adequate mastication and mixing with salivary juice the food content is reduced to a soft, flexible, easily swallowed mass (bolus). 76  Pharynx When food is first swallowed, it passes from the mouth into the pharynx (throat), a funnel-shaped tube that extends from the internal nares to the esophagus posteriorly and to the larynx anteriorly Allow passage of: Food and fluids to the esophagus Air to the trachea Lined with stratified sqaumous epithelium and mucus glands Divided into three parts: the nasopharynx, the oropharynx, and the laryngopharynx. The nasopharynx functions only in respiration, but both the oropharynx and laryngopharynx have digestive as well as respiratory functions 77 Pharynx… 78  Deglutition (Swallowing) It is the propulsion of food from mouth to the stomach. Has 3 stages: 1. Voluntary stage of swallowing: Buccal/oral phase – bolus is collected on the tongue & forced into the oropharynx Upward and backward pressure of the tongue against the palate squeezes the bolus posteriorly into the pharynx. This initiates the involuntary phase of swallowing 2. Pharyngeal stage of swallowing: It is the involuntary process and contributes the passage of food through the pharynx to the esophagus. Controlled by the medulla and lower pons. 79  Deglutition (Swallowing)… Contraction of pharyngeal muscles cause: – soft palate is pulled upward – larynx is pulled upward & epiglottis flap over glottis. – Respiration is temporarily interrupted – Trachea is closed and esophagus is opened – The food bolus enter esophagus 80  Deglutition (Swallowing)… 3.The esophageal stage of swallowing: Involuntary phase, promote the passage of food to the stomach by peristaltic mov’t. Coordinated contractions and relaxations of the circular and longitudinal muscle progressively move the bolus. 81  Esophageal stage of swallowing It functions primarily to conduct food from the pharynx to the stomach It exhibits two types of peristalsis 1. Primary peristalsis: is simply a continuation of the peristaltic wave that begins in the pharynx. 2. Secondary peristalsis: is additional peristaltic wave that is initiated by the bolus of food distending the esophageal wall. It is initiated partly by the enteric NS and partly by the vagus nerve. 82 Swallowing Mechanism 83  Deglutition (Swallowing) BolusBolus of food of food Tongue Tongue Uvula Uvula PharynxPharynx Bolus Bolus Epiglottis Epiglottis Epiglottis Epiglottis Glottis Trachea Trachea Esophagus Esophagus Bolus Bolus (a) Voluntary stage,stage, (a) Voluntary oral oral (b) Involuntary, pharyngeal (b) Involuntary, pharyngeal (c)(c)Esophageal Esophagealstage stageofof phase phase of swallowing of swallowing stage of swallowing swallowing swallowing stage of swallowing Relaxed Relaxed Relaxed Relaxed muscles Circular muscles Circular contract, muscles contract, muscles muscles muscles constricting passageway constricting passageway and and pushing bolus pushing down bolus down Gastroesophageal Gastroesophage BolusBolus of food of food sphincter open al sphincter open Longitudinal muscles Longitudinal muscles contract, contract, shortening shortening Gastroesophageal reflux? passageway aheadahead passageway of of Achalasia? bolus bolus Gastroesophageal sphincter closed Stomach Stomach 84 (d) (d) (e)(e) Deglutition (Swallowing) 85  Esophagus Esophagus is muscular tube, about 25 cm long, that lies posterior to the trachea going from the laryngopharynx to the stomach. Has two sphnicters: Upper esophageal sphincter Lower esophageal sphincter Travels through the mediastinum and pierces the diaphragm at hiatus. Sometimes, part of the stomach protrudes above the diaphragm through the esophageal hiatus. This condition, termed a hiatus hernia. Joins the stomach at the cardiac orifice 86  Esophagus… Structural and regulatory aspects: Upper one third of the esophagus: circular and longitudinal muscle layers are skeletal;  Innervation via somatic nerves Lower two third: smooth muscle,  Enteric nerve system  Vagal input to enteric nerve system 87  Peristalsis: – Produced by a series of localized reflexes in response to distention of wall by bolus. Wave-like muscular contractions: Insert 18.4a – Circular smooth muscle contract behind, relaxes in front of the bolus. – Followed by longitudinal contraction (shortening) of smooth muscle. Rate of 2-4 cm/sec. – After food passes into stomach, LES constricts. 88  Sphincters prevent back flow of GI content 7 sphincters along the GIT: 1. Upper esophageal sphincter/pharyngoesophageal sphincter, 2. Lower esophageal sphincter/Gastroesophageal sphincter, 3. Pyloric sphincter, 4. Sphincter of Oddi,  Regulate the flow of pancreatic secretion and bile to duodenum 5. Ileocecal sphincter,  B/n ileum and cecum & prevent back flow from cecum to ileum 6. External anal sphincter 7. Internal anal sphincter 89 90 Esophageal sphincters Upper esophageal sphincter (UES): prevents entry of air. o Some air is unavoidably swallowed in the process of eating and drinking (aerophagia). o Some of the swallowed air is regurgitated (belching), and some of the gases it contains are absorbed, some of it passes on to the colon. Lower esophageal sphincter (LES):  Prevents reflux of corrosive acidic stomach content.  LES tone is regulated by nerves and hormones. o Release of acetylcholine from vagal endings causes the intrinsic sphincter to contract, and o Release of NO and VIP from interneurons innervated by other vagal fibers causes it to relax. 