1. Gastrointestinal Physiology I Part 1 Dr Lwiindi (Medical Physiologist)

2. Functions 4 major activities of GI tract 4 major activities of GI tract 1. Motility Propel ingested food from mouth toward rectum Propel ingested food from mouth toward rectum 2. Secretion Aid in digestion and absorption Aid in digestion and absorption 3. Digestion Food broken down into absorbable molecules Food broken down into absorbable molecules 4. Absorption Nutrients, electrolytes, and water are absorbed Nutrients, electrolytes, and water are absorbed

3. Structure of GI Tract Arranged linearly in following sequence Arranged linearly in following sequence Mouth, esophagus, stomach, small intestine, large intestine, and anus Mouth, esophagus, stomach, small intestine, large intestine, and anus Other structures of GI tract Other structures of GI tract Salivary glands, pancreas, liver, and gallbladder Salivary glands, pancreas, liver, and gallbladder

4. Structure of GI Tract Layers of GI Wall Layers of GI Wall 1. Mucosa Innermost layer (faces lumen) Innermost layer (faces lumen) It consists of an epithelium, the lamina propria, and the muscularis mucosae Layer of epithelial cells specialized for absorption and secretion Layer of epithelial cells specialized for absorption and secretion 2. Submucosa Consists of collagen, elastin, glands, and blood vessels Consists of collagen, elastin, glands, and blood vessels 3. Circular and Longitudinal Smooth Muscle Provides motility for GI tract Provides motility for GI tract 4. Serosa Faces the blood Faces the blood

5. Layers of GI Wall

6. Innervation of GI Tract Autonomic Nervous System has an extrinsic and an intrinsic component Autonomic Nervous System has an extrinsic and an intrinsic component Extrinsic Extrinsic Sympathetic and Parasympathetic innervation of GI tract Sympathetic and Parasympathetic innervation of GI tract Intrinsic Intrinsic Called Enteric Nervous System Called Enteric Nervous System Contained within wall of GI tract Contained within wall of GI tract Communicates with Extrinsic component Communicates with Extrinsic component

7. Intrinsic Innervation Can direct all functions of GI in absence of extrinsic innervation Can direct all functions of GI in absence of extrinsic innervation Controls contractile, secretory, and endocrine functions of GI tract Controls contractile, secretory, and endocrine functions of GI tract Receives input from Receives input from 1. Parasympathetic and sympathetic nervous systems 2. Mechanoreceptors and chemoreceptors in mucosa Sends information directly to smooth muscle, secretory, and endocrine cells Sends information directly to smooth muscle, secretory, and endocrine cells

9. EXTRINSIC NERVES I. PARASYMPATHETIC FIBERS I. PARASYMPATHETIC FIBERS are supplied by the vagus nerve and pelvic nerves which are of sacral origin. Parasympathetic fibers are cholinergic and innervate both plexuses of the enteric NS. Increased parasympathetic activity increases smooth muscle activity. Motility and secretion is increased, there is a reduction in constriction of sphincters. An increase in parasympathetic activity promotes digestive and absorptive processes. are supplied by the vagus nerve and pelvic nerves which are of sacral origin. Parasympathetic fibers are cholinergic and innervate both plexuses of the enteric NS. Increased parasympathetic activity increases smooth muscle activity. Motility and secretion is increased, there is a reduction in constriction of sphincters. An increase in parasympathetic activity promotes digestive and absorptive processes. The proximal half of the nervous system is innervated from the cranial parasympathetic nerve fibers via the vagal nerve. The distal half is innervated via Sacral Parasympathetic nerves, which gives supply to the sigmoid colon, rectum and anus, and are important in controlling defecation The proximal half of the nervous system is innervated from the cranial parasympathetic nerve fibers via the vagal nerve. The distal half is innervated via Sacral Parasympathetic nerves, which gives supply to the sigmoid colon, rectum and anus, and are important in controlling defecation

