1) 05_Gastrointestinal system-1.pdf

DIGESTIVE SYSTEM GASTROINTESTINAL SYTEM (GIS) General Organization 2024 Learning outcomes 1. Explain the basic functions of the gastrointestinal system (GIS) including immune, digestive, reflexive responses. 2. Identify the segments of the gastrointestinal tract and the specialized functions attribu...

DIGESTIVE SYSTEM GASTROINTESTINAL SYTEM (GIS) General Organization 2024 Learning outcomes 1. Explain the basic functions of the gastrointestinal system (GIS) including immune, digestive, reflexive responses. 2. Identify the segments of the gastrointestinal tract and the specialized functions attributed to each. 3. Explain the cellular specialization; mucosa, submucoza, muscularis externa and seroza. 4. Define gastrointestinal motility by means of smooth muscle contraction and releases Ca2+ as a result of different stimulations. 5. Explain the role of Cajal cells and electrical activity of GI smooth muscle (slow waves and spikes) on GI motility 6. Describe the neural regulation of GIS by explaining the special features of the enteric nervous system (myenteric and submucosal) and its relationship with autonomic nervous system. 7. Explain the regulation of splanchnic blood circulation during the postprandial and fasting time. 8. List the factors that control different mechanisms of GI functions (hormonal, neural, paracrine effects) 2 The digestive system Digestion & absorption Immune defense Reflexive responses 3 ACCESORY ORGANS DIGESTIVE TRACT (ALIMENTARY) CANAL 4 Digestive Processes Movement of food (motility) – Propulsion (e.g. swallowing, peristalsis) – Mixing – (e.g. segmentation) Secretions Digestion – Chemical Digestion – Mechanical Digestion (e.g. chewing) Absorption – Active – Passive 5 Overview of Digestive Processes The mouth and oropharynx are responsible for chopping food into small pieces, lubricating it, initiating carbohydrate and fat digestion, and propelling the food into the esophagus. The esophagus acts as a conduit to the stomach. The stomach temporarily stores food and initiates digestion by churning and by secreting proteases and acid. The small intestine is the primary site for the absorption and digestion. The large intestine reabsorbs fluids and electrolytes and stores the fecal matter before removal from the body. 6 Overview of Digestive Processes The accessory glands and organs include the salivary glands, pancreas, and liver. Salivary glands – saliva includes enzymes, electrolytes & mucus The pancreas secretes digestive enzymes into the duodenum, secretes HCO3− to neutralize gastric acid. The liver secretes bile, the gallbladder stores for future delivery to the duodenum during a meal. Bile contains bile acids that play a key role in the fat digestion. 7 The GI tract plays important role in fluid and electrolyte balance Alimentary tract handles around 9-10 L of fluid/day: 1000 g solid + 1500 ml fluid intake 8500 ml total secretion volume 9850 ml of the mixture is absorbed 150 ml liquid + 50 g solid EXCRETED Physiology and Anatomy 3rd ed., Clancy & McVicar, Hodder Education, 2009 General Characteristics of the Digestive Tract Wall of the GI tract consist of four leyers: 1. Mucosa (mucous membrane): epithelium + connective tissue (lamina propria) + small amount of smooth muscle (muscularis mucosae) + glands which secrete mucus and digestive enzymes. The mucosa protects the tissues beneath it and carries on secretion and absorption. Human Physiology: An Integrated Approach 6e Pearson 2014 2. Submucosa: loose connective tissue + glands + blood vessels + lymphatic vessels and nerves. Its vessels nourish surrounding tissues and carry away absorbed materials. 9 Peyer’s patches - Gut associatated lymphoid tissue (GALT) Muscularis mucosaecontraction alters the effective area for absorption Submucosal & myenteric plexus Human Physiology: An Integrated Approach 6e Pearson 2014 3. 