91  Function of the lower esophageal sphincter Or Gastro esophageal Sphincter The stomach secretions are highly acidic and contain many proteolytic enzymes. The esophageal mucosa, except in the lower one eighth of the esophagus, is not capable of resisting the digestive action of gastric secretions. The tonic constriction of the LES helps to prevent significant reflux of stomach contents into the esophagus under normal conditions. 92 Pyrosis(heartburn/esophagitis)—common esophageal discomfort Result of regurgitation or reflux of gastric content into lower esophagus  Acid reflux can cause esophagitis Due to incompetence of the LES  Allows return of stomach contents into esophagus  This is called Gastroesophageal reflux disease (GERD) Drinking alcohol and smoking can cause the sphincter to relax. 93  Achalasia  Occurs when LES fails to relax during swallowing   Food swallowed into esophagus fails to pass from esophagus into stomach.  Due to damage in the neural network of the myenteric plexus in the lower two thirds of the esophagus (the release of NO and VIP is defective)   Myenteric plexus has lost its ability to transmit a signal to cause "receptive relaxation" of GES as food approaches the sphincter   Musculature of the lower esophagus remains spastically contracted  This is called Achalasia 94  When achalasia becomes severe  Esophagus becomes tremendously enlarged (can hold 1L of food)  Infected during the long periods of esophageal stasis   The infection cause ulceration of esophageal mucosa, sometimes leading to- severe substernal pain, esophageal rupture and death Treatment: – Stretching the lower end of the esophagus by means of a balloon inflated on the end of a swallowed esophageal tube – Antispasomdic drugs (drugs that relax smooth muscle) – Inhibition of acetylcholine release by injection of botulinum toxin into the LES – Surgical cutting of the LES (i.e., an esophageal myotomy or Heller procedure). 95  B. Motility: Movement of food through the GI tract Functional types of movements in the GIT: 1. Propulsive movements  Peristalsis 2. Mixing movements  Segmentation/churning 96 Peristalsis and Segmentation (mixing) 97  1. Propulsive Movements Peristalsis is the basic propulsive movements of the GIT It appears in the form of contractile rings around the gut and propels to the anal direction. Peristalsis is an inherent property of the smooth muscles in the GIT due to generation of action potential rhythmically (basic electrical rhythm, BER). This basic electrical rhythm (BER) is initiated by the interstitial cells of Cajal. Causes food to move forward along the tract at an appropriate rate to accommodate digestion & absorption The usual stimulus for intestinal peristalsis is distention of the gut 98  Function of the Myenteric Plexus in Peristalsis Effective peristalsis requires an active myenteric plexus. – If congenital absence of the myenteric plexus  – Peristalsis occurs only weakly or not at all in any portion of the gastrointestinal tract – If a person is treated with atropine to paralyze the cholinergic nerve endings of the myenteric plexus  – Peristalsis is greatly depressed or completely blocked in the entire gut 99  Propulsive Movements in Small Intestine Peristalsis move toward the anus at a velocity of 0.5- 2.0 cm/sec Controlled by Nervous and Hormonal Signals 1. Nervous signal- is greatly increased after a meal  Entry of chyme into the duodenum causing stretch of the duodenal wall  Stimulate myenteric plexus  Gastro enteric reflex (distention of the stomach stimulates the myenteric plexus of small intestine)   Peristalsis in the Small Intestine 2. Hormones:  Gastrin, CCK, motilin, and serotonin   All of which enhance intestinal motility 100  2. Mixing Movements – mix the food with the GI content Differ in different parts of the alimentary tract – In some areas, the peristaltic contractions themselves cause most of the mixing. – At other areas local intermittent constrictive contractions occur every few cms in the gut wall. 101  Hunger contractions Is rhythmical peristaltic contractions in the body of stomach Occurs when the stomach is empty for several hrs When the successive contractions become extremely strong,  Fuse to cause a continuing tetanic contraction, lasts 2-3 min  The person can experiences mild pain in the pit of the stomach, called hunger pangs – Usually begin 12 to 24 hrs after the last ingestion of food; – In starvation, reach greatest intensity in 3 to 4 days and gradually weaken in succeeding days. 102  Functions of the stomach  Stomach has the following functions: 1. Storage of large quantities of food until it can be pumped into the duodenum. – Stomach can accommodate up to 1.5 Lts of food. 2. Mixing of food with gastric secretion to form a semi-fluid chyme. 3. Slow emptying the food from the stomach into the small intestine at a rate suitable for proper digestion and absorption by the small intestine. 4. Secretes gastric juice, which contains HCl (kills bacteria and denatures protein), pepsin (begins the digestion of proteins), intrinsic factor (aids absorption of vitamin B12), and gastric lipase (aids digestion of triglycerides). 5. Secretes gastrin into blood. 103  Functional structure of the stomach Cardiac region: surrounds the cardiac orifice Fundus: dome-shaped region beneath the diaphragm Body: mid-portion of the stomach Pyloric region: made up of the antrum and canal which terminates at the pylorus  The muscularis has three layers of smooth muscle (rather than the two found in the esophagus and small and large intestines): an outer longitudinal layer, a middle circular layer, and an inner oblique layer.  The oblique layer is limited primarily to the body of the stomach. 