Smooth Muscle and the Enteric Nervous System

Question 1

List the areas of the GIT that contain skeletal muscle.

Answer 1

Skeletal muscle in the GIT is located in the:

1 - Pharynx.

2 - Top 1/3 of the oesophagus.

3 - External anal sphincter.

Question 2

List the general functions of the GIT.

Answer 2

General functions of the GIT include:

1 - Digestion.

2 - Absorption.

3 - Secretion.

4 - Motility.

Question 3

Describe the arrangement of smooth muscle in the GIT.

Answer 3

• The outer layer consists of longitudinal muscle.

- Running perpendicular to the longitudinal muscle is an inner layer of circular muscle.

Question 4

List the types of contractions of smooth muscle in the GIT.

Describe the nature of these contractions.

Where do these contractions occur?

Answer 4

1 - Phasic contractions.

• These involve rapid contraction and relaxation.
• They occur in the body of the oesophagus, stomach antrum, small intestine and large intestine.

2 - Tonic contractions.

• These involve sustained contractions.
• They occur in sphincters and the upper stomach.

Question 5

How is the electrical activity of smooth muscle in the GIT initiated?

Answer 5

• Pacemaker cells known as interstitial cells of cajal (ICC) are electrically coupled to the smooth muscle cells through gap junctions.
• They have a slowly oscillating resting membrane potential, creating slowly-spreading contractile waves throughout the GIT.

Question 6

How do action potentials travel between adjacent smooth muscle fibres?

Answer 6

Action potentials travel between adjacent smooth muscle fibres through gap junctions known as nexuses.

Question 7

Describe the cellular mechanism that brings about contraction and relaxation in the smooth muscle of the GIT.

Answer 7

Contraction:

1 - Ca2+ influx occurs by two mechanisms:

• Membrane depolarisation opening Ca2+ channels.
• Muscarinic receptors triggering the Gq (PLC) pathway, which opens Ca2+ channels via IP3.

2 - Ca2+ binds to calmodulin.

3 - The calmodulin-Ca2+ complex activates myosin light chain kinase.

4 - Myosin light chain kinase phosphorylates myosin.

5 - This allows myosin to bind to actin, producing contraction.

Relaxation 1:

1 - SERCA, a Ca2+ pump, causes Ca2+ reuptake into the sarcoplasmic reticulum, decreasing free intracellular Ca2+ to resting levels.

2 - This activates myosin light chain phosphatase.

3 - Activated myosin light chain phosphatase dephosphorylates myosin, causing it to dissociate from actin.

or

Relaxation 2:

1 - Vasoactive intestinal peptide (VIP) binds to beta adrenergic receptors.

2 - This triggers the Gs (PKA) pathway, which causes phosphorylation of myosin light chain kinase via PKA.

3 - This disables myosin light chain kinase, meaning myosin cannot be phosphorylated and so cannot bind to actin to produce contraction.

Question 8

What is the name of the intrinsic innervation of the GIT?

Answer 8

The intrinsic innervation of the GIT is known as the enteric nervous system.

Question 9

List the components of the enteric nervous system.

Where is each component of the enteric nervous system located?

How does their location reflect their function?

Answer 9

The enteric nervous system is composed of:

1 - An outer myenteric plexus, which is located between the circular muscle and longitudinal muscle layers.

• This is beneficial because the myenteric plexus is implicated in the control of GIT motility.

2 - An inner submucosal plexus, which is directly above the submucosa of the GIT.

• This is beneficial because the submucosal plexus is implicated in the control of GIT secretion.

Question 10

List the functions of the myenteric plexus.

Answer 10

Functions of the myenteric plexus:

1 - INcreases tonic contraction.

2 - Increases the intensity of rhythmic contractions.

3 - Increases the rate of rhythmic contractions.

4 - Increases the velocity of conduction of action potentials.

Question 11

List the functions of the submucosal plexus.

Answer 11

Functions of the submucosal plexus:

1 - Increases secretory activity.

