T1 L2: Motility of the GI tract

• Accessory organs of the GI sysem


  • parotid salivary gland
  • sublingual & submandibular salivary gland
  • teeth/tongue
  • liver
  • gall bladder
  • pancreas
• Sphincters of the GI tract?

  label

  1. upper oesophageal
  2. Lower oesophageal
  3. pyloric
  4. ileocaecal
  5. anal (internal & external)

  
• Layers of the gastrointestinal wall

  4 distinct layers:

  1. Serosa
  2. Muscularis externa
  3. Submucosa
  4. Mucosa

  
• Serosa


  Outermost layer of the GI wall

  • Connective tissue and layer of squamus epithelial cells
  • Referred to as the adventitia in the oesophagus

  
• Muscularis externa


  2nd layer of GI wall

  • outer longitudinal layer of smooth muscle
  • inner circular layer of smooth muscle
  • contains myenteric nerve plexus, part of the enteric nervous system

  
• Submucosa


  3rd layer of GI tract wall

  • connective tissue that links the mucosal and muscular layers
  • also contains blood supply and lymph vessels
  • contains submucosal nerve plexus, part of the enteric nerve system

  
• Mucosa


  innermost layer of the GI wall

  • Muscular mucosae is a very thin layer of smooth muscle
  • Lamina propria is mostly connective tissue, but also includes some lymphatic tissue
  • epithelium containing both endocrine and exocrine cells

  
• Region specialisation

  1. Oesophagus
  2. Stomach
  3. Small intestine
  4. Large intestine

  
• Oesophagus 


  smooth muscle facilitated transport

  
• Stomach 


  Storage, secretion, mixing, digestion (inner oblique muscle)

  
• Small intestine


  secretion, mixing, majority of digestion, absorption

  
• Large intestine


  limited absorption (water, ions), faeces formation, gut microbiota

  
• Hormones secreted in GI wall

  1. Gastrin (G cells in stomach and small intestine): increase gastric acid secretion and mucosal growth
  2. Cholecystokinin (CCK) (I cells in small intestine): increase pancreatic secretions, decrease gastric emptying
  3. Secretin (S cells in small intestine): increase pancreatic secretions, decrease gastric acid secretion
  4. Gastric Inhibitory Peptide (GIP) (K cells in small intestine): increase insulin release, decrease gastric acid secretion
  5. Motilin (M cells in small intestine): increase gastric and intestinal motility
• Smooth muscle functional syncytium

  digestion dependent on coordinated activity of smooth muscle

  Interstitial cells of Cajal (ICC) act as specialised pacemaker cells

  Individual cells joined with gap junctions to allow electrical coupling, which allow muscle cells to act as a single functional unit (syncytium)

  
• Basal electric rhythm

  GI smooth muscle cells have a negative resting membrane potential (-55mV)

  Interstitial cells of Cajal (ICCs) drive cyclical slow waves that form the basic electrical rhythm (BER)

  If a slow wave crosses the threshold potential, spike potentials occur which drive muscle contraction through calcium influx

  
• Enteric nervous innervation

  Enteric nervous system (ENS) provides fine tuning of the basic electrical rhythm of GI tract

  Nutrients, stretch, pH and osmolarity can trigger ENS activity

  ENS can act independently of the CNS

  Is compromised of 2 interconnected plexuses:

  1. myenteric plexus (motility)
  2. submucosal plexus (secretion, blood flow)
• Autonomic nervous innervation

  ANS can interface with the ENS or with smooth muscle directly

  Whilst under involuntary control, emotions such as fear and anxiety can alter the balance

  Parasympathetic:

  • excitatory to motility and secretion
  • innervate by vagus and sacral nerves
  • acetylcholine

  Sympathetic:

  • inhibitory to motility and secretion
  • innervated by thoraco-lumbar nerves
  • Norepinephrine

  
• Excitation-contraction coupling

  1. Membrane depolarisation induces calcium influx through voltage dependent calcium channels (VDCC)
  2. G-protein coupled receptors can induce Ca2+ release from sarcoplasmic reticulum
  3. Increased intracellular calcium activates calmodulin
  4. Calmodulin activates myosin light chain kinase which phosphorylates myosin light chains
  5. Myosin heads pull actin filaments along, contracting muscle cell
• Antimuscarinics

  smooth muscle relaxants

  eg Atropine
• D2 agonists

  prokinetic drugs

  eg domperidone
• Segmentation & peristalsis

  Segmentation (for mixing)

  • bursts of circular muscle contraction and relaxation (pendular movements)
  • No net movement
  • mechanical mixing facilitates chemical digestion

  Peristalsis (for propulsion)

  • digestion triggers conduction behind and relaxation in front of bolus
  • coordinated movement propels food along GI tract
  • relies on innervation from the myenteric plexus
• Hirschsprung's disease 


  nervous innervation pathophysiology

  rare congenital absence of the myenteric plexus in a distinct portion of the distal colon

  symptoms: excessive treatment resistant constipation

  treatment: surgical removal of the affected section
• Process of swallowing

  (deglutition) enables the movement of food from mouth to the stomach

  coordinated muscular contractions result in peristalsis

  facilitated by:

  salivary secretions in mouth

  mucus in the pharynx and osephagus

  
• Three phases of deglutition (swallowing)

