Regulation of the Gut

Regulation of the gut • • • • Smooth muscle and some skeletal muscle → myogenic responses (what happens if stretched) o Inherent response of smooth muscle Enteric nervous system → intrinsic regulation Autonomic nervous system: interacts with ENS and sometimes smooth muscle → reflex responses (intrinsic) Central nervous system: spinal cord → thalamus → cortex → perception o Voluntary control e.g. defecation Function of muscular activity • Transport in an orderly fashion and discharge (defecate) unabsorbed residua • Conversion of ingestion good to a soluble form by grinding and kneading with digestive juices • Mixing of luminal contents so that material in contact with the absorptive surface is continually replenished Types of muscle • Striated muscle: ‘gate keepers’ that keep boundaries at the end of smooth muscle o Under voluntary control or reflexes o Pharynx and proximal 1/3 of oesophagus o External anal sphincter o Pelvic floor • Smooth muscle: 3 layers o Muscularis mucosae o Inner (circular) o Outer longitudinal layers Smooth muscle • Structure within myocyte: o Fusiform bundles separated by collagen → contract in all axis o Electrically coupled due to gap junctions → syncytial activity o Sarcoplasmic reticulum stores Ca2+ → released by a depolarising current • Myocytes don’t have a regular assembly of fibres (unliked striated) • Innervated by: o ANS o Enteric nervous system • Nerve terminals ramify (branch out) over surface of membrane releasing neurotransmitters o At the point of release there are pearl-like structures called varicosities o Individual nerve wanders across numerous nerve fibres • Neurotransmitters released at surface: (regulate motility and secretory function of gut) o SNS: noradrenaline + co-release of ATP and NPY (neuropeptide Y) o PNS: ACh, VIP (vasoactive intestinal peptide) • • o Intrinsic nerves: VIP, SP (substance P), NO Motor nerve are those causing a contraction (or even relaxation) of smooth muscle via local polarisation o Depolarisation → make more positive → contraction ▪ Depolarisation spreads to adjacent cells o Hyperpolarisation → make more negative Slow wave activity = periodic/spontaneous depolarisations i.e. changes in membrane potential o Slow onset and decay (seconds) o Driven by interstitial cells of Cajal that are intrinsically leaky and depolarise frequency → once this occurs it propagates via the smooth muscle of the gut o Sub threshold (no AP) o Super threshold → AP → muscle contraction ▪ After a meal there is increased GI activity → more likely to generate AP Enteric nervous system • • • • Oesophagus → anus ~100 million neurons (as many as spinal cord) Intrinsic motor nerves (VIP, SP, ATP, NO etc.) + intrinsic sensory nerves Aggregation of nerves = plexus o Submucosal plexus ▪ Secretory ▪ Contract submucosal muscle → infolding of mucosa → folds of Kerckring o Myenteric plexus ▪ Coordinated contraction and relaxation of circular and longitudinal muscle layers Segmentation • Small intestine: as one set of segmentations contractions relaxes, a new set often begins (typically at intervening points of prior contractions) • • Function: o Chop and mix and chyme o 2-3 per minute → slow net movement in anal direction ▪ Allows time for absorptive processes ▪ Replenishes nutrients at surface ▪ Frequency of segmentation is determined by the frequency of electrical slow waves in the intestinal wall Suppressed in the absence of the enteric nervous system e.g. failure of development → loss of segmentation Peristalsis • Polarised response that has a preference to work oral → anal (but will also work anal → oral) • Dependent on myenteric plexus o Neurally mediated ▪ Hirschsprung’s disease → colonic absence due to failure of neural crest ingrowth → poor relaxation • Blocked by atropine (competitive muscarinic antagonist) • Hormonal integration: o Enhanced by: gastrin, CCK, insulin, motilin o Inhibited by: secretin and glucagon Colon • Functions: o Absorption of H2O and electrolytes ▪ Segmentations in the colon = haustrations → 2.5cm bands of circular muscle contraction • Teniae coli (aggregates of longitudinal muscle) contract and cause bulging in unstimulated regions = haustra o Faecal storage ▪ Mass movements from cecum to sigmoid ▪ Occur 1-3 times/day and last ~15 minutes ▪ Typically after breakfast ▪ Modified peristalsis Reflex responses – peristalsis and segmentation • • • • • • Sensory input → myenteric plexus → contraction of the oral end and relaxation of the anal end o Myenteric plexus: synaptic transmission from sensory to motor nerves o ACh (nicotinic) + ATP + serotonin → EPSP → synaptic relay Localised distension via increased luminal pressure Chemical stimulation via increased acidity, irritants (e.g. mustard oil, terpene, capsaicin) Nerves extending to circular and longitudinal muscle o Orally directed contraction: ACh + substance P → EPSP (depolarisation) → contraction ▪ Atropine antagonises ACh at muscarinic receptors (but not all depolarisation and hence contraction is blocked) o Anally directed relaxation ▪ Circular muscle: ATP + VIP + NO → IPSP (hyperpolarisation) → relaxation ▪ Longitudinal muscle: ACh + SP → EPSP (depolarisation) → contraction/shortening Parasympathetic modulation: pre-ganglionic (cholinergic) fibres… o Myenteric plexus → excite orally directed enteric motor nerves → ↑ force and rate of contraction o Submucosal plexus → increased secretory function Sympathetic modulation o Post-ganglionic adrenergic fibres terminate: ▪ Myenteric plexus • Preferentially target pre-synaptic terminals of cholinergic fibres • Release NA/NPY → pre-synaptic inhibition of ACh release → decreased motility ▪ Submucosal plexus • Preferentially target pre-synaptic terminals of cholinergic fibres • Release NA/NPY decreased secretion