104 Functional structure of the stomach… 105 Functional structure of the stomach… 106  Stomach Emptying – flow of the chyme to the duodenum The distal opening of stomach is called pylorus – Allows water and other fluids emptying with ease – Prevents passage of food particles until mixed in the chyme to almost fluid consistency – Its degree of constriction ↑ or ↓ under the influence of nervous & humoral reflexes Most of the time, the rhythmical stomach contractions are weak – Function mainly to cause mixing of food and gastric secretions For about 20% of the time while food is in the stomach, the contractions become intense – Function mainly to cause strong peristaltic constrictions  – Cause stomach emptying 107 Pyloric sphincter - Regulates emptying of the chyme - Prevents regurgitation of duodenal content Pyloric sphincter 108  Pylorospasm and Pyloric stenosis  Two abnormalities of the pyloric sphincter can occur in infants.  In pylorospasm, the smooth muscle fibers of the sphincter fail to relax normally, so food does not pass easily from the stomach to the small intestine, the stomach becomes overly full, and the infant vomits often to relieve the pressure. Pylorospasm is treated by drugs that relax the muscle fibers of the pyloric sphincter.  Pyloric stenosis is a narrowing of the pyloric sphincter that must be corrected surgically. The hallmark symptom is projectile vomiting (the spraying of liquid vomitus some distance from the infant). 109  Regulation of Stomach Emptying Gastric factors that promote emptying: 1. Gastric food volume Increased food volume in the stomach  gastric emptying – Stretching of the stomach wall  – Elicit local myenteric reflexes  heighten activity of the pyloric pump. 2. Fluidity: increased fluidity allows more rapid emptying 3. Hormones: Gastrin – Stimulates motor functions in the body of the stomach and enhance peristaltic contractions Duodenal factors that inhibit stomach emptying: Enterogastric inhibitory reflex Hormonal factor: Cholecystokinin  emptying – Stimulated mainly by fats in the duodenum – Fat digestion takes longer time 110  Function of the Ileocecal Valve and sphincter Gastroileal reflex – Immediately after a meal nervous signals from the stomach intensifies peristalsis in the ileum  – Increased emptying of ileal contents into cecum Fluidity of ileal content  – Increases emptying But the valve and sphincter prevent backflow of fecal contents from colon into the small intestine Fig. Regulation of Emptying at the ileocecal valve 111  Movements of the Colon  Movements of the colon are normally very sluggish – Important for the principal functions of the colon, which are: 1. Absorption of water and electrolytes from the chyme to form solid feces In the proximal portion of the colon 2. Storage of fecal matter until it can be expelled In the distal portion of the colon 112  Mixing Movements-"Haustrations" – Large circular muscle constrictions occur in the large intestine – At the some time the longitudinal muscle of the colon contracts  – Cause the unstimulated portion of the large intestine to bulge outward into baglike sacs called haustrations 113 Mass movements- propulsive movement Propulsion in Cecum and ascending colon – Results from slow but persistent haustral contractions propel the contents forward, Requirs 8 to 15 hrs to move the chyme from ileocecal valve through colon Mass movement from cecum to sigmoid colon:  Propels the feces from colon towards the anus  Occur only one to three times each day 114 Fig. Absorption and storage function of large intestine 115  C. Secretory Functions of the GIT – Secretary glands subserve three primary functions:  Production of digestive enzymes  Production of mucus  Production of electrolytes The quantity secreted in each segment is almost exactly the amount needed for proper digestion 116 Daily Secretion of gastrointestinal Juices 117  General Principles of GIT Secretion Types of Alimentary Tract Glands Mucous cells or goblet cells – On the surface of the epithelium in most parts of the GIT – Release mucus in response to local irritation of the epithelium  – Act as a lubricant that also protects the surfaces from excoriation and digestion. Pits - invaginations of the epithelium into the submucosa. – Secret mucous, large amount of water and electrolytes. – Eg. crypts of Lieberkühn in the small intestine and in the large intestine. Tubular glands – eg. HCl and pepsinogen-secreting gland of the stomach Complex glands -These glands lie outside the walls of the alimentary tract – Eg. The salivary glands, pancreas, and liver 118 119  Basic Mechanisms of Stimulation of the GIT Glands - Contact of Food with the Epithelium   Direct contact stimulation of the surface glandular cells by the food  Enteric Nervous Stimulation - Autonomic Stimulation of Secretion A. Parasympathetic B. Sympathetic Stimulation - Hormonal Hormones are liberated from the gastrointestinal mucosa in response to the presence of food in the lumen of the gut.  