UPPER GIT

Dr. Alcon
October 27, 2009

CONTROL OF THE GIT I. NEUROCRINE - regulate the secretory and motor functions a. Autonomic Nervous System (extrinsic)

THE GASTROINTESTINAL SYSTEM Consist of the gastrointestinal tract (GIT) and associated glandular organs that produce secretions (Berne)

SYMPATHETIC postganglionic and preganglionic fibers w/ cell bodies in prevertebral and paravertebral ganglia adrenergic Innervation by celiac, superior & inferior mesenteric and hypogastric plexuses (indirect innervation; through ENS) inhibit motor and secretory function of GIT induce contraction of muscularis mucosa & some sphincters

PARASYMPATHETIC

preganglionic fibers

Structures: mouth, pharynx, esophagus, stomach, small intestine (duodenum, jejunum, ileum), colon, rectum and anus Glandular organs: salivary glands, liver, gallbladder, pancreas Functions: digest food and absorb nutrient molecules into the blood stream by motility (movements that mix and circulate GIT contents and propel them through anterograde/forward movement), secretion, digestion (chemical degradation of food to small molecules) and absorption into the bloodstream.

cholinergic Innervation by vagus n. (esophagus-transverse colon) pelvic n. (remainder of colon, rectum & anus) stimulation of motor and secretory function of GIT

b. Enteric Nervous System (intrinsic) - little brain of the gut; specific for the GIT Page 1 of 9 Fajardo, Maja & Garcia, Cookie

A complete reflex circuit which integrates and coordinates motility, secretory and endocrine functions of the GIT Uses local reflexes to relay information in the GIT Directly controls motor and secretory activities of the GIT, so these activities continue even if sympathetic and parasympathetic nerves to the gut are cut

Submucosal/Meissners plexus Located between the muscularis mucosae and circular smooth muscle layers of muscularis externa contains sensory cells that communicate with the myenteric plexus and motor fibers that stimulate secretion of fluids in the lumen receives sensory information from chemoreceptors and mechanoreceptors in the GIT primarily controls secretion and blood flow Myenteric/ Auerbachs plexus Located between the circular and longitudinal smooth muscle layers of the muscularis externa contains neurons responsible for regulating the enzyme output of adjacent organs primarily controls the motility of the GI smooth muscle

STRUCTURE OF THE GASTROINTESTINAL TRACT

c. Somatic Nervous System - Responsible for voluntary movements (initiation of chewing) - Skeletal muscles in the GIT ***different controls for complex functions and need for localized control Layers: 1. Mucosa- innermost a. Epithelium- lining b. Lamina propria- connective tissues with collagen and elastin fibrils c. Muscularis mucosae- thin, innermost layer; contractions cause mucosal folds and ridges

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2. Submucosa- consists of loose connective tissue with collagen and elastin fibrils; some regions have glands a. Submucosal (Meissners) plexus 3. Muscularis externa- contractions mix and circulate contents of the lumen and propel them a. Circular layer- inner i. Inner dense circular layer ii. Outer circular layer b. Longitudinal layer c. Myenteric (Auerbachs) plexusbetween the circular and longitudinal layers 4. Serosa (adventitia)- outermost layer - Consists mainly of connective tissue covered with a layer of squamous mesothelial cells BASIC ELECTRICAL RHYTHM Pacemaker cells Interstitial cells of Cajal - Located in interstitium near the smooth muscle - Pacemaker sites of slow waves Slow waves spontaneous depolarizations in smooth muscle membranes Threshold opening of voltage-gated Ca++ channels Spike potentials action potentials Smooth muscle contraction ***not all depolarizations lead to contraction; it must reach the THRESHOLD Slow Waves and Smooth Muscle Contraction ***shows the different pacing between different organs RMP- approximately -40 to -70 mV Slow waves (basic electrical rhythm) - Oscillating membrane potentials - Not action potentials, but determine pattern of muscular contraction - Amplitude and frequency can be modulated by activity of intrinsic and extrinsic nerves and by hormones and paracrine substances - Amplitude can be decreased by sympathetic nerve activity; parasympathetic activity on the other had increases amplitude - When not accompanied by action potentials, it elicits weak contractions - More action potentials will result to stringer contractions Action potentials- more prolonged than those of skeletal muscles - Have little or no overshoot - Rising phase is caused by ion flow through slow conducting Ca and Na channels - Extent of depolarizartion and frequency are enhanced by some hormones, paracrine agonists and compounds released from excitatory nerve endings - Inhibitory hormones and neuroeffector substances hyperpolarize smooth muscle cells and may diminish or abolish action potential spikes II. ENDOCRINE- HORMONES - Hormones are produced by endocrine cells and are released into the blood to reach their target cells via the circulation (Berne) - Endocrine cells are found in the mucosa or submucosa of the stomach, intestine and pancreas Page 3 of 9 Fajardo, Maja & Garcia, Cookie

