PHYSIOLOGY LECTURE 16 DEFECATION MECHANISMS_ REGULATION OF GASTROINTESTINAL FUNCTIONS ABDUL-RAHUF A FEYITIMI.pdf

PHYSIOLOGY LECTURE 16 TOPIC: DEFECATION MECHANISMS; REGULATION OF GASTROINTESTINAL FUNCTIONS Abdul-Rahuf Aderemi FEYITIMI Department of Medical Physiology, College of Medicine and Health Sciences (CMHS), University of Rwanda. Pho...

PHYSIOLOGY LECTURE 16 TOPIC: DEFECATION MECHANISMS; REGULATION OF GASTROINTESTINAL FUNCTIONS Abdul-Rahuf Aderemi FEYITIMI Department of Medical Physiology, College of Medicine and Health Sciences (CMHS), University of Rwanda. Phone: +250791703685 Email: [email protected]; [email protected]  DEFECATION MECHANISMS 7/29/2024 2 LEARNING OBJECTIVES INTRODUCTION IMPORTANT STRUCTURES Ileocecal valve Large intestine Anal sphincters & associated muscles of the colon Defecation centers FORMATION, DISPLACEMENT & ELIMINATION OF STOOL QUANTIFICATION AND COMPOSITION OF FECES MAINTENANCE OF CONTINENCE DEFECATION DEFECATION REFLEXES PATHOPHYSIOLOGY 7/29/2024 3 INTRODUCTION Defecation is the term given for the act of expelling feces from the digestive tract via the anus. It is a spinal reflex triggered by distension of the rectum. It is a complex function that requires coordinated involvement from the gastrointestinal system, the nervous system, as well as the musculoskeletal system. The frequency of defecation within a 24-hour period varies depending on age and diet, but most people tend to have a bowel movement 1 to 3 times daily. 7/29/2024 4 IMPORTANT STRUCTURES Ileocecal valve This valve connects ileum to the cecum, and prevents relux of colonic contents into sterile ileum. The portion of the ileum containing the ileocecal valve projects slightly into the cecum. The valve is normally closed. Each time a peristaltic wave reaches it, it opens briefly, permitting some of the ileal chyme to squirt into the cecum. Increases in colonic pressure squeeze it shut, whereas increases in ileal pressure open it. Similarly, a weak functional sphincter exists about 20 centimeters from the anus at the juncture between the sigmoid colon and the rectum, keeping the rectum empty. Also, sharp angulation is also present at this colorectal junction that contributes additional resistance to filling of the rectum. 7/29/2024 5  Large intestine The large intestine is further divided into the following parts: (1) Caecum -compresses food product received from the ileum into faecal materials. (2) Ascending, transverse and descending colons, (3) Sigmoid colon, and -The colon serves as a passageway for these materials and for reabsorption of water, salts, sugar and vitamins. (4) Rectum - The rectum expands to hold faecal materials before it passes through the anorectal canal to the anus through which it is extruded. Fig. 1: Parts of the large intestine. 7/29/2024 6 Anal sphincters Internal anal sphincter: It is a thickening of the internal, circular layer of the muscularis. Length: 3-4 cm; involuntary command. External anal sphincter (EAS):  It is constituted by striated muscular fibers and surrounds completely the internal anal sphincter. After toilet training, the EAS permits delaying the elimination of wastes until a time when it is socially convenient. Its role is to control defecation Other muscles from the caecum to the rectum are divided into: An internal circular layer; An external longitudinal layer, whose fibers are assembled into 3 longitudinal tapes, the teniae coli. Because these tapes are shorter than the rest of the large intestine, the large intestine wall forms haustrations between teniae. 7/29/2024 7 INNERVATION Intrinsic: Auerbach plexus Extrinsic: parasympathetic: - via the vagus and the pelvic nerves – Stimulation of the contraction of smooth muscle of the intestine and Relaxation of sphincters. Sympathetic: - origin : thoraco-lumbar spinal cord – Relaxation of smooth muscles of the large intestine and contraction of sphincters. 7/29/2024 8  Defecation center Sacral center: It is located at the level of the sacral spinal cord. Afferences: from the rectum (whose wall contains stretch receptors) and the cerebral center. Efferences: towards the large intestine and the smooth anal sphincter. Cerebral center: responsible for the conscious control of defecation. Afferences: from the rectum Efferences: towards the sacral center, - The striated muscles of the abdominal wall and the pelvis (notably the striated sphincter). 