2 - Modulates intestinal absorption.

Question 12

List the types sensory receptors of the enteric nervous system.

Give an example of each type, and a reflex involving them.

Answer 12

1 - Mechanoreceptors.

• E.g. stretch receptors in smooth muscle cells activate a reflexive contractile response.

2 - Chemoreceptors.

• E.g. enterochromaffin cells stimulate enterocytes to increase absorption.
• This is mediated by serotonin.

Question 13

How does the autonomic nervous system influence contractile activity of the enteric nervous system?

Answer 13

• Parasympathetic neurones increase depolarising events of the enteric nervous system, resulting in stronger contraction of the GIT and increasing motility.
• Sympathetic neurones increase hyperpolarising events of the enteric nervous system, resulting in relaxation of the GIT and inhibiting motility.

Question 14

Describe the distribution of nerves constituting the extrinsic parasympathetic innervation of the GIT.

Answer 14

• The dorsal vagal nerve innervates all of the GIT from the oesophagus to the ascending colon (and part of the transverse colon).
• Spinal segmental nerves of roots S1-S3 innervate the rest of the GIT (the rest of the transverse colon to the anus).
• These are all preganglionic fibres.

Question 15

List 6 reflexes of the enteric nervous system.

Which of these reflexes are excitatory and which are inhibitory?

Answer 15

Excitatory reflexes:

1 - Gastroenteric.

2 - Gastroileal.

3 - Gastrocolic.

4 - Duodenocolic.

Inhibitory reflexes:

5 - Ileogastric.

6 - Intestinointestinal.

Question 16

Describe the gastrocolic reflex.

Answer 16

• The gastrocolic reflex is initiated by distension of the stomach.
• This causes excitation of both absorptive and smooth muscle cells of the large intestine, preparing it for digestion.

Question 17

Describe the ileogastric reflex.

Answer 17

• The ileogastric reflex is initiated by distention of the ileum.
• This inhibits emptying of the stomach, preventing further chyme from entering the duodenum.

Question 18

What is Hirschsprung’s disease (HD)?

Describe the possible patterns of disease.

What causes it?

Answer 18

• Hirschsprung’s disease is a congenital lack of any ganglionic cells in ENS plexi.
• It tends to start in the rectum and anus, and can extend throughout the whole large intestine.
• It is caused by mutations to the RET gene.

Question 19

List the classes of Hirschsprung’s disease (HD).

Answer 19

1 - Classical HD.

• The aganglionic segment does not extend beyond the upper sigmoid colon.

2 - Long-segment HD.

• The aganglionic segment extends beyond the upper sigmoid colon but does not affect the entire large intestine.

3 - Total colonic aganglionosis.

Question 20

How is Hirschsprung’s disease treated?

Answer 20

Hirschsprung’s disease is treated by surgically removing the aganglionic segment of large intestine, and anastomosing the leftover proximal and distal sections of large intestine.

Question 21

What is Chagas disease?

Answer 21

• Chagas disease is an infectious disease of parasitic nature that causes a significant reduction in the number of ganglionic cells in ENS plexi.
• It is caused by Trypanosoma cruzi.

Question 22

What is achalasia?

Answer 22

• Achalasia is a significant reduction in the number of inhibitory neuronal cells in ENS plexi innervating the lower oesophagus.
• It causes failure of relaxation of the gastroesophageal sphincter and lower oesophagus.

Question 23

List 4 treatments for achalasia.

Answer 23

1 - Nitrates (direct relaxant effect).

2 - Ca2+ channel blockers.

3 - Botulinum toxin (prevents ACh release at the NMJ).

4 - Pneumatic dilation (disrupts the circular muscle of the lower oesophageal muscle).

5 - Surgical myotomy.

Question 24

What is megacolon?

Give an example of a cause of megacolon.