The hormones are then absorbed into the blood and carried to the glands, where they stimulate secretion 120  Mucus secretion – Mucus is a thick secretion – Composition: mainly water, electrolytes, and a mixture of several glycoproteins Importance of Mucus in the GIT – Excellent lubricant and a protectant for the GIT wall – Has adherent qualities - adhere tightly to the food and to spread as a thin film over the surfaces. – It coats the wall of the gut and prevents actual contact of most food particles with the mucosa. – Has a low resistance for slippage - the particles can slide along the epithelium with great ease. – Strongly resistant to digestion by the GI enzymes – Buffering function 121  Secretion of Saliva – The principal glands of salivation are a pair of: Parotid Submandibular Sublingual glands – The mucosa of the mouth and tongue contains many small salivary glands that open to the oral cavity. – These glands include: labial, buccal, palatal and lingual glands, all of which make a small contribution to saliva. – Daily secretion normally ranges between 800 and 1500 ml – Average value of 1000 milliliters 122 Salivary Glands 123  Saliva contains two major types of protein secretion: – 1. Serous secretion - contains ptyalin (an α-amylase), Ptyalin is an enzyme for digesting starches – 2. Mucus secretion - contains mucin For lubricating and surface protective purposes. – The parotid glands secrete almost entirely the serous type of secretion, whereas the submandibular and sublingual glands secrete both serous secretion and mucus. – 99.5% water, & the remaining 0.5% includes: Electrolytes (K+, Na+, Cl-, and HCO3- …), Digestive enzymes like salivary amylase and lingual lipase. Bacteriolytic enzyme (lysozyme) Glycoproteins, antibodies (immunoglobulin A) – Saliva has a pH between 6.0 and 7.0, a favorable range for the digestive action of ptyalin. 124 Mechanisms of salivary secretion A. Clusters of cells called acini secrete electrolytes, enzymes, proteins etc causing primary secretions which are isotonic. B. The primary secretion are modified by active absorption of (Na +) and passive absorption of (Cl-) ions. C. K+ and HCO3- are secreted into the lumen as they pass through the ducts causing: secondary hypotonic secretions 125 Mechanism of salivary secretions… Reasons for hyptonicity of the saliva, includes: 1. Na+ and Cl- reabsorption from the lumen to the plasma is greater than K+ and HCO3- secretion into the lumen 2. The ducts are relatively impermeable to water (i.e. H2O does not follow the osmotic gradient of NaCl) 126 Mechanism of salivary secretions… Fig. Formation and secretion of saliva by a submandibular salivary gland. 127  Function of Saliva Saliva performs a number of important functions: – It facilitates swallowing(by adhering form a bolus) – Keeps the mouth moist. – Aids speech by facilitating movements of the lips and tongue, and keeps the mouth and teeth clean. – The saliva has some antibacterial action. – Saliva also help in neutralizing gastric acid. 128  Function of Saliva for Oral Hygiene Saliva has important role for maintaining healthy oral tissues – Because it has bacteriolytic enzymes and antibodies – The flow of saliva itself helps wash away pathogens and food particles Xerostomia- dryness (sicca) of the mouth (low production of saliva)  It leads to infection of mouth bad oral smell Causes: Dehydration ,Sjögren's syndrome, Radiation therapy, xerogenic drugs (Anticholinergic, Sympathomimetics, Diuretic etc) Sialorrhoea - drooling or excessive salivation/hypersalivation. Symptom of neurological diseases (e.g. Parkinson’s disease, cerebral palsy…) GERD and pregnancy Infections of throat, tonsil and sinusitis 129  Nervous Regulation of Salivary Secretion Salivatory nuclei located in the medulla – Excited by both taste and tactile stimuli. – The smell, sight, sound, or thought of food may also stimulate secretion of saliva. Impulses are conveyed from the taste buds to two salivary nuclei in the brain stem (superior and inferior salivatory nuclei). Returning parasympathetic impulses in fibers of the facial (VII) and glossopharyngeal (IX) nerves stimulate the secretion of saliva. Salivation can also be stimulated or inhibited by nervous signals arriving in the salivatory nuclei from higher centers of the CNS. The parasympathetic branch of the ANS playing the most prominent role in increasing secretion. Sympathetic stimulation dominates during stress, resulting in dryness of the mouth (thick viscid secretion) 130 131 CN IX CN VII 132 Phases of salivary secretion 3-phases of salivary secretions include 1. Cephalic (brain) phase: triggered by thought, smell, or sight of food 2. Oral phase: triggered by food that stimulate touch & test receptors in the mouth 3. Gastric phase: triggered by substances which stimulate the gastric mucosa (acids or sour tastes) in the stomach. 133 Esophageal Secretion  Entirely mucous in character  provide lubrication for swallowing  No digestive enzyme secretion 134  Gastric Secretion i. Mucus-secreting cells - line the entire surface of the stomach – Secrete large quantities of mucus that coats the stomach mucosa  – Provide a shell of protection for the stomach wall – Contribute to lubrication of food transport – It is alkaline  neutralization of the acid ii. Oxyntic glands (gastric glands) – in the fundus & body  Secrete HCl, pepsinogen, intrinsic factor, histamine, and mucus. iii. Pyloric glands – in the antrum of stomach  Secrete:  Mainly mucus for protection of the pyloric mucosa from the stomach acid,  Gastrin from G cells,  Somatostatin from D cells 135 Gastric Secretary glandular mucosa 136  Secretions from the Oxyntic (Gastric) Glands The glands are located on the inside surfaces of the body and fundus of the stomach, Constitute the proximal 80% of the stomach Contain different secretary cells: 1. Mucous neck cells - mainly secrete mucus 137 2. Chief or peptic cells – produce pepsinogen – When pepsinogen is first secreted, it has no digestive activity – Pepsinogen is activated to pepsin by: HCl in the stomach Pepsin itself via a positive feedback mechanism – Pepsin is active proteolytic enzyme in a highly acid medium (optimum pH 1.8 to 3.5) Regulation of Pepsinogen Secretion i. Stimulation of the peptic cells by Ach released from the vagus nerves or from the gastric enteric nervous plexus, and ii. Stimulation of peptic cell secretion in response to acid in the stomach. 