Gastrointestinal Neural and Hormonal Signaling

Function of the GI system is highly regulated through neural and hormonal signaling. Much of this regulation comes from the ANS. Parasympathetic stimulation is excitatory, triggering digestive secretions, an increase in GI blood flow, and movement of material through the tract, while sympathetic stimulation is inhibitory and has the opposite effects. The GI tract also has its own enteric nervous system, which controls numerous local GI reflexes. For example, the presence of a particular nutrient may be detected by chemoreceptors and may trigger release of a particular digestive enzyme, which is coordinated entirely by the enteric nervous system (without input from the brain). In addition, there are numerous hormones and paracrine signaling molecules released by GI organs that similarly affect GI function.

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Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Table of Contents

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Overview of GI Tract Physiology

Functions of the GI tract

The GI system is constantly working to meet human energy demands. To achieve this end, the GI system has several major functions:

  • Digestion Digestion Digestion refers to the process of the mechanical and chemical breakdown of food into smaller particles, which can then be absorbed and utilized by the body. Digestion and Absorption of complex nutrients:
    • Mechanical 
    • Chemical
  • Absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption of nutrients and water (its critical function)
  • Secretion of:
    • Digestive enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body's constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes
    • Lubricating fluid
    • Signaling molecules
  • Motility and storage: moves material through the tract at the appropriate times
  • Excretion of waste

Anatomical structures and their associated functions

  • Pharynx Pharynx The pharynx is a component of the digestive system that lies posterior to the nasal cavity, oral cavity, and larynx. The pharynx can be divided into the oropharynx, nasopharynx, and laryngopharynx. Pharyngeal muscles play an integral role in vital processes such as breathing, swallowing, and speaking. Pharynx:
    • Mouth and teeth Teeth Normally, an adult has 32 teeth: 16 maxillary and 16 mandibular. These teeth are divided into 4 quadrants with 8 teeth each. Each quadrant consists of 2 incisors (dentes incisivi), 1 canine (dens caninus), 2 premolars (dentes premolares), and 3 molars (dentes molares). Teeth are composed of enamel, dentin, and dental cement. Teeth: mechanical digestion
    • Salivary glands Salivary glands The salivary glands are exocrine glands positioned in and around the oral cavity. These glands are responsible for secreting saliva into the mouth, which aids in digestion. There are 3 major paired salivary glands: the sublingual, submandibular, and parotid glands. Salivary Glands: chemical digestion, lubrication
  • Esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: motility/transport to the stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach
  • Stomach:
    • Blends food (mechanical digestion)
    • Secretes acid and enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body's constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes to assist in chemical digestion and sterilization
    • Acts as a reservoir (storage); releases chyme into the small intestine Small intestine The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine at a controlled rate
  • Small intestine (duodenum, jejunum, and iIeum): 
    • Receives contents from the stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach and neutralizes acidity
    • Receives secretions from the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver, gallbladder Gallbladder The gallbladder is a pear-shaped sac, located directly beneath the liver, that sits on top of the superior part of the duodenum. The primary functions of the gallbladder include concentrating and storing up to 50 mL of bile. Gallbladder and Biliary Tract, and pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas to aid in chemical digestion
    • Nutrient absorption
    • Motility
  • Large intestine Large intestine The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix (cecum, colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix): 
    • Water absorption
    • Motility
  • Rectum and anal canal: excretion
  • Associated structures:
    • Liver: metabolism, synthesizes bile (“detergent” used for digesting fats)
    • Gallbladder and biliary duct system: stores and secretes bile
    • Pancreas: secretes digestive enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body's constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes
The gi tract as engineering tube

As a way of understanding the GI system, the GI tract can be envisioned as an “engineering tube,” as shown here, with different segments having specialized functions.

Image by Lecturio.

Autonomic Control of the GI Tract

Autonomic control of the GI tract relies on the enteric, parasympathetic, and sympathetic nervous systems.

