The Enteric Nervous System

Question 1

what is the enteric NS?

Answer 1

It is the 3rd division of ANS
It forms the Intrinsic innervation of the GI tract
The ENS can be described as intrinsic as all necessary components to produce an effect are located in the GI tract. It does not need connection elsewhere to function (but can communicate with the brain)
The ENS runs from the oesophagus all the way to the rectum (Entire GI tract)
ENS also involved in the control of the pancreas and biliary system.
It has a huge network of neurones (80-100 million)
Because it is so complex it is sometimes called the “little” brain in GI tract.

Question 2

what is the enteric NS and why is it relevant?

Answer 2

Function: Associated with the process of Digestion
When it is functioning abnormally it can cause disease of GIT
The enteric NS can interact with the brain

Question 3

if you stain the GI tract, what would you see histologically?

Answer 3

Green fluorescent circles are the nuclei or neurones and the long fibres are axons
There are lots of connections between neurones in the wall of GI tract.
Neurones clump together and send their axons off together

Question 4

what are plexuses?

Answer 4

The collections of neurones in the ENS are called plexuses.

Question 5

what are the 2 major plexuses in the enteric NS?

Answer 5

There are two major plexuses of ganglion cells and fibre bundles:

• Submucosal (Meissner’s) plexus
  Found in the stomach and intestines ONLY
• Myenteric (Auerbach’s) plexus
  Found in full length of GIT

The 2 plexuses are extensively interconnected

Question 6

describe this cross section of the GI tube

Answer 6

Part of GI tube (hole in the middle is where food passes through)
Various layers contain different cell types.
(Region shown by circle is shown in 2D in the next flashcard)

Question 7

describe this zoomed in 2D diagram of the GI tube

Answer 7

food goes through the lumen
the myenteric plexus is always found between the 2 layers of smooth muscle
the longitudinal arranged SM cells are on the outside, then myenteric plexus in the middle and another layer of SM cells arranged in circular fashion
‘my’ in myenteric –> ‘myo’ in muscle

the submucosal plexus contains BV and assorted pieces of CT
Its found in between the circular SM layers and the submucosa

Question 8

what types of neurones are found within the plexuses?

Answer 8

Afferent neurones:
Associated with sensory receptors e.g mechanoreceptors and chemoreceptors
Mechanoreceptors detect physical presence of food in GIT
Chemoreceptors detect sensory chemicals released by food

Interneurons – coordinate input and output
They can be: excitatory and inhibitory

Efferent (secretomotor) neurones:
Secretomotor as they impact smooth muscles and secretory glands (the effectors)
Can be excitatory or inhibitory
Many neurotransmitters including ACH and various peptides

Question 9

how does the ENS carry out reflexes?

Answer 9

Receptors, sensory neurones, interneurons, efferent neurones and effectors are all put together to produce a reflex arc.
Most of the ENS actions are carried out via reflexes
They are often known as short reflexes because they only involve neurones in the GI tract.

Question 10

what is the function of enteric reflexes?

Answer 10

Controls motility, secretion and blood flow in the gut
Motor reflex in ENS:
e.g. Peristalsis: the movement of food in a rhythmic fashion along GI tract.
involves the myenteric plexus.

Question 11

explain how the myenteric plexus is involved in reflexes in the gut?

Answer 11

sensory neurones are associated with mechanoreceptors and chemoreceptors.
This means they can detect the contents of the lumen (chemoreceptors) and the amount of food stuff via the degree of stretch of the wall of GI tract (mechanoreceptors) in response to the food enter.
The information from receptors are transmitted into the plexus.
This information is then distributed via the interneurons to alter the impact of efferent neurones which interact with the muscular layers.

