Lecture Outline • Basic GI functions • Regulation of GI function Digestive Physiology • Phases of Digestion • Absorption • Protective Function of the GI tract Basic GI Functions Basic GI Functions • Primary function • Secondary functions – Movement of – Mass balance nutrient molecules • Ensuring daily fluid input from the external and output are equal environment to the internal environment –Protection • Done through the • GI tract provides a huge processes of: external surface for – Motility pathogens to gain – Secretion entrance into the – Digestion – Absorption internal environment 1 Lecture Outline Regulation of GI Function • Basic GI functions • What is regulated? – All aspects of the GI processes • Regulation of GI function • Regulated by • Phases of Digestion – In general the signals are: • Neural • Absorption • Hormonal • Protective Function of the GI tract • Paracrine – Specifically the controls and systems are: • The Long & Short Reflexes • GI peptide reflexes • The autonomous function of the enteric nervous system (ENS) Regulation of GI Function Regulation of GI Function Long & Short Reflexes Long & Short Reflexes external stimuli • Long Reflexes long reflex pathway – Integrated within in the CNS short reflex pathway sensory • May originate in or outside of the GI tract receptors – Feedforward & emotional reflexes are initiated and integrated entirely outside the GI tract » Called cephalic reflexes the muscle cephalic contraction • Short Reflexes brain and/or relaxation, – Integrated in the enteric nervous system exocrine • Initiated by changes in pH, distension, osmolarity, products of secretion, paracrine digestion neurons of smooth sensory release, • Submucosal plexus contains the sensory neurons submucosal muscles local receptors inter- endocrine and or • Afferent information to ganglia stimuli and neurons secretion, myenteric secretory neurons defecation • Efferent information to submucosal and myenteric plexuses plexuses cells for control of secretion, motility and growth Digestive Enteric Nervous System Effectors responses 2 Regulation of GI Function Regulation of GI Function GI Peptide Reflexes GI Peptide Reflexes • Peptides released by the GI tract may act – As hormones • Secreted into the blood • Act on accessory organs, other parts of the GI tract or the Gastrin family brain – As paracrine signals • Secreted into the lumen or extracellular fluid Secretin – Lumenal signals bind to apical epithelial receptors family – ECF signals act in the immediate vicinity of secretion Peptide family – Effect • Peptides alter secretion and motility Secretin • Alter behavior related to eating family Regulation of GI Function Lecture Outline Enteric Nervous System • Allows for the autonomous behavior of the • Basic GI functions digestive system – CNS control is not required for digestive functioning • Regulation of GI function – Commonalities between ENS and CNS • Phases of Digestion • Intrinsic neurons – similar to interneurons of CNS • Extrinsic neurons – composed of autonomic neurons • Absorption • Neurotransmitters and neuropeptides – Nonadrenergic and noncholinergic receptors • Protective Function of the GI tract » Same as adrenergic and cholinergic in CNS • Glial support cells – similar to astrocytes in CNS • Diffusion barrier – cells around capillaries in the ganglia are tight, just as the capillaries in the brain, forming the BBB • ENS acts as its own integrating center, just as the CNS does 3 Phases of Digestion Phases of Digestion Cephalic Phase Cephalic Phase • Starts with the external stimulus of food • What goes on once food is in the mouth? – Response from cerebral cortex, hypothalamus and amygdala is to activate neurons [vagus nerve (X)] in – Secretion of saliva the medulla oblongata which – Physical digestion via mastication • Sends ANS signals to – Chemical digestion via salivary amylase and lingual – Salivary glands via branches of facial n. & glossopharyngeal n. (parasympathetic), sympathetic innervation via branches from lipase (from Von Ebner’s Glands) T1-3 » Increases saliva production along with salivary amylase, – Preparation for swallowing (deglutition reflex) lysozymes, immunoglobulins and lingual lipase • Bolus pushed against soft palate by tongue to trigger reflex » Starts chemical digestion – Enteric nervous system via vagus nerve • UES (upper esophageal sphincter) relaxes, larynx elevates » Gastric secretions and motility increase in preparation as epiglottis bends to cover trachea » Accounts for approximately 20% of gastric secretions while • Peristalsis and gravity moves bolus down esophagus to eating stomach Phases of Digestion Phases of Digestion Gastric Phase Gastric Phase • Deglutition reflex What does the stomach do? (swallowing) moves food 1. Stores incoming food to the stomach to start 2. Digests the food into chyme the gastric phase • By action of pepsin and mechanical digestion – 3.5 liters of content/day (churning) enters fundus 3. Protection – Controlled by long (vagal reflex) and short • Acidic gastric environment (distention & • Mucous provides “self” protection peptides/amino acids) reflexes 4 Phases of Digestion Phases of Digestion Gastric Phase Gastric Phase 2. Digests the food into chyme 1. Stores incoming food – By continuation of salivary amylase until denatured – By action of secretions – Fundus exhibits receptive relaxation • Parietal cells secrete HCl (gastric acid) and intrinsic factor – HCl dissociates into H+ and Cl- – controls movement into the duodenum – Intrinsic factor required for B12 absorption in the intestine • Chief cells secrete pepsinogen & gastric lipase • Storage becomes important when more food – Pepsinogen is converted to pepsin by the action of H+ than is required enters the stomach – Pepsin is an endopeptidase • Mucous neck cells • Too much into the duodenum would spell colonic – Secretes mucous for protection disaster! – Secretes bicarbonate for protection • Enterochromaffin-like cells – Secretes histamine in response to parasympathetic activity and gastrin and increases parietal cell • D cells – Secretes somatostatin when pH drops to inhibit further parietal cell secretions • G cells – Secrete gastrin to stimulate parietal cells, also relaxes ileocecal sphincter, increases pyloric sphincter activity and lower stomach motility Phases of Digestion Phases of Digestion Cephalic Phase Gastric Phase 3. Protection – Acidic gastric environment –Mucous provides “self” protection 5 Phases of Digestion Phases of Digestion Integration of Cephalic & Gastric Phases Intestinal Phase • The final products of the cephalic and gastric phase is – Digestion of proteins – Formation of chyme – Controlled entry of chyme into the intestine • Starts the intestinal phase which contains loops that – Feed back to further control gastric emptying – Feed forward to promote digestion, secretion, motility and absorption of nutrients – Signals are hormonal & neural Phases of Digestion Phases of Digestion Intestinal Phase Intestinal Phase • Hormonal and neural aspects of the intestinal phase • Major processes occurring in the intestinal phase – entrance of chyme into duodenum gets the enteric nervous – Buffering system going, secreting: • Via pancreatic exocrine secretion •Secretin – slows gastric emptying & gastric acid production – Digestion - – Stimulates bicarbonate (HCO3 ) production from pancreas to buffer • By pancreatic exocrine secretion acidic chyme – Trypsinogen, chymotrypsinogen, procarboxypeptidase, procolipase and • cholecystokinin (CCK) prophospholipase – Secreted in response to lipids and slows gastric motility and gastric • By bile release from gallbladder (stimulated by CCK) acid secretion – Acts hormonally on the hypothalamus, – Bile emulsifies the lipids, increasing surface area for pancreatic lipases • Incretin hormones (GIP and GLP-1) • By intestinal mucosal enzymes (brush border enzymes) that are – GIP (gastric inhibitory peptide) “anchored” to apical surface – GLP-1 (glucagon-like peptide1) – Peptidases, disaccharidases, enteropeptidase » Slow gastric acid and emptying – Absorption » stimulate insulin release from pancreas • Most of the water & nutrients are absorbed in the small intestine 6 Phases of Digestion Phases of Digestion Intestinal Phase Integration of Intestinal & Gastric Phases • Activation of pancreatic proteolytic enzymes Phases of Digestion Lecture Outline Intestinal Phase • The large intestines main processes are – Concentrating waste • Basic GI functions • Removal of water – Only about .1L of water lost daily through feces • Regulation of GI function – Movement & defecation • Ileocecal valve controls chyme entrance into colon • Phases of Digestion – Relaxes in sequence with intestinal peristalsis as well as when gastric emptying starts (gastrocolic reflex) • Absorption » CCK, serotonin and gastrin are potential initiators of the gastrocolic reflex • Defecation reflex • Protective Function of the GI tract – Increases abdominal pressure, relaxes anal sphincters – Digestion and absorption • Digestion mainly through bacterial action which produces – Lactate and fatty acids which are absorbable by simple diffusion – Bacterial action also produces vitamin K – By product of bacterial fermentation is gas (CO2, methane & HS) 7 Absorption Absorption • Carbohydrate •Protein absorption absorption Absorption Absorption • Lipid digestion • Absorbed & absorption nutrients and water are returned via the hepatic portal system 8 Lecture Outline Protective Functioning • Basic GI functions • Large surface area of GI tract warrants protective function • Regulation of GI function – Salivary enzymes and immunoglobulins – Gastric acid • Phases of Digestion – Toxins and pathogens in the intestine initiate • Absorption • Diarrhea • vomitting • Protective Function of the GI tract – GALT & M cells • M cells overly the immune cells in the GALT (Peyers patches) – M cells activate lymphocytes of GALT when pathogens are detected – Actiavated GALT increase Cl- secretion, fluid secretion and mucous secretion » Results in diarrhea & potentially vomitting » Both are protective reflexes 9.