138 Fig. Conversion of pepsinogen to pepsin in the lumen of the stomach 139 3. Parietal or oxyntic cells – secrete HCl and intrinsic factor – HCl provides acidic medium for stomach Important for digestive enzymes: – Pepsin (activated from pepsinogen) ( pH = 1.8-3.5) – Lingual lipase (pH optimum 4). – pH at the canalculus of parietal cells is as low as 0.8 – HCl softens food – Gastric acidity has antibacterial activity 140  Function of intrinsic factor (IF) – Produced from parietal cells – IF is essential for absorption of vitamin B12 in the ileum IF binds Vit B12 and protects from gastric and intestinal digestion Vit B12 is important for maturation of RBCs Destruction of parietal cells eg. Due to gastritis, gastroectomy….  – Pernicius anemia due to failure of RBC maturation (due to lack of Vit B12) 141 4. Enterochromafin like cells (ECL cells) – Secrete histamine with paracrine effect on parietal cells – Ach, gastrin  act on ECL cells histamine  HCl secretion by parietal cells 142 Fig. Structure of a gastric gland from the fundus and body of the stomach. 143 Acid Secreting cells; parietal cells 144 Secretions of the stomach 145  HCl Secretion Parietal cells secrete HCl which converts inactive pepsinogen to pepsin Mechanism of acid secretion: 1. Within the cell, CO2 which diffused from ECF combines with H2O to form H+ and HCO3- 2. At basolateral membrane, HCO3- absorbed into blood in exchange with Cl- via a Cl--HCO3- exchanger 3. At apical membrane, H+ secreted into lumen of stomach via H+-K+ ATPase or H+-K+ pump 4. Cl- follows H+ into the lumen by diffusing through Cl- channels in the apical membrane 146  HCl Secretion… Parietal cells secrete hydrogen ions (H+) and chloride ions (Cl-) separately into the stomach lumen. Proton pumps powered by H+/K+ ATPases actively transport H+ into the lumen and (K+) into the cell. H+ At the same time, Cl- and K+ diffuse out into the lumen through Cl- and K+ channels in the apical membrane. 147 HCl Secretion… 148  Regulation of HCl Secretion – Stimulation of Gastric Acid Secretion By:  Vagal activation (Ach), Gastrin, histamine, Proteins in the food ACh – Released from vagus nerve – Binds to receptors on parietal cells – Produces H+ secretion by parietal cells – Atropine blocks muscarinic receptors on parietal cells Gastrin – Released into circulation by G cells of stomach antrum – Binds to receptors on parietal cells – Stimulates H+ secretion Histamine – Released from mastlike cells in gastric mucosa called ECL cells – Binds to H2 receptors on parietal cells – Produces H+ secretion by parietal cells – Cimetidine, Ranitidine  blocks H2 receptors 149  Regulation of HCl Secretion… The parietal cell expresses receptors for several stimulants of acid secretion, including: – Histamine (H2) H2R – Acetylcholine (muscarinic, M3) & – Gastrin receptor M3R GR Cl- = ↑HCl H+ K+ Other factors Distension Parietal Tactile stimulation cells Alcohol Drugs inhibiting HCl secretion Omeprazole Cemetidin, Ranitidin 150 Regulation of acid secretion… 151 152  Stomach mucosal barrier The stomach is exposed to the harshest conditions in the digestive tract To keep from digesting itself, the stomach has a mucosal barrier with: – 1. Gastric glands that have cells impermeable to HCl – 2. Epithelial cells are joined by tight junctions Prevent penetration of HCl between cells – 3. A thick coat of bicarbonate-rich mucus on stomach wall (pH7) Protects gastric mucosa from gastric juice (pH 2) – 4. Damaged epithelial cells are quickly replaced. 153 Protection against self- 154 digestion  Phases of Gastric Juice Secretion Neural and hormonal mechanisms regulate the release of gastric juice Stimulatory and inhibitory events occur in three phases: – Cephalic (reflex) phase: prior to food entry to stomach – Gastric phase: once food enters the stomach – Intestinal phase: as partially digested food enters the duodenum 155  A. Cephalic Phase  Occurs before food enters the stomach, especially while it is being eaten.  Stimulation results from :  Sight, thought, smell, or taste of food  Stimulation of taste or smell receptors  Mediated by vegus nerve  Accounts for about 30% of the gastric secretion associated with eating a meal. Inhibitory events include: – Loss of appetite or depression – Decrease in stimulation of the parasympathetic division 156  B. Gastric Phase Occurs when the food entered to the stomach  Under nervous & hormonal control 1. Long vagovagal reflexes from the stomach to the brain and back to the stomach - nervous mechanism 2. Local enteric reflexes – nervous mechanism 3. The gastrin – hormonal mechanism Accounts for about 60%(1500ml) of the total gastric secretion. 157 Long vagovagal reflexes 158  Excitatory events of the gastric phase include: – Stomach distension  Activation of stretch receptors (neural activation) – Activation of chemoreceptors by peptides, caffeine, and rising pH – Release of gastrin to the blood Inhibitory events include: – A pH lower than 2 – Emotional upset that overrides the parasympathetic division 159  C. Intestinal Phase Excitatory phase : – Partially digested food enters the duodenum  Small amount of gastrin released by duodenal mucosa  Cause small amount of stomach secretion (10%) Inhibitory phase : – Distension of duodenum, – Presence of fatty product – Hypertonic chyme, and/or irritants in the duodenum  – Inhibition of local reflexes and vagal nuclei – Releases enterogastrones that inhibit gastric secretion – Closes the pyloric sphincter 160 Fig. Phases of Gastric Juice Secretion and their regulation 161  Gastritis- Inflammation of the Gastric Mucosa Usually superficial and therefore not very harmful, When sever, it can penetrate deeply into gastric mucosa  – Causes almost complete atrophy of the gastric mucosa 162  Causes of gastritis: Chronic bacterial infection of the gastric mucosa. – Can be treated successfully by intensive regimen of antibacterial therapy Certain ingested irritant substances – Can damage the protective gastric mucosal barrier  – leading to severe acute or chronic gastritis by the stomach's own peptic secretions. Alcohol or aspirin 163  In many people who have chronic gastritis, the mucosa gradually becomes atrophic until little or no gastric gland digestive secretion remains  – Loss of the stomach secretions in gastric atrophy  – leads to achlorhydria (lack of acid secretion) and, occasionally, to pernicious anemia. 