Principles of Secretion and Motility

Principles of Secretion and Motility

Principles of Secretion and Motility

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Enteric Nervous System

  • May be considered a third division of autonomic nervous sytem
  • Communicates with sympathetic and parasympathetic divisions but can function completely independently 

Enteric Nervous System

  • The enteric nervous system has two major networks:
    • Myenteric plexus (Auerbach's plexus)
      • Muscularis mucosa
      • Control of smooth muscle tone (motility)
    • Submucosal plexus (Meissner's plexus)
      • Submucosa of vessel
      • Control of secretion
      • Blood flow
      • Afferent sensory information
        • Chemical, stretch
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GI Tract Secretion and Motility

  • GI smooth muscle contracts and relaxes
    • Peristalsis, mass movement, segmentation
  • GI secretions are essential for specific nutrient digestion
    • saliva, gastric juice, pancreatic juice
  • Three principle mechanisms regulate motility and secretion in the GI tract:
    • endocrine hormones
    • paracrine mediators
    • neural transmission ('neurocrines')
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Endocrine Mechanism

  • Mediator (hormone) secreted directly into the circulation - action on cells distant to the site of production
  • Five major GI peptide hormones:
    • secretin - decreases gastric acid secretion, increases bicarbonate from pancreas and bile from liver
    • gastrin - increases gastric acid secretion, motility
    • cholecystokinin (CCK) - increases pancreatic juice and bile, decreases gastric acid secretion
    • gastric inhibitory peptide (GIP; glucose-dependent insulinotropic peptide) - increases insulin secretion
    • motilin - increases gastric emptying, peristalsis, pepsin
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Endocrine Hormones Production

Endocrine Hormones Production

  • GI tract is the largest endocrine organ but secretory cells are diffusely distributed
  • Principal endocrine cells of the GI tract are APUD cells (amine precursor uptake decarboxylase)
  • Located in basal portion of gastric glands
  • Enteroendocrine cells
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Cells of the Small Intestine

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Endocrine Hormones Production

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Physiological Stimuli for Hormone Release

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Paracrine Mediators

  • Mediator diffuses locally with action on neighbouring cells of different type
  • Derived from various cell types:
    • vascular endothelium, mast cells, enterochromaffin cells, macrophages
  • Non-peptide: histamine, nitrogen monoxide, serotonin (5-HT)
  • Peptide: bradykinin, somatostatin
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Example of Paracrine Regulation

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Neurotransmitters

  • Mediator released from neurones to act locally
  • May be a classical neurotransmitter or co-transmitter (more than one released at a time)
  • Mainly under autonomic control
    • independent of central nervous system and voluntary control
  • Parasympathetic and sympathetic nervous systems - extrinsic
  • Enteric nervous system - intrinsic
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Enteric Nervous System

  • Principal neurotransmitters of the enteric nervous system:
    • Excitatory
      • Acetylcholine - contraction of smooth muscle via intrinsic nerve
      • 5-HT (serotonin) - increase contraction of the gut
      • substance P - increase saliva production, muscle contraction
      • cholecystokinin (CCK) - stimulates pancreatic enzyme secretion and gallbladder contraction
    • Inhibitory
      • Enkephalins (opioid peptides) - modulates smooth muscle activity
      • vasoactive intestinal polypeptide (VIP) - inhibits gastrin release and acid secretion
      • somatostatin - modulates release of acid, pepsin, gastrin and insulin
      • NO - modulated motility
      • ATP - modulates motility
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Parasympathetic and Sympathetic Innervation

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Arrangement of Muscle in GI Tract

  • Muscle in the gastrointestinal tract is arranged mainly in two layers
    • outer longitudinal layer
    • inner circular layer
  • Muscle is predominantly smooth muscle (non-striated) therefore is not under voluntary control
  • Skeletal muscle found in:
    • pharynx
    • upper part of oesophagus
    • external anal sphincter
  • Involved in voluntary control of swallowing and defaecatioj
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Electrical Activity of Smooth Muscle

  • Slow wave activity is seen in most phasic smooth muscle
    • Do not cause contraction
    • Action potential is required
  • Spontaneous, regular oscillations of membrane potential = basal electrical rhythm of visceral smooth muscle
  • Origin of slow waves are specialised pacemaker cells - interstitial cells of Cajal
  • Basal rate of electrical firing of cells of Cajal varies from 3-20 cycles per minute
  • Amplitude and rate of slow waves may be modulated by neurotransmitters and hormones
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Oesophageal Peristalsis

  • Propulsion of food from pharnx to stomach by coordinated contraction of oesophageal muscle
    • wave of contraction followed by wave of relaxation
  • Oesophagus contains both skeletal and smooth muscle
  • Oesophageal peristalsis is controlled by autonomic nerves, co-ordniated by the swallowing centre of the medulla

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Perceptive Relaxation of the Stomach

  • Proximal region of stomach relaxes to accommodate passage of food with minor changes in intragastric pressure
  • Peristaltic contractions arising in the mid-stomach move food towards the antrum and pylorus, and some food into the body of the stomach
  • Wave of peristalsis moves caudad and increases in intensity, the distal antrum is intensely constricted
  • Chyme passes through the pylorus with each contraction (3ml)
  • Most chyme is squirted back into the body by retropulsion
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Receptive Relaxation of the Stomach

  • Stomach emptying is determined by the tone of the pyloric muscle (pyloric pump)
  • Stomach emptying is regulated by
    • myenteric reflexes in stomah due to stretch (increase)
    • gastrin (increase)
    • duodenal distension (enterogastric reflex) (decrease)
    • fats in duodenum via CCK release (decrease)
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Small Intestine Contraction

  • Mixing movement (segmentation)
    • sustained contraction of rings of circular muscle
    • followed by contractions of adjacent segment
    • promotes mixing of digestive secretions with chyme
  • Propulsive peristalsis
    • migrating peristaltic waves moving caudad
    • slow and interrupted by episodes of segmentation
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Migrating Myoelectric Complex

  • Between meals (interdigestive phase), powerful regular cycles of peristalsis occur (~80-90 mins)
  • Spontaneous contractions originate in distal stomach, possibly regulated by motilin
  • Migrating myoelectric complex migrates down the duodenum and ileum at rate of the slow waves
  • Migrating myoelectric complex finished in terminal ileum and another begins
  • Important for preventing accumulation of debris and microbial overgrowth
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Colon Function

  • Four principal functions
    • storage
    • absorption of water and electrolytes
    • bacterial synthesis of vitamin K
    • regulation of chyme entry (ileo-caecal sphincter)
  • Motility generally slower than in ileum with  2 major patters:
    • Haustration (formation of sacs that store and propel contents)
    • Peristalsis movement of contents caudad and backward (anti-peristalsis or retropulsion)
      • 'mass movements' are periods of intense caudad peristalsis
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