Regulators of GI Function (Part I)

Question 1

What are the 2 main regulators of the gastrointestinal tract?

Answer 1

1. Autonomic Nervous system as the extrinsic regulator

2. The Enteric nervous system as the intrinsic regulator

Question 2

What is the function of Acetylcholine in GI function?

Answer 2

ACh has a stimulatory effect on effector tissues of the GI tract. It increases salivary secretions, peristalsis (intestinal motility) and relaxes sphincters. It is an important regulator of overall GI function.

Question 3

What is the function of Norepinephrine in GI function?

Answer 3

NE increases fluid reabsorption, decreases peristalsis and constricts sphincters. It is an important regulator of VASCULAR tone but a much less important regulator of overall GI function.

Question 4

What is VIP and what is its function?

Answer 4

Vasoactive Intestinal peptide is an inhibitory NT that is the primary Non-cholinergic, Non-adrenergic (NANC) nerve transmission . VIP opposes the normal SMC tone, relaxes GI smooth muscle and stimulates epithelial secretion of fluid and HCO3-.

Question 5

What role does ACh play in the esophagus? How does this differ from the effect of VIP?

Answer 5

Acetylcholine excites SM cells of the esophagus. VIP is inhibitory but is also involved with functional relaxation of the normally high-toned esophagus.

Question 6

What is the deal with Achalasia? What is the cause?

Answer 6

This condition is linked with the failure of the Lower esophageal sphincter (LES) to relax. There is no peristalsis leading to vomiting of undigested food. This is caused by the loss of inhibitory neurons resulting in high LES tone.

Question 7

What nerve provides most of the parasympathetic innervation to the GI tract? What effect does it have?

Answer 7

Vagal nerves provide PSNS innervation to most of the GI tract. It functions to stimulate peristalsis and secretions.

Question 8

All preganglionic nerves of the PSNS release acetylcholine to act on ____ receptors. All postganglionic PSNS nerves release ____ that acts on _______ receptors.

Answer 8

Pregang PSNS nerves release ACh that acts on nicotinic (N2) receptors; Postgang PSNS release ACh on muscarinic (G-protein coupled) receptors.

Question 9

Preganglionic fibers of PSNS synapse on _____.

Answer 9

Effector tissue of the enteric nervous system

Question 10

Do PSNS afferents relay nociceptive signals? If not, what input do they relay?

Answer 10

PSNS afferents DO NOT carry pain signals to the CNS. These fibers relay changes in pH, distension and muscle tone either to the brainstem of spinal cord, depending on the signal.

Question 11

Walk through the process of the “Vago-vagal Reflex”, notably in the stomach.

Answer 11

Distension of the GI is detected by mechanoreceptors. These relay a signal to the dorsal vagal complex (DVC) via afferent nerves. The DVC sends a response signal for secretion of HCl, pepsinogen or gastrin from stomach cells.

Question 12

List the prevertebral ganglia for the foregut, midgut and hindgut, respectively.

Answer 12

Foregut - Celiac ganglia;
Midgut - Superior Mesenteric ganglia;
Hindgut - Inferior Mesenteric ganglia

Question 13

Preganglionic nerves of the SNS release _____. Postganglionic nerves of the SNS release ______ which acts on ________ receptors.

Answer 13

Pregang SNS release ACh; Postgang SNS release NE that acts on G-protein coupled receptors. This stimulates pro-kinetic and pro-secretory functions.

Question 14

What are the 2 types of pain afferents in that can be perceived from the abdomen or retroperitoneum?

Answer 14

1. Visceral peritoneum - autonomic pain related to the peritoneal covering, hollow organ or mesentery.
2. Parietal peritoneum - somatic pain pertaining to the peritoneal lining of the abdominal wall

Question 15

Describe the types of input that visceral pain relays from the abdominal organs.

Answer 15

Visceral pain relays tension, mesenteric traction, overdistension, visceral muscle spasms, ischemia and inflammation.

Question 16

There is inflammation of a gallbladder that does not touch the parietal peritoneum. Will the victim be able to lateralize the pain?

Answer 16

No. Since this inflammation is visceral pain (since it doesn’t touch the parietal peritoneum), he or she will not be able to pinpoint which side it’s coming from. This is because visceral pain does not lateralize.

Question 17

Why does visceral pain not lateralize?

Answer 17

Visceral pain does not lateralize because GI structures originated from the midline.

Question 18

A visceral muscle spasm from the pyloric sphincter of the stomach will be relayed to what prevertebral ganglia? Where will this discomfort be felt?

