Key concepts in Digestion. Overview of digestion introduction to the GI system Prof. Barry Campbell Cellular & Molecular Physiology e-mail: bjcampbl@liv.ac.uk http://pcwww.liv.ac.uk/~bjcampbl
DIGESTION The progressive breakdown of food into a form suitable for absorption and the associated transport processes Digestion therefore also includes: - The processes of secretion The processes of absorption Movement of the gut contents growth & differentiation The mechanisms protecting the gut from damage or attack, and the mechanisms controlling and integrating all of the above
SCHEMATIC REPRESENTATION OF MAIN REGIONS OF THE GASTROINTESTINAL TRACT REGION: Oesophagus - Transit FUNCTION: Small intestine Stomach duodenum jejunum ileum - storage, H + /peptic digestion & intrinsic factor - fat, protein, carbohydrate digestion & absorption, Ca 2+ /Fe 2+ - water and electrolyte transport - bile salt & vit B12 transport Large intestine Colon - Storage - water and electrolyte transport rectum & anus - defaecation
SECRETIONS OF THE GUT Salivary glands - synthesis/secretion: amylase, mucus. Water, electrolytes Exocrine pancreas - synthesis/secretion: proteases,lipase,amylase. HCO - 3, water Liver - bile salt synthesis, bile secretion. Gall bladder - storage and concentration of bile
Physiological control systems in the gut Endocrine - Gut hormones Paracrine - Local regulators Neural Intrinsic Extrinsic - Myenteric & submucosal nerve plexuses - Afferent & efferent nerves vagal & splanchnic trunks (autonomic nervous system)
Major hormones of the gut STOMACH Gastrin Somatostatin UPPER SMALL INTESTINE Cholecystokinin (CCK) Secretin Gastric inhibitory peptide Motilin ILEUM AND COLON Glucagon-like peptide 1 (GLP-1) Peptide YY (PYY) Neurotensin
Overview of extrinsic innervation: Voluntary (Conscious control) Hypoglossal nerve (XII) LOS UOS Superior cervical ganglion Autonomic (non-perception) Vagus nerve (X) Paraspinal cord Pudendal nerve EAS IAS Pelvic splanchnic nerve
The autonomic nervous system Sympathetic system: Parasympathetic system: Noradrenaline Acetylcholine (Ach) EFFECTS ACTION (+) secretion of saliva salivary glands Mid brain Pons/ medulla Cranial nerves VII ACTION Salivary glands EFFECTS (+) secretion of saliva (+) vasoconstriction 2 (-) vasodilation gut blood vessels X IX Gut wall Gut sphincters (+) increased motility and tone (-) reflex relaxation 1/2 (-) decrease motility gut wall, (+) contraction sphincters Spinal cord Gut secretions Pancreas (+) e.g acid, enzymes & electrolytes (+) exocrine & endocrine secretion adrenaline (+) secretion Adrenal medulla Rectum (+) defaecation
Organisation of the gut wall Lumen epithelium Lamina propria MUCOSA Muscularis mucosa SUBMUCOSA Circular muscle Myenteric plexus MUSCULARIS PROPRIA Longitudinal muscle Mesothelium (SEROSA)
Intrinsic and extrinsic nerves of the digestive tract ABORAL e.g. secretory cell ORAL Submucosal plexus e.g. Stretch & chemosensitive neurons INTRINSIC NERVES Myenteric plexus e.g. post-ganglionic nonadrenergic or cholinergic fibres EXTRINSIC NERVES Visceral afferents Parasympathetic efferents
Control of smooth muscle contraction Interstitial cells of Cajal are pacemakers of the gut ICC cell network Slow wave mechanism Action potentials Slow wave conducted to smooth muscle L type Ca 2+ current & action potential mechanism 25 mv BER 1.5g Mechanical recording Basal electrical rhythm (BER) originates in ICC, but itself does not cause contraction; when spike potentials occur at maximum depolarisation of BER due to Ca 2+ entry, the result is contraction
Motility in the interdigestive period - The Migrating Myoelectic Complex (MMC) 71% antrum III motilin, ghrelin & vagus nerve 29% duodenum III somatostatin, Serotonin (5-HT) and xenin Phases of MMC I II III IV ~130 min Distal small intestine Colon Feeding disrupts the cycle I - quiescence; II - random contractions; III - burst of contractions (max. amplitude & duration); IV - rapid decrease of contractions.
Intestinal movement - segmentation Alternate contraction and relaxation of adjacent segments causes thorough mixing of contents
> > Intestinal movement - peristaltic reflex Animation at www.westga.edu/~lkral/peristalsis/ Excitatory motor neurons interneurons > ACh > TK/ACh Intrinsic primary afferent neurons (IPAN) > interneurons > ACh Ach = acetylcholine NO = nitric oxide TK = tachykinin VIP = vasoactive intestinal polypeptide 5-HT = 5-hydroxytryptamine (serotonin) Inhibitory motor neurons ACh/TK Distension (5-HT) VIP/NO Circular smooth muscle Orad Caudad Ascending contraction Descending relaxation
Removing indigestible material reflexes in the colon and rectum Food in duodenum Food in stomach Distention + Spinal cord rectum Ach + Colon + + Mass movements Faeces - Pudendal nerve FAECES IAS EAS anus VIP ATP - Defaecation reflex
Function & Dysfunction in the GI tract Physiology Growth/development secretion absorption motility & signalling to CNS surveillance (immuno/metabolic) co-ordination (neurons/hormones) cancer Pathology peptic ulcer, cystic fibrosis malabsorption oesophagitis, gastroparesis, non-ulcer dyspepsia and irritable bowel ulcerative colitis, Crohn s disease, Coeliac disease aganglionic colon (Hirschsprung s)
GI system case-based learning (CBL) 1. A problem that s difficult to swallow Achalasia 2. Troubles with gastrin Indigestion 3. No more fish and chips! Gallstone pancreatitis 4. Gap year travels in India Cholera