GI motility

what are the 3 layers of a nerve?

• epineurum

what is the epineurium

• outermost protective layer - dense connective tissue, rich in collagen

what is the perineurium

• surrounds each fascicle - an epithelial layer that isolates axon bundles from the surrounding connective tissue

• encloses fluid filled space b/w perineurium and underlying nerve axons

what is the connective tissue w/in perineural sheath called?

• endoneurium

what is the endoneurium

• include seams of loose connective tissue to provide pathways for small arterioles, venules and axons

how are neurotransmitters moved along the neurone?

1. axoplasmic flow

2. axonal forward/retrograde transport

what is the neurolemma?

• outer most layer of nerve fibres in PNS - cytoplasmic layer of Schwann cells that surround multiple wrapping of myelin

what neurones are contained in the ENS?

• sensory, motor and interneurones related to circular and longitudinal layers of smooth muscle.

what are the two plexuses in the ENS?

• submucosal

where does the ENS start and end?

• starts at the oesophagus

• ends at the anal sphincter

what does the ENS have branches to?

• liver

• gall bladder

• biliary tract

• pancreas

what is the basis of the GI motility patterns?

• peristaltic reflex

what reflex does the ENS trigger for peristalsis?

• proximal contraction and distal distension via inhibition

what muscle is associated with peristaltic motion?

• circular

what muscle is associated with segmentation motilities?

• lognitudinal

how is peristalsis brought about?

1. distension of gut wall by a bolus

2. circular muscle layer contracts via mechanosensitive sensory neurone proximally → motor neuron

3. inhibition of muscle contraction distally

4. unidirectional movement

why is movement unidirectional in the gut?

• the axon/dendrites project proximal for the excitatory neuron and distal for inhibitory neurone

what does each nervous unit in the gut contain?

• excitatory motor neuron - more proximal

• sensory neuron (middle)

• inhibitory motor neuron - more distal

what neurotransmitter results in the excitatory motor neuron effect?

• ACh

what neurotransmitters result in the inhibitory motor neuron action?

• NO

• ATP

• VIP

what is the general frequency of peristaltic waves?

• 3-7/min

what is the function of segmentation?

• result in the breaking of ingesta into smaller segments along the intestine, which provides a larger surface area for enzymes to act on → better absorption

what contributes to effective mixing of ingesta contents

1. segmentation

2. alternating contraction and relaxation of longitudinal muscle in wall

what is EGC?

• equine grass syndrome

what is equine grass syndrome

• frequently fatal multisystem neuropathy of equids

• unknown aetiology

• there’s neuronal degeneration in pre-and post-ganglionic sympathetic and parasympathetic nerves → GI paralysis

what does multisystem neuropathy mean?

• something’s gone wrong in the signal transmission in neurons

which species do we see myasthenia gravis?

• dog

what is myasthenia gravis in dogs?

• decreased functional ACh receptors at NM junction

what may myasthenia gravis cause?

• widespread abnormailities with muscle contraction in the GIT → may include megaoesophagus

how do we treat myasthenia gravis?

• AChE inhibitors to amplify ACh signal

4 theories of appetite regulation?

1. lipostat - fat deposits and leptin

2. gut peptides - CCK

3. glucostat - glucose/VFA/AAs

4. thermostat

what is the main regulatory organ for hunger

• hypothalamus

where specifically in the hypothalamus does appetite regulation take place

• ventromedial nucleus of hypothalamus

what is the lipostat hypothesis of appetite regulation?

• leptin is produced by adipose tissue, proportionate to amount of fat

• this signal decreases food intake and increases E output

• levels increase after a meal and fall in the interprandial period

how do gut peptides regulate appetite

• glucagon and CCK - released in response to food → hypothalamus → inhibit food intake

• ghrelin - increases before meal and decreases afterwards - also reduced leptin levels.

do we find CCK in the brain? how is it released

• yes

• it’s released in response to stomach distension after a meal

how do glucostats regulate appetite?:

1. glucose

2. FFA

3. amino acids

1. increase, stimulates satiety centre. Insulin involved

2. the same in ruminants

3. have the same effect as glucose

how is thermostat involved in appetite regulation?