  1. Voluntary (bolus into oropharynx)
  2. Pharyngeal (involuntary passage of bolus through pharynx into oesophagus)
  3. oesophageal (pharynx to stotmach)
• Phase 1 of deglutition - Voluntary phase


  • upwards and back movement of tongue against palate forces bolus towards back of oral cavity
  • passage of bolus into oropharynx stimulates sensory receptors

  
• Phase 2 of deglutition - Pharyngeal phase 


  • impulses travel to the medulla oblongata and pons in the CNS
  • efferent signals drive muscular contractions
  • soft palate and uvula block the nasopharynx
  • Epiglottis closes the larynx
  • relaxation of upper esophageal sphincter
  • pharyngeal muscle contractions push bolus into oeophagus

  
• Oesophageal phase 


  • Peristaltic waves propel bolus along oesophagus towards stomach
  • relaxation of lower oesophageal sphincter allows passage into stomach
  • coordinated activity of myenteric plexus and vagal nerve innervation

  
• Oesophageal motility pathophysiology - Achalasia 


  absence of relaxation

  • lower oesophageal sphincter fails to relax
  • causing food to remain in oesophagus
  • causes distention, inflammation, infection and ulceration
  • treatment: physical manipulation, surgical cutting of lesion

  
• Oesophageal motility pathophysiology - Gastro-oesophageal reflux (GERD)


  lower oesophageal sphincter tone lost

  leading to flow of acidic gastric contents into oesophagus

  causing inflammation, ulceration

  treatment: gastric acid secretion inhibitors

  
• Motor functions of the stomach

  Storage:

  Receptive relaxation - fundus and upper body of stomach relax to accommodate larger columes, controlled by the vagovagal reflex

  Mixing:

  Propulsion: slow peristaltic waves move stomach contents towards pyloric antrum

  Retropulsion: food forced back for further mixing

  Cyclical propulsion and retropulsion drives chyme production

  
• Regulation of gastric emptying

  more powerful peristaltic contractions force chyme through pyloric sphincter

  Duodenal enterogastric reflexes

  acidity - chemoreceptors

  volume - mechanoreceptors

  osmolarity - osmoreceptors

  affect through endocrine system - secretin, CCK (cholecystokinin), GIP (gastric inhibitory peptide) all inhibit gastric emptying

  Signalling from duodenum slows gastric emptying by:

  • increasing pyloric sphincter contraction
  • reducing pyloric antrum contraction
• Gastric motility pathophysiology - Dumping syndrome


  rapid emptying of gastric contents into small intestine

  causing abdominal cramping and diarrhoea within minutes

  sweating and fainting within hours

  treatment: dietary changes

  
• Gastric motility pathophysiology - Gastroparesis 


  gastric cancer or ulcers can prevent the stomach from emptying

  causing bloating and nausea

  treatment: prokinetic (increase motility) and antiemetic (treat nausea) medication

  
• Motility in the small intestine

  nutrient absorption in small intestine

  Plicae circulares, mucosal vili and microvilli provide huge surface area

  Stretch receptors in small intestine trigger:

  • segmentation for maximum exposure to absorptive epithelium
  • propulsion of cyme via peristaltic waves

  Hormonal regulation of motility:

  • Excitation: motilin, insulin
  • Inhibition: secretin and glucagon

  
• Propulsive peristaltic reflexes

  Autonomic reflexes drive peristaltic propulsion in small intestine

  Gastric distension promotes:

  • Gastroenteric reflex (peristalsis in duodenum)
  • Gastroileal reflex (peristalsis in ileum)

  Migrating motor complex

  • series of peristaltic contractions, between meals, every 90 mins, sweeping contents into colon
  • intrinsic enteric control - motilin
  • absence can lead to bacterial imbalances
• Final stages of digestion in large intestine

  • water absorption in ascending and transverse colon
  • faeces formation and storage in descending colon
  • commensal microbiome in large intestine further aids digestion and formation of vitamins B and K

  
• Motility in the large intestine

  Longitudinal muscle thickened in large intestine, contracting lenghtwise to form haustral bulges

  mixing via haustral churning

  propulsion via mass movements

  • forceful peristaltic contractions force contents into sigmoid colon and rectum (2-3x a day)
  • gastro-colic and duodeno-colic reflexes in response to stretch following a meal

  
• Defecation reflex

  occurs in three step process:

  1. Faecal matter activates stretch receptors
  2. activating ENS
  3. signalling sacral spinal chord and parasympathetic ANS
  4. Parasympathetic innervation triggers involuntarily
  5. contraction of longitudinal muscle in rectum (shortening), increasing pressure and creating urge
  6. relaxation of internal anal sphincter
  7. External anal sphincter is voluntarily relaxed to allow defecation