Neuroendocrine Control Of Gi

Front 1

Control Mechanisms in the gut

Back 1

-Long Neural reflexes (Neurocrine - Involve the CNS)
-Short neural reflexes (neurocrine - enteric)
-Hormones (endocrine)
-local chemical control (paracrine)

Front 2

General scheme of control

Back 2

-Cephalic Phase (long reflexes)
-Gastric Phase (long, short reflexes & hormones)
-Intestinal Phase ( long, short reflexes &hormones)
-Excitatory and Inhibitory

Front 3

Conditioned and non-conditioned reflexes

Back 3

-Non-conditioned (eg: taste buds on tongue- higher centres not involved)
-Conditioned (eg: pavlov dog's- higher centres involved)

Front 4

Long Neural reflexes

Back 4

-Receptors ( Extra-oral: eyes, ears, nose. Oral: taste. Alimentary wall: chemo- and stretch receptors)
-Afferent nerves
-GI secretomotor centres (brain)
-efferent nerves
-effector organs

Front 5

Short neural reflex

Back 5

Example: Enterogastric reflex
-Acid in duodenum
-Pathway (intramural nerve plexi or coeliac plexus)
-Stomach Wall
-Inhibitory

Front 6

Cholecystokinin

Back 6

Source: I Cells of duodenum and jejunum and neurons in ileum and colon.
Target: Pancreas and Gallbladder
Action: increased enzyme secretion and increased contraction
Release:Amino Acids in duodenum

Front 7

Gastric-Inhibitory Peptide

Back 7

Source: K cells in duodenum and jejunum
Target: Pancreas
Action: Exocrine- decreased fluid absorption Endocrine- increased insulin release.
Release: Amino acids in duodenum.

Front 8

Gastrin

Back 8

Source: G cells, antrum of stomach.
Target: Parietal cells in body of stomach.
Action: increased H+ secretion.
Inhibition: acid in stomach

Front 9

Gastrin-releasing peptide

Back 9

Source: Vagal Nerve endings.
Target: G cells in antrum of stomach.
Action: Increased gastrin release.

Front 10

Glucagon

Back 10

Source: a cells of pancreatic islets of Langerhans.
Target: Liver
Action: - increased glycogenolysis. - Increased Gluconeogenesis.

Front 11

Guanylin

Back 11

Source: Ileum and colon.
Target: Small and large intestine
Action: increased fluid absorption.

Front 12

Motilin

Back 12

Source: Endocrine Cells in upper GI tract.
Target: Esophageal Sphincter, stomach, duodenum.
Action: increased smooth muscle contraction.

Front 13

Neurotensin

Back 13

Source: endocrine cells, wide-spread in GI tract.
Target: Intestinal Smooth muscle
Action: vasoactive stimulation of histamine release.

Front 14

Peptide YY

Back 14

Source: endocrine cells in ileum and colon.
Target: Stomach & Pancreas
Action: decreased vagally mediated acid secretion. Decreased enzyme and fluid secretion (pancreas)
Release: Fat in ileum.

Front 15

Secretin

Back 15

Source: S cells in small intestine
Target: Pancreas & Stomach
Action: Increased HCO3- and fluid secretion by pancreatic ducts. Decreased gastric-acid secretion (stomach)
Release: Acid in duodenum

Front 16

Somatostatin

Back 16

Source: D cells of stomach and duodenum, gamma cells of pancreatic islets.
Target: Stomach, intestine, Pancreas and Liver.
Action: decreased gastric release (stomach)
increased fluid absorption/decreased secretion, increased smooth muscle contraction (intestine).
decreased endocrine/exocrine secretions (pancreas)
decreased bile flow (Liver)
Release: Acid in stomach.

Front 17

Substance P

Back 17

Source: Enteric neurons.
Target: Enteric neurons.
Action: neurotransmitter.

Front 18

Vasoactive intestineal peptide

Back 18

Source: ENS neurons
Target: Small Intestine, Pancreas
Action: decreased smooth muscle relaxation, increased secretion by small intestine
increased secretion by pancreas.

Front 19

Paracrine Regulators

Back 19

-Histamine - increased gastric acid secretion.
-Prostaglandin - decreased gastric acid secretion, increased gastric mucosal blood flow, increased mucus & HCO3- secretion, increased intestinal secretion.

Front 20

Neurons of the Enteric nervous system

Back 20

Sensory (Afferent) Neurons
-mechanical - distension.
-Chemical - pH, specific nutrients, osmolality.
-Thermal.
Secretomotor (efferent) Neurons
-Motility -smooth muscle.
-Secretion -epithelial & endocrine, vasculature.
Interneurones
-integration of information.

Front 21

Integration of the ANS and ENS

Back 21

Parasympathetic (generally stimulates)
-Vagus: Oesophagus to proximal colon.
-Pelvic: Distal large intestine.
Sympathetic (generally inhibits)

Combine with Myenteric Plexus and Submucosal Plexus of the ENS.

