Gastrointestinal Physiology Lecture 27 PDF

GASTROINTESTINAL PHYSIOLOGY Dr. Kelly Roballo LERNING OBJETIVES 1. Describe the major structures of the gastrointestinal system. 2. Identify general mechanics of gastrointestinal motility. 3. Describe the physiological mechanisms which enable the Gastrointestinal Smooth muscle to function as a syn...

GASTROINTESTINAL PHYSIOLOGY Dr. Kelly Roballo LERNING OBJETIVES 1. Describe the major structures of the gastrointestinal system. 2. Identify general mechanics of gastrointestinal motility. 3. Describe the physiological mechanisms which enable the Gastrointestinal Smooth muscle to function as a syncytium. 4. Describe Myenteric and Submucosal Plexuses. 5. Identify the anatomical characteristics of the enteric nervous system and function of the myenteric and submucosal plexuses. 6. Identify the process of autonomic control of the GI Tract function. 7. Define the hormonal and nervous control of GI motility and blood flow. 8. Compare and contrast the neuronal afferent and autonomic efferent pathways that innervate the enteric nervous system regulating the functions of the gastrointestinal tract. 9. Differentiate the major neurotransmitters and hormones secreted from the gastrointestinal tract. General Principles of Gastrointestinal Motility ◦ Role of Motility ◦ ◦ ◦ ◦ Propulsion throughout the GI tract and beyond Mixing with digestive juices Grinding and fragmenting Storage (stomach and colon) ◦ Types of muscle ◦ Skeletal ◦ Smooth ◦ Motility patterns differ from region to region in different phases: ◦ ◦ ◦ ◦ ◦ ◦ Oropharyngeal: swallowing Esophageal: peristalsis (primary and secondary) Gastric: propulsion and retropulsion Small intestinal: peristalsis Large intestinal: mass movements, defection Interdigestive phase: migrating motor complex ◦ There is a “program library” of characteristic patterns initiated by the ENS ◦ Movement is highly regulated and coordinated with other functions ◦ Regulation and coordination of movement has neural and hormonal influences involving complex reflexes Function ◦ Clinical correlation: Malformations?? Digestive processes Secretion/Excretion Motility Absorption The structure of the wall of the GI tract The nervous system of the GI tract ◦ The extrinsic component is the sympathetic and parasympathetic innervation of the gastrointestinal tract. The intrinsic component is called the enteric nervous system. The extrinsic nervous system of the GI tract Intrinsic nervous system of the GI tract Gastroparesis ◦ Delayed gastric emptying with no outlet obstruction. ◦ Occurs in post-op patients, Diabetics and after viral illness. ◦ S/Sx: ◦ Nausea ◦ Vomiting ◦ Bloating ◦ Early satiety ◦ Treatment: ◦ Metaclopromide (Reglan) ◦ Domperidone ◦ Erythromycin Neurotransmitters and Neuromodulators in the Enteric Nervous System Opioid-Induced Constipation ◦ Opioids (morphine, hydrocodone, oxycodone etc.) can cause constipation by decreasing the motility of the GI tract. ◦ This is due to direct inhibition of Ach receptors in the GI tract. ◦ Common after surgery, must distinguish from post-op ileus. ◦ Treatment: ◦ Stimulates- Senna/Biscodyl ◦ Laxatives- Miralax, Magnesium Citrate ◦ Lubiprostone (Amitiza) Postoperative Ileus ◦ Decreased motility of the GI tract after abdominal surgery. ◦ Peristalsis impaired at different points along GI tract. ◦ Complex mechanism but essentially impairs the enteric nervous system. ◦ S/Sx: ◦ Bloating ◦ Pain ◦ Absent/hypoactive bowel sounds ◦ Constipation ◦ Treatment: ◦ Peripheral opioid inhibitors: Relistor, Entereg GI Reflexes ANS Components of a Reflex ANS ◦ Stimuli ◦ Sensory (afferent) neurons ◦ Interneurons to relay information ◦ Secretomotor (efferent) neurons to exert response stimulus ◦ Effector