4. Muscular layer : two coats of smooth muscle tissue (circular & longitudinal). Inner circular layer  diameter of the tube changes Outher longitudinal layer  length of the tube changes Serous layer (visceral peritoneum): epithelium + connective tissue Protect & secrete serous fluid which moistens and lubricates the tube’s outer surface  organs within the abdominal cavity slide freely against one another 10 The peritoneum also forms sheets of mesentery that holds the intestine in place In some regions, the mucosa is folded, with tiny projections that extend into the lumen, of the digestive tube  increase the absorptive surface area. 11 Different regions of GI tract exhibit differentiations in the layers Human Physiology: An Integrated Approach 6e Pearson 2014 Stomach has an incomplete third muscle layer between the submocosal layer and circular muscle – oblique muscle layer 12 The GI tract is approximately 8 m* long and has a surface area of 186 m2. Largest area of contact between internal environment and outside world (potential direct contact with infectious, toxic, and immunogenic material) Largest collection of lymphoid tissue – gut associated lymphoid tissuse (GALT) * Measurement of intestinal length made during autopsies, because the longitudinal muscles of the intestinal tract relax it is measured 2 times longer. (Normal length is approximately 450 cm). 13 14 The GI tract also contributes to immune function the GI tract has the largest area of the body in potential direct contact with infectious, toxic, and immunogenic material. Mucosal immune system or Gut-associated lymphoid tissue (GALT) consist of both organized aggregates of lymphoid tissue (e.g. Peyer’s patches) and immune cells are scattered throughout the mucosa. GALT has two primary function: (1) to protect against potential microbial pathogens (2) to permit immunological tolerance to potentially immunogenic dietary products and bacteria that normally reside in the lumen of large intestine. 15 Motility of GI tract Peristalsis - progressive waves of contraction and relaxation of muscles in the organ walls. (2-25 cm/sec) Waves of muscular contractions move along the wall of the stomach from one end to the other. These waves mix food with digestive juices that the mucosa secretes. Peristalsis in esophagus propels material from pharinx to stomach Peristalsis {peri-, surrounding +stalsis, contraction} Churning 16 Motility of GI tract Segmental contraction in the small intestine, aids mixing movements by alternately contracting and relaxing the smooth muscle in nonadjacent segments of the organ. Propel content for short distances 17 Segmental contractions in small intestine- distention of small intestine with chyme elicits either regularly or irregulary spaced contractions (they form segments). Segmentation contractions “chop” the chyme two to three times per minute, in this way promoting progressive mixing of the food with secretions of the small intestine. Motility of GI tract during fasting state Migrating motor complex (MMC) “housekeeping” function Between meals, when the GI tract is largely empty, a series of contractions begins in the stomach and passes slowly from section to section (each series 90 min). This movement sweeps food remnants and bacteria out of the upper GI tract and into the large intestine. Initiated by cyclic secretions motilin during fasting. Ingestion food immediately stops motilin secretions and MMC 19 Different regions of GIS exhibit different types of contraction Sustained/tonic contractions (up to hours): e.g. sphincters Rhythmic/phasic contractions (a few sec.): contraction & relaxation cycle e.g. intestine 20 Motility in the GI tract 1. 2. Movement of the food (propelling) Mechanical mixing (churning, segmentation) – to break food into small particles – to maximize exposure of the particles to digestive enzymes 3. Reservoir function (the stomach and large intestine hold the luminal content) This is made possible by sphincters that separate the organs of the GI tract.  