GIT Physiology 2024 PDF

PHL 211 Part 1: Gastrointestinal Physiology Dr Buhari Aliyu MB;BS, MSc, PhD. Department of Physiology, Faculty of Basic Medical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto. aliyu.buhari@ud...

PHL 211 Part 1: Gastrointestinal Physiology Dr Buhari Aliyu MB;BS, MSc, PhD. Department of Physiology, Faculty of Basic Medical Sciences, College of Health Sciences, Usmanu Danfodiyo University, Sokoto. [email protected] Copyright © 2011 by Saunders, an imprint of Elsevier Inc. GIT Physiology Copyright © 2011 by Saunders, an imprint of Elsevier Inc. GIT Physiology Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Introduction Beyond air exchange, the body depends on nutrients that should be taken, digested and absorbed to supply energy and other micronutrients needed. This course covers the organization of the gastrointestinal system, the secretions, the hormones and the processes of digestion and absorption. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Introduction Digestive system is responsible for these functions. The gastrointestinal system performs digestive functions that provide the nutrients needed for energy and other organic functions. The GIT system is organized with different organs that also allow for the control release of contents through sphincters. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Modules Module1 Module 2 Module 3 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  MODULE 1 – Organization of the gastrointestinal tract – The sphincters – Characteristics of sphincters – Functions of sphincters – Salivary glands and secretions – Gastric, pancreatic, gall bladder and intestinal secretions Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Introduction In this section, you will learn about the organization and the functions of some of the organs in the GIT. Digestion is defined as the process by which food is broken down into simple chemical substances that can be absorbed and used as nutrients by the body. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Introduction Most of the substances in the diet cannot be utilized as such. These substances must be broken into smaller particles so that they can be absorbed into the blood and distributed to various parts of the body for utilization. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Learning Objectives By the end of this section, you will be able to: explain the Organization of the gastrointestinal tract GIT describe the sphincters in the GIT describe the salivary glands and the secretions. describe other secretions (pancreatic, intestinal, gall bladder) of the GIT and their functions. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Learning Objectives describe the gastric hormones explain the process of digestion in human discuss the process of digestion of proteins and fats discuss the absorption processes of carbohydrate, fat, proteins and vitamins. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Organization of the Gastrointestinal tract The gastrointestinal system includes alimentary canal, extending from pharynx to anus and accessory organs like salivary gland, liver and pancreas. Figure 1 shows the entire alimentary tract. Copyright © 2011 by Saunders, an imprint of Elsevier Inc. Organization of the gastrointestinal tract Figure 1: The Alimentary tract Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Organizational structure The digestive tract includes the mouth, pharynx, esophagus, stomach, small intestine, large intestine, rectum and anus. The histology is similar in all parts except the esophagus and the anus where serous attachment is not present. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Organizational structure Figure 2 shows a typical cross-section of the intestinal wall. The basic structures include: (i) serous coat (ii) muscular layer – longitudinal and circular layer (iii) sub-mucosa (iv) Mucosa Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Organizational structure Figure 2: Typical cross section of the gut Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Innervation of G I T The wall of gastrointestinal tract (GIT) has intrinsic nervous system (enteric nervous system) beginning from the esophagus extending down the anus. It is composed mainly of two plexus. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Innervation of G I T The outer one lies between the longitudinal and circular layer and is called Auerbach’s or Myenteric plexus. submucosa plexus or Meissner’s plexus lies in the submucosa layer. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Innervation of G I T The myenteric plexus control GIT movement. It is sensitive to stretch while the submucosal or meissner’s control secretion and local blood flow. It is sensitive to osmolar changes, pH changes and chemical composition of food. The enteric nervous system can function on its own, independently of the extrinsic nerves supply to the gut. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Innervation of G I T The extrinsic innervation can modify the activity of the enteric nervous system. The extrinsic supply comes from the autonomic nerves. The sympathetic fibres gives relaxation of smooth muscle and vasocontraction of smooth muscle, vasodilation and secretion of the digestive juice. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Sphincter A sphincter is a circular muscle that normally maintains constriction of a natural body passage or orifice and which relaxes as required Sphincters are circular muscles that open and close passages in the body to regulate the flow of substances, such as bile, urine, and faeces, through the body. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Sphincters Although many are found in the gastrointestinal tract, there are also sphincters in the urinary tract and blood vessels. There are even those in the eyes that regulate the flow of light. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  G I T Sphincters The alimentary tract is divided into functional compartment by sphincter. They include: Upper esophageal sphincter Lower esophageal sphincter Pyloric sphincter Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  G I T Sphincters Sphincter of Oddi Ileocecal sphincter Internal anal sphincter (smooth muscle/involuntary) External anal sphincter (skeletal muscle/voluntary) Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Characteristics of GIT Sphincters They have high tension/pressure area. The tensions within the sphincter are very high. The resting tone is greater than the other two adjacent segments which result in intraluminal high pressure zone that separate the two lumen to compartments. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Characteristics of GIT Sphincters It relaxes in response to appropriate stimulus, so that flow may occur from one compartment to the next. It regulates or maintains aurocaudal (mouth to anus) flow of GIT contents Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Functions of Sphincters The upper esophageal sphincter prevent air into the esophagus during respiration. The lower esophageal sphincter prevents irritant gastric contents from refluxing into the esophagus The pyloric sphincter separates the acidic environment of the stomach from the alkaline environment of the duodenum. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Functions of Sphincters The ileocecal sphincter separates ileum from the cecum, disallowing the faeces in the cecum from refluxing back into the ileum. The sphincter of Oddi allows intermittent flow of pancreatic, hepatic and bile secretions. The internal anal sphincter has smooth muscle and it shows involuntary movement of defecation, while the outer anal sphincter has skeletal muscle and shows voluntary movement. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Salivary glands and Secretions The digestive secretion in the mouth comes from salivary gland. There are three major salivary glands. Parotid Submaxillary (Submandibular) Sublingual Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Salivary glands and Secretions They are exocrine glands. Each has acini and duct cells. In the acini, two types of secreting cells have being found: Serous secretion containing an alpha-amylase; this is the enzyme for the digestion of starches. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Salivary glands and Secretions A mucous secretion, containing mucin, which is important for lubrication purposes. There is also lingual lipase, secreted by the Ebner’s glands. The parotid glands produce entirely the serous type of secretion; the submandibular glands secrete both the serous and mucous types and the sublingual produce only the mucous type of secretion. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Salivary glands and Secretions The submaxillary produces 10% secretion, sublingual produced 5% secretion and parotid produced 75%. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Innervation of salivary glands aso The salivary glands are supplied by both sympathetic and parasympathetic nerves. The sympathetic action gives vasoconstriction which causes secretion to be viscous and scanty. The parasympathetic effect causes vasodilation and causes copious secretion. Copyright © 2011 by Saunders, an imprint of Elsevier Inc. Innervation of salivary glands The parasympathetic fiber of cranial nerve-7 supplies some submaxillary and sublingual and cranial nerve-9 supplies the parotid gland. The parasympathetic is mediated via the release of acetylcholine that can be blocked by atropine. