Gastrointestinal Tract: Control Systems and Enteric Nervous System

The gut is an important system in the body.
The study of the GI system is divided into general and special aspects.
Four general points to cover:
- Definition
- Histology
- Control System
- Functions (special functions will be discussed separately later).
Definition of the Gastrointestinal (GI) Tract: A structure that extends from the mouth to the anus and supplies the body and itself with water and electrolytes. Its major functions include digestion, absorption, excretion, and motility.
Divisions of the Gastrointestinal Tract:
- Esophagus
- Stomach
- Small Intestine:
  - Duodenum
  - Jejunum
  - Ileum
- Large Intestine:
  - Colon
  - Rectum

Consists of the following layers (from inner to outer):
- Mucosa
- Submucosa
- Muscularis Proprius (or Muscularis Externa)
- Serosa
Layers of the Mucosa:
- Epithelium
- Lamina Propria
- Muscularis Mucosae
Most Important Mucosal Layer: The epithelium, due to its roles in absorption and secretion.
Second Most Important Overall Layer: The serosa, due to its involvement in conditions like peritonitis.
Muscle Layers (Muscularis Proprius): Contains two distinct layers:
- Inner thick circular muscle layer.
- Outer thin longitudinal muscle layer.

Purpose: To orchestrate, regulate, and organize the various functions of the gut, such as digestion, secretion, motility, and absorption.
- Example: Prevents immediate defecation after eating.
Two Main Control Systems:
- Intrinsic Control System: Located within the walls of the gastrointestinal tract.
- Extrinsic Control System: Located outside the gastrointestinal tract, but still controls its functions.
Both intrinsic and extrinsic systems are comprised of two components:
- Nerves
- Endocrine cells

Location: The primary branch of the intrinsic control system, located within the walls of the gastrointestinal tract, sandwiched between the layers (mucosa, submucosa, muscularis, serosa).
Known as "the second brain".
Definition: A collection of neurons located entirely within the wall of the gastrointestinal tract.
Components: Consists of two ganglionated plexuses:
- 1. Myenteric Plexus (Auerbach's Plexus):
  - Location: Sandwiched between the two muscle layers (the inner thick circular and the outer thin longitudinal muscle layer).
  - Primary Concern: Motility (e.g., duration of contraction, strength of contraction, velocity, rhythm).
  - Unique Action: Inhibits sphincters.
- 2. Submucosal Plexus (Meissner's Plexus):
  - Location: Located underneath the mucosa, within the submucosa.
  - Primary Concern: Secretion and absorption, primarily by regulating blood flow (blood acts as the vehicle for absorption and secretion).
Neural Density: The ENS contains more neurons than the spinal cord, highlighting its importance.

Compared to other neurons in the body (e.g., radial, ulnar, sciatic nerves), enteric neurons exhibit several key differences:

1. Slow Opening Ion Channels: The ion channels in enteric neurons open more slowly.
2. Prolonged Action Potential: Due to the slow opening of ion channels, ions ( $Ca^{2+}$ ) continue to flow in for a longer duration, resulting in a prolonged action potential.
3. Calcium-Mediated Depolarization: In the smooth muscle cells of the GI tract ( $99.99\%$ of muscles), action potentials are primarily due to the influx of calcium ions ( $Ca^{2+}$ ) into the cell, rather than sodium ions ( $Na^{+}$ ) as seen in many other neurons.
4. Presence of Varicosities: Enteric neuron axons have bulges or swellings called varicosities along their entire length. These varicosities contain and release neurotransmitters.
- Significance: This widespread release of neurotransmitters along the axon allows for the stimulation of multiple smooth muscle cells simultaneously, facilitating coordinated actions like peristalsis along significant lengths of the GI tract.
- Contrast: In regular neurons, neurotransmitters are typically secreted only from the presynaptic terminal at the very end of the neuron.
- Clinical Implication: Improper functioning of varicosities can lead to a lack of neurotransmitter release, resulting in no contraction and no peristalsis.

To simplify the understanding of the over $100,000,000$ enteric neurons, they are classified into three main categories:

1. Based on Morphology (Shape of the Enteric Neuron):
- Dogiel Type 1 Neurons:
  - Shape: Small cell bodies with multiple short dendrites (spikes).
  - Nature: Motor neurons.
- Dogiel Type 2 Neurons:
  - Shape: Large cell bodies with one long dendrite.
  - Nature: Sensory neurons.
2. Based on Electrophysiological Properties (Electrical Activity):
- S-type (Synaptic) Neurons:
  - Electrical Activity: Exhibit short, quick action potentials (duration of milliseconds).
  - Nature: Motor in nature (corresponds to Dogiel Type 1).
- AH-type (After Hyperpolarization) Neurons:
  - Electrical Activity: Exhibit long action potentials (duration of seconds) due to prolonged opening of calcium ion channels.
  - Nature: Sensory in nature (corresponds to Dogiel Type 2).
3. Based on Chemical Coding (Neurotransmitter Content):
- Excitatory Neurons:
  - Neurotransmitters: Acetylcholine ( $ACh$ ) and Substance P.
  - Action: Excitatory, causing muscle contraction.
- Inhibitory Neurons:
  - Neurotransmitters: Vasoactive Intestinal Peptide (VIP) and Nitric Oxide (NO).
  - Action: Inhibitory, causing muscle relaxation.

Understanding these classifications and unique properties of enteric neurons is critical for comprehending various clinical cases.
Example: Gallstones, a common issue in companion animals, can lead to symptoms like vomiting, diarrhea, and fatty stools. The proper functioning and interactions of these enteric neuron types are fundamental to addressing such gastrointestinal pathologies.