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Control of gastrointestinal motility and secretion


Introduction

In Chapter 24 , we saw that the acquisition of energy and building blocks requires digestion and absorption. We now focus on two other critical gastrointestinal (GI) capabilities, without which digestion and absorption could not occur:

  • Motility is the muscular capacity for movement by which the digestive organs agitate food mechanically and propel it through the GI tract.

  • Secretion is the process that delivers digestive enzymes, emulsifiers, and fluid at low or high pH into the intestinal lumen to enable digestion and absorption.

Particular sequences of muscular contractions and secretions of specific digestive agents must be orchestrated perfectly in time for digestion and absorption to occur normally. Consequently, motility and secretion are controlled by an elaborate neurohormonal regulatory system.

There are three major components to this regulatory system:

  • The central nervous system (CNS), which provides extrinsic innervation and control to the GI tract.

  • The enteric nervous system (ENS), sometimes called the “minibrain” of the intestines, which provides intrinsic innervation and control to the GI tract.

  • Enteroendocrine cells, which are distributed throughout the GI mucosa.

System structure

As described in the previous chapter, the entire length of the GI tract shares a similar structural foundation (see Fig. 24.1 ). Recall that the muscularis has an inner circular and an outer longitudinal sublayer of smooth muscle tissue. The action of these two layers, which constrict the gut in diameter and in length, respectively, provides the basis for peristalsis.

  • Between the inner circular and outer longitudinal muscle layers of the muscularis lies the myenteric plexus (Auerbach’s plexus), one major component of the ENS ( Fig. 25.1 ).

    Fig. 25.1, The enteric nervous system (ENS). The myenteric plexus, which controls motility, and the submucosal plexus, which controls secretion and blood flow, make up the ENS.

  • The other major component of the ENS is the submucosal plexus (Meissner’s plexus), found between the muscularis and the submucosa.

Muscles of the gastrointestinal tract

Many muscles and organ systems are involved in chewing and swallowing food.

  • Masseter muscle: closes the mandible during biting

  • Tongue

  • Pharyngeal muscles

  • Upper esophageal sphincter: demarcates the transition from the pharynx to the esophagus

  • Esophagus

  • Lower esophageal sphincter: a tonically contracted zone in the terminal 2 to 4 cm of the esophagus that divides the esophagus from the stomach

  • Pyloric sphincter: separates the stomach from the duodenum

  • Ileocecal valve: separates the ileum from the large intestine

  • Sphincter of Oddi: separates the duodenum and the ampulla of Vater, which carries the bile and pancreatic secretions

  • Stomach, small intestine, and large intestine: lined with smooth muscle and myenteric plexus

    • Gap junctions between adjacent smooth muscle cells coordinated contraction and relaxation of the GI tract.

    • The large intestine also possesses three strips of longitudinal muscle called the taenia coli.

  • Rectum

  • Internal anal sphincter: involuntary smooth muscle

  • External anal sphincter: voluntarily controlled striated muscle

Innervation of the gastrointestinal tract

As stated earlier, the regulatory system governing GI function includes three components:

  • CNS

  • ENS

  • Enteroendocrine cells

All three are interconnected by nerves, and neurons and enteroendocrine cells both serve as sensors and effectors for the combined CNS/ENS control center. The entire regulatory apparatus is referred to as the brain-gut axis.

  • The transmission of information from the GI tract to the brain for processing is via afferent sensory axons, whose cell bodies are located in the submucosal or myenteric plexus.

  • Neural commands from the brain and spinal cord—the CNS—are sent in the opposite direction via efferent axons to the computational circuits in the enteric minibrain.

Intrinsic innervation

The ENS, composed of the submucosal and myenteric plexuses, provides intrinsic innervation of GI tract structures.

  • Each plexus is composed of ganglia.

    • The myenteric ganglia form a continuous network from the upper esophagus to the internal anal sphincter.

    • The submucosal ganglia are concentrated in the small and large intestine. The ganglia within each layer are connected longitudinally and circumferentially via “highways” of internodal axons.

  • The two plexuses are connected via processes akin to bridges traversing the circular muscle layer. These internal highways and bridges are critical for the coordination of activity along the intestinal wall.

  • The enteric neurons connect with the intestinal mucosa, secretory cells, blood vessels, smooth muscle cells, sympathetic neurons, parasympathetic neurons, and enteroendocrine cells.

Enteric sensory neurons are responsive to mechanical and chemical stimuli. Interneurons participate in enteric reflexes and are regulated by the hormonal milieu created by surrounding enteroendocrine and neuroendocrine cells.

Extrinsic innervation

The GI tract is connected extrinsically to the CNS by nerves ( Fig. 25.2 ).

  • Above the esophagus, this connection is partly through somatic nerves, which give the CNS partly voluntary control over chewing and swallowing.

  • Muscles in the mouth and pharynx are innervated by cranial nerves:

    • V (trigeminal)

    • IX (glossopharyngeal)

    • X (vagus)

    • XII (hypoglossal)

  • Taste in the oral cavity is mediated by cranial nerves:

    • VII (facial)

    • IX (glossopharyngeal)

  • Afferent and efferent neurons complete a reflex arc through the swallowing center in the brain stem.

  • The external anal sphincter is also innervated with a somatic nerve (the pudendal), and therefore the CNS can consciously control either end of the GI tract.

Fig. 25.2, Extrinsic innervation of the gastrointestinal (GI) tract. In the parasympathetic nervous system, nerves project from the medulla oblongata (vagal nerves) and the sacral spinal cord (pelvic nerves). In the sympathetic nervous system, neurons project from the thoracic and first lumbar segments of the spinal cord to form the superior cervical ganglion, as well as the prevertebral ganglion (celiac, superior mesenteric, and inferior mesenteric).