Enteric nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. General Structure of the Nervous System (ENS)

A specialized portion of the autonomic nervous system Autonomic nervous system The ANS is a component of the peripheral nervous system that uses both afferent (sensory) and efferent (effector) neurons, which control the functioning of the internal organs and involuntary processes via connections with the CNS. The ANS consists of the sympathetic and parasympathetic nervous systems. Autonomic Nervous System located within the walls of the GI tract.

  • Consists of:
    • Meissner plexus (also called the submucosal plexus):
      • Located in the submucosa
      • Controls the muscularis mucosa (independent of the muscular layer of the intestines)
    • Auerbach plexus (also called the myenteric plexus):
      • Located in the muscularis, between the circular and longitudinal layers 
      • Includes both motor and sensory neurons Sensory neurons Neurons which conduct nerve impulses to the central nervous system. Autonomic Nervous System
      • Provides motor input to the smooth muscle → generates contractions
      • Receives sensory input from chemoreceptors and mechanoreceptors and coordinates appropriate responses (often as a reflex) 
    • Interstitial cells of Cajal (ICCs): 
      • Specialized pacemaker cells located in the muscularis
      • Generate the slow wave of smooth muscle contraction Smooth muscle contraction Smooth muscle is primarily found in the walls of hollow structures and some visceral organs, including the walls of the vasculature, GI, respiratory, and genitourinary tracts. Smooth muscle contracts more slowly and is regulated differently than skeletal muscle. Smooth muscle can be stimulated by nerve impulses, hormones, metabolic factors (like pH, CO2 or O2 levels), its own intrinsic pacemaker ability, or even mechanical stretch. Smooth Muscle Contraction responsible for baseline GI motility
  • Function: local control of GI function
    • Controls peristalsis: coordinated, wave-like contractions that move material through the tract, ultimately toward the rectum Rectum The rectum and anal canal are the most terminal parts of the lower GI tract/large intestine that form a functional unit and control defecation. Fecal continence is maintained by several important anatomic structures including rectal folds, anal valves, the sling-like puborectalis muscle, and internal and external anal sphincters. Rectum and Anal Canal
    • Segmentation: circular muscle contraction allows for mixing of food material to aid in absorption
    • Stimulates the secretion of regulatory hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and neurotransmitters (see sections below)
  • The ENS does not routinely act on its own; it receives input from:
    • Vagus nerve (parasympathetic, stimulatory)
    • Prevertebral ganglia (sympathetic, inhibitory)
  • Mechanisms of control:
    • Parasympathetic or sympathetic fibers synapse Synapse The junction between 2 neurons is called a synapse. The synapse allows a neuron to pass an electrical or chemical signal to another neuron or target effector cell. Synapses and Neurotransmission with myenteric motor neurons → adjust their activity
    • Myenteric motor neurons synapse Synapse The junction between 2 neurons is called a synapse. The synapse allows a neuron to pass an electrical or chemical signal to another neuron or target effector cell. Synapses and Neurotransmission with ICCs → ICCs adjust rate of firing/contraction waves
    • Smooth muscle cells communicate the signal via gap junctions
Layers and folds in intestinal walls

Structure of the intestinal walls:
The Meissner plexus is located within the submucosa, and the Auerbach plexus (also known as the myenteric plexus) is located between the circular and longitudinal muscular layers.

Image by Lecturio.

Parasympathetic nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. General Structure of the Nervous System (PNS)

  • Activates GI function
  • Effects of parasympathetic signaling:
    • ↑ GI motility 
    • ↑ GI secretions
    • ↑ Blood flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure
    • ↓ Constriction of GI sphincters (allows food to move through the tract)
  • Nerves:
    • Facial nerve (cranial nerve (CN) VII): controls the salivary glands
    • Glossopharyngeal nerve (CN IX) controls the:
      • Tongue Tongue The tongue, on the other hand, is a complex muscular structure that permits tasting and facilitates the process of mastication and communication. The blood supply of the tongue originates from the external carotid artery, and the innervation is through cranial nerves. Oral Cavity: Lips and Tongue
      • Oropharynx 
      • Upper esophagus
    • Vagus nerve (CN X) controls the:
      • Lower esophagus
      • Stomach 
      • Pancreas
      • Small intestines
      • Part of the large intestines
    • Pelvic nerves: 
      • Large intestine Large intestine The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix
      • Rectum
      • Anus
  • Primary neural signaling molecules:
    • Acetylcholine
    • Vasoactive intestinal peptide (VIP)
Parasympathetic innervation of the gi tract