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Innervation of salivary glands The parasympathetic fiber of cranial nerve-7 supplies some submaxillary and sublingual and cranial nerve-9 supplies the parotid gland. The parasympathetic is mediated via the release of acetylcholine that can be blocked by atropine. Copyright © 2011 by Saunders, an imprint of Elsevier Inc. Innervation of salivary glands Figure 4: Major salivary glands Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Composition of Saliva – The secretion of saliva per day ranges from 1000 ml- 1500ml. – It has a pH of 6.8 which ranges from 6.7- 7. – It contains 99.5% water and 0.5% solid Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Composition of Saliva The solid consists of organic and inorganic substances. The major inorganic constituent are: Na+, K+, Cl-, HCO3-, Ca++ and Mg2+. The organic substances include the enzyme- α- amylase, mucin, lysozymes, IgA, blood group antigens, urea, uric acid, etc. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Mechanism of salivary secretion Salivation should occur rapidly because food normally stays in the buccal cavity for a very short time For this reason, it is normally under nervous control only through reflexes: -Conditioned and - Unconditioned reflexes Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Conditioned (Psychic) reflexes These are acquired reflexes that develop by learning and training It need an intact cerebral cortex Seeing, Smelling or even thinking of food stimulates salivation especially if the subject is hungry Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Conditioned (Psychic) reflexes The sight of food excites the visual receptors in the eye from which impulses arise The impulses are transported via the afferent nerve fibres (in the optic nerve) to the visual center (in the occipital lobe of the cerebral cortex) Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Conditioned (Psychic) reflexes This in turn, stimulates salivary nuclei in the brain stem From the brainstem impulses are transported via efferent parasympathetic and sympathetic nerve fibres to the salivary glands to stimulate their secretions Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Pavlov Experiment Ivan Pavlov- a Russsian Physiologist proved that conditioned reflexes are not inherent but they are acquired by learning and training He showed dogs a flash light or made them hear the sound of an alarm clock just before eating and such pairing process was repeated for several days Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Pavlov Experiment After this period, he found that only the light or sound was enough to produce salivation in these dogs So the dogs have learnt an association between the light or sound and the food Because this response was learned (or conditioned), it is called conditioned response Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Unconditioned reflexes These are inherent (inborn) reflexes that do not require learning or an intact cerebral cortex The introduction of food in the buccal cavity (or mechanical stimulation e.g. by dental instrument) leads to reflex salivary secretion Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Unconditioned reflexes This occurs due to stimulation of the taste and other receptors in the buccal cavity From these receptors impulses arise and are transported via the afferent fibres in 7th and 9th CNs to the brainstem where they stimulate the salivary nuclei resulting in salivary secretion Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Regulation of salivary secretion Salivary secretion is regulated mainly by neural mechanisms. It shows both conditional and unconditional reflexes. Conditional reflex is established by learning, and the secretion can be seen from sight, smell and thought of food. Unconditional reflex comes from presence of food in the mouth. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Regulation of salivary secretion The secretion of saliva in both sides of reflexes is caused by activity of parasympathetic nerves (VII) and (IX) supplying the glands. Secretion is almost abolished (reduced) during sleep. There is a decrease in resting flow rate when there is dehydration, anxiety, fear and severe mental effort. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Inhibitors of salivary secretion Sympathetic stimulation will reduces salivary secretion Rough objects in the mouth Diseased condition such as xerostomia also reduces salivary secretion Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Functions of saliva The enzyme α- amylase acts on boiled starch and convert it to maltose. The beginning of carbohydrate digestion occurs in the mouth. The mucin present in the saliva lubricate the food which helps in mastication Saliva is necessary for swallowing Helps in taste perception of food materials by dissolving them Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Functions of saliva It facilitates speech; speech is difficult in dry mouth Lysozymes and IgA present in the saliva gives birth to bactericidal and immunity functions respectively. It neutralizes the gastric acid that refluxes into the esophagus and release heart burn. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Disorders of Salivary secretion i. Hyposalivation Decrease secretion of saliva Can be: -Temporary - Permanent Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Disorders of Salivary secretion Temporary Occurs in: - Emotional condition like fear -Fever and - Dehydration Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Disorders of Salivary secretion Permanent Occurs in: - Sialothiasis (Obstruction of salivary duct) - Congenital absence or hypoplasia of salivary glands - Bell’s Palsy (Facial nerve paralysis) Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Disorders of Salivary secretion ii. Hypersalivation Excess secretion of saliva Can be: - Physiological (occurs in pregnancy) - Pathological iii. Drooling (Ptyalism) Uncontrolled flow of saliva in association with inability to retain saliva in the mouth Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Disorders of Salivary secretion iv. Xerostomia Dry mouth It is due to hyposalivation or absence of salivary secretion (Aptyalism) v. Mumps Inflammation of the parotid gland usually caused by viral infections Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  T The Stomach (Gastrum) The human stomach is divided into 3 parts: Cardiac region The upper part of the stomach where esophagus opens The opening is guarded by a sphincter (cardiac sphincter) - Fundus: Small dome shape structure It is elevated above the esophageal opening Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  The Stomach (Gastrum) Body (Corpus) Is the largest part of the stomach forming 75- 80% of the whole stomach It extends just below the fundus up to the pyloric region Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  The Stomach (Gastrum) Pyloric region Has 2 parts: - Antrum - Pyloric canal The body of the stomach ends in the antrum Copyright © 2011 by Saunders, an imprint of Elsevier Inc. The Stomach (Gastrum) 60 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Gastric Mucus membrane Contains simple tubular glands which opens at the mucosal surface at the special gastric pits The glands in the cardiac and pyloric region contain mainly mucous cells 61 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Gastric Mucus membrane Those in the fundus and body contains the following cells: (i) Oxyntic (Parietal) cells: These secrete hydrochloric acid (HCl) and intrinsic factor which is essential for Vitamin B12 absorption 62 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Gastric Mucus membrane (ii) Peptic (Chief) cells - which secrete proteolytic enzymes (pepsinogens) and other enzymes (iii) Mucus cells- These secrete mucus and are present in the neck of the glands as in the surface epithelium (iv) Enterochromaffin like cells-These secrete histamine 63 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Composition of Gastric Mucus Mucus produced by gastrum contains mixture of: - mucin -water -electrolytes -sloughed off cells -enzymes and -other materials like bacterial and its products 64 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Composition of Gastric Mucus - Water content = 90-94% - Mucin 5-10% (aggregates of mucin forms mucus granules) - Electrolytes ≥1% - Others: Enzymes, Nucleic acid, Lipid, Plasma protein, secretory IgA, bacteria plus its products 65 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Mechanisms of protection of Gastric mucosa The gastric mucosa is protected from damage, by HCl and autodigestion by pepsin through the following mechanisms: (i) Naturally mucosal cell membrane resist autodigestion and the tight junction between mucosal cells also prevent diffusion of HCl 66 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Mechanisms of protection of Gastric mucosa (ii) The mucus gel layer together with HCO3 secreted by the surface mucosal cells constitute a mucosal barrier that protect the gastric mucosa against damage by the gastric HCl (through reducing the PH from 1-2 at the luminal side to 6-7 at the surface of the epithelial cells) 67 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Mechanisms of protection of Gastric mucosa (iii) The gastric prostaglandin helps in protection of gastric mucosa because they stimulate mucus and HCO3 secretion and inhibit acid secretion (iv) The oxyntic cells are protected from HCl by forming that acid in the intracellular canaliculi and secreting it in the gastric lumen 68 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Mechanisms of protection of Gastric mucosa (v) The gastric mucosa contain certain peptides which are acid resistant 69 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Physiological Relevance of Gastric mucus 1. Maintains the lubrication of the gastric mucosa. 