164  Peptic Ulcer is an excoriated area of stomach or intestinal mucosa – Occurs when the rate of gastric secretion is greater than degree of protection – Protection is afforded by 1. Gastroduodenal mucosal barrier 2. Neutralization of the gastric acid by duodenal juices Basic Cause: the digestive action of gastric juice The most frequent sites: – within a few centimeters of pylorus – along lesser curvature of antral end of stomach More rarely, in lower end of esophagus due to GER 165  Bacterial Infection by Helicobacter pylori Many PUD patients have chronic infection of the terminal portions of gastric mucosa and initial portions of duodenal mucosa The bacterium is capable of penetrating the mucosal barrier by: – Its physical capability to burrow through the barrier – Releasing bacterial digestive enzymes that liquefy the barrier.  – The acidic stomach secretions can then penetrate into the underlying epithelium  – Literally digest the gastrointestinal wall  peptic ulceration 166  Other factors that predispose to ulcers include: 1. Smoking – Because of increased vegal stimulation of the stomach secretory glands 2. Alcohol – Because it tends to break down the mucosal barrier 3. Aspirin and other non-steroidal anti-inflammatory drugs – Strong tendency for breaking down the mucosal barrier 167 Causes and major sites of PUD 168  Treatment for PUD: -can be treated by: 1. Use of antibiotics :- to kill infectious bacteria (H. pylori) 2. Administration of acid-suppressant drugs – Eg. Ranitidine, cimitidine Histamine receptor (H2) blockers – Blocks the stimulatory effect of histamine on gastric gland Reduce gastric acid secretion by 70 to 80 % – Eg. Omeprazole Proton pump inhibitor Inhibit the H+/K+ pump 3. Anti-acids: for neutralization – Eg. Aluminum trisilcate, magnesium hydroxide 169  Vomiting or Emesis Is the means by which upper GIT forcefully rids itself of its contents Occurs when almost any part of upper tract becomes: – Excessively irritated, – Overdistended, or – Overexcited 170  Sensory signals that initiate vomiting originate mainly from: – Pharynx, esophagus, stomach, and upper portions of the small intestines  The nerve impulses are transmitted by both vagal and sympathetic afferent nerve fibers to vomiting center in brain stem  Motor impulses that cause actual vomiting are transmitted from vomiting center by way of: – 5th, 7th, 9th, 10th, and 12th cranial nerves to upper GIT – Through vagal and sympathetic nerves to the lower tract, and – Through spinal nerves to diaphragm and abdominal muscles 171 Fig. Neural connections of the 172 “vomiting center.”  (Vestibular nuclei ) The motion stimulates receptors in the vestibular labyrinth of the inner ear Fig. Neural connections of the 173 “vomiting center.”  Vomiting Response/Vomiting Act Vomiting starts with salivation and the sensation of nausea. – The glottis closes, preventing aspiration of vomitus into the trachea. – lifting of the soft palate to close the posterior nares. – The breath is held in mid inspiration. – The upper esophageal sphincter open, – The muscles of diaphragm and abdominal wall contract, and the contraction increases intra-abdominal pressure. – The lower esophageal sphincter and the esophagus relax, and the gastric contents are ejected Lesions of the area postrema have little effect on the vomiting response to gastrointestinal irritation or motion sickness, but abolish the vomiting that follows injection of apomorphine and a number of other emetic drugs. There are dopamine D2 receptors and 5-HT3 receptors in the area postrema that trigger vomiting 5-HT3 antagonists such as ondansetron and D2 antagonists such as chlorpromazine and haloperidol are effective antiemetic agents 174  Gastrointestinal obstruction The GIT can be obstructed at almost any point along its course  Obstructions of upper GIT ( pyloric, small intestine) cause vomiting  Obstructions of large intestine cause constipation Fig. Obstruction in different parts of the 175 gastrointestinal tract.  Pancreas A retroperitoneal gland which is about 12–15 cm long. Consists of a head, body, and tail. Connected to the duodenum by two ducts, the hepato-pancreatic duct and the accessory duct. Each day the pancreas produces 1200–1500 mL of pancreatic juice. Pancreas contains two types of secretory glands: 1. Endocrine cells (islets of Langerhans) secrete hormones and 2. Exocrine cells (acinar cells): secrete pancreatic juice. 