Front 22

Innervation of intestinal smooth muscle by the ENS

Back 22

Classical theory: neurotransmitters from the ENS act directly on smooth muscle.
Alternative theory: Neurotransmitters from the ENS act on smooth muscle via interstitial cells of cajal.

Front 23

Interstitial cells of Cajal

Back 23

Specialised mesenchymal cells:
-Intramuscular ICC (ICC-IM)
May act as mediator of neurotransmission.
-ICC located alongside myenteric plexus (ICC-MY)
Intrinsic pacemaker of the gasstrointestinal tract.
Generates slow waves (control phasic contractions) - 3/min in stomach -12/min in duodenum.
Electrical activity spread to muscle cells.
Action potentials (&tension) only seen in muscle cells depending on neurotransmitter & hormonal influences.

Front 24

Myenteric Interstitial cells of Cajal

Back 24

- Uptake & periodic release of ca2+ from Ip3 receptor-operated stores appears to be the basis of GI autorhythmicity
-Conduction of slow waves.
- Slow waves conducted to muscle - may lead to action potentials & contraction (opening of voltage-gated Ca2+ channels)

Front 25

Regulation by the ANS - direct

Back 25

Parasympathetic
-Acetylcholine -Excitatory, muscarinic.
Sympathetic
-Noradrenalin - Inhibitory: B, Sphincters: B relaxation; a contraction.
Pre-synaptic: a inhibition of ACh release from interneurons.

Front 26

Regulation by the ENS

Back 26

Interneurones (plexi)
- Excitatory - Acetylcholine
- Inhibitory - 5HT, NA, Enkephalin

Front 27

Pharmacological Regulation

Back 27

Opiates
-Loperamide - Inhibit - Mimic endogenous enkephalin.

Anticholinergics - Inhibit - block cholinergic transmission (IBS)

Prokinetics
-Metoclopramide - Inhibits dopamine induced relaxation ACh stronger effect increasing motililty LOS increases tone to prevent reflux. Inhibition of 5-HT release?

Front 28

Motility of the Oesophagus

Back 28

Swallowing Reflex
-Reflex orchestrated centrally by the swallowing program generator in brainstem, via Vagal fibres.
-Upper oesophageal sphincter opens.
-Wave of contraction of circular muscle, peristalsis, along the oesophageal sphincter.
-10-15 seconds.

Front 29

Motility of the Oesophagus

Back 29

-Upper third is striated muscle.
-peristalsis controlled by vagus.
-myelinated nerves - direct contact with striated muscle fibres.
-Excitatory neurotransmitter is ACh (nicotinic)
-Primary (swallow) peristalsis result of sequential activation of lower motor neurons in the NA.
-Secondary (distension peristalsis mediated by central reflex.
- Lower third is smooth muscle.
-Primary peristalsis controlled by vagal nerves.
- Preganglionic fibres synapse with enteric nervous system.
- Excitatory pathway originates in the rostral DMN.
- Inhibitory pathway originates in the caudal DMN.
- Secondary (distension peristalsis mediated by local reflex.

Front 30

Function of Oesophageal sphincters - LOS

Back 30

Lower Oesophageal Sphincter
-Tonically contracted at rest - Myogenic & Cholinergic tone.
-LOS relaxes after swallowing &/or distension. -mediated by NO and possibly VIP.
-After contraction - wave from oesophageal body - mediated by ACh& possibly Substance P.

Achalasia
-Failure of LOS to relax - Defective innervation/ defective enteric nervous system.

Incompetence
-GORD

Front 31

The stomach as a reservoir

Back 31

Receptive relaxation
- LOS & proximal stomach relax; anticipation.
- Vaso-vagal reflex.
-Inhibitory neurotransmitters: NO, VIP, ATP

Gastric Accommodation.
-relaxation upon entry of material into stomach.
-Controlled by ENS.
-No change in intragastric pressure.

Front 32

Mixing & Emptying of Stomach

Back 32

Propulsion
-Persistaltic contraction propelling material towars antrum & occlusion of pylorus.
-Initiatedby pacemaker in greater curvature.

Grinding
- Churning of trapped material in antrum.
-Only particles <2mm in diameter pass through pylorus.

Retropulsion
-Most of bolus is returned to the gastric body to be broken down.

Front 33

Gastric Emptying

Back 33

Feedback control of gastric emptying "intestinal brake"
-Emptying inhibited by stomach contents entering the small intestine -eg: HCl, amino acids, long chain fatty acids.
-Release of intestinal hormones - CCK, glucagon-like peptide & PYY
-Entero-gastric neural reflexes - vagus

Front 34

Vomiting

Back 34

Retching
-Dry Heaves
-Chyme into the oesophagus followed by immediate backflow. Due to the relaxation of distal and contraction of the proximal oesophagus.

Voimiting
-Emesis.
-Associated with contraction of intecostal muscles & increased intrathoracic pressure

N.B. result of skeletal muscle contractions.