10. SYMPATHETIC INNERVATION SYMPATHETIC INNERVATION The fibers originate in the sympathetic ganglia of T-5 to L-2 and terminate on the enteric nervous plexus, but also a few nerves terminate in the mucosa it self The fibers originate in the sympathetic ganglia of T-5 to L-2 and terminate on the enteric nervous plexus, but also a few nerves terminate in the mucosa it self SYMPATHETIC FIBERS innervation of the GI is noradrenergic postganglionic. Increased sympathetic discharge inhibit acetylcholine secretion from cholinergic neurons. SYMPATHETIC FIBERS innervation of the GI is noradrenergic postganglionic. Increased sympathetic discharge inhibit acetylcholine secretion from cholinergic neurons. Some sympathetic fibers innervate smooth muscle cells directly and some innervate splanchnic blood vessels and act to cause vasocostriction, leading to decreased motility and secretions, increase in constriction of sphincters. Some sympathetic fibers innervate smooth muscle cells directly and some innervate splanchnic blood vessels and act to cause vasocostriction, leading to decreased motility and secretions, increase in constriction of sphincters.

11. Gastrointestinal Reflexes GI reflexes can be considered; GI reflexes can be considered; 1. Local 1. Local 2. Regional 2. Regional 3. Systemic 3. Systemic Local reflexes are processed entirely within the enteric system and control secretion, local motility, and mixing contractions. Local reflexes are processed entirely within the enteric system and control secretion, local motility, and mixing contractions. Regional reflexes go to the sympathetic ganglia, and are important for reflexes at a distant, such as the gastro- colic reflex causing evacuation of the colon, and messages from the intestine to the stomach to inhibit emptying, the entero- gastric reflex, or the colono- ilial reflex that inhibits emptying of the ilial contents into the colon. Regional reflexes go to the sympathetic ganglia, and are important for reflexes at a distant, such as the gastro- colic reflex causing evacuation of the colon, and messages from the intestine to the stomach to inhibit emptying, the entero- gastric reflex, or the colono- ilial reflex that inhibits emptying of the ilial contents into the colon. Systemic reflexes are processed in the spinal cord or brainstem and will control overall activity f the GI system, for example pain reflexes that will inhibit the entire GI system. Systemic reflexes are processed in the spinal cord or brainstem and will control overall activity f the GI system, for example pain reflexes that will inhibit the entire GI system.

12. GIT REGULATION Includes hormones, neurocrines, and paracrines Includes hormones, neurocrines, and paracrines Regulate functions of GI tract Regulate functions of GI tract Contraction and relaxation of smooth muscle wall and sphincters Contraction and relaxation of smooth muscle wall and sphincters Secretion of enzymes for digestion Secretion of enzymes for digestion Secretion of fluid and electrolytes Secretion of fluid and electrolytes Trophic (growth) effects Trophic (growth) effects Some regulate secretion of other GI peptides Some regulate secretion of other GI peptides

13. GI Peptides Hormones Hormones Peptides released from endocrine cells of GI tract Peptides released from endocrine cells of GI tract Secreted into portal circulation and enter systemic circulation Secreted into portal circulation and enter systemic circulation Target cells may be in GI tract or may be located elsewhere in body Target cells may be in GI tract or may be located elsewhere in body Gastrin, Cholecystokinin, Secretin, and Gastric Inhibitory Peptide Gastrin, Cholecystokinin, Secretin, and Gastric Inhibitory Peptide Paracrines Paracrines Secreted by endocrine cells of GI tract Secreted by endocrine cells of GI tract Act locally within same tissue that secretes them Act locally within same tissue that secretes them Somatostatin (inhibitory actions) Somatostatin (inhibitory actions) Neurocrines Neurocrines Released by neurons of GI tract following an AP Released by neurons of GI tract following an AP ACh, norepinephrine, Vasoactive Intestinal Peptide (VIP), Gastrin- Releasing Peptide (GRP), Neuropeptide Y, and Substance P ACh, norepinephrine, Vasoactive Intestinal Peptide (VIP), Gastrin- Releasing Peptide (GRP), Neuropeptide Y, and Substance P

15. GI Hormones Gastrin Gastrin Secreted by G cells in stomach in response to eating Secreted by G cells in stomach in response to eating Stimuli include proteins, distention of stomach, and vagal stimulation Stimuli include proteins, distention of stomach, and vagal stimulation Gastrin-releasing peptide (GRP) is released from vagal nerve endings onto G cells Gastrin-releasing peptide (GRP) is released from vagal nerve endings onto G cells Secretion is inhibited by low pH in stomach Secretion is inhibited by low pH in stomach Promotes H + secretion by gastric parietal cells Promotes H + secretion by gastric parietal cells Stimulates growth of gastric mucosa Stimulates growth of gastric mucosa