176  Pancreas… Has endocrine and exocrine function The endocrine function : islets of langrhans with cells releaseing: – Insulin from beta cells – Glucagon from alpha cells – Somatostatin from Delta cells – Pancreatic polypepeptide from PP cells  – Essential for regulation of metabolism Exocrine function – Secretes pancreatic juice: breaks down all categories of foodstuff – Acini (clusters of secretory cells) contain zymogen granules with digestive enzymes 177 Pancreatic exocrine secretion – The pancreatic digestive enzymes are secreted by pancreatic acini – Large volumes of HCO3- secreted by the small ductules and larger ducts leading from the acini  – Flows through a long pancreatic duct  – Empties into the duodenum through the papilla of Vater, surrounded by the sphincter of Oddi – The sphincter controls the emptying 178 179 Acini of the Pancreas 180  Regulation of Pancreatic Secretion Basic Stimuli That Cause Pancreatic Secretion: 1. Parasympathetic nervous stimulation  Causes release of pancreatic juice 2. Cholecystokinin  Secreted by the duodenal and upper jejunal mucosa  When fatty food enters the small intestine 3. Secretin  Secreted by the duodenal and jejunal mucosa  When highly acid food enters the small intestine 181  Acinar cells (enzymatic secretion) – Receptors for CCK and muscarinic receptors for ACh – CCK is most important stimulant I cells secrete CCK in presence of amino acids and fatty acids in intestinal lumen – ACh also stimulates enzyme secretion Ductal cells (aqueous secretion of HCO3-) – Receptors for CCK, ACh, and secretin – Secretin (from S cells of duodenum) is major stimulant Secreted in response to H+ in intestine – Effects of secretin are potentiated by both CCK and ACh 182 Regulation of pancreatic juice secretion 183 184  Phases of Pancreatic Secretion Cephalic phase, gastric phase, and intestinal phase 1. Cephalic and Gastric Phases. – The same nervous signals from the brain that cause secretion in the stomach – 20 % of the total secretion of pancreatic enzymes after a meal. 2. Intestinal Phase – After Chyme leaves the stomach and enters the small intestine  – Pancreatic secretion becomes copious – Mainly in response to the hormones secretin and CCK 185 Functions of pancreatic secretions i. Digestive function Secretion of digestive enzymes ii. Protective function Neutralization of acidic chyme --> protection from acid damage of intestinal mucosa 186  Pancreatic Digestive Enzymes – Contains multiple enzymes for digesting all of the three major types of food: Proteins Carbohydrates, and Fats – Also contains large quantities of bicarbonate ions, Important in neutralizing the acidity of the chyme Provide optimal environment for pancreatic enzymes 187  Enzymes of Pancreatic Juice Some enzymes are released in inactive form and activated in the duodenum Examples of inactive form enzymes include: – trypsinogen, chymotrypsinogen, procarboxypolypeptidase and proelastase Activated only after they are secreted into theduodenum – Trypsinogen Enterokinase Trypsine – Chymotrypsinogen Trypsine Chymotrypsin – Procarboxypeptidase Trypsine Carboxypeptidase – Proelastase Trypsine Elastase Active enzymes secreted – Amylase, lipases, and nucleases – These enzymes require ions or bile for optimal activity 188  Pancreatic enzyme for digesting carbohydrates is  pancreatic amylase Fat digestion enzymes are:  Pancreatic lipase - hydrolyze neutral fat into fatty acids + monoglycerides  Cholesterol esterase - causes hydrolysis of cholesterol esters  Phospholipase - splits fatty acids from phospholipids Protein digesting enzymes  Trypsin  Chymotrypsin  Carboxypolypeptidase 189  Composition of Pancreatic Juice Pancreatic juice is a clear, colorless liquid consisting: – Mostly of water, – Cations: Na+, K+, Ca2+, Mg2+ – Anions: Rich in HCO3–, Cl–, SO42–, HPO42–. – pH approximately 8.0 – Enzymes: Pancreatic amylase- starch digesting enzyme Several protein digesting enzymes (trypsin, chymotrypsin, carboxypeptidase, and elastase The principal triglyceride-digesting enzyme, called pancreatic lipase 190  Composition of Pancreatic Juice… The protein-digesting enzymes of the pancreas are produced in an inactive form just as pepsin is produced in the stomach as pepsinogen. Trypsin is secreted in an inactive form called trypsinogen. 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. When trypsinogen reaches the lumen of the small intestine, it encounters an activating brush- border enzyme called enterokinase, which splits off part of the trypsinogen molecule to form trypsin. In turn, trypsin acts on the inactive precursors (called chymotrypsinogen, procarboxypeptidase, and proelastase) to produce chymotrypsin, carboxypeptidase, and elastase, respectively. 191  To prevent self digestion of the pancreaes – Trypsine inhibitor is also secreted along with the other secretions – No or weak trypsin inhibitor  pancreatic damage  pancreatitis Pancreatitis – inflamation of pancreas – When pancreas is severely damaged or duct is blocked,  – Pancreatic secretion may be pulled in the damaged areas of pancreas  – The effect of trypsin inhibitor is often overwhelmed,  – The pancreatic secretions rapidly become activated  – Can digest the pancreas  a condition called acute pancreatitis 192  Secretion of bile Bile is secreted by the liver hepatocytes + ductules – Stored in the gallbladder until needed in duodenum. – Ejected from gallbladder into small intestine when gallbladder contracts Bile is secreted by hepatocytes in the liver for two purposes. 1. It facilitates digestion and absorption of fat 2. Serves as a means of excretion of waste products: Bilirubin Lipid soluble end products of metabolism, drugs & toxins. Is the only means to dispose cholesterol Bile secretion has two stages: Primary secretion from hepatocytes in to bile canaliculi: contains bile salt, cholesterol, lecithin, electrolytes (Na, Ca, K ions) Secondary secretions from epithelial cells of bile ducts: contains mainly water, NaHCO3, Cl. 193  Secretion of bile... Average daily biliary out put: 600 -1000 ml/day Yellow-green in color b/c of bilirubin pH = 7.6 - 8.6  Composition of Human Hepatic Duct Bile Water...............................97.0% Bile salt................0.7% Bile pigments...................0.2% Cholesterol.......................0.06% Inorganic salts..................0.7% Fatty acids........................0.15% Phosphatidylcholine........0.2% Fat......................................0.1% 194  Secretion of bile...  