96 Hormonal and neural regulation of digestive processes

The human digestive system is a complex and finely tuned network that relies on both neural and hormonal signals to ensure the efficient breakdown and absorption of nutrients. Central to this intricate system is the enteric nervous system (ENS), often referred to as the “second brain” due to its autonomous control over digestive functions. The ENS, along with the sympathetic and parasympathetic branches of the autonomic nervous system, plays a crucial role in regulating digestive processes through both short and long reflexes. Additionally, the phases of digestion—cephalic, gastric, and intestinal—further modulate digestive activities, guided by various gastrointestinal (GI) hormones such as gastrin, cholecystokinin, and secretin.

The Enteric Nervous System (ENS)

The enteric nervous system is a vast network of neurons embedded within the walls of the gastrointestinal tract, stretching from the esophagus to the anus. It consists of two main plexuses: the myenteric plexus (Auerbach’s plexus), which primarily controls GI motility, and the submucosal plexus (Meissner’s plexus), which regulates local blood flow, secretions, and absorption. The ENS operates independently of the central nervous system (CNS) but can also communicate with it to integrate gut function with overall bodily needs.

The ENS coordinates peristalsis, the rhythmic contractions that propel food through the digestive tract, and segmentation, which mixes the contents of the intestines. It also modulates the secretion of digestive enzymes, mucus, and hormones, ensuring that digestive processes occur in a synchronized manner. By integrating sensory information from the gut, such as the presence of nutrients, pH levels, and mechanical distention, the ENS adjusts digestive activity to optimize nutrient absorption and maintain gut homeostasis.

Sympathetic and Parasympathetic Innervation

The autonomic nervous system, comprising the sympathetic and parasympathetic divisions, exerts significant influence over digestive functions, often with opposing effects.

Sympathetic Innervation The sympathetic nervous system prepares the body for “fight or flight” responses, generally inhibiting digestive activities. Sympathetic activation results in decreased blood flow to the digestive organs, reduced motility, and inhibition of secretions. For instance, norepinephrine released from sympathetic nerves binds to alpha-adrenergic receptors on smooth muscle cells, causing relaxation and decreased peristalsis. This conservation of energy and redirection of blood flow away from the GI tract is advantageous during periods of stress or physical exertion.

Parasympathetic Innervation In contrast, the parasympathetic nervous system promotes “rest and digest” activities, enhancing digestive processes. The vagus nerve is the primary conduit for parasympathetic signals to the GI tract. Acetylcholine released from parasympathetic neurons binds to muscarinic receptors, stimulating smooth muscle contractions, increasing motility, and promoting the secretion of digestive enzymes and gastric acid. This support of digestive activities ensures efficient breakdown and absorption of nutrients during times of rest and feeding.

Short and Long Reflexes

Digestive system reflexes are categorized into short and long reflexes based on their pathways and mechanisms.

Short Reflexes, or enteric reflexes, are confined entirely within the walls of the GI tract. They involve the ENS and are independent of the CNS. For example, the distention of the stomach wall by food triggers mechanoreceptors, which activate interneurons within the myenteric plexus. This, in turn, stimulates smooth muscle contractions to enhance gastric motility and mixing of the stomach contents.

Long Reflexes involve the CNS and the autonomic nervous system, allowing integration of digestive activities with the body’s overall state. These reflexes often begin with sensory signals from the GI tract being relayed to the CNS via the vagus nerve. The CNS then processes this information and sends efferent signals back to the GI tract, modulating activity. For example, the sight or smell of food triggers a cephalic phase response, where the brain sends signals to the stomach via the vagus nerve to increase gastric secretions in anticipation of food intake.

Phases of Digestion

The digestive process is regulated through three overlapping phases: cephalic, gastric, and intestinal, each characterized by specific neural and hormonal responses.

Cephalic Phase The cephalic phase is initiated by the sight, smell, taste, or even thought of food, triggering the brain to prepare the digestive system for incoming food. This phase involves the vagus nerve, which stimulates the release of gastric juice, including hydrochloric acid (HCl) and pepsinogen, from the stomach’s parietal and chief cells, respectively. The increase in gastric secretions enhances the stomach’s readiness to process food.

Gastric Phase The gastric phase begins when food enters the stomach. Stretch receptors in the stomach wall detect distention, while chemoreceptors sense the presence of proteins and an increase in pH. These stimuli activate local ENS reflexes and long reflexes via the vagus nerve, further promoting the secretion of gastric juices and enhancing gastric motility. Gastrin, a hormone produced by G cells in the stomach, is also released during this phase. Gastrin stimulates parietal cells to secrete more HCl, aiding in protein digestion and creating an acidic environment to kill pathogens.

Intestinal Phase The intestinal phase starts when chyme enters the small intestine. The presence of acidic chyme and partially digested nutrients triggers the release of hormones such as secretin and cholecystokinin (CCK) from the duodenal enteroendocrine cells. Secretin stimulates the pancreas to release bicarbonate-rich fluid to neutralize the acidity of the chyme, protecting the intestinal lining. CCK stimulates the gallbladder to contract and release bile into the duodenum, facilitating the emulsification and digestion of fats. CCK also signals the pancreas to secrete digestive enzymes. Additionally, the intestinal phase involves inhibitory feedback mechanisms that slow gastric emptying, allowing the small intestine time to process and absorb nutrients efficiently.

Gastrointestinal Hormones

Several hormones play pivotal roles in regulating digestive functions, each with specific sources, stimuli for release, targets, and actions.

Gastrin is produced by G cells in the stomach. Its release is stimulated by the presence of peptides and amino acids in the stomach, stomach distention, and vagal stimulation. Gastrin primarily targets the parietal cells in the stomach, prompting them to secrete HCl. This increase in HCl secretion aids in protein digestion and enhances stomach motility, facilitating the churning and breakdown of food.

Cholecystokinin (CCK) is released by I cells in the duodenum in response to the presence of fatty acids and amino acids in the small intestine. CCK has multiple targets, including the gallbladder, pancreas, and stomach. In the gallbladder, CCK induces contraction, resulting in the release of bile into the duodenum to assist in fat emulsification and digestion. CCK also stimulates the pancreas to secrete digestive enzymes, further aiding in the breakdown of fats, proteins, and carbohydrates. Additionally, CCK inhibits gastric emptying, ensuring that the chyme is processed at a rate that allows for optimal nutrient absorption in the small intestine.

Secretin, another key digestive hormone, is produced by S cells in the duodenum. Its release is triggered by the presence of acidic chyme entering the small intestine from the stomach. Secretin primarily targets the pancreas, stimulating it to release bicarbonate-rich fluid. This bicarbonate neutralizes the acidic chyme, protecting the intestinal lining and creating an optimal pH environment for enzyme activity in the small intestine. Secretin also inhibits gastric acid secretion, providing a negative feedback mechanism to regulate the acidic environment in the stomach.

Gastric Inhibitory Peptide (GIP) is produced by K cells in the small intestine in response to the presence of glucose, fatty acids, and amino acids. GIP has dual functions, targeting both the pancreas and the stomach. In the pancreas, GIP stimulates the secretion of insulin, which is crucial for glucose metabolism. In the stomach, GIP inhibits gastric acid secretion and motility, slowing down the digestive process to allow for proper nutrient absorption in the small intestine.

These hormones—gastrin, CCK, secretin, and GIP—work in concert to regulate the secretion of digestive juices and the movement of food through the digestive tract. They ensure that each phase of digestion is finely tuned, promoting efficient breakdown and absorption of nutrients necessary for the body’s metabolic needs.