Answer 18

Nociceptive afferents will relay the muscle spasm as visceral pain to the celiac ganglion. This will be felt around the epigastric region of the abdomen (upper quadrants above the umbilicus).

Question 19

Internal rectal hemorrhoids (above the pectinate line) will have pain signals relayed to what prevertebral ganglia? Where will this discomfort be felt?

Answer 19

Pain afferents will relay this pain from the hindgut to the inferior mesenteric ganglia. This can be felt at the hypogastric region (below the umbilicus).

Question 20

Describe the function and composition of the myenteric plexus.

Answer 20

The Myenteric plexus can be found within the GI tract form the esophagus all the way to the rectum. It is involves peristalsis of 2 or more smooth muscle layers and is responsible for motility (contraction/relaxation) when stimulated.

Question 21

Describe the function and compostion of the submucosal plexus.

Answer 21

The Submucosal plexus of the enteric nervous system can only be found in the small and large intestines. It is closer to the lumen than the myenteric plexus and contains sensory neurons and mucosa. It is responsible for timed secretion of fluid when distended.

Question 22

Describe a pre-programmed response that the enteric nervous system might elicit. What is the goal of this response?

Answer 22

Overdistension of the GI tract or bacterial endotoxins can lead to A LOT of fluid/electrolyte secretion and GI propulsion. This is done to clear out the bowels and move any fluid past the obstruction or toxin.

Question 23

What is G-RP and its function?

Answer 23

Gastrin-releasing Peptide is a NANC that stimulates Gastrin and CCK release. This functions to upregulate gastric acid and pancreatic enzyme secretion.

Question 24

The upper esophagus is composed of _______ muscle that is regulated by _____ neurotransmitter. Whereas, the lower esophagus consists of _____ muscle that is modulated by ________ and _______ which has ______ and _______ effects, respectively.

Answer 24

Upper esophagus made of striated skeletal muscle is regulated by Acetycholine. The lower esophagus is made up of smooth muscle cells whose functions are stimulated by ACh or inhibited by VIP/ Nitric Oxide.

Question 25

Describe what leads to the high Lower esophageal tone present in the Achalasia condition.

Answer 25

The normal wave of peristalsis associated with a progressing slow wave is absent. This is due to the loss of VIP/NO neurons that is associated with the relaxation that is necessary for an effective swallow. This results in smaller propulsion waves and a higher LES tone.

Question 26

Explain the clinical significance of “VIPomas”.

Answer 26

Rare neuroendocrine tumors in the pancreas pump out XS amounts of VIP that results in excessive watery diarrhea, hypokalemia and dehydration. This conditon even persists with fasting.

Question 27

Where do preganglionic PSNS fibers synapse in the GI tract? What is the significance of this?

Answer 27

PSNS Pre-G fibers synapse DIRECTLY on the enteric plexus of the GI tract. This makes the enteric nervous system Post-ganglionic PSNS fibers.

Question 28

What is the function of enteroendocrine cells? What makes them so unique?

Answer 28

Enteroendocrine cells are neuroendocrine cells that secrete hormones into circulation and connect to the enteric nervous system. These do not have neural crest origin like those of the ENS. Instead they are derived from ENDODERM.

Question 29

What occurs if there is a knockout of Enteroendocrine cells (EECs) ?

Answer 29

KO of enteroendocrine cells results in INTENSE diarrhea, severe dehydration and ultimately death. Plainly stated, these cells are essential for life!

Question 30

List some factors that regulate the release of GI hormones from EECs.

Answer 30

Nutrient chemosensors (lipid, proteins), Luminal pH, Gut Microbiome, other hormones, intraluminal factors.

Question 31

Name some roles that GI hormones have in the proper functioning of the digestive system.

Answer 31

Regulate water, electrolyte metabolism, enzyme secretion. Regulate GI motility and mucosal growth. Stimulate release of other GI hormones (trophic effect)

Question 32

What is the significance of hormone families from EECs?

Answer 32

Hormones of related families usually have terminal peptides which infers that they originated from similar pre-hormones or proteins. The active hormones start out big but are then modified into smaller molecules via post-translational processing.

Question 33

What are the 2 general hormone families revolved around enteroendocrine cells? Where do a lot of the EECs and their hormones overlap in the GI tract?

Answer 33

1. Gastrin and CCK
2. Secretin and related molecules
   Although GI hormones are distributed throughout the GI, they overlap in the proximal portion of the small intestine (duodenum). Moving more distally from there, the numbers drop then pick back up in the rectum.