Answer 24

• Megacolon is a condition in which the colon fills with excessive amounts of faeces.
• In an attempt to expel the faeces, the colon becomes hypertrophic.
• Megacolon can occur in patients with Hirschsprung’s disease or Chagas disease (proximal to the section of large intestine affected by HD / Chagas).

Question 25

What is the volume of the stomach when empty?

Answer 25

The volume of the empty stomach is ~50ml.

Question 26

How does the intragastric change when filling?

What explains this pressure change?

What is the implication of this?

Answer 26

• The intraluminal pressure of the stomach changes only very slightly when filling. This is due to the large number of folds in the stomach.
• Intragastric pressure only starts to increase once filling continues beyond opening of these folds.
• Opening of the folds is mediated by the vago-vagal reflex, termed ‘receptive relaxation.
• This means that failure of vagal innervation causes intragastric pressure to increase.

Question 27

List the functions of the stomach.

Answer 27

1 - Storage function.

2 - Digestive function.

3 - Sieving function (liquids and small particles leave the stomach more rapidly than large particles).

Question 28

Describe the gross anatomy of the stomach.

Answer 28

• The cardia is the area where matter enters the stomach from the oesophagus.
• The fundus is the uppermost section of the stomach.
• The body is largest area covering the central part of the stomach.
• The pylorus is the area of the stomach preceding the small intestine.

Question 29

Describe the process by which matter is processed in the pylorus.

Answer 29

1 - Propulsion (rapid flow of liquids and suspended small particles towards the pylorus, with delayed flow of large particles).

2 - Grinding (emptying of liquids with suspended small particles into the small intestine, and retention of large particles, forming a bulge. The large particles are subject to grinding at the antrum).

3 - Retro-propulsion (flow of large particles back to the body of the stomach and clearing of the terminal antrum into the pylorus where the cycle starts again).

Question 30

List 2 functions of the pylorus.

Answer 30

1 - Allows regulated emptying of the gastric contents.

2 - Prevents regurgitation of the duodenal contents into the stomach.

• This is important because although the gastric mucosa is highly resistant to acid, it can be damaged by bile regurgitated from the duodenum.
• Likewise, the duodenum is highly resistant to bile but may be damaged by excessive acid emptying into the duodenum.

Question 31

List the phases of gastric secretion.

When does each phase occur?

Answer 31

1 - Cephalic (initiated by the approach of food into the stomach or sight / smell of food).

2 - Gastric (initiated by food in the stomach).

3 - Intestinal (initiated by food in the intestine).

Question 32

Describe the cephalic phase of gastric secretion.

Which nerve mediates this phase?

Answer 32

• The cephalic phase of gastric secretion is inhibitory.
• It results in the relaxation of the stomach, enabling it to store large volumes of food.
• It is mediated by the inhibitory vagal fibres.

Question 33

Describe the gastric phase of gastric secretion.

Which nerve mediates this phase?

Answer 33

• The gastric phase of gastric secretion is excitatory.
• It results in:

1 - Emptying of the stomach at a rate proportional to the volume of food in it.

2 - The myogenic reflex, in which stretching smooth muscle causes a reflexive contraction.

• The myogenic reflex is activated by pressure receptors, which send impulses in local nerve plexi and in the vagus nerve.

3 - The gastroileal reflex.

4 - Release of enzymes in response to metabolites.

Question 34

Describe the intestinal phase of gastric emptying.

Which nerve mediates this phase?

Answer 34

• The intestinal phase of gastric secretion is mainly inhibitory.
• The inhibition involves adapting the workload of the GIT as a function of the state of the digestive process (giving the GIT time to digest food before more food is eaten).
• It involves mechanisms activated by duodenal chemoreception:

1 - Low pH in the duodenum stimulates the secretion of secretin.

2 - High levels of lipids in the duodenum stimulates the secretion of CCK.

3 - High levels of amino acids stimulate the secretion of gastrin.

4 - High levels of carbohydrates stimulate the secretion of GIP.

• It also involves motor reflexes such as the ileogastric reflex.