Gastrointestinal Tract Structure and Layers

Structure of the Gastrointestinal Tract

• The gastrointestinal tract (GI) is arranged linearly, beginning with the mouth and ending with the anus
• The order is as follows: mouth, esophagus, stomach, small intestine (duodenum, jejunum, ileum), large intestine, and anus
• Other structures with secretory functions related to the GI tract are the salivary glands, pancreas, liver, and gallbladder
• The GI tract wall has a mucosal surface facing the lumen and a serosal surface facing the blood

Layers of the Gastrointestinal Wall

• Mucosal layer: Innermost layer including a layer of epithelial cells used for absorption and secretion, lamina propria, and muscularis mucosae
• Lamina propria: Primarily connective tissue containing blood and lymph vessels
• Muscularis mucosae: Smooth muscle cells that contract to change shape and surface area of the epithelial cell layer
• Submucosal layer: Contains collagen, elastin, glands, and blood vessels of the GI tract
• Two layers of smooth muscle provide motility: Circular and longitudinal muscle
• Longitudinal muscle layer: Thin with few nerve fibers
• Circular muscle layer: Thick and densely innervated
• Neurons release transmitters from varicosities instead of forming true synapses
• Submucosal plexus and myenteric plexus: Two plexuses containing the nervous system of the GI tract
• Submucosal plexus (Meissner plexus): Located between the submucosa and circular muscle
• Myenteric plexus: Located between the circular and longitudinal muscle

Innervation of the Gastrointestinal Tract

• The autonomic nervous system regulates the GI tract, with extrinsic and intrinsic components
• Extrinsic component: Sympathetic and parasympathetic innervation
• Intrinsic component: Enteric nervous system
• Enteric nervous system: Contained within the submucosal and myenteric plexuses that are in the GI tract. It communicates with the parasympathetic and sympathetic nervous systems

Parasympathetic Innervation

• Vagus nerve (cranial nerve X) and pelvic nerve provides parasympathetic innervation
• Vagus nerve innervation: Upper GI tract, including the upper esophagus, stomach, small intestine, ascending colon, and part of the transverse colon
• Pelvic nerve innervation: Lower GI tract, including the transverse, descending, and sigmoid colons
• Parasympathetic nervous system: Possesses long preganglionic fibers synapsing in ganglia near target organs. In the GI tract, lies within the myenteric and submucosal plexuses
• Information from the parasympathetic nervous system is coordinated in the plexuses and relayed to smooth muscle, endocrine, and secretory cells
• Postganglionic neurons are either cholinergic, releasing acetylcholine (ACh), or peptidergic, releasing peptides like substance P and vasoactive intestinal peptide (VIP)
• Vagus nerve: A mixed nerve with 75% afferent fibers and 25% efferent
• Afferent fibers deliver sensory information to the central nervous system (CNS) from mechanoreceptors and chemoreceptors
• Efferent fibers deliver motor information from the CNS to smooth muscle, secretory, and endocrine cells
• Mechanoreceptors and chemoreceptors relay information to the CNS via vagus nerve, triggering vagovagal reflexes that contain both afferent and efferent limbs

Sympathetic Innervation

• Sympathetic nervous system: Short preganglionic fibers that synapse in ganglia outside the GI tract
• Four sympathetic ganglia that serve the GI tract: Celiac, superior mesenteric, inferior mesenteric, and hypogastric
• Postganglionic nerve fibers release norepinephrine (adrenergic) and synapse on ganglia in the myenteric and submucosal plexuses, or directly innervate smooth muscle, endocrine, and secretory cells
• Approximately 50% of the sympathetic nerve fibers are afferent and 50% are efferent
• Sensory and motor information is relayed between the GI tract and the CNS and is coordinated by the submucosal and myenteric plexuses

Intrinsic Innervation

• Enteric nervous system: Directs GI tract functions, even without extrinsic innervation
• Located in ganglia in the myenteric and submucosal plexuses to control contractile, secretory, and endocrine functions
• Ganglia receive input from parasympathetic and sympathetic systems
• Ganglia receive sensory information from mechanoreceptors and chemoreceptors in the mucosa and send motor information to smooth muscle, secretory, and endocrine cells
• Information is relayed between ganglia by interneurons
• Enteric nervous system neurons: Contain neurochemicals (neurocrines) classified as neurotransmitters and neuromodulators, and can cosecrete two or more neurocrines upon stimulation

