Enteric nervous system regulation of the GI tract: motility and function

Enteric Nervous System Regulation of the GI Tract

Learning Outcomes

• By the end of this lecture you will:
• Know what makes up the enteric nervous system
• Understand the role played by the enteric nervous system in regulating the gastrointestinal tract
• Describe examples of both long and short enteric nervous system reflexes and their role in regulating motility and function of the gastrointestinal tract

Functions of the GI Tract

Ingestion, digestion, absorption and Excretion . These functions are aided by: - GI motility - GI secretion . Both motility and secretion are regulated by hormones and nerves . GIT functions are regulated by 3 mechanisms - Neural - Endocrine - Paracrine

Neuronal Regulation of the GI Tract

• There are 2 types of innervations:
  • Intrinsic innervation
    • Consists of plexus of neurons and synapses (ganglia), located within the wall of the GI tract
    • Called the Enteric Nervous System and it consists of:
      • Submucosal plexus
      • Myenteric plexus
  • Extrinsic innervation
• Nerve supply from the Autonomic Nervous system both from the Parasympathetic and Sympathetic systems

Sympathetic and Parasympathetic Systems

Sympathetic system: Noradrenaline Parasympathetic system: Acetylcholine (Ach) EFFECTS ACTION ACTION EFFECTS Mid brain B(+) salivary glands „Poňš medulla Salivary glands (+) IX X Gut wall (+) a (+) ₿2 (-) gut blood vessels Spinal cord Gut sphincters (-) B1/2 (-) α (+) gut wall, sphincters adrenaline Adrenal medulla Rectum (+)defaecation Gut secretions (+) Pancreas (+) (+) secretion Cranial nerves VII

General GI Effects

• Sympathetic
  • Decrease secretion
  • Decrease motility
  • Decrease blood flow
  • Increase sphincter tension
• Parasympathetic
  • Increase muscle contraction
  • Increase secretion
  • Increase blood flow

Enteric Nervous System Components

• Network of nerve fibers and ganglion cell bodies only associated with the alimentary canal consisting of
  • Afferent sensory neurons
  • Efferent neurons to smooth muscle and secretory cells
  • Interneurons

Organization of Enteric Nervous System

Serosa Organization of enteric nervous system Longitudinal muscle (outer layer) Myenteric plexus Circular muscle (inner layer) LUMEN Submucous plexus Submucosa Mucosa Chemoreceptors Mucosa Mechanoreceptor C O O Submucosal plexus Blood vessel Circular muscle Myenteric plexus Longitudinal muscle layer Serosa

Submucosal Plexus (Meissner's Plexus)

• Also called Meissner's plexus
• Situated between the submucosa and the circular muscle
• Controls mainly the secretory functions of GIT both endo- and exocrine secretion and local blood flow
• Associated with mechano- and chemoreceptors

Myenteric Plexus (Auerbach's Plexus)

• Also known as Auerbach's plexus
• Situated between the circular muscle and the longitudinal muscle
• Controls mainly the motor (contraction of smooth muscle) functions of GIT
• Has both parasympathetic and sympathetic input

Autonomic Reflexes

Central integration Medial and ventral forebrain Nucleus of the solitary tract Visceral sensory input Reflex activity Visceral motor response Hormonal and behavioral response

• Autonomic reflex control:
  • Afferent sensory input
  • Central integration
  • Efferent response
• Sensory input from:
  • Mechanoreceptors
  • Chemoreceptors
  • Thermoreceptors
  • nociceptors

Long and Short Reflexes

• Long Reflexes
  • Integrated within in the CNS
  • May originate in or outside of the GI tract
  • Feed forward & emotional reflexes are initiated and integrated entirely outside the GI tract
  • Called cephalic reflexes
• Short Reflexes
  • Integrated within the enteric nervous system
  • Initiated by changes in pH, distension, osmolarity, products of digestion
  • Submucosal plexus contains the sensory neurons
  • Afferent information to ganglia
  • Efferent information to submucosal and myenteric plexuses for control of secretion, motility, etc

Local Reflex Arc of Enteric Nervous System

Interneuron Motor neuron: Excitatory or Inhibitory to: Sensory neuron

• Smooth muscles
• Gland cells,
• Blood vessels,
• Endocrine cells Receptor

Neurotransmitters of the Enteric Nervous System

• Many neurotransmitters are released by the neurons of submucosal and myenteric plexus
  • Acetylcholine
  • Stimulate motility and secretion
  • Norepinephrine
• Inhibit motility and secretion
  • 5-Hydroxytryptophan (serotonin)
  • Motility, secretion and pain sensation
  • Vasoactive intestinal peptide (VIP)
  • Increases intestinal secretions
  • Increases pancreatic secretions
  • Relaxation of smooth muscles

Additional Neurotransmitters

• Nitric oxide
  • Relaxation of smooth muscles, inhibits motility
• Substance P
  • Stimulate motility
• Gastrin releasing peptide (GRP)
  • Increases gastrin secretion