• decrease body temp → stimulates appetite (at a certain point)

• inhibited above a certain point

what are the three layers of muscles in the GIT

• oblique

• longitudinal

• circular

what are the 3 exocrine cells in the GIT

1. mucin-producing cells

2. parietal cells

3. chief/principal cells

what do principal/chief cells secrete in the GIT

• pepsinogen + lipase

what are the endocrine cells in the stomach

1. histamine producing cells - ECL

2. gastrin producing cells - G cells

outline the long reflex in the stomach

1. stomach expansion + peptides → sensory nerve ending stimulation

2. to CNS

3. back via vagal nerve → ACh → stimulation of secretion

which nerves are targetted by the long reflex?

• submucosal plexus

what is the short reflex in the stomach?

• stomach expansion and peptides → gastrin release

also

• sensory nerve ending → CNS → vagus nerve → ACh → release

what regulates stomach emptying?

• cajal cells that regulate contraction

where are Cajal cells located?

• between circular and longitudinal muscle layers

how do Cajal cells stimulate muscle contraction?

• gap junctions

with which nerve plexus do Cajal cells interact?

• mesenteric nerve plexus

what is stomach emptying inhibited by?

• duodenal factors → stim sympathetic fibres

what hormones are involved with inhibited stomach emptying?

• secretin

• GIP

• CKK

which part of the nervous system si involved with stomach emptying?

• PSNS

outline the pathway of stomach emptying

1. food homeostasis change

2. gastric pH increases, wall distension

3. mechano/chemoreceptors

4. influx to submucosal plexus

5. PSNS influx to stomach effectors

6. evacuation

what is the production of pancreatic juices maintained by?

• vagal nerves

what stimulates hormone production ni the duodenum and what hormones? what further effect do these hormones have

• chyme → low pH/FAs/peptides → CKK and secretin release

  • this furthers pancreatic juice and bile flow into duodenum

what 2 movements take place in the small intestine

• segmentation

  • peristalsis

when does segmentation occur

• when mixing stops; once intestine is cleared from nutrient-mechanical aspect

what types of movement take place in the large intestine?

1. segmentation

2. peristalsis

3. antiperistalsis

4. mass movement

what promotes large intestine contraction?

1. stomach and duodenum via long reflex mesenteric

what do we call the reflex of the large intestine contraction

• gastro-colic reflex

what is the mass movement in the large intestine triggered by?

• stretch of wall → sensed by mechanoreceptors

how is vomiting triggered

• receptors on floor of the fourth ventricle on the brain act as a chemoreceptor trigger zone

  • if stimulated → vomiting

where is the vomiting centre located and what does this mean about how it can be triggered?

• floor of fourth ventricle OUTSIDE of the BBB

  • this means that it can be stimulated by blood borne chemicals

what 2 sources of input to the vomiting centre are there in relation to the GIT?

1. CNX

2. vagal and enteric NS

how does CNX → vomiting?

• activated when pharynx is irritated → gag reflex

how do the vagal and ENS → vomiting?

• irritation/infection → 5-HT3 (serotonin) receptor activation

what are the 4 categories of sensory input that initiate vomiting?

1. sensory vagal and sympathetic

2. CRTZ

3. vestibular

4. cortex

what is the efferent outcome of emetic centre stimulation?

• abdominal muscle contraction

• oesophageal sphincters (proximal and distal) opening/relaxing

• contraction of the duodenum and stomach

• gastroesophageal reflex

Where does the sensory information for motion sickness go to within the vomiting pathway:

1. dogs

2. cats

1. CRTZ

2. emetic centre

where do the sympathetic fibres emerge from that innervate the abdomen?

• T2-L3

where does the PSNS supply for the abdomen come from?

• the cervical + sacral spinal cord

  • vagus cranial

  • pelvic sacral nerves caudally

what is the stomach supplied by (nervous)

1. PSNS from vagus - drives foregut/midgut digestion, from sacrum - hindgut/colon

2. SNS from celiac plexus -

3. ENS - gut motility

what abdominal organs do the spinal nerves from the pelvis supply

• bladder

• urethra

• rectum

• anal canal

• reproductive organs

where does the sympathetic outflow come from?

• L1-L4

what is the role of the sympathetic lumbar outflow?