2. Covers the ingested food for the process of mixing and adhesion 3. It helps for digestion 4. It protects the surface epithelium from irritation by forming a thick mucus gel layer thereby providing “gastroprotection”. 70 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Physiological Relevance of Gastric mucus Gastroprotection is a reduction or prevention of chemically induced acute haemorrhagic erosions by compounds such as prostaglandins and somatostatin derivatives without acid inhibition 71 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Functions of the Stomach Storage of food (Reservoir) Mixer of food Squirts the food out at a controlled rate into the duodenum It also secretes HCl and some enzyme such as pepsinogen 72 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Functions of the Stomach HCl stops bacteria action and also provides acidic medium for pepsinogen to function Provides fluid for stomach contents Antibacterial action 73 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Gastric secretion Gastric juice is secreted by gastric glands present in the gastric mucosa of fundus and body of the stomach. There are 3 types of cells namely: Neck and surface epithelial cell that secrete mucous The chief cell that secretes enzyme Parietal or Oxyntic cells that secrete Hydrochloric acid (HCl) and intrinsic factors. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Composition of Gastric secretion The volume of secretion per day is about 2 liters and the pH varies between 1.8 – 2.0. The inorganic constituents include Na+, Cl-, PO4-, K+ and SO4-. The organic substances present in the secretion are digestive enzyme (pepsinogen, renin, lipase), mucin and intrinsic factors. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Functions of HCl (Hydrochloric acid) The concentrated Hcl in the gastric juice is necessary to activate pepsinogen to pepsin, the extreme acidity is bactericidal. The acid pH in the upper part of duodenum facilitates ion absorption. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Functions of gastric juice The beginning of protein digestion takes place in the stomach. Pepsin acts on protein and convert it to peptone. The enzyme is secreted by chief cell as active pepsinogen. Gastric renin: Is a milk curdling enzyme which is absent in human but present in cows. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Functions of gastric juice Gastric lipase: Is a weak fat-splitting enzyme. Intrinsic factor: Is secreted by the parietal cell of the fundus. It is required for the absorption of vitamin B12 (cyanocobalamin or extrinsic factor). The absorption of vitamin B12 occurs in the terminal ileum. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Functions of gastric juice Mucus: Is secreted by surface epithelial cell and neck cell of the gland. The surface epithelial cell also secrete bicarbonates, the mucus and the bicarbonate form gel in the lining of the gastric mucosa. This gel protects the mucosa from the action of the acid. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Functions of gastric juice There is a pH gradient from the lumen to the mucosal wall of the stomach. The pH in the mucosal is 7 and that of the lumen is 2. The presence of HCO3- and mucus form the acid mucosa barrier. Certain condition like chronic stress, alcohol and aspirin tends to arose the acid mucosa barrier. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Hydrochloric acid secretion Hydrochloric acid (HCl) is the gastric juice secreted from the parietal cells. The secretion of Hcl is an active process and it is transported against the electrochemical gradient. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Hydrochloric acid secretion The concentration of Hcl in gastric juice is 150 mEq/L whereas it is 00004 mEq/L in plasma. The source of H+ is from the dissociation of H2CO3. The H2CO3 is formed from hydration of CO2 in the presence of carbonic anhydrase enzyme. Carbonic acid dissociates to H+ and HCO3-. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Hydrochloric acid secretion The hydrogen ion formed is exchanged with potassium ion and the transport carrier is H+- K+ ATPase. The energy released from the breakdown of ATP is utilized for the active transport of H+. Chloride ion is also actively transported from the cell into the lumen and coupled with H+ to form Hl. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Hydrochloric acid secretion The active transport of Hcl is followed by the passive transport of water into the lumen. The secretion of H+ leaves bicarbonate ion within the cell. The HCO3- combines with Na+ and enters the blood as NaHCO3. It is known during digestion, alkaline level in the blood and urine rise and it is called Postprandial alkaline tide. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Agents causing Hydrochloric acid secretion Gastrin is released from pyloric antrum Acetylcholine is secreted from the vagal ending ii. Histamine comes from enterochromaffin cell lining the mucosa and when vagus is activated it releases acetylcholine. This stimulates the release of GRP (Gastric Releasing Peptide) followed by secretion of gastrin. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Regulation of Gastric secretion It involves nervous and humoral control. The nervous control is through the vagus and intrinsic Vagal Stimuli Gastrin Releasing Peptide Gastric Secretion The intrinsic N plexus is through the Meissner’s Acetylcholine Secretion plexus. Increased Acid + Pepsin Humoral secretion is as a Secretion result of stomach distention and presence of products of protein digestion. These lead to gastric secretion thus acid and pepsin secretion. 86 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Regulation of Gastric secretion Vagal stimulation also causes the release of histamine. All these cause release of Hcl. When there is peptic ulcer, treatment could be induced by inhibiting acid secretion, and this could be achieved from the following Inhibiting H2 receptors by cimetidine Blocking hydrogen ion – potassium ion ATPase by omeprazole. Regulation of gastric secretion Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Regulation of Gastric secretion Gastric juice secretion is regulated by both neural and hormonal mechanisms. Neural regulation is mediated via the vagus. Acetylcholine is released by vagal ending. The acetylcholine activates phospholipase C which in turn raises intracellular Ca2+. The intracellular Ca2+ promotes the secretion of gastric juice. Hormonal regulation is by gastrin which is secreted from the pyloric antrum. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Regulation of Gastric secretion The intracellular Ca2+ promotes the secretion of gastric juice. Hormonal regulation is by gastrin which is secreted from the pyloric antrum. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Phases of Gastric secretion There are 3 phases of gastric secretion: (1) Cephalic phase (2) Gastric phase (3) Intestinal phase Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Cephalic Phase Nervous or Psychic Phase Occurs before food reaches the stomach aiming at preparing it to receive the incoming meal Involves the higher centers of the brain Requires an intact cerebral cortex 91 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Cephalic Phase It take place by conditioned and unconditioned reflexes which stimulate gastric secretion through impulses discharged in the vagi nerves Conditioned reflexes Is an acquired reflexes that develop by learning and training 92 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Cephalic Phase - Looking at food, - the smell from the food - thinking about food and - taking of food All stimulates - the intrinsic nerve plexus - vagus nerve and - activity of CNS 93 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Cephalic Phase The mechanism is similar to that described in salivary secretion But here, the impulses to the stomach are discharged from the vagus nucleus in the medulla oblongata 94 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Cephalic Phase Unconditioned reflexes Are inherent (inborn) Do not require learning or an intact cerebral cortex In this phase, introduction of food in the buccal cavity leads to gastric secretion by: Stimulating taste and sensory receptors from which impulses arise and send to the medulla where they stimulate the vagus nucleus resulting in gastric secretion 95 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Cephalic Phase These reflexes are proved by sham feeding experiment An experiment that demonstrate the role of unconditioned reflexes in the control of gastric secretion……….. 96 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Cephalic Phase *Stimulation of the anterior Hypothalamus will increase vagal activity and gastric secretion. Fear and depression decreases gastric secretion and blood flow. Anger and hostility increases gastric secretion Excitement increases appetite. 97 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Cephalic Phase Conditional reflexes like sight, smell and thought of food causes secretion of gastric juice. The presence of food in the mouth also causes secretion in the stomach. The cephalic phase occurs by the activity of the vagus. Shaming-feeding experiments in animals like a dog gives an example of cephalic secretion. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Cephalic Phase The quantity of juice secreted is small. The cephalic phase accounts for about 10% of the total secretion associated with a meal. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Gastric Phase The gastric phase accounts for about 80% of the total secretion of gastric juice. This phase is initiated by the presence of food in the stomach. The food stretches the stomach wall and this distension stimulates the gastric glands via both the extrinsic (vagal) and intrinsic (nerve plexuses) reflex pathways to produce gastric juice. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Gastric Phase Distension of the pyloric antrum also results in the release of gastrin into the blood by an intrinsic reflex. In addition, some substances in the food, known as secretagogues, elicit release of gastrin by the intrinsic reflex. Such substances include meat extracts, protein digestion products, alcohol, bile acids and caffeine. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Gastric Phase Constitute the main mechanism of gastric secretion because it continues for about 3 hours It occurs via 2 mechanisms: -Nervous - Hormonal 102 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Gastric Phase 1. Nervous mechanism This includes: (a) Local enteric (short or local) reflexes Mechanical distension of fundus and body of the stomach as well as chemical stimulation of the gastric mucosa by the products of digestion Initiates local reflexes involving mainly the submucosal nerve plexus resulting in gastric secretion 103 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Gastric Phase (b) Vago-vagal (long) reflexes Mechanical distension and chemical stimulation of the gastric mucosa Initiates impulses that are transported via afferent vagal nerve fibres to the vagus nucleus in the medulla oblongata This in turn, discharge impulses via efferent vagal nerve fibres to the stomach leading to gastric secretion 104 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Gastric Phase 2. Hormonal mechanism This is the main mechanism of gastric secretion The mechanical distension of the pyloric antrum or chemical stimulation of its mucosa results in secretion of gastrin hormone from G-cells (gastrin secreting cells) The release of gastrin occurs mainly by local enteric reflexes 105 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Gastric Phase Vago-vagal reflexes also plays an important role in gastric secretion in which the efferent vagal nerve fibres releases gastrin- releasing polypeptide (GRP) GRP causes release of gastrin hormone from the G-cells Gastrin is transported via the blood stream to the fundus and body of the stomach where it stimulate gastric secretion 106 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Summary of Gastric Phase Presence of food in the stomach causes - distension of the stomach - stretch of the stomach muscles - stimulation of receptors on the stomach wall - stimulation of Meissner plexus - thus stimulating the gastric cells to secrete gastric juice 107 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Summary of Gastric Phase Chemical in stomach (products of protein digestion e.g amino acids, alcohol, caffeine, histamine) All these will tend to: (i) Cause receptors on the stomach wall to stimulate the Meissner plexus which then stimulates the gastric cells to secrete gastric juice 108 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Summary of Gastric Phase (ii) Increased secretion of gastrin which stimulates the gastric cells to secrete more gastric juice It is also stimulate the peptide cells to secrete enzyme. 109 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Intestinal Phase The arrival of food and the product of digestion in the intestine also stimulates gastric secretion. The quantity produced is very small. However, the presence of food in the duodenum inhibits secretion of gastric juice. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Intestinal Phase This inhibition is mediated through enterogastric reflex. The presence of acid and fat in the duodenum causes the release of secretin and cholecystokinin. Also, there is the release of VIP, GIP- all of which are enterogastrones. i.e. they cause inhibition of gastric secretion. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Intestinal Phase The amino acids present in the chyme (products of gastric digestion) stimulate secretion of gastrin from the duodenal mucosa This produces little secretion of the gastric juice However, the intestinal influences on gastric activities are mostly inhibitory rather than excitatory 112 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Intestinal Phase The intestinal factors that inhibit gastric secretion includes: - Mechanical distension of the duodenum - Chemical (presence of excess acid, fat, CHO as well as the irritant substances and hypertonic fluid in the duodenum) Both factors (mechanical and chemical) inhibits gastric secretion through the enterogastric reflex (reflex inhibition of gastric secretion) 113 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Intestinal Phase In addition, the chemical factors stimulate secretion of certain hormones from the duodenal mucosa that inhibits gastric secretion These hormones includes: - CCK, Secretin, VIP, GIP and Somastostatin 114 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Summary of Intestinal Phase It is inhibitory in nature - Presence of fat, carbohydrates, fatty acids and irritants in the S.I., will causes: (i) Stimulation of CCK, secretin and GIP which cause decrease acid secretion and motility (ii) Enterogastric reflex which will lead to decrease gastrin secretion 115 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Factors Affecting gastric secretion These are divided into: -Stimulatory - Inhibitory 116 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Factors Affecting gastric secretion Stimulatory factors (i) Food ingestion especially if associated with increased appetite (through conditioned & unconditioned reflexes) (ii) Food entry into the stomach (mainly through secretion of gastrin hormone) as well as taking alcohol or caffeine which directly stimulate the gastric mucosa 117 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Factors Affecting gastric secretion (iii) Emotional stress- e.g. anger and anxiety (through impulses from the hypothalamus that stimulate the vagus nucleus in the medulla) (iv) Hypoglycaemia (through stimulating the feeding center in the hypothalamus which in turn stimulate the vagus nucleus) (v) IV injection of certain amino acids such as glycine and alanine 118 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Factors Affecting gastric secretion Inhibitory factors (i) Reduction of PH in the pyloric antrum below 2 inhibits the release of gastrin hormone (ii) Duodenal distension as well as presence excess acids, fat, irritants or hypertoninc fluid in the duodenum (through enterogastric reflex and release of inhibitory hormones) 119 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Factors Affecting gastric secretion (iii) Emotional states such as fear and depression (through impulses from the hypothalamus that inhibit the vagus nerve nucleus) 120 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Pathophysiology Effects of undersecretion Effects of excess secretion Ulcers Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Effects of Under secretion of gastric juice a. a. Gastric Atrophy In many people with chronic gastritis, the mucosa gradually becomes atrophic until little or no gastric gland activity remains It is also believed that some people develop auto immunity against the gastric mucosa eventually leading to gastric atrophy Hence, there is decreased gastric motility 122 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Effects of Under secretion of gastric juice b. Achlorhydria (and Hypochlorhydria) Refers to a condition whereby the stomach fails to secrete hydrochloric acid, even in its minute form 123 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Effects of Under secretion of gastric juice c. Pernicious Anemia In all mammals, Vitamin B12 is essential for maturation of erythrocytes Deficiency of this vitamin leads to the development of anaemia (Pernicious). Disease conditions such as gastric atrophy and achlohydria decreases secretion of intrinsic factor resulting in decrease absorption of vitamin B12 leading to pernicious anaemia 124 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Effects of Excessive gastric secretion a. Gastritis - refers to the inflammation of the gastric mucosa. - Gastritis may be either * Acute- affecting the superficial layer = not very harmful *Chronic- affecting the deep layer = deep inflammation which may penetrate deeply into the gastric mucosa and cause almost complete atrophy of the gastric mucosa in long lasting cases. 