III. PARACRINES - Diffuse over short distances to act on target cells located in the GI tract Examples: - Histamine o Secreted by mast cells o Increases gastric H secretion - Somatostatin o Inhibits release of Gi hormones o Secreted in response to H in lumen of GIT o Inhibits gastric H secretion

GASTROINTESTINAL PROCESSES 1. MASTICATION/CHEWING - mechanical digestion of food to facilitate enzymatic digestion - initiated voluntarily (input from higher centers) but continued as a reflex a. Breaks food into smaller pieces b. Mixes food with saliva (lubrication) c. Brings food into contact with taste receptors and releases odors Chewing reflex: mouth opens --- stretch receptors --- orofacial afferents --- center: pons/trigeminal nucleus --- CN V, VII & XII -- mouth closes --- touch receptors --- jaw drops Major Characteristics of Saliva - Large volume relative to the mass of the salivary glands - High potassium concentration - Low osmolarity - Contains specialized organic materials Composition of Saliva - Water, electrolytes and some organic compounds: - Ptyalin alpha amylase - Lingual lipase - triglycerides - Lysozyme muramidase: cell walls - Binding protein for IgA secretory IgA - Lactoferrin chelates iron - Kallikrein - bradykinin Secretion of Saliva

**Secreted by 3 major glands: parotid, submaxillary and sublingual

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CNS Regulation of the Salivary Glands

3. glottis and vocal cords are closed and epiglottis swings down over the larynx, guiding food toward the esophagus 4. bolus of food is pushed into the esophagus by peristaltic contraction of the pharynx and the opening of the upper esophageal sphincter (UES) **UES prevents entry of air into the esophagus **peristaltic wave is initiated by contraction of pharyngeal superior constrictor muscles Swallowing Reflex - An ordered sequence of events that propels food from the mouth to the stomach - Inhibits simultaneous respiration and prevents entrance of food into the traches during swallowing

Saliva production is both controlled by parasympathetic and sympathetic NS Both increases saliva production, but parasympathetic has more control Both PNS and SNS cause myoepithelial cells contraction or salivary acini initial (isotonic) saliva is ejected into the ducts for re-absorption (of Na and Cl) and secretion (of K and HCO3) hypotonic saliva is secreted into the mouth

Receptors tactile receptors in pharynx Afferent nerves CN V and IX Center medulla and lower pons Efferent nerves CN V, IX, X and XII Effectors muscles of pharynx and upper esophagus

a. Parasympathetic stimulation Synthesis and secretion of salivary amylase and mucins by transport activities of acinar and ductal cells Vasodilation which causes increased blood flow to salivary gland Glandular metabolism and growth b. Sympathetic stimulation Production/ secretion of saliva Glandular growth - Sympathetic fibers originate from the superior cervical ganglion (refer to figure above) - Receptors on the acinar and ductal cells are adrenergic, secondary messenger is cAMP 2. SWALLOWING/DEGLUTITION Phases: a. Oral (voluntary) phase: tongue pushes bolus up and back against the hard palate b. Pharyngeal phase: 1. nasopharynx is closed by the soft palate to prevent regurgitation of food to nasal cavities 2. palatopharyngeal folds are pulled medially, forming a passage for food to move into the pharynx

c. Esophageal Phase 1. Primary Peristalsis follows a swallow - UES contracts and LES relaxes - food travels at 2-6 cm/sec 2. Secondary Peristalsis when food remains or is stuck in the esophagus - Enteric Nervous System Neural Pathways in Pharyngeal and Esophageal Peristalsis