Regulated by  autonomic nervous system  hormones  paracrine* signals If food moves too rapidly – there will be no enough time for everything in the lumen to be digested and absorbed. *A paracrine signal {para−, beside + krinen, to secrete} is a chemical that acts on cells in the immediate vicinity of the cell that secreted the signal Human Physiology: An Integrated Approach 6e Pearson 2014 21 Neurocrine: Refers to both endocrine messengers that influence neurons and messengers that are released from neurons which have endocrine effects 22 Contractile tissue of GI tract is smooth muscle, except for pharynx, upper 1/3 esophagus, and external anal sphincter. The cells are electrically coupled (electrical stimulation of one cell is followed by stimulation of adjacent cells), often has spontaneous action potentials. 23 Human Physiology: An Integrated Approach 6e Pearson 2014 Modulation of intestinal smooth muscle contraction is largely a function of Ca2+ 24 Electrical activity in GI smooth muscles Membrane potential of the smooth muscles can either oscillate in a subthreshold range at a low frequency (several per minute, slow wave activity) or reach a threshold for initiating a true action potential. Human Physiology: An Integrated Approach 6e Pearson 2014 Slow wave activity occurs as voltage-gated Ca2+channels depolarize the cell and increase in intracellular [Ca2+] , the opening of K+ channels repolarize the cell 25 INTERSTITIAL CELLS OF CAJAL (the pacemakers of GI tract) They are located in circular and longitudinal muscle layers and in submucosal layer of GI tract from esophagus to anus. These slow waves are transmitted to muscle cells and waves spread by gap junctions. Slow waves: Intrinsic electrical activity, slow fluctuations in membrane potential of smooth muscle cells. Amplitude of the waves: 5-15 mV Frequency: GI segments have characteristic slow wave frequency - Stomach : 3-5/min; Duodenum : 12/min -Terminal ileum : 8-9/min ; -Large intestine : 1-5 /min Excitation-contraction coupling in the gut Excitation does not increase frequency of the characteristic slow intrinsic rhythm but increase the amplitude of the slow waves. Action potentials (spike potentials): When stimulated, the amplitude of the slow waves increase  the time window above action potential threshold (dashed line on the figure) extends  more action potentials occur increased muscle tone. Berne and Levy Physiology 6th edition Inhibition decreases the amplitude of the slow waves, action potentials does not occur  No contraction MODULATION of ELECTRICAL ACTIVITY IN GIS Stretch is a main stimulus for spike potentials. Inhibition by * ---- dashed line shows the threshold for action potentials Many neurotransmitters and /or neurocrine also modulates the spike generation. REGULATION OF GASTROINTESTINAL FUNCTION The enteric nervous system (ENS) is a “minibrain” with sensory neurons, interneurons, and motor neurons The ENS consists of ∼100 million neurons, roughly the number in the spinal cord or in the rest of the entire autonomic nervous system The submucosal (or Meissner's) plexus is found in the submucosa only in the small and large intestine. The myenteric (or Auerbach's) plexus is located between the circular and longitudinal muscle layers throughout the GI tract from the proximal end of the esophagus to the rectum. 30 Hierarchical loop in ANS The ENS is an independent system consisting of afferent neurons, interneurons, and motor neurons. One level up, the autonomic ganglia control the autonomic end organs, including the ENS. One further level up, the spinal cord controls certain autonomic ganglia and integrates response among different levels of the spinal cord. The brainstem receives inputs from visceral afferents and coordinates the control of all viscera. Finally, forebrain CNS centers receive input from the brainstem and coordinate the activity of the ANS via input to the brainstem. 