125 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Effects of Excessive gastric secretion b. Ulceration - An ulcer is a discontinuity of the mucosa surface of some part of the gastrointestinal tract (GIT) with an inflammatory base - It affect the duodenum (first part of the small intestine), and the stomach - Duodenal ulcers are generally benign 126 Copyright © 2011 by Saunders, an imprint of Elsevier Inc. Gastric Ulcers 127 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Classification of Gastric Ulcers i. Stomach (called gastric ulcer) ii. Duodenum (called duodenal ulcer) iii. Oesophagus (called Oesophageal ulcer) iv. Meckel's Diverticulum (called Meckel's Diverticulum ulcer) 128 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Vomiting Vomiting is the forceful expulsion of contents of the stomach and often, the proximal small intestine. It is a manifestation of a large number of conditions, many of which are not primary disorders of the gastrointestinal tract. Regardless of cause, vomiting can have serious consequences, including acid-base derangments, volume and electrolyte depletion, malnutrition and aspiration pneumonia. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Act of Vomiting Vomiting is usually experienced as the finale in a series of three events, which everyone of us has experienced: - Nausea - Retching - Emesis Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Act of Vomiting Nausea is an unpleasant and difficult to describe psychic experience in humans and probably animals. Physiologically, nausea is typically associated with decreased gastric motility and increased tone in the small intestine. Additionally, there is often reverse peristalsis in the proximal small intestine. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Act of Vomiting Retching ("dry heaves") refers to spasmodic respiratory movements conducted with a closed glottis. While this is occurring, the antrum of the stomach contracts and the fundus and cardia relax. Studies with cats have shown that during retching there is repeated herniation of the abdominal esophagus and cardia into the thoracic cavity due to the negative pressure engendered by inspiratory efforts with a closed glottis. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Act of Vomiting Emesis or vomition is when gastric and often small intestinal contents are propelled up to and out of the mouth. It results from a highly coordinated series of events that could be described as the following series of steps (don't practice these in public): Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Control of Vomiting The complex, almost sterotypical set of activities that culminate in vomiting suggest that control is central, which indeed has been shown to be true. Within the brainstem are two anatomically and functionally distinct units that control vomiting: Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Control of Vomiting Bilateral vomition centers in the reticular formation of the medulla integrate signals from a large number of outlying sources and their excitement is ultimately what triggers vomition. Electric stimulation of these centers induces vomiting, while destruction of the vomition centers renders animals very resistant to emetic drugs. The vomition centers receive afferent signals from at least four major sources: Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Control of Vomiting The chemoreceptor trigger zone Visceral afferents from the gastrointestinal tract (vagus or sympathetic nerves) - these signals inform the brain of such conditions as gastrointestinal distention (a very potent stimulus for vomition) and mucosal irritation. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Control of Vomiting Visceral afferents from outside the gastrointestinal tract - this includes signals from bile ducts, peritoneum, heart and a variety of other organs. These inputs to the vomition center help explain how, for example, a stone in the common bile duct can result in vomiting. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Control of Vomiting Afferents from extramedullary centers in the brain - it is clear that certain psychic stimuli (odors, fear), vestibular disturbances (motion sickness) and cerebral trauma can result in vomition. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Control of Vomiting The chemoreceptor trigger zone is a bilateral set of centers in the brainstem lying under the floor of the fourth ventricle. Electrical stimulation of these centers does not induce vomiting, but application of emetic drugs does - if and only if the vomition centers are intact. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Control of Vomiting The chemoreceptor trigger zones function as emetic chemoreceptors for the vomition centers - chemical abnormalities in the body (e.g. emetic drugs, uremia, hypoxia and diabetic ketoacidosis) are sensed by these centers, which then send excitatory signs to the vomition centers. Many of the antiemetic drugs act at the level of the chemoreceptor trigger zone. Copyright © 2011 by Saunders, an imprint of Elsevier Inc. Control of Vomiting Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Vomiting Reflex The vomiting reflex is mediated by both the autonomic and somatic systems, and consists of two phases: Prodomal phase (pre-ejection): Relaxation of gastric muscles followed by small intestinal retrograde peristalsis; Ejection phase: Comprises of retching and vomiting including expulsion of gastric contents. Copyright © 2011 by Saunders, an imprint of Elsevier Inc. Vomiting Reflex Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Mechanism of Vomiting The act of vomiting is control by a vomiting centre located in the medulla oblongata 144 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Mechanism of Vomiting Excitation of this centre through the discharging impulses in the 5th, 7th, 9th 10th and 12th CN and spinal nerves that supply the diaphragm and abdominal muscles leads to effects that results in vomiting These effects are: (i) Forced inspiration which move the diaphragm downwards 145 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Mechanism of Vomiting (ii) Closure of the glottis and elevation of the soft palate to prevent the vomitus from entering the trachea and nasal cavities (as occurs in deglutition) (iii) The body of the stomach and cardiac sphincter relax while pyloric antrum contracts 146 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Mechanism of Vomiting (iv) The abdominal wall muscles contracts and this together with the downward movement of the diaphragm markedly increases the intra abdominal pressure (v) The raised intra abdominal pressure squeezes the relax stomach to contract 147 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Mechanism of Vomiting This is followed by relaxation of esophageal sphincter leading to ejection of gastric contents into the esophagus and oral cavity then outwards 148 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Function of Vomiting Functions of Vomiting In cases of irritation of the upper part of the GIT (which is the commonest cause of vomiting), vomiting provides relieve and helps to drive out the irritant. However, in many conditions such as pregnancy, myocardial infarction, motion sickness etc vomiting performs no function 149 Copyright © 2011 by Saunders, an imprint of Elsevier Inc. Effects of prolonged Vomiting Effects of prolonged (excessive) vomiting Dehydration Loss of electrolytes especially Na+ and K+ Alkalosis due to loss of H+ (HCl) 150 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Pancreatic Secretion The pancreas is a gland. It is leaf-like in shape and the pancreatic duct runs along the pancreatic gland. The pancreas are divided into two types 1. Exocrine pancreas (The GIT only deals with it) 2. Endocrine pancreas 151 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Pancreatic Secretion The exocrine secretes enzymes for the digestion of the three main classes of food – protein, fat and CHO. The enzymes are secreted in the villi cells of the pancreas. The secretion comes from zymogen granules. 152 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Pancreatic Secretion These granular secretions are released in small ducts which coalesces to form pancreatic duct and through this duct, the product enters the duodenum. The ductule cells secretes bicarbonate and water 153 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Pancreatic Secretion The junction where the gall bladder joins the pancreatic duct is known as the Ampulla of Vatar This junction has a sphincter known as Sphincter of Oddi that regulates the entry of bile and pancreatic duct mixture into the duodenum 154 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Composition of Pancreatic Secretion About 1500 ml of pancreatic juice are secreted daily. Pancreatic juice is a watery alkaline fluid; isotonic with plasma and rich in digestive enzymes. The alkalinity is due to HCO3- secreted from the duct epithelial cells. Other inorganic substances are Na+, K+, Cl- and SO4-. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Pancreatic Secretion CHARACTERISTICS OF PANCREATIC SECRETION The organic constituents includes: peptidase, amylase, lipase, nuclease. pH of 8 i.e alkaline Abundant HC032- It contains enzyme for the 3 classes of food - carbohydrate = Amylase - fats = lipase and Esterase 156 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Pancreatic Secretion - Protein= inactive precursor called proenzymes the proteins proenzymes: * trypsinogen * chymotrypsinogen * procarboxypeptidase * proelastase 157 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Pancreatic Secretion The enzyme enterokinase activates trypsinogen to become trypsin Then trypsin will activate Chymotrypsinogen to trypsinogen and carboxypeptidase to carboxypeptide. Then proelastase will become elastase. All these process is known as autocatalytic chain reaction. 158 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Regulation of Pancreatic Secretion The regulation could be: Humoral or Nervous. 