Gastrointestinal Physiology Parts 1-2 PDF

## Learning Objectives * List the major functions of the GI tract * Describe food and water intake and differences between species * Describe deglutition; voluntary and reflective phases * Explain the control of hunger and satiety * Make a morphological description of a salivary gland * Describe th...

## Learning Objectives * List the major functions of the GI tract * Describe food and water intake and differences between species * Describe deglutition; voluntary and reflective phases * Explain the control of hunger and satiety * Make a morphological description of a salivary gland * Describe the function, production, and the composition of saliva * Explain the control of saliva production * Explain and compare endocrine, paracrine, neurocrine, and autocrine action mechanisms * Synthesis, function, and regulation of gastrin, GIP, secretin, CCK, and motilin * Describe the different parts of the monogastric stomach * List the cell types of the stomach and their function * Explain the production of gastric acid in parietal cells * Explain the production of enzymes in the stomach * Explain the production of hormones in enteroendocrine cells * Explain the production of mucus in the stomach * Explain the different regulation levels of gastric secretion * Explain the regulation of enzyme production in the stomach * Explain the effects of non-steroidal anti-inflammatory drugs (NSAIDs) on gastric mucosa * List causes of gastric ulcer in animals ## Digestive System * Gastrointestinal tract + liver, pancreas, gallbladder (aka accessory organs) * Depending on the source, digestive system = gastrointestinal tract * Similarities in all animals include: * GI tract = concentric muscle cylinders lined with an epithelium * Accessory organs = teeth, tongue, salivary glands, liver pancreas * Species will have different specialized digestive systems * Citation in lecture provides diagrams of different specialized digestive systems. * Specialization depends upon their primary energy source (diet). * Carnivores: A big stomach and a relatively short intestinal tract * Ruminants: Fermentation in the forestomach system * Horses: Fermentation in the large intestine * Birds: Food store (the crop), a glandular stomach (pro-ventriculus), and a muscular stomach (gizzard) ## Main functions of GI tract * Transportation of food * Digestion of food into absorbable particles * Absorption of food components and transport into the blood * Regulation of water and electrolyte balance * Immunologic barrier (GALT - Gut Associated Lymphoid Tissue) * Thermoregulation (fluid intake, panting in dogs) ## Prehension * Short definition = the process of getting food into the mouth * Species differences in prehension * Horses: Lips (when eating from manger/grain bucket) or incisors (when grazing) * Cattle: Tongue (wrap the tongue around forage) and incisors * Goat and sheep: Tongue and lips * Pigs: Snout and mandible * Carnivorous: Canines, incisors, and forelimbs ## Mastication * First act of digestion * Involves the actions of the teeth, the jaws, the tongue, and the cheeks working together to break up food into small particles * Depending on the species there will be differences * Carnivores: * Movement of the mandible is vertical, limited motion. * Molars and premolars in the upper (Maxilla) and lower (Mandible) jaws move against each other like scissor blades * Herbivores: * Spend long time masticating (chewing). * Upper and lower jaws are large providing room for teeth with large chewing surfaces. Mastication movements are horizontal ## Movements of the GI Tract * After mastication, motility of different GI tract segments will be activated. * Movements of the GI tract have several functions: 1. Propel: To propel ingested feed from one location to the next 2. Retain: To retain ingested feed at a given site for digestion, absorption, or storage 3. Break up: To break up food material physically and mix it with digestive secretions 4. Circulate: To circulate ingested feed so that all portions come in contact with absorptive surfaces ## Deglutition * Term for swallowing * The first motility pattern in the GI tract * Deglutition involves voluntary and involuntary stages and occurs after food has been masticated **Voluntary Phase** (oral phase): * Food is in the oral cavity and is molded into a bolus * Food bolus = ball of food particles * The tongue will push the bolus back into