16. GI Hormones Cholecystokinin Cholecystokinin Secreted by I cells of small intestine in response to fatty acids and small peptides Secreted by I cells of small intestine in response to fatty acids and small peptides 5 Actions: 1. Contraction of gallbladder Eject bile from gallbladder into small intestine necessary for emulsification lipids Eject bile from gallbladder into small intestine necessary for emulsification lipids 2. Secretion of pancreatic enzymes Digest lipids, carbohydrates, and proteins Digest lipids, carbohydrates, and proteins 3. Secretion of bicarbonate (HCO 3 -) from pancreas 4. Growth of exocrine pancreas and gallbladder 5. Inhibition of gastric emptying Ensures adequate time for digestive and absorptive Ensures adequate time for digestive and absorptive

17. GI Hormones Secretin Secretin Secreted by S cells of duodenum in response to H + and fatty acids Secreted by S cells of duodenum in response to H + and fatty acids Promotes secretion of pancreatic HCO 3 - Promotes secretion of pancreatic HCO 3 - Neutralizing H + allows for pancreatic enzymes to digest fats Neutralizing H + allows for pancreatic enzymes to digest fats Inhibits effects of gastrin on parietal cells (H + secretion and growth) Inhibits effects of gastrin on parietal cells (H + secretion and growth) Gastric Inhibitory Peptide (GIP) Gastric Inhibitory Peptide (GIP) Secreted by small intestine in response to all 3 types of nutrients Secreted by small intestine in response to all 3 types of nutrients Stimulates insulin secretion by pancreas Stimulates insulin secretion by pancreas Inhibits gastric H + secretion Inhibits gastric H + secretion

18. GI Paracrines Somatostatin Somatostatin Secreted by endocrine cells in response to decreased luminal pH Secreted by endocrine cells in response to decreased luminal pH Inhibits secretion of other GI hormones Inhibits secretion of other GI hormones Inhibits gastric H + secretion Inhibits gastric H + secretion Histamine Histamine Secreted in H + -secreting region of stomach Secreted in H + -secreting region of stomach Stimulates H + secretion by gastric parietal cells (along with gastrin and ACh) Stimulates H + secretion by gastric parietal cells (along with gastrin and ACh)

19. GI Neurocrines Synthesized in cell bodies of GI neurons Synthesized in cell bodies of GI neurons AP causes release of neurocrine which interacts with receptors on postsynaptic cell AP causes release of neurocrine which interacts with receptors on postsynaptic cell ACh (released from cholinergic neurons) ACh (released from cholinergic neurons) Norepinephrine (released from adrenergic neurons) Norepinephrine (released from adrenergic neurons)

20. HormoneSourceStimulus Stomach Motility and Secretion PancreasGall bladder 1. Secretin S cells lining the duodenum Acid entering duodenum Inhibits Stimulates fluid secretion (HCO 3 - ) 2. CCK Cells lining the duodenum Fat and amino acids entering duodenum Inhibits emptying Stimulates enzyme secretion 1.Contraction 2.Relaxation sphincter (Oddi) 3. Gastrin G cells of stomach Antrum Duodenum Stomach distension Parasymp Peptides Stomach acid inhibits Stimulates 4. GIPDuodenumFat, CH0, amino acids Inhibits CCK = Cholecystokonin, GIP = Gastric inhibitory peptide (glucose insulintropic peptide) Note: In a non-acid producing stomach (e.g, chronic gastritis), the reduced negative feedback increases circulating gastrin. All four hormones stimulate insulin release.

21. Esophagus Muscular tube that conveys food from pharynx to stomach Muscular tube that conveys food from pharynx to stomach Inner circular muscle Inner circular muscle Outer longitudinal muscle Outer longitudinal muscle Food passes through quickly because of peristalsis Food passes through quickly because of peristalsis

22. Esophagus

23. Esophagus Pyrosis (heartburn)—common esophageal discomfort Pyrosis (heartburn)—common esophageal discomfort Result of regurgitation of food and gastric fluid into lower esophagus Result of regurgitation of food and gastric fluid into lower esophagus Acid reflux can cause esophagitis Acid reflux can cause esophagitis