Parasympathetic influence on the GI tract:
Note the vast reach of the vagus nerve.
CN: cranial nerve

Image by Lecturio.

Sympathetic nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. General Structure of the Nervous System (SNS)

  • Restricts GI function during the fight-or-flight response (so that energy can be diverted to skeletal muscle)
  • Effects of sympathetic signaling (opposite to parasympathetic signaling):
    • ↓ Motility
    • ↓ Secretion
    • ↓ Blood flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure
    • ↑ Sphincter tone
  • Nerves: sympathetic ganglia in the thoracolumbar region (primarily T8‒L2): 
    • Celiac ganglia
    • Superior mesenteric ganglia
    • Inferior mesenteric ganglia
  • Primary neural signaling molecules:
    • Norepinephrine (NE)
    • ATP
Sympathetic innervation of the gi tract

Sympathetic nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. General Structure of the Nervous System influence on the GI tract

Image by Lecturio.

Regulation of blood flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure

Vasodilation:

  • Increases blood flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure
  • Stimulated by:
    • Parasympathetic nerves, via acetylcholine (ACh) and VIP
    • Local reflexes in the enteric nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. General Structure of the Nervous System via ACh and VIP
    • Sensory afferents (lesser degree) via:
      • Calcitonin gene–related peptide (CGRP)
      • Substance P

Vasoconstriction:

  • Decreases blood flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure
  • Stimulated by the SNS via NE and ATP
Regulation of the blood flow to the gi tract

Flowchart detailing the regulation of blood flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure to the GI tract
ACh: acetylcholine
CGRP: calcitonin gene–related peptide
EPAN: extrinsic primary afferent neuron
IPAN : intrinsic primary afferent
NE: norepinephrine
SP: substance P
VIP: vasoactive intestinal

Image by Lecturio.

Neural Signaling Molecules

The nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. General Structure of the Nervous System sends signals to mediate activity in the GI tract. Nerves in the PNS, SNS, ENS, and sensory afferent nerves release different types of signaling molecules, which have different effects on their target tissue.

Table: Neural signaling molecules
Molecule Primary releasing nerve(s) Structure(s) acted on Primary function
Released by the PNS and/or ENS
Acetylcholine PNS
  • Glands
  • Smooth muscle
  • Blood vessels
Increases secretions, motility, and blood flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure
VIP PNS and ENS
  • Glands
  • Smooth muscle
  • Blood vessels
Increase motility and blood flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure
GRP PNS and ENS Glands Increase gastrin secretion
Enkephalins (related to opioids Opioids Opiates are drugs that are derived from the sap of the opium poppy. Opiates have been used since antiquity for the relief of acute severe pain. Opioids are synthetic opiates with properties that are substantially similar to those of opiates. Opioid Analgesics) ENS Smooth muscle Constrict sphincters (prevents forward movement)
Released by sensory afferents
CGRP Sensory afferents Blood vessels Increase blood flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure via vasodilation
Substance P Sensory afferents and PNS
  • Blood vessels
  • Glands
Increase blood flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure
Released primarily by the SNS
Norepinephrine SNS
  • Glands
  • Smooth muscle
  • Blood vessels
Decrease secretions, motility, and blood flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure
ATP SNS Blood vessels Decrease blood flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure via vasoconstriction
CGRP: calcitonin gene–related peptide
ENS: enteric nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. General Structure of the Nervous System
GRP: gastric-releasing peptide
PNS: parasympathetic nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. General Structure of the Nervous System
SNS: sympathetic nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. General Structure of the Nervous System
VIP: vasoactive intestinal peptide

GI Hormones

The GI hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview are secreted by enteroendocrine cells and modulate function of the GI tract. Enteroendocrine cells are spread throughout the GI tract.