cells to carry out the demands Types of reflexes in the GI tract • Short reflexes: contained entirely in the wall of the GI tract (peristalsis) • Long reflexes: involves extrinsic nervous system +/- CNS • Vagovagal reflexes: reflex with afferent and efferent limbs in the vagus nerve Key Reflexes in the GI Tract Reflex Purpose Afferent Efferent Swallowing reflex Propel food to esophagus Ingested material in pharynx Swallow Receptive Relaxation Accommodate ingested meal in the stomach Distension of the stomach Relaxation of the proximal stomach Peristaltic Reflex Propulsion of a bolus through the intestine Distension of the intestine by the bolus Contraction proximal to the bolus, relaxation distal to the bolus Gastrocolic Prepare the colon for the next meal Distension of the stomach Increased motility in the colon Enterogastric Slow delivery of chyme to allow for digestion and absorption Acid and chyme in the duodenum Reduced gastric emptying Colonoileal (“Ileal Brake”) Slow delivery of contents to large intestine Lipid in the proximal colon Contraction of the ileocecal sphincter Rectosphincteric Reflex Anal sampling, can lead to defecation Increased pressure due to contents in the rectum Relaxation of the internal anal sphincter Control Mechanisms of the GI Tract: Basics Three principal mechanisms of control: Endocrine control: • • Occurs when a substance (hormone or candidate hormone) is released by enteroendocrine cells into the bloodstream and circulates to its target cell. Benefits: can affect multiple targets and be highly regulated Paracrine control: • Occurs when a substance is released from a cell and diffuses the interstitial space to its target organ • Some substances can have both endocrine and paracrine function (somatostatin) • Benefits: can act quickly and locally Neurocrine control: • Occurs when a substance released from a neuron (neuron) exerts its effect on a target cell. • Involves reflexes • Neuron to act on a target cell. • Benefits: can act quickly over short and long distances Regulatory molecules: Endocrine regulation Hormones ◦ Released in the blood and is independent of neural control ◦ 4 major hormones: ◦ Gastrin, CCK, Secretin, GIP (Glucose-dependent Insulinotropic Polypeptide) Candidate Hormones ◦ Function like hormones but don’t meet all the criteria ◦ 2 candidates hormones ◦ motilin, GLP-1 (Glucagon Like Peptide-1) Hormones and candidate hormones participate in endocrine regulation “Hormone families”: • Molecules whose active fragments are structurally related (homologues) • 2 Key families: Gastrin-CCK and SecretinGlucagon Regulatory molecules: Paracrine regulation • Paracrine substances diffuse through the interstitium to reach their target • Enteroendocrine cells or Enterochromaffin-like cells release paracrines into the lamina propria • Key paracrines in the GI tract: • Histamine, serotonin*, somatostatin* *somatostatin can also function as a hormone, serotonin can function as a neurocrine Regulatory Molecule Tables – Adapted from Costanzo Target Action Gastrin Family: Gastrin-CCK Stomach (G cells in the antrum) AA’s in stomach Stomach distension Vagal stimulation (GRP) Stomach ↑ H+ secretion Stimulates growth of gastric mucosa ↑ antral contractions Cholecystokinin (CCK) Family: Gastrin-CCK Duodenum and Jejunum (I cells) Fat and protein digestion products in small intestine Gallbladder Pancreas Stomach Contraction of gallbladder, relaxation of sphincter of Oddi ↑Pancreatic enzyme secretion and bicarbonate ↓ Gastric emptying (inhibits gastric motility) Stimulates growth of pancreas and gallbladder Secretin Family: SecretinGlucagon Duodenum (S cells) H+ in the duodenum Fatty acids in the duodenum Pancreas Stomach ↑ Pancreatic HCO3- secretion ↑ Bile duct HCO3- secretion ↓ Gastric H+ secretion Body water homeostasis Glucose-dependent insulinotropic polypeptide (GIP) Family: SecretinGlucagon Duodenum and jejunum Glucose, amino acids and fatty acids in small intestine Pancreas ↑ insulin secretion ↓ Gastric H+ secretion (inhibits gastric motility) Motilin Duodenum and jejunum Fasting Stomach Duodenum ↑ GI motility (migrating motor complex) GLP-1 Jejunum and ileum Glucose in small intestine Pancreas ↑ insulin secretion ↑ satiety Histamine (paracrine) Enterochromaffin-like cells (ECLs) Mast cells ACh, Gastrin, Local factors Local Factors Stomach Intestines ↑ Gastric H+ secretion ↑ Intestinal secretion Serotonin (paracrine) Enterochromaffin-like cells (ECLs) Mast cells, Neurons* Distension of gut wall Interacts with ENS Indirectly excitatory; increases motility and secretion, water regulation Somatostatin (paracrine and endocrine) Stomach, intestine (D cells) Pancreas (delta cells) Hypothalamus Decreased pH in lumen Multiple other stimuli Stomach Multiple locations ↓ Gastric H+ secretion Inhibits many GI hormones leading to inhibition of secretion, relaxation of stomach and gallbladder, vasoconstriction PARACRINES Stimulus CANDIDATES Source HORMONES Molecule Hunger and Satiety ◦ Molecules that decrease appetite: ◦ ◦ ◦ ◦ Prader-Willi Syndrome What hormone may be elevated? Leptin Insulin GLP-1 Peptide YY ◦ Molecule that increases appetite: ◦ Ghrelin (levels rise before meals and fall after meals. Fasting results in elevated ghrelin levels) ◦ Key regions of the hypothalamus involved in appetite: ◦ Satiety center ◦ Feeding center ◦ Arcuate nucleus in the floor of 3rd ventricle integrates signals about hunger and satiety Characterized by an increased appetite, hyperphagia, and obesity Associated with gene deletions on chromosome 15 Patients have ghrelin levels 3 times higher than controls GI Vasculature ◦ Arteries supply abdominal viscera come from three main arteries off the aorta ◦ Celiac ◦ Superior mesenteric ◦ Inferior mesenteric ◦ Veins draining these organs travel in the portal circulation to the liver ◦ This allows the liver to process whatever has been absorbed ◦ Hepatic veins drain the liver and blood returns to the heart ◦ Organs in the head and thorax (salivary glands, cervical and thoracic esophagus) and the lower part of the rectum and anus do NOT drain into the portal system. Regulation of GI Vasculature: Increase in Blood Flow ◦ Local increased activity can lead to increased flow: – Increased secretion or absorption leads to increased mucosal and submucosal flow – Increased motility leads to flow in the muscularis externa – Several mediator molecules can increase flow – Local injury can lead to histamine release and vasodilation ◦ There is indirect increase in blood supply to the GI tract by the parasympathetic system Regulation of GI Vasculature: Decrease in blood flow When would you want decreased flow to the GI tract? Exercise • Decrease flow to GI tract • Increase flow to skeletal muscle and heart Circulatory Shock • Minimal flow to GI tract • Blood diverted to vital organs Main Mechanism: • Sympathetic nervous system causes vasoconstriction of vessels to GI tract • Somatostatin can also cause vasoconstriction Clinical Correlation: Octreotide, a somatostatin analog, is given to patients with bleeding esophageal varices caused by cirrhosis to stop the bleeding The Immune System, Lymphatics and the Defense of GI Tract Lymphatics in the intestines aid in fat absorption Gastric Acid Mucous Epithelial Barrier Lacteal Gut flora: • Are protective • Aid in digestion • Synthesize Vitamin K The gut microbiome is a hot topic in medicine Lymphatic nodules and diffuse immune cells Kupffer cells in the liver THANK YOU