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Innervation by vagus nerve; motor (efferent) neurons reach the esophagus by branches of vagus nerve; sensory feedback to the swallowing center is carried by afferent fibers Enlarged picture at the right of the figure emphasizes the dual innervation of skeletal muscles

** increase in pressure closes LES; while decrease in the pressure opens it LES ABNORMALITIES 1. Achalasia - neuromuscular disorder of lower 2/3 of esophagus and failure of LES to relax 2. Gastroesophageal Reflux Disease (GERD) - LES unable to maintain normal tone - heartburn, Scleroderma PHYSIOLOGY OF THE STOMACH
***NOTE: text in italics are sound bites from Dr. Alcons lecture

Pressure events in the esophagus following a swallow

Lower esophageal Sphincter (LES) - Prevents reflux of acidic gastric contents into the esophagus - Receptive relaxation: mediated by vagus nerve (VIP or NO) when food is brought by peristalsis into the esophagus ***associated with relaxation in orad regions of the stomach Factors Influencing LES Pressure

FIGURE 1: Muscular layers of the stomach This picture shows the layers of the stomach, indicating the location of the plexuses (take note!), as well as the different muscle layers that allow for the processing of food, as described below. Gastric Motility The functions of gastric motility can be summarized as follows: Storage Fundus and the body of the stomach enlarges as food enters the stomach, without a great increase in intragastric pressure, a phenomenon called receptive relaxation. o Food stays in stomach for 3-6 hours, which is the time it takes for contents to be extruded into the duodenum, also called the total gastric emptying time. o Gastric emptying time is dependent on what you eat or more specifically the chemical make-up of food (i.e. more complex, longer gastric emptying time) Mixing Food in the body and antrum increases contraction: peristalsis and retropulsion; this increases mixing of food with gastric juices. o Food that is not broken down in upper structures is broken down in the stomach

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Emptying Chyme is propelled through the pyloric sphincter into the intestine o Chyme food mixed with gastric juices o Extra digestion occurs in intestine, where digestion is mostly chemical in nature (enzymatic) o Dumping syndrome decreased or absent ability of duodenum to tell the stomach that it is ready to receive food products from stomach

The pyloric sphincter ensures that particles less than 1 mm enter the duodenum, to ensure that the particles are easily degraded by the enzymes in the intestines. Particles larger than this are kept in the stomach, where the continuous peristaltic contractions and retropulsions mechanically break down food into the right size. Gastric Emptying

Between meals synchronous contractions of fundus, body and antrum (interdigestive motor cycle/ IDMC) o Food not digested during or right-after meals will come out between meals During or right-after a meal fundus: quiescent, stores food body and antrum: crush food to <1 mm peristalsis intensity increases from body to antrum o retropulsion food particles impact on pyloric sphincter

The mechanisms regulating gastric emptying are both neural and hormonal mechanism.
A. Local Reflexes 1. Excitatory stretching of antrum due to an increase in the volume of liquid 2. Inhibitory enterogastric reflexes

B. Hormones (non-local) a. Excitatory Gastrin b. Inhibitory Cholecystokinin, Secretin: reactive to hypotonic/hypertonic substances, high caloric content (esp. fat), acidity, consistency; secreted by the mucosa of small intestines * More oily foodone feels full faster and longer Example: Green mango with bagoong mango is acidic and bagoong has fat and is hypertonic, which is why one feels full faster and longer with this food. Yum! C. Interdigestive Motor Cycle