31 Neural regulation of GIS  Enteric nervous system (ENS) also known as Intrinsic Nervous System of GIS Myenteric (Auerbach) plexus The 2 plexuses are linked by neural transmission Submucosal (Meissner) plexus  Autonomic nervous system (extrinsic nerves of GI tract) Parasympathetic nervous system (PNS) Sympathetic nervous system (SNS) Autonomic nerves include both efferent and afferent fibers. ENTERIC NERVOUS SYSTEM (ENS) consists of ∼100 million neurons Myenteric (Auerbach’s) plexus Located between circular & longitudinal muscle layers Coordinates activity of muscular layers. Submucosal (Meissner’s) plexus Innervates epithelial cells and muscularis mucosae + mucosal, deep muscular, and tertiary plexus Guyton & Hall: Textbook of Medical Physiology 12e The ENS is able to function autonomously, independent of efferent signals from the CNS. 33 In addition to submucosal and myenteric plexuses that have ganglia, three others— mucosal, deep muscular, and tertiary plexus— are also present. The ENS consists of sensory neurons, interneurons, and motor neurons. Some sensory signals travel centrally from the ENS. Both the parasympathetic and the sympathetic divisions of the ANS modulate the ENS. ORGANIZATION OF THE GASTROINTESTINAL SYSTEM Binder, Henry J., Medical Physiology, CHAPTER 41, 883-894 Copyright © 2012 Copyright © 2012 by Saunders, an imprint of Elsevier Inc. EFFECT OF AUTONOMIC NERVOUS SYSTEM ON GI TRACT Parasympathetic discharges enhances the activity of GI tract through Vagal nerve (esophagus, stomach, gallbladder, pancreas, small intestine, proximal part of the colon) and Pelvic nerves from S2-S4 segments the distal part of the colon (transverse, descending, and sigmoid colons) and the anorectal region Preganglionic neuron release ACh Post ganglionic neuron is an enteric neuron ACh Some of the postganglionic neurons release ACh Some of them release peptides like Substance P and VIP (vasoactive intestinal peptide) AUTONOMIC NERVOUS SYSTEM EFFECT ON GI TRACT T5- L1 segments ACh NE NE NE NE Parasympathetic outflow (efferents) influence the GI tract through ENS modulation. AUTONOMIC NERVOUS SYSTEM EFFECT ON GI TRACT Sympathetic discharges inhibits the activity of GI tract (by inhibiting exocrine secretions and motility; by contraction of sphincters; vasoconstriction of GI tract blood vessels) through superior cervical ganglion and prevertebral ganglia (celiac, superior & inferior mesenteric ganglia) Preganglionic neuron release ACh ACh NE AUTONOMIC NERVOUS SYSTEM EFFECT ON GI TRACT T5- L1 segments Post-ganglionic fibers ACh NE NE NE NE Sympathetic outflow (efferents) influence the GI tract both directly (on blood vessels, exocrine glands, smooth muscles) and indirectly through ENS modulation. 39 AFFERENT NEURONS Sensory neurons in gut wall transmit signals about: 1- Degree of stretch, contractile states of the muscles 2- Chemical features (Osmolality, pH, existence of several nutrients) of the luminal content 3-Pain Both parasympathetic and sympathetic nerves carry the fibers of sensory nerves (mechanoreceptors and chemoreceptors of GI tract) toward CNS. How does the gut “know” what’s in a meal? GI tract has the ability to sense and respond specifically and differentially to the composition of a meal. Fats and proteins do not stimulate the same endocrine and exocrine responses as a meal of pure carbohydrate. Traditional sensory receptors, such as osmoreceptors and stretch receptors do not respond to biomolecules. Some of the endocrine cells in the gut express the same type of receptors as taste buds. 41 Secretions Water & electrolytes Acid Bicarbonate Digestive enzymes Mucus – viscous secretion composed primarily of glycoproteins 42 Mucus Primary function – protective coating – lubrication     Parasympathetic stimulation Enteric nervous system Cytokines Infection and inflammatory process increase secretion  fortify the protective barrier 43 Average pH throughout GI tract pH Mouth & esophagus 6 -7 Stomach 1,5 – 3,5 Small intestine 7-8 Large intestine 6-7 Normal pH levels in the lumen of a digestive compartment corresponds to the optimal pH ranges for the maximal activity of the digestive enzymes or the receptive proteins for absorption of that particular compartment. 