159 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Regulation of Pancreatic Secretion Humoral Control The humoral secretion gives more juice which contain all the enzymes In humoral control: Presence of acid chyme in the duodenum, stimulates the duodenal mucosa which causes the cells of the mucosa to secrete secretin. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Regulation of Pancreatic Secretion The regulation is mainly from hormones. The 2 types of hormone regulating 2 types of secretion. Secretin is produced by the duodenal mucosa. Presence of acid chyme in the duodenum is the main stimulus resulting in secretion of watery fluid which is rich in bicarbonate that helps to neutralize the acid pH. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Regulation of Pancreatic Secretion Cholecystokinin (CCK) causes secretion of the pancreatic juice which is rich in digestive enzymes. It also acts on the gut bladder. Stimulus is product of food digestion entering the duodenum. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Regulation of Pancreatic Secretion This goes into the pancreas through the blood stream causing the ductules cells of the pancreas to secrete watery juice which is alkaline -rich If there are products of protein and fat digestion, they also stimulate the duodenal mucosa, which stimulates CCK which in turn stimulates acini cells of the pancreas to secrete juice rich in enzyme. 163 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Regulation of Pancreatic Secretion Nervous Control = Occurs mostly during the cephalic phase of gastric secretion = Stimulation of vagus nerve leads to moderate enzyme secretion 164 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Regulation of Pancreatic Secretion = Acetylcholine also acts on the acini cells causing the zymogen granules to secrete small quantity of enzyme but very rich juice through activating phospholipase C. 165 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Physiological functions of Pancreatic Secretion Involved in digestion Provides alkaline medium to the intestinal juice and this provides the necessary pH for the pancreatic enzyme because they function best in alkaline medium. 166 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Physiological functions of Pancreatic Secretion These pancreatic secretion also neutralize the acidity from the stomach chyme. Pancreatic secretion helps in micellar formation which are required for the absorption of fat. The alkaline pH is also required for the formation of micelles. 167 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Deficiency of Pancreatic Secretion Deficiency in fat and carbohydrate digestion due to pancreatic secretion leads to a condition known as steatorhea. The stool is bulky, fatty and clay coloured 168 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Gall Bladder Gall bladder stores, releases and makes the bile into concentration by active reabsorption of Na+ and HCO3-, passively by the reabsorption of water. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Bile Secretion Bile is an important juice secreted by the liver and stored in the gall bladder Bile is made up of bile acids, bile pigments and other substances dissolved in an alkaline solutions that resemble pancreatic secretions 170 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Bile Secretion The liver cells secretes bile into fine biliary canaliculi which coalesce together to form the right and left hepatic ducts These ducts joined outside the liver forming the common hepatic duct This unites with cystic duct of the gall bladder forming the ampulla of Vater that opens at the duodenal and the opening is controlled by the sphincter of Oddi 171 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Bile Secretion Bile is secreted by the liver cells (liver lobules) and stored in the gallbladder. The volume secreted per day is 500-700 ml, and secretion occurs when chyme enters the duodenum. PH is 7.6-7.8. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Composition of Bile Bile released from the gall bladder into the duodenum has the following composition. Water- 92% Bile Salts - 6% Bilirubin - 0.3% Cholesterol – 0.3% Fatty acids - 0.3% Lecithin – 0.3% Other lipids – 0.2% Na+ - 130mEq/L K+ - 12mEq/L Ca2+ - 23mEq/L Cl- - 25mEq/L HCO3- - 10mEq/L Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Bile Secretion When produced, two things occur: i. Bile can go straight to the duodenum through the hepatic duct. This is known as Hepatic Bile. It is highly alkaline with pH of 7.8-8.6 174 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Bile Secretion ii. Bile can go to the gall bladder for storage (Gall Bladder bile). The one that goes into the gall bladder, two things happen: - it will be acidified in the gall bladder i.e pH reduces - also water is removed from it i.e pH is 7-7.1 175 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Functions of Bile Bile salts are required for digestion and absorption of fats in the intestine. Therefore, functions of bile salts includes: Emulsification of Fats (breakdown of fatty acid into smaller molecules) Absorption of Fats Cholagogue Action Choleretic Action Laxative Action Prevention of Gallstone Formation Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Functions of Bile For micellar formation Activation of lipase Provides alkaline medium for digestion to take place Digestion and absorption of fats and fat soluble vitamins (ADEK) depends on presence of bile. The fat is lipid soluble while the digestive enzyme lipase is enzyme soluble. 177 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Functions of Bile To facilitate the action of lipase on lipids, bile via the following effects: The bile produces emulsification of fat. By this, large molecules are broken down into smaller ones. They show hydrotropic effects. This action of bile enables lipase enzyme to digest the fat. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Functions of Bile Bile reduces surface tension. This effect facilitates the lipase enzyme action. The micelles that is formed after digestion promotes absorption. The micelles consist of digested glycerides combined with bile. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Summary: Functions of Bile Most of the functions of bile are due to the bile salts. – digestive function – absorptive functions – excretory functions – laxative action Copyright © 2011 by Saunders, an imprint of Elsevier Inc. Summary: Functions of Bile – antiseptic action – choleretic action – maintenance of pH – prevention of gallstone formation – lubrication function – cholagogue action Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Regulations of Bile from the Gall bladder 1. When there are products of = fat digestion, = protein digestion = presence of acid and Calcium All stimulates the duodenal mucosa which leads to release of CCK by the duodenal cell. 182 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Regulations of Bile from the Gall bladder This release of CCK cause strong contraction of the gall bladder which helps it to release its content into the duodenum. 2. During the cephalic phase of gastric secretion = food in the mouth, = contraction of the gall bladder, 183 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Regulations of Bile from the Gall bladder 3. Vagal stimulation will lead to weak contraction of the gall bladder. 184 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Regulations of Bile from the Gall bladder Those that are not absorbed back will now be released with the products of digestion and is passed out as waste product (contributes to the colour of faeces) 185 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Regulations of Bile from the Gall bladder When bile has been released and carried into the SI most of the bile are reabsorbed into the blood stream and carried to the liver. This is then released again. This is known as the Enterohepatic circulation, i.e circulation between the GIT and hepatic cells. 186 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Regulations of Bile from the Gall bladder Bile secretion is regulated by hormones. There are 2 mechanisms: Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Regulations of Bile from the Gall bladder 1. Hormone secretin produced from duodenum when acid chyme enters acts on the biliary duct cells to increase secretion of water and electrolytes which helps to neutralize the acid chyme, and this action is known as hydrocholeretic effects. The bile salt in the bile causes stimulation of the liver to secrete more bile. This action is called choleretic effect. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Regulations of Bile from the Gall bladder 2. Hormone cholecystokinin (CCK) also acts on gall bladder smooth muscle causing contraction and expulsion of bile. This action of CCK on gall bladder is called chologugue effect. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  The Liver Is the largest single organ in the body (about 1.5kg) The functional unit of the liver is the lobule (50,000- 100,000 in the human liver) Each lobule consist of the radiating columns of cells (hepatocytes) around a central vein and these columns are separated by blood sinusoids 190 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Functions of the Liver The functions of the liver can be classified as follows: 1. Functions of the hepatic vascular system: (a) Blood storage (reservoir function) The liver is expandable organ that normally stored about 10% of the total blood volume (450ml) in the sinusoids and hepatic vein 191 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Functions of the Liver When needed blood can be added to the general circulation (e.g. in cases of severe hemorrhage) (b) Blood filtration The hepatic kupffer cells engulf and digest 99% of the bacteria that enter the portal blood from the intestine and also removed foreign and unwanted substance (e.g. small blood clots) 192 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Functions of the Liver 2. Bile formation This include synthesis and secretion of bile salts and excretion of bile pigments. 