FIGURE 2: Regions of the stomach The different regions (anatomic and functional) are shown, in relation to their function between, during and after meals. (please refer to text in the figure above ). Antral systole and Retropulsion FIGURE 4: Parts of the gastric mucosa and its gastric pits Composition of Gastric Juice 1. Mucus and Bicarbonate (HCO3-) - mucus: gel-forming glycoproteins (mucins) - NaHCO3- : o Prevents gastric acid from harming the mucosa o increased by mucosal irritation, PNS, prostaglandins, empty stomach o decreased by - stress (NE, Epi), aspirin, NSAIDs, smoking Page 7 of 9 Fajardo, Maja & Garcia, Cookie

FIGURE 3: Regulation of food particle entry into the duodenum by the pyloric sphincter

FALLACY: not eating on time causes ulcers. FACT: bicarbonate is increased by empty stomach so mucosa is still well protected from gastric acids

2. Enzymes: Pepsins - secreted as inactive pepsinogens I and II activated by decreased pH (HCl) - endoproteases digest aromatic amines - increased by: PNS (Ach) major; hormones (gastrin, CCK, secretin); others (gastric lipase triglycerides, cathepsin, gelatinase) 3. Hydrochloric acid (HCl) 2-3 L/day up to 3-4 L/day variable ionic composition and acidity provides optimal pH for activation of pepsins kills ingested bacteria

4. Intrinsic Factor (IF) - binds Vitamin B12 and aids its absorption in the ileum - More HCL, more IFsimultaneously produced Physiologic Regulation of Gastric Secretion

Clinical correlation: proton-pump inhibitors are drugs that inhibit acid secretions. Hydrogen-potassium pumps are permanently inhibited but the stomach produces new parietal cells daily so these drugs are usually taken only once a day, to ensure that acidity is decreased but not totally terminated.

FIGURE 6: Representation of Parietal Cell processes

FIGURE 7: Diagram of the physiology of gastric acid secretion

FIGURE 5: Summary table of stimulatory and inhibitory factors regulating the release of gastric juice The table enumerates the various substances or factors that influence the release of gastric juices as seen in the different phases namely: cephalic (anticipatory), gastric and intestinal phases. FIGURE 8: Summary of the mechanisms for stimulating gastric acid secretion Page 8 of 9 Fajardo, Maja & Garcia, Cookie

FIGURE 9: Physiologic events during the gastric phase of Gastric acid release, indicating the stimulatory and inhibitory substances involved. Mechanisms Inhibiting Gastric Acid Secretion

FIGURE 10: Illustration of the Vomiting Reflex center in the brain Of note in this picture are the different factors that may stimulate the vomiting reflex center, either from the stomach or small intestine or the higher brain centers. Various factors include chemicals, surgery, sensory input (noxious smells or sights) and even heightened emotional states. Sequence of events: (generally a reverse of peristalsis) Reverse peristalsis distal small intestines to duodenum (where retching starts) Pyloric sphincter and stomach relax Forced inspiration against a closed glottis decreased intrathoracic pressure Forceful contraction of abdominal muscles increased intrabdominal pressure LES relaxes UES relaxes as the gastric contents are propelled toward the mouth --FIN

Vomiting or Emesis forceful expulsion of gastric or duodenal contents a normally abnormal process of expelling foreign a reflex behavior controlled and coordinated by a vomiting center in the medulla oblangata Preceded by: o nausea subjective sensation o retching overcomes anti-reflux mechanisms Triggered by: Stimulation of vomiting center o chemoreceptor trigger zone o duodenal receptors (intestine) How do you know if the vomitus is Gastric or

and often harmful material from the body

duodenal in origin? note the presence of bile, which indicates duodenal involvement.

References: Dr. Alcons lecture Berne, R., Levy, M., Koeppen, B., & Stanton, B. (2004). Physiology. 5th ed. Elsevier, USA Page 9 of 9

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