Question 12

using the diagram, explain how the motor reflex of ENS works

Answer 12

Involves myenteric plexus
(M for movement and myenteric)
Bolus (food) moves from the mouth to the Anus.
At the top of the diagram you can see a representation of the diameter of the GI tract
In order to propel the bolus along the GI tract we need to contract the muscle of the GI tract behind the bolus to constrict the diameter of the lumen. This will apply pressure forcing the bolus forward.
This will be helped if the GI tract in front of the bolus is relaxed so the bolus can easily move into it.

Question 13

explain the step by step mechanism of motor reflexes in the ENS?

Answer 13

Mechanism:
1. The Bolus stimulates the mucosal sensory receptors (either mechano or chemo).
2. This information is transmitted up to the myenteric plexus.
3. Here via a series of interneurons we can produce two effects
4. Behind the bolus we can use excitatory interneurons to cause an increase in activity of Efferents which cause smooth muscle contraction which decrease the size of the lumen and so squeezes the bolus forward.
5. Infront of the bolus we can use inhibitory interneurons to decrease activity in Efferents which cause smooth muscle in front of the bolus to relax.
6. This occurs simultaneously to give rhythmic movement of the bolus down the GI tract.

Question 14

what does the sensory reflex of the ENS involve?

Answer 14

Occur via the submucosal plexus (S for secretory and submucosal)
1. The food stimulates mechano and chemo receptors which bring the information into the submucosal plexus.
2. Information can also come via the myenteric plexus as well.
3. The interneurons of the submucosal plexus process this information, passing it on to the efferent neurones which then interact with the secretory cells
4. Secretory cells secrete their products into the lumen to help with the digestion and lubrication processes (e.g. enzymes, mucus and acid).

Question 15

explain the general process by which secretions are produced in the ENS

Answer 15

presence of food –> stimulates receptors –> goes to ENS –> submucosal plexus –> secretory neurones –> produce the right kind of secretion (will vary depending on where you are in the GI tract)

Question 16

how is blood flow in the ENS controlled?

Answer 16

Involves both Myenteric and submucosal plexus.
Blood flow to the gut is controlled to match the activity of the gut at a certain time
e.g. if you have eaten a large meal and you need to absorb the products of the digestion and distribute them around the body you need good blood flow, but when GI tract is at rest you don’t need much blood flow.
Some of the efferent neurones are able to innervate the blood vessels and produce vasoactive neurotransmitters which then influence the contraction state of smooth muscle in the vasculature.

Question 17

how does the ENS integrate with the CNS?

Answer 17

ANS (SNS and PNS) afferents are used as an intermediate to send information from the ENS to CNS.
If you eat a large meal you are consciously aware of this. This means information relating to stretch in the GI tract is detected by mechano receptors and makes its way up to the brain.
This is a two-way process i.e. the brain also influences the activity of enteric neurones and thus the GI tract. This occurs via ANS (PNS and SNS) efferents.
The brain also influences enteric activity.
E.g. if you have eaten a large meal and are in a situation where putting a lot of resources into digestion of that meal would be inappropriate the brain can override the activity of the ENS e.g. fight or flight response.

This is a LONG reflex - Sensory information detected in ENS is transmitted up to the brain and the brain responds and causes changes in enteric function.

Question 18

how does CNS influence vary along the GIT?

Answer 18

CNS influence varies along GIT
Once food swallowed, ENS cannot be overridden to stop food travelling
CNS has large control over sphincters which means we can control when we defecate.
Young babies can’t do this. One faeces arrive in their rectum and anus, the pressure of them causes a short reflex to be activated to open the sphincter.
As we get older, we learn to control this so defecation becomes a conscious activity.

Question 19

what happens to the ENS with age?

Answer 19

With age the ENS appears to not function as well
This can influence appetite and nutritional status
May be due to ↓ in neuron number (due to death) so intrinsic reflexes are compromised.

Question 20

what causes diseases in the ENS?