Neural Pathways in the GI Tract

Mucosa ACh or peptides Muscularis mucosae Endocrine cells Secretory cells NE NE ACh Submucosal plexus NE ACh or peptides NE NE Circular muscle ACh Myenteric plexus NE ACh or peptides Longitudinal muscle Vagus nerve or pelvic nerve ACh - Acetyl choline NE - Nor epinephrine Sympathetic ACh ganglia Parasympathetic Sympathetic 12

Reflex Integration

• Long reflexes are integrated in the CNS. Some long reflexes originate outside the GI tract, but others originate in the enteric nervous system.
• Short reflexes originate in the enteric nervous system and are carried out entirely within the wall of the gut. Cephalic phase of digestion (feedforward) KEY Stimulus Target Sensor Tissue response Integrating center Output signal The cephalic brain Sympathetic and parasympathetic neurons Local stimuli: . Changes in GI motility Distention Presence of food Osmolarity Acid Sensory receptors and neurons Inter- neurons Enteric neurons Smooth muscles, exocrine cells . Release of bile and pancreatic secretions . Enzyme, acid, and bicarbonate synthesis/release Enteric nervous system "The little brain" Secretory cells of the stomach and small intestine Gl peptides Brain Hunger/satiety 1 + Insulin Endocrine pancreas ¥ Glucagon

Gastric Secretion Reflexes

(sight, smell, etc.) 1 Sensory receptorsFood! Food Medulla oblongata Stomach Preganglionic parasympathetic neuron in vagus nerve Lumen of stomach Gastric mucosa LONG REFLEX Sensory input Enteric plexus SHORT REFLEX Distension or peptides and amino acids initiate short reflexes. Postganglionic parasympathetic and intrinsic enteric neurons Effector cells Secretion and motility Negative feedback pathway Histamine ECL cell H+ Parietal cell 3 Enteric sensory neuron Pepsin Pepsinogen Chief cell 1 Input via vagus nerve Lumen of stomach Amino acids or peptides Enteric sensory neuron G cell Gastrin 2 D cell Somatostatin 4 ------------- Copyright 2009 Pearson Education, Inc. 1 Food Gastric mucosa 1 Food or cephalic reflexes initiate gastric secretion. 2 Gastrin stimulates acid secretion by direct action on parietal cells or indirectly through histamine. 3 Acid stimulates short reflex secretion of pepsinogen. 4 Somatostatin release by H+ is the negative feedback signal that modulates acid and pepsin release.

Long Reflex Example: Gastric Extrinsic Reflex

• Gastric extrinsic reflex
  • The stomach responds to sight, smell, taste or thought of food
  • Mental inputs converge on the hypothalamus, to the medulla oblongata
  • Vagus nerve fibres from medulla to the stomach
  • Acetylcholine through M3 receptors directly stimulates HCI release from parietal cells
  • Gastrin releasing peptide released from vagal nerves increases gastrin release from G cells
  • Gastrin directly stimulates HCI release from parietal cells
  • Gastrin also stimulates histamine release from ECL cells which then also stimulates HCI release
  • Acetylcholine through M3 receptors stimulates Chief cells to release pepsinogen
  • Receptors in the duodena; mucosa are sensitive to acid and distension, impulses over sensory and motor fibres in the vagus nerve cause a reflex inhibition of gastric peristalsis, enterogastric reflex

Phases of Gastric Secretion

"Food! Medulla oblongata L. Cephalic Phase of Gastric Secretion (approx. 30% of total) (initiated by brain) 2. Gastric Phase of Gastric Secretion (approx 60% of total) (initiated by gastric events) vagus nerve vagus nerve FOOD O- HCl Distension Peptides circulation G gastrin gastrin TO HCl circulation GCNS NTS taste, smell, sight chewing, fear, emotional stress Vagus nuclei DMN Vagus nerve Parietal cell ACH ECL cell ACH PACAP G + + H + ACH G GRP G + D cell G cell Gastrin

Long Reflex Example: Intestinal Intrinsic Reflex

• Intestinal intrinsic reflex
  • Duodenum responds to and moderates gastric activity
  • Initially enhances gastric acid secretion
  • Mechanoreceptors detecting stretch and chemoreceptors detecting pH and lipids and carbohydrates trigger the enterogastric reflex to:
  • Inhibit vagal nuclei
  • Stimulate sympathetic neurons to inhibit peristalsis in stomach wall
  • Release secretin and cholecystokinin to inhibit gastric activity

Regulation of Gastric Activity

Food into stomach Acid secretion STOMACH Pepsin and lipase secretion Gastric motility Chyme into small intestine Enteric nervous system SMALL INTESTINE Hyper- osmotic solution Carbohydrates Fats, proteins Acid ? Endocrine cell GIP GLP-1 CCK Secretin PANCREAS Insulin secretion Pancreatic enzyme secretion Pancreatic bicarbonate secretion Copyright @ 2009 Pearson Education, Inc.