Appetite regulation

Question 1

3 methods of regulation of function

Answer 1

1) Nervous sytem:
a) Intrinsic (enteric)
b) Extrinsic (autonomic)- interfaces with CNS through this
2) Paracrine
3) Endocrine

Question 2

Enteric (intrinsic) nervous system description

Answer 2

Rich plexus (network) of ganglia (nerve cells + glial cells) interconnected by tracts of fine, unmyelinated nerve fibres.

Question 3

Enteric (intrinsic) nervous system function

If the sympathetic and parasympathetic nerves to the gut are cut?

Answer 3

Integrates the motor and secretory activities of the GI system.
Can function independently of central control.
If SNS/ PNS cut, many motor and secretory activities continue as controlled by the enteric nervous system.

Question 4

Enteric Neural Dysfunction/Degeneration caused by?

Answer 4

Inflammation (ulcerative colitis; Crohn’s disease)
Post-operative injury
Irritable bowel syndrome
Ageing (constipation)

Question 5

Enteric nervous system regulates

Answer 5

Motility
Blood flow
Water and electrolyte transport
Secretion
Absorption

Question 6

Types of neurones in enteric nervous sytem

Feature of all of them?

Answer 6

Sensory: respond to mechanical (stretch), thermal, osmotic and chemical stimuli.

Motor: axons terminate on smooth muscle cells of the circular or longitudinal layers, secretory cells of the gastrointestinal tract, or gastrointestinal blood vessels.

Interneurons: neurons between neurons integrate the sensory input and effector output

Most are multipolar (one axon, multiple dendrites)

Question 7

Nervous plexuses in gut
Location
What does it control?

Answer 7

Major plexuses: Myenteric+ Submucosal;

1) Myenteric plexus: located between the circular and longitudinal smooth muscle layers. Controls activity of muscularis externa. Controls gut motor function.
2) Submucosal plexus: Sensing environment within lumen, Blood flow, epithelial and endocrine cell function.

Minor plexuses
including deep muscular plexus (inside circular muscle), and the ganglia supplying biliary system and pancreas

Question 8

Autonomic nervous system regulates?
Description?
Branches?

Answer 8

Regulates smooth muscle, cardiac muscle and glands.
Not accessible to voluntary control.
Two branches:
i) Sympathetic
ii) Parasympathetic

Question 9

Sympathetic nervous system anatomy in relation to gut

Final effect

Answer 9

Cell bodies of preganglionic neurons in the thoracic and lumbar spinal cord.
Cell bodies of postganglionic neurons in the pre- and para- vertebral ganglia.
Lumbar splanchnic nerves carry sympathetic innervation to the remainder of the gut.
Thoracic splanchnic nerves carry innervation to fore and midgut.
Neurotransmitter= Norepinephrine

Activation of the sympathetic nerves usually inhibit the activities of the GI system.

Question 10

Parasympathetic nervous system anatomy in relation to gut

Final effect

Answer 10

Cell bodies of preganglionic neurons in the brainstem and sacral spinal cord (cranio-sacral)
Cell bodies of postganglionic neurons close to target organs.
Preganglionic neurons synapse on ganglia close to gut wall or directly with enteric plexi
Most of the GI tract via branches of the vagus nerve (down to the level of the transverse colon).
Remainder of the colon, the rectum and the anus receive parasympathetic fibers from the pelvic nerves.
Neurotransmitter =Acetyl Choline

Excitation usually stimulates the activities of the GI tract. (mostly stomach+ duodenum)

Question 11

Autonomic nervous system overall action diagram

slide 16, lecture 11

Answer 11

-

Question 12

Interaction of gut with central nervous system diagram

slide 17, lecture 11

Answer 12

-

Question 13

GI tract is innervated by?

Answer 13

Intrinsic innervation:
Neurons of the enteric nervous system.

Extrinsic innervation:
Afferents (pain, nausea, fullness)
Efferents (coordination - sympathetic and parasympathetic nervous systems).
Complexity allows fine control of the GI tract.

Question 14

Innervation of Autonomic Nervous System (PNS, SNS)

Answer 14

The parasympathetic nervous system innervates the gut via long preganglionic neurones (mostly via the vagus nerve) and short postganglionic neurones to promote gut motility, secretion and digestion

The sympathetic nervous system innervates the gut via short preganglionic and long post ganglionic fibres to inhibit gut motility and secretion, and cause constriction of blood vessels and contraction of sphincters.

Question 15

Function of the gastrointestinal endocrine system

Hormones released by?

Answer 15

Produced by endocrine cells in the mucosa or submucosa of the stomach, intestine and pancreas.

Can act as paracrine or neurocrine (hormones released from neurone e.g. hypothalamus) factors as well as endocrine.

Functions:

1) Regulation of the mechanical processes of digestion (e.g. smooth muscle of GI tract and sphincters, gall bladder).
2) Regulation of the chemical and enzymatic processes of digestion (e.g. secretory cells located in the wall of the GI tract, pancreas and liver).
3) Control of post absorptive processes involved in the assimilation of digested food and CNS feedback regulating intake (e.g. GIP stimulates insulin release from pancreatic beta cells, PYY3-36 acts on the CNS to suppress appetite)
4) Effects on the growth and development of the GI tract (long term effect) (e.g. GLP-2 promotes small intestinal growth).