Gastrointestinal Regulatory Substances

• Gastrointestinal peptides like hormones, neurocrines, and paracrines regulate GI tract functions.
• GI tract functions include:
  • Contraction and relaxation of smooth muscle and sphincters
  • Secretion of digestive enzymes and fluid/electrolytes
  • Trophic effects on GI tract tissues
• Some GI peptides regulate the secretion of other GI peptides, such as somatostatin inhibiting all GI hormones

Characteristics of Gastrointestinal Peptides

• Gastrointestinal peptides: Classified as hormones, paracrines, or neurocrines, based on their release from endocrine cells or neurons and their route to target cells
• Hormones: Released from endocrine cells into portal circulation, pass through the liver, and enter the systemic circulation to reach target cells with receptors
• The target cells may be in the GI tract or elsewhere in the body
• Endocrine cells are dispersed, not concentrated in glands
• Four GI hormones: Gastrin, cholecystokinin (CCK), secretin, and glucose-dependent insulinotropic peptide (GIP)
• Paracrines: Peptides secreted by endocrine cells that act locally within the same tissue by diffusing through interstitial fluid or through capillaries
• Site of secretion must be close to the site of action
• Somatostatin is a major GI paracrine that inhibits functions throughout the GI tract
• Neurocrines: Substances synthesized in neurons, released after an action potential, diffuse across the synapse, and act on target cells
• GI tract neurocrines: Acetylcholine (ACh), norepinephrine, vasoactive intestinal peptide (VIP), nitric oxide (NO), gastrin-releasing peptide (GRP) or bombesin, enkephalins, neuropeptide Y, and substance P

Gastrointestinal Hormones (Enteroendocrine cells)

• Specialized hormone-secreting cells must meet the criteria to qualify as an official gastrointestinal hormone:
• Secreted in response to a physiologic stimulus and carried to a distant site via the bloodstream to produce a physiologic action
• Function independently of any neural activity
• Be isolated, purified, chemically identified, and synthesized
• Official GI hormones: Gastrin, CCK, secretin, and GIP
• Other candidate hormones: Motilin, pancreatic polypeptide, somatostatin, 5-hydroxytryptamine (5-HT; serotonin), ghrelin, leptin, glucagon-like peptides 1 and 2 (GLP-1 and GLP-2), enteroglucagon, peptide YY (PYY), and neurotensin

Gastrin

• Hormone crucial for digestive processes, with two forms based on amino acid length: G 17 (little gastrin) and G 34 (big gastrin)
• G 17 promotes digestion after a meal. G 34 is secreted between meals
• Both gastrin forms originate from progastrin and follow separate biosynthetic pathways
• C-terminal tetrapeptide: The biologically active component of gastrin
• Gastrin secretion stimulants: Food intake (amino acids like phenylalanine and tryptophan), stomach distension, and vagal stimulation through gastrin-releasing peptide (GRP) or bombesin release
• Gastrin secretion inhibitors: Low gastric pH and somatostatin
• Two major actions: Stimulate hydrogen ion (H+) secretion by gastric parietal cells Promote growth of gastric mucosa
• Gastrin excess (Zollinger-Ellison syndrome) has effects: Increased H+ secretion causes duodenal ulcers, hypertrophy of the gastric mucosa, and fat digestion due to intestinal lumen acidification
• Treatment for Zollinger-Ellison syndrome: H2 receptor-blocking drugs, H+ pump inhibitors, tumor removal, or gastric resection

Cholecystokinin (CCK)

• 33-amino acid peptide structurally related to gastrin, it is part of the “gastrin-CCK family”
• C-terminal five amino acids (CCK-5): Identical to gastrin, including the tetrapeptide for gastrin activity. Thus, CCK has some gastrin activity
• CCK 1 receptors: selective for CCK
• CCK 2 receptors: equally sensitive to CCK and gastrin
• C-terminal heptapeptide (CCK-7): The minimum fragment for its biologic activity
• CCK secretion stimulants from I cells of the duodenal and jejunal mucosa:
• Monoglycerides and fatty acids
• Small peptides and amino acids
• These alert the I cells to presence of fat and protein
• Five major actions that contribute to fat, protein, and carbohydrate digestion and absorption:
• Contraction of the gallbladder with simultaneous relaxation of the sphincter of Oddi for bile ejection to emulsify and solubilize dietary lipids
• Secretion of pancreatic enzymes for digestion
• Secretion of bicarbonate (HCO3–) from the pancreas (potentiates the effects of secretin)
• Growth of exocrine pancreas and gallbladder
• Inhibition of gastric emptying