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Structure of the Gastrointestinal Tract

• The gastrointestinal tract includes the mouth, esophagus, stomach, small intestine (duodenum, jejunum, and ileum), large intestine, and anus arranged linearly.
• Salivary glands, pancreas, liver, and gallbladder are other important structures of the gastrointestinal tract and serve secretory functions.
• The gastrointestinal tract wall has mucosal and serosal surfaces.
• The mucosal surface faces the lumen.
• The serosal surface faces the blood.
• The gastrointestinal wall layers (from lumen to blood) include:
  • Mucosal layer: Consisting of epithelial cells, lamina propria, and muscularis mucosae
  • Epithelial cells: Specialized for absorption and secretion
  • Lamina propria: Primarily connective tissue, including blood and lymph vessels
  • Muscularis mucosae: Smooth muscle cells that change the shape/surface area of the epithelial cell layer upon contraction
  • Submucosal layer: Contains collagen, elastin, glands, and blood vessels
  • Circular and longitudinal muscle: Two layers that provide motility, interposed between the submucosa and serosa
  • Longitudinal muscle layer: Thin, few nerve fibers
  • Circular muscle layer: Thick, densely innervated
• Neurons release transmitters from varicosities, not true synapses.
• The nervous system of the gastrointestinal tract includes two plexuses:
  • Submucosal plexus (Meissner plexus): Located between the submucosa and circular muscle
  • Myenteric plexus: Located between the circular muscle and longitudinal muscle

Innervation of the Gastrointestinal Tract

• The autonomic nervous system regulates the gastrointestinal tract with extrinsic (sympathetic & parasympathetic) and intrinsic components.
• The enteric nervous system is the intrinsic component.
• The enteric nervous system is within the submucosal and myenteric plexuses, communicating extensively with sympathetic and parasympathetic nervous systems.

Parasympathetic Innervation

• The vagus nerve (cranial nerve X) and pelvic nerve provide parasympathetic innervation.
• The vagus nerve innervates the upper gastrointestinal tract, including the upper esophagus, the striated muscle of the upper third of the esophagus, stomach, small intestine, ascending colon, and part of the transverse colon.
• The pelvic nerve innervates the lower gastrointestinal tract, including the transverse, descending, and sigmoid colons.
• Parasympathetic nervous system has long preganglionic fibers that synapse in ganglia located in the myenteric and submucosal plexuses within organ walls.
• Information from the parasympathetic nervous system is coordinated in plexuses then relayed to smooth muscle, endocrine, and secretory cells.
• Postganglionic neurons are classified as cholinergic (releasing acetylcholine) or peptidergic (releasing substance P or vasoactive intestinal peptide (VIP)).
• The vagus nerve is a mixed nerve with 75% afferent and 25% efferent fibers.
• Afferent fibers send sensory information (e.g., from mechanoreceptors, chemoreceptors) to the central nervous system (CNS).
• Efferent fibers send motor information from the CNS to target tissues.
• Mechanoreceptors and chemoreceptors in the gastrointestinal mucosa relay afferent information to CNS, triggering vagovagal reflexes using the vagus nerve for both afferent and efferent limbs.

Sympathetic Innervation

• Preganglionic fibers are short, synapsing in ganglia outside the gastrointestinal tract.
• Four sympathetic ganglia serve the gastrointestinal tract: celiac, superior mesenteric, inferior mesenteric, and hypogastric.
• Postganglionic nerve fibers are adrenergic and release norepinephrine; then synapse on ganglia in the myenteric and submucosal plexuses or directly innervate smooth muscle, endocrine, or secretory cells.
• Sympathetic nerve fibers are 50% afferent/sensory and 50% efferent/motor, with sensory and motor information relayed between the gastrointestinal tract and the CNS via the submucosal and myenteric plexuses.

Intrinsic Innervation

• The enteric nervous system (intrinsic) can independently direct all gastrointestinal tract functions.
• The enteric nervous system is in ganglia in the myenteric and submucosal plexuses, controlling contractile, secretory, and endocrine functions.
• Ganglia receive input from the parasympathetic and sympathetic nervous systems, modulating activity, and receive sensory information from mechanoreceptors/chemoreceptors while sending motor information to smooth muscle/secretory/endocrine cells.
• Information is relayed between ganglia by interneurons.
• Neurons of the enteric nervous system contain neurochemicals/neurocrines that are classified as neurotransmitters and neuromodulators.
• Most neurons contain multiple neurochemicals that can be co-secreted upon stimulation.

Gastrointestinal Regulatory Substances

• Gastrointestinal peptides including hormones, neurocrines, and paracrines regulate the functions of the gastrointestinal tract.
• These functions include contraction/relaxation of smooth muscle and sphincters, secretion of enzymes/fluid/electrolytes, and trophic (growth) effects.
• Somatostatin inhibits secretion of all gastrointestinal hormones.

Characteristics of Gastrointestinal Peptides

• Gastrointestinal peptides are classified as hormones, paracrines, or neurocrines, based on their release location and route to target cells.
  • Hormones: Released from endocrine cells into the portal circulation, pass through the liver, enter systemic circulation, and act on target cells (in the gastrointestinal tract, like gastrin on parietal cells, or elsewhere in the body, like gastric inhibitory peptide on pancreatic beta cells). Gastrin, cholecystokinin (CCK), secretin, and glucose-dependent insulinotropic peptide (GIP) are classified as hormones.
    • Endocrine cells of the gastrointestinal mucosa consist of single cells or groups of cells dispersed over large areas instead of concentrated in glands.
  • Paracrines: Released from endocrine cells and act locally within the same tissue, diffusing through interstitial fluid or via short capillaries; Secretion site must be close to target. Somatostatin is a major gastrointestinal paracrine. (Histamine is another paracrine).
  • Neurocrines: Synthesized in neurons and released after action potential, diffusing across the synapse to act on target cells. Neurocrines include: ACh, norepinephrine, vasoactive intestinal peptide (VIP), nitric oxide (NO), gastrin-releasing peptide (GRP), enkephalins, neuropeptide Y, and substance P.

Gastrointestinal Hormones

• Enteroendocrine cells are specialized hormone-secreting cells of the gastrointestinal tract.
• To qualify as an official gastrointestinal hormone, a substance must:
  • Be secreted in response to a physiologic stimulus traveling in the bloodstream to a distant site and produce a physiologic action.
  • Have a function independent of any neural activity.
  • Be isolated, purified, chemically identified, and synthesized.
• Only gastrin, CCK, secretin, and GIP meet these criteria.
• Candidate hormones include motilin, pancreatic polypeptide, somatostatin, 5-hydroxytryptamine (5-HT or serotonin), ghrelin, leptin, glucagon-like peptides 1 and 2 (GLP-1/GLP-2), enteroglucagon, peptide YY (PYY), and neurotensin; these meet some, but not all, criteria.
• Table 8.2 describes the four “official” gastrointestinal hormones with respect to hormone family, site of secretion, stimuli producing secretion, and physiologic actions.
• Table 8.2 can be used as a reference for discussions about motility, secretion, and absorption.