the pharynx * When food enters the pharynx activation of sensory nerve endings initiation of the involuntary part of deglutition **Involuntary Phase** (swallow reflex): * It occurs within the pharynx and esophagus it directs food into the digestive system (away from the upper airways) * The epiglottis will close and block the trachea * We do not think about this hence it is an involuntary action **Steps of Deglutition** * During deglutition, breathing stops momentarily, and while breathing is stopped the following occurs * The soft palate is elevated closing the pharyngeal opening of the nasopharynx * This prevents food from exiting via the nostrils * The tongue is pressed against the hard palate closing off the oral opening * This prevents food from exiting via the mouth * The epiglottis is moved backwards covering the entrance to the trachea preventing the movement of food into the respiratory system * prevents aspiration of food * The upper esophageal sphincter opens food is transported through the esophagus by peristaltic contractions * The entrance to the trachea is reopened and respiration continues ## Deglutition Disorders * Videos: [https://www.youtube.com/watch?v=v9oiaLAISvg](https://www.youtube.com/watch?v=v9oiaLAISvg) * Videos: [https://www.youtube.com/watch?v=adJHdrQ4CRM](https://www.youtube.com/watch?v=adJHdrQ4CRM) * Difficulty in SWALLOWING which may result from neuromuscular disorder or mechanical obstruction * Dysphagia is classified into two distinct types: 1. Oropharyngeal dysphagia due to malfunction of the pharynx and upper esophageal sphincter 2. Esophageal dysphagia due to malfunction of the esophagus * Aspiration: When one of the types of dysphagia above lead to food particles/fluids or stomach contents (acid reflux) reaching the upper airways ## Regulation of Food Intake * Hypothalamus * Regulatory center for energy homeostasis * Are you hungry or full? * Nucleus paraventricularis: Hunger center * General location: lateral hypothalamus fields, perifornical region * Nucleus Ventromedialis: Satiety center * Neuropeptides in the hypothalamus: * Stimulatory: Neuropeptide Y (NPY), Orexin * Inhibitory: Melanocyte-stimulating hormone (MSH) inhibits hunger and increases energy consumption * Non-hypothalamic hormones: * Stimulatory: Ghrelin * Inhibitory: * Cholecystokinin (CCK), Peptide YY (PYY), * Leptin (fat cells -> inhibits NPY release and activates MSH release and activity), * Insulin (pancreas -> glucose availability) * **Quick pause, definition review** * Agonists * Molecules bind to the receptor and induce all the post-receptor events that lead to a biologic effect. * In simpler terms, they function as the regular hormone, but may be more or less potently. * Receptors may be bound by different hormones * The different agonists may have more or less potency when bound to receptors. * Antagonists * Molecules bind to the receptor and block binding of the agonist. The receptor is made nonfunctional (aka no activation of intracellular signaling events). * In simpler terms, they block the hormones who would cause intracellular signaling events. * Hormone antagonists are widely used as drugs. ## Note on Ghrelin * Produced in stomach * Mainly by endocrine cells within the mucosal epithelium of oxyntic glands (in gastric fundus) * Plasma ghrelin increases during fasting and decreases postprandially * Postprandially = after eating * Many functions * Of particular note is it helps to increase appetite and food intake * Capromorelin is a drug that is a ghrelin receptor agonist that stimulates the appetite * Approved for use in dogs ## Salivary Glands * Major salivary glands: * Parotis (parotid gland) * Mandibularis (mandibular gland) * Sublingualis (sublingual gland) * Small salivary glands: * Ventral jaw glands * Palate, pharyngeal glands * Lip glands (abiales) * Zygomatic glands * Classified according to the type of secretion * Serous, mucous, seromucous glands ## Primary functions of the saliva (digestive functions): * Protection of the oral mucosa and teeth * Facilitation of deglutition * Initiation of enzymatic carbohydrate digestion * (human and pigs amylase) * More on this later * pH regulation thru bicarbonate (HCO3¯) secretion * By secretion, it refers to bicarbonate being contained within the salivary gland secretions ## Secondary functions: * Immunologic function (Lysozyme, Ig's) * Thermoregulation (panting in dogs) * Defense mechanism in some species (llamas, alpacas, guanacos) ## Saliva consists of * Water (99%) * Electrolytes (Na+, K+, Cl-, HCO3¯) ## Salivary gland components * Acini * Basic secretory units of salivary glands * Clusters of cells (glandular epithelium) * These cells secrete a fluid that contains water, electrolytes, mucus and enzymes, all of which flow out of the acinus into collecting ducts. * Location where the primary saliva is produced * Composition H20, Cl, and Na+ * Ducts: In the ducts the secondary saliva is produced * Addition of K+ and HCO3 ## Disturbances in saliva production: * Dry mouth, bucal ulceras, dysphagia, proliferation of bacterial population and ... caries! ## Regulation of saliva secretion: * Parasympathetic system: * Nerves: facialis und glossopharyngeus * Act thru/on M3-Receptors * results in contraction of myoepithelial cells * increases secretion of saliva (saliva more dilute) * Sympathetic system: * First three thoracic segments * Act thru/on alpha-1 receptors * results in secretion of small volumes consistent (mucous) saliva ## Stimulation of saliva secretion: * Innate (reflex): * Triggered through contact with oral mucosa (mechanoreceptors) * i.e. a lion is eating its prey * i.e. you eating your favorite food * Conditioned: through sight, smell, or imagination of food * i.e. You smell your favorite food cooking ## Gastric secretion types * Endocrine secretions * Substances distributed in blood and binds to distant target sites * Paracrine substances * Substances which act locally by diffusing through the interstitial space to affect other cells (nearby). * Affects neighbor cells * Autocrine substances * Substances acts on the same cell that produced it * Neurocrine * Refers to secretions by enteric neurons that affect muscle cells, glands, and blood cells ## Digestive hormones * Need to be secreted by one cell and affect another cell * Must be transported in the blood * Will be stimulated by food and its action must be mimicked by a synthetic analog molecule * The "big five" GI hormones **Secretin** * Produced in the duodenum (primarily), jejunum (very minor) * Actions: * Stimulates bicarbonate secretion * Inhibits acid secretion * Stimuli: * Acids, fats, protein **Gastrin** * Produced in stomach (antrum) and duodenum * Actions: * Stimulates acid secretion * Stimuli: * Protein, high pH (alkaline stomach environment) **CCK** * Produced in the duodenum, jejunum, and ileum * Actions: * Stimulates pancreatic enzyme secretion * Stimulates gallbladder contraction **GIP** * Produced in the duodenum, jejunum * Actions: * Inhibit gastric secretion * Stimulates insulin secretion * Stimuli: * Fats, glucose **Motilin** * Produced in the duodenum, jejunum * Actions: * Induction of intestinal motility during fasting (MMC) * Stimuli: * Acetylcholine ## Monogastric stomach * Stomach regions: * Esophageal part, cardia, fundus, corpus, pylorus * Glandular zones: * Cardia: Mucus production prominent here * Fundus: * HCl and enzyme production prominent here * Pylorus: * Mucus production prominent here * Secretion of gastric acid varies * Dogs: 0.2-0.5 liters/day * Humans: 1.0-2.0 liters/day * Pigs: 2.0-3.0 liters/day * Horses: 6.0-8.0 liters/day * Glandular mucosa has invaginations * Surface mucous cells * Produced thick mucous to protect the stomach from acid * Gastric pits: * Lined with mucus-secreting cells at the luminal surface * Leads to a deep gastric gland * Gastric glands: * Parietal cells located in the neck of the gastric glands * Chief cells located in the neck of the gastric glands * Mucous neck cells * Produce a less viscous secretion * A thin mucus * Serves as progenitor cells for the gastric mucosa * After division they migrate down or up into the pit and differentiate into several types of gastric pit cells * Cell types within monogastric stomach (gastric pit & gastric gland) * Surface mucous cells * Produce mucous * Parietal cells * Produce HCl * Protons (H+) are produced within the parietal cell when carbonic acid dissociates. * Carbonic acid is produced within the parietal cell during the chemical reaction of water and CO2. * Catalyzed via carbonic anhydrase * When stimulated to produce HCl, vesicles containing H+/K+ ATPase pumps are targeted to the apical membrane (aka brought to and join the apical membrane) * H+ and Cl- are actively pumped into the lumen of the canaliculus (intracellular canaliculus) * 2H+ via H+/K+ ATPase * Cl- via conductance channels * When cells