• sympathetic tone to pelvic organs

• inhibit detrusor and rectal smooth muscle

• excitatory control of internal sphincters

Species differences in sympathetic lumbar outflow:

1. horses

2. ruminants

3. dogs/cats

1. large caudal mesenteric ganglion - strong hypogastric nerves

2. more extensive lumbar splanchnic branching

3. similar pattern but smaller ganglia and plexuses

what are the thoracic sphlanchnic nerves?

• paired sympathetic nerves that carry preganglionic fibres from thoracic sympathetic trunk to prevertebral ganglia

what do the thoracic splanchnic nerves supply?

• adrenal medulla

• nerve plexuses around celiac and cranial mesenteric arteries

what are the groupings of splanchnic nerves?

• greater

• lesser

• least

where do the thoracic splanchnic nerves arise from in:

1. carnivores

2. ruminants

3. equidae

4. rabbits

1. 6-9th thoracic ganglia

2. 6-10th

3. 6-15th

4. 11th, also from 6-12th ganglia

where does the pelvic splanchnic nerve arise from in the dog

• the ventral branch of first and second sacral nerves

why are the pelvic splanchnic nerves unique among splanchnic nerves?

• carry preganglionic parasympathetic fibres

where do the pelvic splanchnic nerves exit the pelvis from?

• the anterior sacral foramina and enter pelvic cavity

function of the pelvic splanchnic nerves?

• supply PSNS innervation to pelvic organs and distal hindgut

what does the pelvic splanchnic nerve supply?

• urinary bladder and urethra

• distal colon, sigmoid colon + rectum

• reproductive organs

• ureters

4 things the ENS controls?

1. motility

2. microcirculation

3. immune and inflammatory processes

4. secretion

function of the ENS in terms of motility?

• detect stretch and contents

• activates excitatory + inhibitory neurones in myenteric plexus

• contraction + relaxation of smooth muscle

• generates peristalsis + segmentation

How does the ENS help with microcirculation?

• detects local digestive activity

• releases neurotransmitters → vasodilation

• increase blood flow → active regions

• matches blood supply to absorption needs

how is the ENS involved in immune + inflammatory processes

• communicatees with immune cells w/in the gut wall

• detects inflam mediators and pathogens

• alters motility/secretion and blood flow during infection

• helps coordinate protective responses such as diarrhoea + increase mucous production

what does electrical coupling in the GIT enable?

• coordinated and slow contraction of the GIT

  • facilitates food movement

  • allows segmentation

where do we find ICCs, what are these?

• ICCs b/w nerve endings and smooth muscle cells w/in muscularis propria

• these are the interstitial cells of Cajal

how are the waves of excitation initiated by the ICC cells?

• increased internal Ca2+ activates Cl- channels → efflux → depolarisation

• depolarisation spreads → smooth muscle cells via gap junctions

• threshold reached → smooth muscle contraction

• after depolarisation K+ channels open → efflux → membrane potential becomes more negative

consequences of absent/slow waves?

1. paralytic ileus

2. stasis of intestinal contents

3. poor nutrient uptake

4. delayed gastric emptying

what is segementation and what is its function?

• altering contraction and relaxation of smooth circular muscles in SI

• mixes and breaks down digestive contents - maximised contact with intestinal wall for nutrient absorption

define propulsive peristalsis

• coordinated, wave-like contraction of smooth circular and longitudinal muscles

How does osmotic pressure affect gastric emptying?

• high OP → slower emptying

• osmoreceptors in duodenum detect high solute conc → inhibitory enterogastric reflex via vagus nerve + hormonal feedback to reduce motility

how does a low osmotic pressure affect gastric emptying, why

• increases it

• less stimulation of osmoreceptors → less inhibitory feedback

How do each of these chemical components affect gastric emptying:

1. fats

2. proteins

3. carbohydrates

4. low pH

1. slows

2. moderately slows

3. increases

4. slows

what is the ‘kiss and run’ mechanism

• transient vesicle fusion where a synaptic vesicle only briefly contacts presynaptic membrane - opens a small fusion pore and releases neurotransmitter content and detaches → pore re seals

what is the importance of the ‘kiss and run’ mechanism

• as short, allows only a small, controlled amount of neurotransmitter to enter synaptic cleft