Between the pharynx and the external anal sphincter, the GI tract is extrinsically innervated only by the autonomic nervous system (ANS). The brain thus has little voluntary control over most of the GI tract; it is regulated involuntarily.

The parasympathetic and sympathetic divisions of the ANS regulate the functions of the GI tract, as shown in Fig. 25.3 .

Fig. 25.3, A closer look at the extrinsic innervation of the gastrointestinal tract. The vagovagal reflex receives afferent signals from the mucosa and enteric nervous system (ENS) and delivers efferent signals back to the ENS and mucosa.

The parasympathetic nervous system connects the medulla to the myenteric and submucosal plexuses via the following nerves:

  • Vagus nerve innervates the GI tract from the upper esophageal sphincter to the transverse colon.

    • Sensory-motor reflexes carried in the vagus nerve are called vagovagal reflexes (see Fig. 25.3 ).

    • The vagovagal reflex should not be confused with the vasovagal reflex, which parasympathetically drops the heart rate in response to stress-related spikes in blood pressure.

  • Pelvic nerves, originating in the sacral spinal cord (S2–S4), innervate the GI tract from the splenic flexure of the colon to the internal anal sphincter.

The sympathetic nervous system innervates the entire GI tract with neurons that arise from the sympathetic chain (located alongside spinal cord levels T5–L2) and travel to the prevertebral ganglia (celiac, superior mesenteric, inferior mesenteric, and hypogastric).

  • From the prevertebral ganglia, sympathetic neurons travel along blood vessels to penetrate the intestinal wall.

  • Sympathetic fibers synapse with neurons in the enteric plexuses, as well as directly on smooth muscle cells, blood vessels, and the muscularis mucosa.

Overall, parasympathetic stimulation increases smooth muscle contraction, whereas sympathetic stimulation decreases it.

Enteroendocrine cells

Unlike the endocrine cells of the thyroid or pancreas, which are collected into discrete, isolated glands, GI endocrine cells are distributed over large mucosal areas and are more heterogeneous in nature. This distribution enables them to respond to a diversity of stimuli over the length of the GI tract with a wide variety of endocrine signals.

GI endocrine cells are derived from the same crypt stem cells that differentiate into enterocytes, as well as goblet cell and Paneth cell lineages.

  • They are continuously differentiating from pluripotent intestinal stem cells into specialized cells that secrete one specific agent.

  • Like other endocrine cells, they contain many secretory granules full of peptides.

  • GI endocrine cells are stimulated at their apical (luminal) surfaces by nutrients, by neural input, or by distention of the GI tract wall.

Gastrointestinal hormones and neurotransmitters

GI hormones and neurotransmitters are secreted by enteroendocrine cells and neurons at their axon terminals. They are the final common pathway shared by the nervous and endocrine systems to control the GI system. These factors govern:

  • Enzymatic secretion from the stomach

  • Enzymatic secretion from the pancreas

  • Bile secretion from the liver

  • Contraction and relaxation of GI smooth muscle

There are three hormone communication pathways used by GI regulatory substances ( Fig. 25.4 ):

  • Endocrine communication occurs when a hormone is released from one tissue into the bloodstream to reach a distant target cell with a receptor for that hormone.

    • Five of the GI peptides—secretin, gastrin, cholecystokinin (CCK), glucose-dependent insulinotropic peptide (GIP), and motilin—are considered endocrine hormones.

  • Paracrine communication occurs when an agent is released from endocrine cells into the interstitial fluid to affect neighboring cells with a receptor for that agent.

    • The primary GI paracrine agents are somatostatin and histamine.

  • Neurocrine communication occurs when an agent is synthesized and released from neurons in response to an action potential and behaves as a neurotransmitter.

    • The primary neurotransmitters are acetylcholine and norepinephrine.

  • Minor neurotransmitters include: gastrin-releasing peptide, nitric oxide (NO), tachykinins (e.g., substance P), enkephalins, and vasoactive intestinal peptide (VIP)

Fig. 25.4, Classification of the neurohormonal substances of the gastrointestinal (GI) tract. A, Paracrine substances are released into the interstitium to affect neighbouring cells. B, Neurocrine substances are released directly onto their targets from neuronal axon terminals. C, Endocrine substances are released into the blood stream and circulate to their targets. Not shown are autocrine substances that are released from a given cell and stimulate that same cell. ACh , Acetylcholine; CCK , cholecystokinin; GIP , glucose-dependent insulinotropic polypeptide; GRP , gastrin-releasing peptide; NE , norepinephrine; NO , nitric oxide; VIP , vasoactive intestinal peptide.

Each regulatory agent exerts its action on the GI tract via binding to a specific receptor on the target cell membrane.

  • Hormone receptors in the GI tract belong to a family of G-protein-linked receptors.

  • Depending on the receptor, ligand binding activates one of two major intracellular pathways to elicit an immediate response, such as enzyme secretion.

    • The binding of gastrin, CCK, and acetylcholine (ACh) to their respective receptors activates phospholipase C, leading to increased intracellular calcium release.

    • The binding of other substances, including secretin, VIP, and histamine, activates adenylate cyclase , which leads to an increased intracellular concentration of cyclic adenosine monophosphate (cAMP).

  • Alternatively, hormone binding can elicit a delayed response, such as the activation of gene expression to exert a trophic effect on GI mucosa.

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