Classification by chemical structure

  • Gastrin
  • Cholecystokinin
  • Secretin family:
    • Secretin
    • Glucagon
    • VIP
  • Other:
    • Somatostatin 
    • Motilin 

Functions

  • Increase enzyme secretion
  • Muscle contraction
  • Decrease gastric emptying
  • Increase motility

The major GI hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview

Table: GI hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview outlined with releasing cell, structure affected, and primary function
Molecule Primarily released from Structure(s) acted on Primary function
Gastrin G cells in the:
  • Stomach
  • Duodenum
Stomach
  • Increases acid secretion
  • Trophic (growth) effects on GI mucosa
Cholecystokinin I cells in the:
  • Duodenum
  • Jejunum
Exocrine pancreas Exocrine pancreas The major component (about 80%) of the pancreas composed of acinar functional units of tubular and spherical cells. The acinar cells synthesize and secrete several digestive enzymes such as trypsinogen; lipase; amylase; and ribonuclease. Secretion from the exocrine pancreas drains into the pancreatic ductal system and empties into the duodenum. Pancreas, gallbladder Gallbladder The gallbladder is a pear-shaped sac, located directly beneath the liver, that sits on top of the superior part of the duodenum. The primary functions of the gallbladder include concentrating and storing up to 50 mL of bile. Gallbladder and Biliary Tract, and stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach
  • Increase pancreatic enzyme and bicarbonate secretion
  • Contracts the gallbladder Gallbladder The gallbladder is a pear-shaped sac, located directly beneath the liver, that sits on top of the superior part of the duodenum. The primary functions of the gallbladder include concentrating and storing up to 50 mL of bile. Gallbladder and Biliary Tract
  • Relaxes the sphincter of Oddi
  • Contracts the pyloric sphincter and decreases gastric emptying
Gastric inhibitory peptide (GIP) K cells in the:
  • Duodenum
  • Jejunum
Stomach, endocrine pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas
  • Stimulates insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin release
  • Inhibits acid secretion
  • Induces satiety
Motilin M cells in the:
  • Duodenum
  • Jejunum
Smooth muscle
  • ↑ GI motility by stimulating the migrating motor complex (MMC)
Secretin S cells in the:
  • Duodenum
  • Jejunum
Pancreas and stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach
  • ↑ Bicarbonate secretion ( pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas)
  • ↑ Pepsin secretion ( stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach)
  • Inhibits gastrin and acid secretion
Location of gi hormones

Diagram showing the locations from which GI hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview are released:
The tapered ends on the gastrin, cholecystokinin, and secretin bars represent the decreasing amounts of hormone secretion in these locations.
GIP: gastric inhibitory peptide

Image by Lecturio.

GI Paracrine Signaling Molecules

Paracrine signaling molecules are similar to hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview; however, instead of traveling to different tissues via the blood, paracrine signaling molecules affect cells close to the site of their release. The major paracrine signaling molecules in the GI system are histamine, NO, prostaglandins, and somatostatin.

Table: Paracrine signaling molecules of the GI tract
Molecule Released from Structure(s) acted on Primary function
Histamine
  • Enterochromaffin like cells
  • Mast cells
Stomach Increase acid secretion
Somatostatin D cells Stomach and pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas Inhibit secretion
Prostaglandins (PGs) Numerous Mucosa Increase mucus and bicarbonate secretion
NO Numerous Smooth muscle, blood vessels Relax smooth muscle and increase blood flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure

Clinical Relevance

  • Zollinger-Ellison Syndrome (ZES): an often-malignant gastrin-secreting tumor arising from the pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas, stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach, duodenum, jejunum, and/or lymph nodes. The syndrome is characterized by recurrent/refractory peptic ulcers, gastroesophageal reflux, and diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea. Diagnosis is based on elevated fasting serum gastrin levels. Management consists of surgical resection of the tumor and/or symptom management.
  • Achalasia Achalasia Achalasia is a primary esophageal motility disorder that develops from the degeneration of the myenteric plexus. This condition results in impaired lower esophageal sphincter relaxation and absence of normal esophageal peristalsis. Patients typically present with dysphagia to solids and liquids along with regurgitation. Achalasia: a primary esophageal motility disorder that develops from degeneration of the myenteric plexus. This degeneration results in impaired lower esophageal sphincter relaxation and absence of normal esophageal peristalsis. Presentation is typically with dysphagia Dysphagia Dysphagia is the subjective sensation of difficulty swallowing. Symptoms can range from a complete inability to swallow, to the sensation of solids or liquids becoming "stuck." Dysphagia is classified as either oropharyngeal or esophageal, with esophageal dysphagia having 2 sub-types: functional and mechanical. Dysphagia for solids and liquids, along with regurgitation. Management options include pneumatic balloon dilation, surgical myotomy, and botulinum toxin injection. Medications are available for those for whom initial intervention failed, but they provide the least benefit.
  • Hirschsprung disease Hirschsprung Disease Hirschsprung disease (HD), also known as congenital aganglionosis or congenital megacolon, is a congenital anomaly of the colon caused by the failure of neural crest-derived ganglion cells to migrate into the distal colon. The lack of innervation always involves the rectum and extends proximally and contiguously over variable distances. M Hirschsprung Disease: congenital anomaly of the colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix caused by the failure of neural crest–derived ganglion cells to migrate into the distal colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix. This lack of innervation always involves the rectum Rectum The rectum and anal canal are the most terminal parts of the lower GI tract/large intestine that form a functional unit and control defecation. Fecal continence is maintained by several important anatomic structures including rectal folds, anal valves, the sling-like puborectalis muscle, and internal and external anal sphincters. Rectum and Anal Canal and extends proximally and contiguously for variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables distances. Most cases are diagnosed in the neonatal period, with a classic triad of symptoms: delayed passage of meconium, abdominal distention, and bilious vomiting. Surgical resection of the aganglionic segment is the standard treatment.

References

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  2. Antunes, L.C., Davies, J.E., Finlay, B.B. (2011). Chemical signaling in the gastrointestinal tract. F1000 Biol Rep 3:4. https://doi.org/10.3410/B3-4
  3. Okonkwo, O., Zezoff, D., Adeyinka, A. (2021). Biochemistry, cholecystokinin. StatPearls. Retrieved December 7, 2021, from: https://www.ncbi.nlm.nih.gov/books/NBK534204/
  4. O’Toole, T.J., Sharma, S. (2021). Physiology, somatostatin. StatPearls. Retrieved
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  6. Purves, D., Augustine, G.J., Fitzpatrick, D., et al. (Ed.) (2001). In: Neuroscience, 2nd ed. Part I, Neural Signaling. Sinauer Associates. https://www.ncbi.nlm.nih.gov/books/NBK10882/
  7. Sullivan, A.M. (2016). Neuronal signaling: An introduction. Neuronal Signal 1(1):NS20160025. https://doi.org/10.1042/NS20160025
  8. Liddle, R. A. (2020). Overview of gastrointestinal peptides in health and disease. UpToDate. Retrieved November 29, 2021, from https://www.uptodate.com/contents/overview-of-gastrointestinal-peptides-in-health-and-disease 
  9. Parikh, A. (2021). Physiology, gastrointestinal hormonal control. StatPearls. Retrieved November 29, 2021, from https://www.statpearls.com/articlelibrary/viewarticle/806/ 
  10. Tobias, A. (2021). Physiology, gastrointestinal nervous control. StatPearls. Retrieved November 29, 2021, from https://www.statpearls.com/articlelibrary/viewarticle/805/ 
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