are not stimulated H+/K+ ATPase will “essentially” not be present on the apical membrane but are on stored on vesicles within the cytoplasm * Secrete (from cell into stomach) intrinsic factor (IF) * Intrinsic factor essential for vitamin B12 absorption in the illeum * Mucous neck cells * Enteroendocrine cells * Triangular in shape with a thin cytoplasmic projection reaching the lumen * Produce hormones depending upon the “subdivision” or "type" of enteroendocrine cell * Enteroendocrine cells are named according to the hormone/secretion they produce * Enteroendocrine cells secrete their granules' content (gastrin, histamine, somatostatin) into the lamina propria, then reach the blood capillaries. * G cells: gastrin * D cells: somatostatin * I cells: CCK * ECL cells: histamine * (Note: Not all of these cells are in stomach) * Chief cells * Produce proenzyme pepsinogen (aka inactive enzyme, precursor to active enzyme) * In the acidic environment of the stomach, pepsinogen will activate itself and become pepsin, an active enzyme * Autoproteolysis = "self activation" under the right conditions * Pepsin hydrolyzes proteins * Aka breaks down proteins * In calves and labs: * Chief cell produces prochymosine (proenzyme) * In the acidic environment of the abomasum it becomes chymosine (active enzyme) * Hydrolysis of milk protein * Aka breaks down milk proteins * In the same region that mucous neck cells are located (neck of the gland) there are stem cells * All the functional cell types of the gastric pit originate from these stem cells * Mucous-producing cells (named above) * Function: mucous producing cells * Mucins (glycoproteins) are secreted by exocytosis * Serves to protect and lubricate the mucosa * Surface mucous cells do not live long * Regeneration every 3-5 days * Evidence of regeneration by the ↑ mitotic activity in the isthmus of the gastric pit ## Gastric acid secretion * HCl secretion is regulated at three levels: * Neural (mediated by acetylcholine) * Hormonal (mediated by gastrin) * Paracrine (mediated by histamine) * Stimulatory substances: * Gastrin, histamine, and acetyl choline * Inhibitory substances: * Somatostatin ## Gastric enzyme secretion * The enzymatic secretion will be stimulated at two levels: * Neural (mediated by acetylcholine and noradrenalin) * Hormonal (mediated by Secretin and CCK) * Release of CCK and secretin from the enteroendocrine cells of small intestine depends on the presence of food particles in the intestinal lumen and the pH: * amino acids and fatty acids cause CCK to be released/secreted * ↓ pH causes secretin to be released/secreted * Regulation of gastric secretion * Gastric secretion is said to occur in three phases: cephalic, gastric, and intestinal phases * Cephalic phase * Before food enters the stomach (sight, smell, thought or taste; the greater the appetite, the stronger the stimulation) * Gastrin will * Gastric phase: induced by vagovagal reflexes from the stomach to the brain (through dilatation of the stomach and through the presence of amino acids and peptides in the Gl lumen) * Intestinal phase, induced by the presence of food in the duodenum (it works as a feed back) * Gastric acid: HCl (pH 1-4) * Defense system (killing microorganisms) * Exception: Helicobacter pylori * Can colonize the mucosa (it goes under the mucus layer) * It neutralizes the acid pH by producing the enzyme urease: * H2N-CO-NH2 + H2O 2 NH3 + CO2 * neutral microenvironment ## Gastric ulcer * Mucus secretion is not so dramatically altered by the presence of food, in comparison to gastric acid and enzymatic secretion * Both acetylcholine (Ach) and prostaglandin E (PGE) stimulate mucus secretion * Decrease pH ↑ Ach and PGE ↑ Mucus * Non-steroidal anti-inflammatory drugs (NSAIDs) block the synthesis of prostaglandins as well as several important processes in the gastric mucosa promoting the formation of gastric ulcer * In other words, NSAIDS can reduce the production of mucus, leading to cellular damage by the stomach acids. * Horses and pigs can be prone to ulcers * Competition horses: 60-90% * Hobby horses: 30% * Grazing horses: < 10% * 2-4 weeks foals: 25-50% * Example of gastric ulcer formation * Horses and pigs pH 4-6 in proximal part of the stomach * colonization of bacteria occurs * rich carbohydrate food is consumed * hydrolysis of carbohydrates in short chain fatty acids and lactate * leads to more acidic pH * Damage of the mucosa * gastric ulcers