24. Control of LES tone. The resting pressure in the LES is about 20 mm Hg. The tonic contraction of the circular musculature of the sphincter is regulated by nerves, both intrinsic and extrinsic, and by hormones and neuromodulators. The resting pressure in the LES is about 20 mm Hg. The tonic contraction of the circular musculature of the sphincter is regulated by nerves, both intrinsic and extrinsic, and by hormones and neuromodulators. A significant fraction of this basal tone in this sphincter is mediated by vagal cholinergic nerves. Stimulation of sympathetic nerves to the sphincter also causes the LES to contract A significant fraction of this basal tone in this sphincter is mediated by vagal cholinergic nerves. Stimulation of sympathetic nerves to the sphincter also causes the LES to contract

25. Relaxation of the LES. The intrinsic and extrinsic innervation of the LES is both excitatory and inhibitory The intrinsic and extrinsic innervation of the LES is both excitatory and inhibitory Vagal excitatory fibers are predominantly cholinergic. Vagal excitatory fibers are predominantly cholinergic. The relaxation of the sphincter that occurs in response to primary peristalsis in the esophagus is primarily mediated by vagal fibers that inhibit the circular muscle of the LES. Although the inhibitory neurotransmitter is not known with certainty, it is thought that VIP and NO mediate this relaxation of the LES. The relaxation of the sphincter that occurs in response to primary peristalsis in the esophagus is primarily mediated by vagal fibers that inhibit the circular muscle of the LES. Although the inhibitory neurotransmitter is not known with certainty, it is thought that VIP and NO mediate this relaxation of the LES.

26. In some individuals, the sphincter fails to relax sufficiently during swallowing to allow food to enter the stomach. In some individuals, the sphincter fails to relax sufficiently during swallowing to allow food to enter the stomach. This condition is known as achalasia. This condition is known as achalasia. Therapy for achalasia involves either mechanically dilating or surgically weakening the LES or administering drugs that inhibit its tone. In individuals with diffuse esophageal spasm, prolonged and painful contraction of the lower part of the esophagus occurs after swallowing, instead of the normal esophageal peristaltic wave. In individuals with incompetence of the LES, gastric juice can move back up into the lower esophagus and erode the esophageal mucosa. Therapy for achalasia involves either mechanically dilating or surgically weakening the LES or administering drugs that inhibit its tone. In individuals with diffuse esophageal spasm, prolonged and painful contraction of the lower part of the esophagus occurs after swallowing, instead of the normal esophageal peristaltic wave. In individuals with incompetence of the LES, gastric juice can move back up into the lower esophagus and erode the esophageal mucosa.

27. Mechanical Digestion Mastication – reducing the food particle size through chewing, and mixes food with saliva Mastication – reducing the food particle size through chewing, and mixes food with saliva Deglutition – swallowing Deglutition – swallowing 1. Oral Stage (moth to oropharynx) 2. Pharyngeal Stage (oropharynx to esophagus) 3. Esophageal Stage (esophagus to stomach)

28. 28 DIGESTION: MECHANICAL Deglutition: process of swallowing; complex process requiring coordinated, rapid movements (Figure 26-2) Deglutition: process of swallowing; complex process requiring coordinated, rapid movements (Figure 26-2) Oral stage (mouth to oropharynx): voluntarily controlled; formation of a food bolus in the middle of the tongue; tongue presses bolus against the palate and food is then moved into the oropharynx Oral stage (mouth to oropharynx): voluntarily controlled; formation of a food bolus in the middle of the tongue; tongue presses bolus against the palate and food is then moved into the oropharynx Pharyngeal stage (oropharynx to esophagus): involuntary movement; to propel bolus from the pharynx to the esophagus, the mouth (tongue), nasopharynx (soft palate), and larynx (epiglottis) must be blocked; a combination of contractions and gravity move bolus into esophagus Pharyngeal stage (oropharynx to esophagus): involuntary movement; to propel bolus from the pharynx to the esophagus, the mouth (tongue), nasopharynx (soft palate), and larynx (epiglottis) must be blocked; a combination of contractions and gravity move bolus into esophagus Esophageal stage (esophagus to stomach): involuntary movement; contractions and gravity move bolus through esophagus and into stomach Esophageal stage (esophagus to stomach): involuntary movement; contractions and gravity move bolus through esophagus and into stomach