The Gastrointestinal Tract, or Gut, Supplies the Body with Nutrients, Electrolytes, and Water by Performing Five Functions: Motility, Secretion, Digestion, Absorption, and Storage

The digestive system consists of two parts, the gastrointestinal (GI) tract and the major digestive accessory glands, which include the liver and pancreas (Figure 27-1). This chapter focuses on the control systems that regulate the various functions of the GI tract. The control systems that regulate the functions of the liver and pancreas will be discussed in Chapter 29.

The GI tract, also known as the gut, is a tube-like structure that extends from the mouth to the anus. Histologically, this tube consists of four main layers: (1) the mucosa, which comprises epithelial cells (enterocytes, endocrine cells, and others), the lamina propria, and the muscularis mucosae; (2) the submucosa; (3) two muscle layers, an inner thick circular layer and an outer thin longitudinal layer; and (4) a serosal layer (Figure 27-2).

Functionally, the GI tract supplies the body, including the gut itself, with nutrients, electrolytes, and water. To supply the body with these substances, the gut performs five functions: motility, secretion, digestion, absorption, and storage. On the basis of the needs of the various organ systems in the body, the GI tract orchestrates and controls these five functions through two control systems, intrinsic and extrinsic. The intrinsic control system elements are located between the different layers of the gut, whereas the extrinsic control system resides outside the wall of the GI tract. Each of these systems consists of two components, namely, nerves and endocrine secretions (Figure 27-3).

Intrinsic and Extrinsic Control Systems Regulate Various Functions of the Gut

The intrinsic control system has two components: the enteric nervous system (ENS) and gut hormones, which include gastrin, gastric inhibitory peptide (GIP), cholecystokinin (CCK), secretin, and motilin. The extrinsic control system elements that regulate gut functions consist of the vagus and splanchnic nerves and the hormone aldosterone.

The secretions of the intrinsic and extrinsic control systems of the gut are regulatory and not digestive in nature (Box 27-1). That is, they regulate the activity of cells and tissues of the GI tract, but are not secreted into the gut lumen. They reach their target tissues by four different routes (Figure 27-4). Endocrine secretions are deposited close to blood vessels, and then blood cells carry the secretions to their target tissues. Paracrine denotes peptides secreted from cells with subsequent diffusion through the interstitial space to contact and affect other cells. Autocrine secretions of a given cell modify or regulate functions of the same cell. Neurocrine refers to secretion by enteric neurons of neuromodulators or regulatory peptides that affect nearby muscle cells, glands, or blood vessels. The endocrine and paracrine cells of the gut are columnar in shape with a wide base and a narrow apex (Figure 27-5). The narrow apex of the cell is exposed to the lumen of the gut, which allows it to “sample” or “taste” the luminal contents and respond to such stimuli by releasing hormones and/or other regulatory substances/peptides. The endocrine and paracrine cells have wide bases that contain secretory granules (storage forms of hormones and paracrine substances). This design allows cells to spread their secretions in a much wider area.

In addition to the previously mentioned control systems, the GI tract contains the highest number of immune cells and immune mediators in the body. Those cells and mediators interact with the intrinsic control system of the gut, both nerves and endocrine cells, to regulate some functions of the GI tract, including motility and secretion. However, because of their unique nature, the immune cells will not be discussed as part of the intrinsic control system, although they are located in the GI tract. Instead, they will be discussed at the end of this section.

The Intrinsic Neuronal Control System of the Gastrointestinal Tract Is the Enteric Nervous System

The enteric nervous system (ENS) is a component of the autonomic nervous system (ANS). The other two ANS components are the sympathetic and parasympathetic systems. The ENS controls the majority of the GI functions independent from the central nervous system (CNS).

Anatomically, the ENS consists of two main ganglionated plexuses, termed the submucosal (Meissner) and myenteric (Auerbach) plexuses. The submucosal plexus is located under the submucosal layer of the gut, and the myenteric plexus resides between the inner circular muscle layer and the outer longitudinal muscle layer (Figure 27-6). The enteric plexuses communicate with each other through interneurons and with the CNS through vagal, pelvic, and splanchnic nerves.

In general, the enteric neurons consist of sensory (afferent) neurons, interneurons, and motor (efferent) neurons. Sensory input comes from mechanoreceptors within the muscular layers and chemoreceptors within the mucosa. Mechanoreceptors monitor distention of the gut wall, whereas chemoreceptors in the mucosa monitor chemical conditions in the gut lumen. Enteric motor nerves supply vascular muscle, gut muscle, and glands within the gut wall. Efferent neurons of the ENS may be stimulatory or inhibitory. The nature of their action is largely determined by the type of neurocrine substance they secrete and the nature of the receptors activated (Table 27-1).

Unlike classical neurons, the enteric neurons release their neurotransmitter/neuromodulator molecules from vesicles located in swellings along often extensive branches of the axon, not just at the level of the distal synaptic terminals. These swellings are referred to as varicosities (Figure 27-7). The varicosities contain regulatory peptides, substances collectively known as neurocrines. These substances are secreted in response to action potentials, and they affect the activities of nearby smooth muscles or glandular cells. The presence of varicosities in the enteric neurons allows these neurons to activate a wider area in the vicinity of the axon compared with most other types of neurons, which release their neurotransmitters in a more focused and localized area at the distal synaptic terminal.

Depending on the species, the number of enteric neurons may reach 100 million. This number, in some cases, is more than the number of neurons in the spinal cord. To simplify the study of these neurons and to understand their physiological importance, four main classification methods have been used. These methods depend on the morphology (different shapes) of enteric neurons, the types of neurotransmitters or peptides they may contain (also known as their chemical coding), the electrical properties of the enteric neurons or electrophysiology, and the function (e.g., sensory, motor, inhibitory, and excitatory) of the enteric neurons.

On the basis of their morphology, three main types of enteric neurons exist: Dogiel type I, II, and III (Figure 27-8). These classifications are named for Alexander Dogiel, the histologist who initially described them. Dogiel type I neurons have small, irregular cell bodies with multiple short dendrites. Dogiel type II neurons have large, oval-shaped cell bodies with one or two long dendrites. Dogiel type III neurons have large cell bodies with different shapes and multiple dendrites.