7/29/2024 9 FORMATION, DISPLACEMENT AND ELIMINATION OF STOOL The colon serves as a reservoir for the residues of meals that cannot be digested or absorbed. Motility in this segment is likewise slowed to allow the colon to absorb water, Na+, and other minerals. By removal of about 90% of the fluid, it converts the 1000 to 2000 mL of isotonic chyme that enters it each day from the ileum to about 200 to 250 mL of semisolid feces. 7/29/2024 10 Fig. 1: Absorptive and storage functions of the large intestine. FORMATION OF FECES 7/29/2024 11 Motor innervation of the colon leads to formation, displacement and elimination of stool. Indeed, the movements of the large intestine are of three types: 1. Segmentation contractions associated with pouch formation Changes of the intrinsic tonus and segmentation contractions as those that occur in the small intestine. Those movements mix the colic content, by renewing the contact between that content and the mucosa, thereby facilitating its absorption. 2. Mass action movements They is a very powerful contractions, occurring 2 to 3 times per day. They are triggered by a local distention of the large intestine. They are generally stimulated by a meal and are caused by the gastrocolic reflex and gastrointestinal hormones. They ensure propulsion of great volumes of colic content on important distances. 3 to 4 mass action movements are necessary to make the colic content pass from the ileum to the rectum. However, they are normally not perceived by the subject and are not directly 7/29/2024 12 related to defecation. FORMATION, DISPLACEMENT AND ELIMINATION OF STOOL 3. Peristaltic waves:  Wave-like contractions that occur in a coordinated, rhythmic manner. They help to propel the colonic content towards the anus. These waves are more frequent than mass movements and play a crucial role in maintaining regular bowel movements. 7/29/2024 13 QUANTIFICATION AND COMPOSITION OF FECES Stool (feces). The average adult excretes 60–80 g of feces/day. Diarrhea can raise this to over 200 g/d. Roughly 1/4 of the feces is composed of dry matter, which in turn, about 1/3 is attributable to bacteria. Input: 1 to 2 L of isotonic chyme comprising: Non-absorbed food (because it is non-digestible, non-digested or digested but not absorbed); Desquamated and non-digested cells; Bile pigments and a little bile salts. Output: 200- 250 mL of stool/24 hours. Stool comprises: fibers, bacteria, mucus, desquamated cells, bile pigments. 7/29/2024 14  Fig. 2: Composition of feces. 7/29/2024 15 MAINTENANCE OF CONTINENCE The anus is normally closed. Anal closure is regulated by the transverse rectal fold, the puborectal muscles, the (involuntary) internal and (voluntary) external anal sphincter muscles, and a venous spongy body. Continual dribble of fecal matter through the anus is prevented by tonic constriction of the internal sphincter and external sphincter muscle. Both sphincters contract tonically, the internal sphincter (smooth muscle) intrinsically or stimulated by sympathetic neurons (L1, L2) via α-adrenoceptors, the external sphincter muscle (striated muscle) by the pudendal nerve. Normally, the angle between the anus and the rectum is approximately 90 degrees, and this plus contraction of the puborectalis muscle inhibit defecation. This helps to maintain continence by preventing stool from passing into the anal canal. 7/29/2024 16  Fig.3: Sagittal view of the anorectal area at rest. 7/29/2024 17 DEFECATION Filling the upper portion of the rectum (rectal ampulla) with intestinal contents stimulates the rectal stretch receptors (Beta 2), causing reflex relaxation of the internal sphincter (via activation of VIP neurons), constriction of the external sphincter, and an urge to defecate. When a mass movement forces feces into the rectum, the desire for defecation occurs immediately, including reflex contraction of the rectum and relaxation of the anal sphincters. Also, the rectum’s distention with feces initiates reflex contractions of its musculature and the desire to defecate. 7/29/2024 18 DEFECATION In humans, the sympathetic nerve supply to the internal (involuntary) anal sphincter is excitatory, whereas the parasympathetic supply is inhibitory. This sphincter relaxes when the rectum is distended. The nerve supply to the external anal sphincter, a skeletal muscle, comes from the pudendal nerve. The sphincter is maintained in a state of tonic contraction, and moderate distention of the rectum increases the force of its contraction. 