Question 16

Enteroendocrine cells general structure

Answer 16

General trend= fingers of cytoplasm into lumen with lots of receptors (e.g. fatty acids, amino acids) which can cause appropriate hormone release at basolateral end which is near a capillary

Question 17

Examples of paracrine actions

Answer 17

Histamine released from stomach wall cells is a key physiological stimulus to HCl secretion by gastric parietal cells.

Somatostatin from the stomach can inhibit acid secretion by paracrine mechanisms.

Question 18

Gut hormones

Answer 18

Gastrin
Somatostatin
Secretin
CCK (Cholecystokinin)
GIP (gastric inhibitory peptide)/ (glucose dependent insulinotropic peptide)
PYY (Peptide YY)

Question 19

Gastrin synthesised?

Answer 19

Synthesised in gastric antrum and upper small intestine

Question 20

Gastrin release stimulated by?

Answer 20

Amino acids and peptides in the lumen of the stomach.
Gastric distension.
Vagus nerve directly

Question 21

Gastrin stimulates?

Answer 21

Gastrin stimulates gastric acid secretion.

Question 22

When is gastrin inhibited?

Answer 22

Release inhibited when pH of stomach falls below pH 3.

Question 23

Where is somatostatin produced?

Answer 23

Synthesized in endocrine D cells of the gastric and duodenal mucosa, pancreas (also hypothalamus)
Also in small and large intestine

Question 24

Function of somatostatin in gut?

Answer 24

Somatostatin is a universal inhibitor
(Endocrine Cyanide) (lots of hormones are suppressed by it)
Release in response to a mixed meal.
Inhibition of: gastric secretion, motility, intestinal and pancreatic secretions, release of gut hormones, intestinal nutrient and electrolyte transport, growth and proliferation.

Analogues used to treat neuroendocrine tumours, e.g. Octreotide which has a longer half life than SS which is very short

Question 25

Secretin produced by?

Answer 25

-Secreted by the S cells of the upper duodenum and jejunum.

Question 26

Secretin stimulus?

Answer 26

• Major stimulus is the presence of acid in the duodenum (pH falls below 4.5).

Question 27

Secretin stimulates?

Potentiated by?

Answer 27

• Stimulates pancreatic bicarbonate secretion (effect potentiated by CCK).

Question 28

High levels of secretin=?

Answer 28

• High concentrations: inhibition of gastric acid and gastric emptying.

Question 29

CCK produced in?

Answer 29

Secreted by cells most densely located in the small intestine.

Question 30

CCK release stimulated by?

Answer 30

Release stimulated by fat and peptides in the upper small intestine.
Independent of vagus nerve

Question 31

CCK action

Answer 31

• stimulates pancreatic enzyme release
• delays gastric emptying
• stimulates gallbladder contraction.
• decreases food intake and meal size.

Question 32

GIP secreted by?

Answer 32

Secreted by mucosal K cells (predominant in the duodenum and jejunum).

Question 33

When is GIP released?

Answer 33

• GIP released following ingestion of a mixed meal.

Question 34

GIP action

What happens without it?

Answer 34

• Stimulates insulin secretion.
• GIP receptor antagonists reduce postprandial insulin release. (injecting glucose into blood directly without ingestion= less insulin release)

Question 35

PYY production?

Answer 35

• Cells found throughout the mucosa of the terminal ileum, colon and rectum.
• Released from L cells post prandially (particularly protein).

Question 36

PYY action?

Answer 36

• PYY reduces intestinal motility, gallbladder contraction and pancreatic exocrine secretion.
• Inhibitor of intestinal fluid and electrolyte secretion.
• PYY3-36 inhibits food intake (makes you think you’re fuller than you are)

Question 37

SBA:
Regarding the nervous control of the gastrointestinal tract:
a) Thoracic sphlanchic nerves carry sympathetic innervation to the internal anal sphincter
b) Enteric nervous system nerve fibres are myelinated
c) Cell bodies of parasympathetic preganglionic neurons are found in the brainstem
d) The pelvic nerves carry parasympathetic innervation to the ascending colon
e) Acetyl choline is the major neurotransmitter of the sympathetic nervous system

Answer 37

a- those are the lumbar sphlanchic nerves that carry sympathetic innervation to internal anal sphincter
b- dont need speed of response so unmyleinate
c- correct, where vagus nerve cell bodies are, for e.g.
d- ascending colon innervated by vagus nerve
e- Ach is major neurotransmitter of PNS

Question 38

SBA;
Regarding the control of gut function:
a) The myenteric plexus is located between the circular muscle layer and submucosa
b) Somatostatin acts solely as a paracrine signal
c) The sympathetic nervous system acts directly on the vascular system to increase blood flow to the gut
d) The vagus nerve stimulates gastrin release
e) The parasympathetic nervous system innervates the gut via short preganglionic and long preganglionic neurones

Answer 38

a- located between longitudinal and circular muscle layers
b-SS can act systemically, not purely paracrine
c- decreases blood flow instead of increase
d- correct
e-SNS innervates gut by long pre-ganglionic rather than short, synapses to post ganglionic close to organs