Answer 20

• ENS is sometimes specifically targeted by pathological processes so we only see changes in enteric neurones
• Sometimes enteric neurones are affected with more general neuropathology associated with body wide disease.
• Sometimes there is a functional change in GI tract. This appears to occur due to changes in the function of enteric neurones sometimes due to changes in interaction with the brain.

Question 21

what are the 3 diseases that can occur in the ENS?

Answer 21

Chaga’s disease
Achalasia
Hirschsprung’s disease

Question 22

what is Chaga’s disease?

Answer 22

ENS specific
endemic in South America
trypanosome parasite is transferred into the blood via bite of an insect
the parasite produces a toxin which causes neuron death in ENS
If the ENS is shutdown it means the parasite can be maintained within the body as it doesn’t get eliminated as easily (can’t be defecated out or destroyed by stomach acid etc.)
can also get into your cardiac muscle

Question 23

what is Achalasia?

Answer 23

It affects patient’s oral cavity and what is happening in the oesophagus - this makes it difficult for them to swallow.
It can affect nutrition as they find in hard to swallow food and for it to pass via the peristaltic process down the oesophagus and down through sphincter into the stomach.
It is more common in the elderly and is thought to be due to the loss of inhibitory neurones either in the myenteric plexus of the oesophagus or at the sphincter at the opening of the stomach
can lead to malnutrition and discomfort
There is some evidence that this is an autoimmune process
some evidence that its related to specifically ACh transmission

Question 24

what is Hirschsprung’s disease?

Answer 24

(also known as megacolon)
There is a congenital absence of ENS neurons due to gene mutation
The enteric neurones that are missing are usually found in the distal colon
As the food passes down the GI tract via peristalsis it is getting digested to where we end up only with the waste products.
When the bolus of waste products gets as far as the distal colon, the distal colon is unable to undertake peristalsis so the faeces can’t pass through the restricted area so the faeces build up and cause the colon to distend - megacolon
The build up of faces are a breeding ground for bacteria which can cause inflammation of the colon causing colitis.

Manifests soon after birth
The missing neurones also impact the rectoanalreflex again greatly affecting defecation.
In the worst cases the only option is surgical treatment to remove the colon as we can’t replace the missing neurones.

Question 25

what are some general neurological conditions that could be related to the ENS?

Answer 25

Parkinson’s disease:
- pathogens enter the nervous system via GI tract then travels by enteric neurons to the brain via ParaNS/SympaNS afferents causing death of neurones in brain.
Many individuals with Parkinson’s report they have disrupted gut functions.

Peripheral neuropathies:
- cause changes in gut functions

Myasthenia gravis:
- It is generally associated with somatic nervous system as it involves the production of antibodies against nAChR that are found on skeletal muscles. However antibodies against the AChR associated with smooth muscles can also be produced.

Question 26

how is the gut- brain axis involved in IBS?

Answer 26

IBS (irritable bowel syndrome)
Seems to be a functional problem not associated with pathology.
histologically, they seem to be okay but this is clearly not the case
It is believed there is some form of dysfunctional interaction between the brain and enteric nervous system so the enteric function is disrupted.
IBS is associated with some mental health conditions, especially those that involve increased anxiety.
It is therefore possible that the changes that individuals report if they have anxiety like conditions is down to change in the enteric function which are being driven by changes in the brain itself.

it appears that what is going on in your gut can influence your brain activity

Question 27

what are the different drugs used for ENS?

Answer 27

The complexity of ENS means there are many neurotransmission processes to target with a variety of drugs.
There are neurones in the enteric which release opioids as their neurotransmitters. Therefore, there are opioid receptors.
We can target opioid receptors to change function of ENS and so GI tract.
Many anti-diarrhoeal agents contain the active agent loperamide which act at opioid receptors acting to reduce gut motility and so act as anti-diarrhoeal.
Many analgesia (pain meds) e.g. morphine and codeine are also opioids so when they are taken they can effect opioid receptors in the GI tract and also cause reduction in gut activity. So, they can cause constipation as a side effect.