193 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Functions of the Liver The liver also perform other synthetic and excretory functions e.g. - it synthesize 25- hydroxycholecalciferol - Plasma proteins and clotting factors - Excretion of dyes such as Bromosulphalein and Tetraiodophenolphthalein 194 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Functions of the Liver 3. Metabolic functions A. CHO metabolism (i) The liver converts galactose and fructose to glucose (which is the form that can be utilizes by the tissue cells) (ii) It is essential for maintaining normal blood glucose level (glucostasis) 195 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Functions of the Liver If the blood glucose level is high, the excess is taken by the liver and is converted to glycogen (glycogenesis) and fat (lipogenesis) If the blood glucose level is low, glucose is added by liver into blood stream through the processes of glycogenolysis and gluconeogenesis 196 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Functions of the Liver B. Protein metabolism (i) Deamination of amino acids in which the resulting products are either oxidized (to supply energy) or converted into CHO and fats (ii) Conversion of ammonia to urea- Ammonia is formed in gut by bacteria and its conversion to urea is life saving because it produces toxic effects especially to the nervous system (hepatic encephalopathy) 197 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Functions of the Liver (iii) Formation of uric acid (end products of nucleoprotein) metabolism (iv) Synthesis of non essential amino acids (through transamination) (v) Synthesis of plasma proteins except gamma-globulins 198 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Functions of the Liver C. Fat metabolism (i) Oxidation of fatty acid to supply energy (ii) Synthesis of cholesterol, lipoprotein and phospholipid (iii) Fat synthesis from CHOs and proteins (lipogenesis) 199 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Functions of the Liver 4. Storage functions Apart from blood, glycogen and fat, liver also stores the following: (i) Vitamins particularly Vitamins A, D and B12 in sufficient amount for over 10/12, 3-4/12 and 12 months respectively (ii) Iron which is stored in the liver cells in the form of ferritin 200 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Functions of the Liver When blood iron level decreases, the liver ferritin releases it content into the blood If blood iron level increases, it is taken by the liver where it is stored (blood iron buffer function) Liver is essential for erythropoiesis- supplies Vitamin B12 and iron in addition to the globin fraction of hemoglobin 201 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Functions of the Liver 5. Detoxification and inactivation functions (i) Many drugs are detoxified in the liver (or excreted in bile) e.g. sulfonamides, penicillin erythromycin etc Similarly, many toxins are detoxified e.g. benzoic acid salt (ii) Many hormones are inactivated in the liver e.g. thyroxine, some polypeptide hormones and steroid hormones 202 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Functions of the Liver Functions of the liver (summary). One of its function is formation and destruction of RBC. Site for formation of foetal red blood cells. It stores vitamin B12. It remove bilirubin from blood to form bile salts 203 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Functions of the Liver. Helps in the formation of plasma proteins such as Prothrombin and fibrinogen. Involved in the metabolism of the three major classes of food. Helps in the maintenance of blood glucose level by converting excess glucose to glycogen. 204 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Functions of the Liver. It converts blood ammonia gotten from the deamination of amino acid to urea. If the ammonia accumulates it causes a condition known as coma.. It also stores fat soluble vitamins (A,D,E,K). It synthesize bile salts which enhances digestion and reabsorption of fat 205 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Functions of the Liver. Production of heat through it’s activities. Detoxification of toxins. Storage of iron 206 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Pathophysiology of the Liver JAUNDICE Is the increase bilirubin level in the blood when there is failure of its excretion from the liver. They are of three types: Physiological jaundice (pre-hepatic or haemolytic jaundice) = Due to excessive break down of red blood cells = Mostly found in newborns. 207 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Pathophysiology of the Liver Hepatocellular jaundice = is as a result of viral attack or destruction of hepatic/liver cells Obstructive/post-hepatic jaundice = bilirubin is absorbed by the bile and it is converted to bile. = It cannot be excreted due to blockage of the common bile duct 208 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Small Intestinal Secretions Complete digestion occurs in the s. intestine by the intestinal and pancreatic juices as well as by bile The products of digestion are then absorbed together with most vitamins, minerals and fluids 209 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Small Intestinal Secretions * Daily secretion is about 2 litres * Two glands are involved: 1. The Brunner’s gland found in the duodenum = secretes thick mucus that helps to protect the walls of small intestine and facilitate smooth movement 210 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Small Intestinal Secretion 2. The crypts of Lieberkuhns found throughout the entire length of the small intestine = The secretions of the crypts of Lieberkuhns are more of extracellular fluid 211 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Small Intestinal Secretion = Have a pH of 6.5 - 7.5 = secretion contains no enzyme. = It is mainly by the secretion of the crypts of Lieberkuhns The mucus (= pH of 8 ) = protect the large intestinal wall and act as an adherent medium (i.e something that causes binding or sticking together e.g faeces) 212 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Small Intestinal Secretion It also neutralizes the acidity of faeces. If there is irritation in the large mucosa, there would be secretion of water, mucus and electrolytes, and this tends to dilute the secretion of the large intestine. It happens mostly in diarrhea. 213 Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Small Intestinal Secretion The small intestine consists of duodenum, jejunum, and ileum. The small intestinal secretion is mainly water, mucus and electrolytes. It is alkaline in nature and ranges between 1000-1500ml/day. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Small Intestinal Secretion Digestive enzymes are not secreted into the lumen, they are present in the apical surface of the villi. At the base of the villi are glands called Crypts of Lieberkuhn which contains cells that secrete mucus. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Small Intestinal Secretion The intestinal gland of the duodenum are called Brunner’s gland which also secrete mucus. The mucus secreted by the Brunner’s gland provides protection to the mucosa lining against mechanical damage and also lubricate the mucosa lining. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Regulation of Small Intestinal Secretion Regulation is neural and hormonal. Vagal stimulation during digestion causes secretion of intestinal hormones. Vasoactive intestinal peptide (VIP) hormones increase secretion of intestinal glands. The most important is the local enteric nervous system. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Summary In this section, you have learnt about the organization of the gastrointestinal tract and the various sphincters with different characteristics and functions. You have also learnt that the salivary glands of different types produce secretions that also perform digestive functions. Gastric, pancreatic, gall bladder and intestinal secretions also perform different functions. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  MODULE 2 GASTROINTESTINAL MOTILITY Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Outline – Chewing – Deglutition (Swallowing) – Gastric motility – Motility of the small intestine – Defaecation Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Learning Objectives By the end of this section, you will be able to: explain the term, Gastrointestinal motility describe the act and use of Mastication (Chewing) describe the process of Swallowing (Deglutition) Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Learning Objectives list the functions of the stomach describe the act of Gastro-intestinal motility describe the process of Defaecation. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Chewing Chewing is the process by which food brought into the mouth is broken down into smaller pieces by the teeth. In the process, the food is mixed with saliva. Chewing makes it easier to swallow the food and contributes to its enjoyment by homogenizing and mixing the food with saliva, thus releasing taste-producing substances. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Chewing Chewing can be carried out voluntarily, but is more frequently a reflex activity. By subdividing the food into smaller particles, chewing makes it possible for the food to mix more readily with digestive secretions of the stomach and duodenum. The tongue and the cheek muscles are used to keep the food mass between the teeth during mastication. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Deglutition (Swallowing) It refers to the act of swallowing. It consists of oral, pharyngeal and esophageal stages. The 1st stage is voluntary, the 2nd and 3rd stages are involuntary and reflex in nature. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Deglutition (Swallowing) Figure 1: Stages of deglutition. A. Preparatory stage; B. Oral stage; C. Pharyngeal stage; D. Esophageal stage Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Oral Stage It is voluntary. The food is masticated by mixing with saliva. The solid food is converted to a soft bolus and positioned in the dorsum of the tongue. In this stage, the bolus passes through the oral cavity toward the pharynx assisted by the tongue pressing against the hard palate. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Pharyngeal Stage The presence of food at the entry of the pharynx stimulates receptors in the tonsil and epiglottis which initiate the reflex. This stage is involuntary: the efferent and afferent impulses are carried by cranial nerves V, IX, X and XII. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Pharyngeal Stage The center is the swallowing center located in the medulla and the lower pons. This reflex allows the bolus to enter the esophagus and not the trachea. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Pharyngeal Stage The entry of the bolus into the nasopharynx is prevented by: 1. The soft palate raises and presses against the posterior pharyngeal wall. 2. There is an upward and forward movement of the larynx which causes the glottis approximately with the epiglottis and seal with the larynx. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Pharyngeal Stage The vocal cord also approximately inhibiting speech. 3. There is ceasation of respiration at this stage. The bolus is therefore directed at the esophagus. Esophageal stage Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Esophageal Stage Is also an involuntary phase Here the peristaltic movement is initiated in the upper part of the esophagus Then extends downward along esophageal wall Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Esophageal Stage presence of food in the lower esophageal sphincter will causes relaxation of the sphincter Resulting in propulsion of the food bolus into the stomach Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Esophageal Stage The bolus enters the esophagus from the pharynx through the upper esophageal sphincter and enters the stomach through the lower esophageal sphincter. Entry of food bolus causes distension and relaxation of upper esophageal sphincter. This is as a result of inhibition of the vagus nerve. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Esophageal Stage This distension initiate a wave of peristalsis which spread along the length of esophagus pushing the bolus forward. These are: primary peristalsis wave travelling at 3-4cm/sec (frequency). The force of gravity helps the wave of movement. Liquid travels faster than solid to reach the stomach. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Esophageal Stage When the bolus reaches the lower esophageal sphincter, it relaxes and allows the bolus to enter the stomach, after which it closes to prevent regurgitation into the esophagus; this action is regulated by the myenteric plexus which secretes VIP or NO (nitric oxide). If the primary peristalsis does not completely empty the esophagus, one or more secondary peristalsis arises from distal part of esophagus. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Esophageal Stage Esophageal peristalsis are of 2 types: Primary - Continuation of peristaltic wave that begins in the pharynx Secondary – Occurs if primary peristalsis fail to propel all the food that has entered the esophagus It originates in the esophagus itself as a result of distension of it wall by food Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Disorders of Swallowing Dysphagia Difficult/pain on swallowing Causes: - Leision of the 9th or 10th cranial nerves (e.g. due to Diphtheria) - Damage of the swallowing center e.g. in poliomyelitis - Malfunction of the swallowing center e.g. Myasthenia gravis Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Disorders of Swallowing Esophageal stricture (narrowing) e.g. due to cancer or scarring Achalasia – difficulty in emptying the food from the esophagus to stomach due to absence of peristalsis in the lower 3rd or failure of cardiac sphincter to relax. Copyright © 2011 by Saunders, an imprint of Elsevier Inc. Motility of the Small Intestine The movement that are seen in small intestine are as follows: Segmental contraction Peristalsis contraction Pendular contraction Villi movement Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Segmental Contraction The frequently occurring movement in the small intestine is the segmental contraction. Slow waves develop in the circular smooth muscle of the wall due to stimulation of the plexus. When the slow wave reaches threshold, segmental contraction that is propagatory develops. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Segmental Contraction The frequency of the slow wave is highest in the duodenum (12/min) and lowest in the ileum (8/min). This facilitates the bolus to be propelled aborally. The segmental contraction involves ring-like regular constriction along the length of the segment of the intestine. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Segmental Contraction The constricted part latter relaxes and the relaxed part constrict. This process is repeated over and over again resulting in the bolus moving back and forth within the lumen. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Functions of Segmental Peristalsis Functions of segmental peristalsis are as follows: – Bolus mixes well with digestive enzymes and facilitate completion of digestion – The segmental contraction causes exposure of digested food to the villi surface for absorption – The occurrence of segmental contraction in the proximal segment and inhibition in the distal segment facilitate propulsion of bolus toward the segment colon. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Functions of Segmental Peristalsis Sometimes the longitudinal muscle contraction gives pendular contraction which facilitates mixing of bolus with digestive enzymes. Villi movement There is contraction of the smooth muscle of the villi that results into forward and backward movement. The hormone- villi kinin stimulates the movement which facilitates absorption of digested food. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Gastroileal Reflex Distension of the stomach by food causes relaxation of ileocecal sphincter and allows emptying of the ileal content into the caecum. Distension of the ileum will also cause the relaxation of the sphincter and emptying. On the other hand, the distension of the caecum will result in contraction of the caeca and prevent reflux of the caecal content into the ileum. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Gastroileal Reflex This is facilitated by the ileocecal valve. The activity of the ileocecal sphincter is controlled by the myenteric plexus. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Functions of the Small Intestine i. It contains pancreatic bile and intestinal secretion ii. Completion of digestion and absorption of digested food occurs in the small intestine iii. Presence of villi facilitates absorption of digested food Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Functions of the Small Intestine vi. The duodenal mucosa secretes gastrointestinal hormones like secretin, CCK, VIP, motilin, etc. v. Payer’s patches in the ileum are lymphoid organs which help in immunity. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Migrating Motor Complex It is an interdigesting peristalsis occurring in the stomach and small intestine. It occurs in between meal at every 70-90 mins interval. Each peristalsis last 10mins. It is developed due to activity of intrinsic myenteric system. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  Migrating Motor Complex It helps in sweeping the content of the stomach and small intestine towards colon toward interdigestive period. Motilin is the hormone responsible. Copyright © 2011 by Saunders, an imprint of Elsevier Inc. The Large Intestine Figure 3: The human colon Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  The Large Intestine It includes the caecum, ascending colon, transverse colon and descending or sigmoid colon, rectum and anus. The mucosa secretes mucus but there are no villi, hence no absorption of food, no digestive enzymes. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  The Large Intestine However, it has important functions: Absorption of water and electrolytes Formation of faeces Secretion of mucus to lubricate the faeces The bacteria fluoride synthesise vit B and vit K. Copyright © 2011 by Saunders, an imprint of Elsevier Inc.  The Large Intestine The large intestine shows haustral shutting (segmental contra