7/29/2024 19  DEFECATION The urge to defecate first occurs when rectal pressure increases to about 18 mm Hg. Voluntary defecation can be initiated by straining before the pressure that relaxes the external anal sphincter is reached, When this pressure reaches 55 mm Hg, the external and internal sphincters relax, and the contents of the rectum are reflexively expelled. This is why reflex evacuation of the rectum can occur even in the setting of spinal injury. With straining, the abdominal muscles contract, the pelvic floor is lowered 1 to 3 cm, and the puborectalis muscle relaxes. 7/29/2024 20  DEFECATION The anorectal angle is increased to appro.130 to 140 degrees or more. This is combined with relaxation of the external anal sphincter and defecation occurs. Defecation is, therefore, a spinal reflex that can be voluntarily inhibited by keeping the external sphincter contracted or facilitated by relaxing the sphincter and contracting the abdominal muscles. When straining during defecation: 1. Increased intra-abdominal pressure 2. Relaxation of the puborectalis muscle (which forms the anorectal angle) 3. Straightening of the anorectal angle Fig.4: Sagittal view of the anorectal area (increased to around 130-140 degrees) during straining. 7/29/2024 21 DEFECATION This straightening of the anorectal angle helps to facilitate the passage of stool by: 1. Aligning the anal canal with the rectum. 2. Reducing the resistance to stool passage. 3. Allowing for more efficient evacuation of stool. After defecation, the anorectal angle returns to its normal position, and the puborectalis muscle contracts to maintain continence. 7/29/2024 22  Fig. 5: (1), (2) and (3). 7/29/2024 23 DEFECATION Voluntary defecation If the (generally voluntary) decision to defecate is made: The rectum shortens. The puborectal and external anal sphincter muscles relax, and Annular contractions of the circular muscles of the descending colon, sigmoid colon, and rectum occur when a spinal parasympathetic reflex (via S2–S4) is activated. This is assisted by increased abdominal pressure. All propel the feces out of the body. 7/29/2024 24  In convenient state for defecation: The defecation reflexes can purposely be activated by taking a deep breath to move the diaphragm downward and then contracting the abdominal muscles. These increase the pressure in the abdomen, thus forcing fecal contents into the rectum to cause new reflexes. Reflexes initiated in this way are almost never as effective as those that arise naturally. Thus, people who too often inhibit their natural reflexes are likely to become severely constipated. In newborn babies and some people with transected spinal cords, the defecation reflexes cause automatic emptying of the lower bowel at inconvenient times during the day. This is because of a lack of conscious control exercised through voluntary contraction or relaxation of the external anal sphincter. 7/29/2024 25 DEFECATION REFLEXES Ordinarily, defecation is initiated by defecation reflexes. Intrinsic reflex One of these reflexes is an intrinsic reflex mediated by the local enteric nervous system in the rectal wall. When feces enter the rectum, distention of the rectal wall initiates afferent signals that spread through the myenteric plexus. It is relatively weak and needs other reflexes for the full control. These initiate peristaltic waves in the descending colon, sigmoid, and rectum, forcing feces toward the anus. As the peristaltic wave approaches the anus, the internal anal sphincter is relaxed by inhibitory signals from the myenteric plexus. If the external anal sphincter is also consciously, voluntarily relaxed at the same time, defecation occurs. 7/29/2024 26 DEFECATION REFLEXES Parasympathetic reflex Another type of defecation reflex called a parasympathetic defecation reflex, involving the sacral segments of the spinal cord. When the nerve endings in the rectum are stimulated, signals are transmitted first into the spinal cord. Then, reflexly back to the descending colon, sigmoid, rectum, and anus by way of parasympathetic nerve fibers in the pelvic nerves. These parasympathetic signals greatly intensify the peristaltic waves and relax the internal anal sphincter, thus converting the intrinsic myenteric defecation reflex from a weak effort into a powerful process of defecation. This combination is sometimes effective in emptying the large bowel all the way from the splenic flexure of the colon to the anus. 7/29/2024 27  Fig. 6: Afferent and efferent pathways of the parasympathetic mechanism for enhancing the defecation reflex. 