45 GASTROINTESTINAL HORMONES  Gastrin  Cholesystokinin (CCK)  Secretin  Vasoactive intestinal peptide (VIP)  GIP (Gastric inhibitory peptide / *glucose dependent insulinotropic peptide)  Glucagon like peptide -1 (GLP-1)  Motilin  Somatostatin 46 Gastrointestinal Hormones 47 Secretions Stimuli for secretion Site of secretion Action Inhibition of secretion Gastrin (endocrine) - Proteins and amino acids in the stomach - Parasympathetic stimulation (via GRP) G cells in stomach & small intestine Stimulates - acid secretion (ECL & parietal cells) - motility in stomach, small & large intestines -Acidity in the stomach - somatostatin CCK (endocrine) + neurotransmitter like effects Lipids and proteins in the small intestine I cells in the small intestine Stimulates - enzyme secretion from pancreas, - contraction of gallbladder, - motility in stomach, small & large intestines Satiety signal Relax sphincter of Oddi Inhibits emptying of stomach Secretin (endocrine) Acid in the small intestine S cells of the small intestine Stimulates –bicarbonate secretion from pancreas - bicarbonate secretion from liver Inhibits – acid secretion and emptying of stomach Motilin (endocrine) Periodic release during fasting Endocrine cells of upper GI tract Stimulates - Gastric and intestinal smooth muscle cells, Migrating motor complex Histamine (paracrine) Vagal stimulation (ACh), Gastrin ECL cells (& Mast cells) Stimulates parietal cells for acid secretion Ingestion of food Secretions Stimuli for secretion Site of secretion Action GIP (gastric inhibitory / “glucose dependent insulinotropic peptide) Carbohydrate & fat in small intestine K cells in small intestine (duodenum & jejunum) Stimulates - insulin secretion from pancreas High doses inhibits gastric secretions and motility Somatostatin (paracrine, endocrine) Acids in the lumen D cells in the GI tract,  cells of pancreas Inhibits gastric acid secretion (inhibits parietal and ECL cells) Inhibits endocrine & exocrine pancreatic secretions and bile secretion Peptide YY (endocrine) Secretion increase after a meal, presence of fat GI tract (especially ileum & colon) Satiety signal Inhibits enzyme and fluid secretions from pancreass Glucagon like peptide (GLP-1) (endocrine) carbohydrate or protein in small intestine L cells in small intestine Stimulates - insulin secretion Inhibits intestinal motility Vasoactive intestinal peptide (VIP) (neurocrine/ neurotransmitter) Enteric nervous system Relaxation of smooth muscle Stimulates – secretions from GIS - bicarbonate secretion from liver Gastrin releasing peptide (GRP) (neurocrine/ neurotransmitter) Vagal nerve endings Stimulates – gastrin release from G cells Inhibition of secretion Vagal stimulation (ACh) Gastrointestinal Blood Flow—Splanchnic Circulation All the blood that courses through the gut, spleen, and pancreas then flows immediately into the liver by way of the portal vein. In the liver, the blood passes through millions of minute liver sinusoids and finally leaves the liver via hepatic veins that empty into the vena cava of the general circulation. hepatic cells absorb and store temporarily from 50% to 75% of the nutrients (except the fats). Also, much chemical intermediary processing of these nutrients occurs in the liver cells. 50 Regulation of blood flow The blood flow in each area of the gastrointestinal tract, as well as in each layer of the gut wall, is directly related to the level of local activity. – several vasodilator substances (hormones like cholecystokinin, and vasoactive intestinal peptide, kinins) are released from the mucosa of the intestinal tract during the digestive process. – decreased O2 concentration in the tissue can increase intestinal blood flow – neural control 51 Nervous control of blood flow Sympathetic stimulation causes intense vasoconstriction of the arterioles and greatly decreased blood flow. After a few minutes of this vasoconstriction, the flow often returns to near normal by means of a mechanism called “autoregulatory escape.” – the local metabolic vasodilator mechanisms that are elicited by ischemia override the sympathetic vasoconstriction Stimulation of the parasympathetic NS increases local blood flow as well as glandular secretion. This increased flow probably results secondarily from the increased glandular activity, not as a direct effect of the nervous stimulation. 52