The bile salts have a number of important actions:  Responsible for the emulsification of lipids. Breakdown of large lipid globules into a suspension of small lipid globules.  Bile salts tend to form cylindrical disks micelles. The micelles play an important role in keeping lipids in solution and transporting to intestinal epithelial cells. 90 to 95% of the bile salts are absorbed from the small intestine. The absorbed bile salts are transported back to the liver in the portal vein and re-excreted in the bile (enterohepatic circulation) 195 Regulation of Bile Secretion 196  Formation of gallstones When the bile becomes excessively concentrated in the gallbladder due to: – too much absorption of water, bile acid from the bile – Too much cholesterol in the bile  cholesterol precipitation  cholesterol gallstones – Inflammation of the epithelium 197  Enterohepatic circulation of bile  Is recirculation of the bile salts  About 94 % of the bile salts are reabsorbed into blood from the small intestine   Then enter the portal blood and pass back to the liver   Salts are absorbed almost entirely back into the hepatic cells and then are resecreted into the bile. 198 Bile Secretion and Recycling 199  Small Intestine Structural modifications of the small intestine wall increase surface area: – Circular folds/Plicae circularis: deep circular folds of the mucosa and sub mucosa – Villi – finger-like extensions of the mucosa – Microvilli – tiny projections of absorptive mucosal cells’ plasma membranes. 200 Small Intestine… 201 Small Intestine… 202  Secretion of the Small Intestine Mucosa of the SI secretes: Digestive enzymes (brush border enzymes) Mucus: protective and lubricant Electrolytes: Intestinal secretory out put = 2-3 L/d, pH,7.0 Hormones Intestinal secretory glands / cells: 1. Brunner’s gland: Duodenal in distribution Secrete large amounts of alkaline mucus in response to: - -Vagal stimulation, and -GI hormones, especially secretin 203  Secretion of the Small Intestine... 2. Crypts of Lieberkun: secret mucous, large amount of water and electrolytes. Distributed in the small intestine below the duodenum and in the large intestine. 3. Goblet cells: which secrete mucus. 4. Enteroendocrine cells: produce hormones 5. Enterochromaffin cells: Serotonin, histamine producing cells 6. Enterocytes: digestive enzymes (brush border enzymes) 204  Secretion of the Small Intestine... Digestive enzymes in the brush border membrane of SI 1. Enterokinase: activate trypsinogen trypsin 2. Peptidases: splits peptides into amino acids 3. Enzymes hydrolyzing disaccharides into monosaccharides are: – Sucrase-sucrose into a molecule of glucose and fructose – Maltase-maltose in to two glucose molecules. – Lactase-hydrolyzes lactose to glucose and galactose 4. Intestinal lipase: splits neutral fats into glycerol and fatty acids. 205  Functions of intestinal juice 1. Digestive function-  by the effect of digestive enzymes 2. Protective function-  the mucus protects the intestinal wall from acidic chime 3. Activator function-  the enterokinase activates trypsinogen 206  Secretions of the Large Intestine Mucus Secretion – from large intestinal crypts of Lieberkühn – The mucosa of the large intestine, like the small intestine, has many crypts of Lieberkühn – Unlike small intestine, large intestinal crypts of Lieberkühn have no villi The epithelial cells secrete almost no digestive enzymes. Instead, they contain mucous cells that secrete only mucus with bicarbonate – The alkaline mucus protects the large intestinal wall against excoriation – Provide adherent medium for holding fecal matter together – Alkalinity of the secretion (pH=8) protects the mucosa from acids formed in the feces 207 D. Digestion in the GI Tract 208  Digestion of Carbohydrates in the Mouth and Stomach When food is chewed, it is mixed with saliva, Saliva contains the digestive enzyme ptyalin (an α-amylase) – Hydrolyzes starch into maltose – Accounts for only 5% of all starches digestion Starch digestion may continues in the body and fundus of the stomach – Before the food is mixed with the stomach secretions. Then activity of the salivary amylase is blocked by acid of the gastric secretions – Salivary amylase initiates the breakdown of starch in to disaccharide and trisaccharide – Salivary amylase in the swallowed food continues to act on the starches until stomach acids inactivate it – Amylase become inactive as the pH of the medium falls below 4.0 209  Digestion of Carbohydrates in the Small Intestine 1. Digestion by Pancreatic Amylase Pancreatic amylase is almost identical in its function with the α-amylase of saliva but is several times as powerful. Convert starch in to maltose 210  2. Digestion by Intestinal Epithelial Enzymes Lining of the villi of the small intestine contain four enzymes; – Lactase, sucrase, maltase, and α-dextrinase  – Capable of splitting the disaccharides lactose, sucrose, and maltose, plus other small glucose polymers,  – Into their constituent monosaccharides 211 212  In the ordinary diet, which contains far more starches than all other carbohydrates combined, – Glucose represents about 80% of the final products of carbohydrate