7/29/2024 28 DEFECATION REFLEXES Defecation signals entering the spinal cord initiate other effects: 1. Taking a deep breath, 2. Closure of the glottis, and 3. Contraction of the abdominal wall muscles They force the fecal contents of the colon downward They cause the pelvic floor to relax downward. They pull outward on the anal ring to evaginate the feces. 7/29/2024 29 Pathophysiology The normal frequency of bowel evacuation can range from 3 times a day to 3 times a week, depending on the dietary content of indigestible fiber (e.g. cellulose, lignin). 1. Constipation The symptoms of constipation are infrequent bowel movements [usually less than 3 per week], passage of hard stools, and sometimes difficulty in passing stool. 2. Fecal incontinence Fecal incontinence means involuntary passage of fecal material in someone over the age of 4 years. The most common causes are: (a) Weakness of the anal sphincter muscles. (b) Loss of sensation for rectal fullness. 3. Diarrhoea Diarrhea is an increase in stool frequency, liquidity, or volume. It further subcategorizes into the following types. 7/29/2024 30  REGULATION OF GASTROAINTESTINAL FUNCTIONS 7/29/2024 31 LEARNING OBJECTIVES INTRODUCTION OVERVIEW OF GI ACTIVITIES CONTROL OF GI ACTIVITIES ENTERIC NERVOUS SYSTEM (ENS) REGULATION OF ENS REGULATION OF GI ACTIVITIES BY SNS REGULATION OF GI ACTIVITIES BY PNS EXCITATORY & INHIBITORY ACTIONS OF SNS AND PNS HORMONAL CONTROL OF GI ACTIVITIES SLOW WAVES & SPIKES REGULATION OF MOTOR FUNCTION LOCAL REFLEXES PATHOPHYSIOLOGY 7/29/2024 32 INTRODUCTION The gastrointestinal tract (GIT) is a continuous, tubular structure that extends from the mouth to the anus. It supplies the body with nutrients, electrolytes, and water by performing five functions: motility, secretion, digestion, absorption and storage. The walls of the different parts of the alimentary canal are distinct and richly innervated by both enteric nervous system (ENS) and autonomic nervous system (ANS). These systems of nerves regulate important GIT functions. Based on the needs of the various organ systems in the body, the GIT orchestrates and controls these five functions through different control systems. 7/29/2024 33 OVERVIEW OF THE GASTROINTESTINAL TRACT FUNCTIONS The principal activities of the GIT include: 1. Ingestion (mastication and deglutition) 2. Movement or motility 3. Mechanical and chemical digestion 4. secretion 5. Absorption 6. Elimination or defecation 7/29/2024 34 OVERVIEW OF THE GI FUNCTIONS Ingestion (mastication & deglutition Elimination absorption Fig. 1: Principal activities of the gastrointestinal tract. 7/29/2024 35  CONTROL OF GI FUNCTIONS The control is through intrinsic & extrinsic control systems, each containing neural & hormonal systems. Many of the controlling systems of the digestive tract are intrinsic nerve plexuses & intrinsic endocrine cells. The intrinsic control system has two components: the Enteric Nervous System (ENS) and gut hormones. The extrinsic control system consists of: The vagus and splanchnic nerves & extrinsic hormone. Most GI functions are controlled by ANS independent of conscious perception but can be influenced by higher brain centers. 7/29/2024 36  Neural regulation: The regulation of GI activities is by: Enteric nervous system (ENS) or intrinsic nervous system, which is semi autonomous. It has its: Afferent neurons (carry in information from other GI parts) Interneuron & Efferent neurons (carry information to other GI parts). These neurons make the ENS capable of carrying out reflexes & acting as an integrating center (IC) without CNS input. Extrinsic neurons (external to the ENS) These include: Extrinsic afferents from GI (carry information from GI system to external ICs). Sympathetic and parasympathetic efferent to GI (from ANS to GI). 7/29/2024 37 CONTROL OF GI FUNCTIONS Overall neural interactions: The sensory flow of information from the gut into intrinsic IC (ENS) and extrinsic ICs (peripheral sympathetic ganglia and CNS [spinal cord and the brain]) Outflow from the ICs to the gut. NOTE: The efferent parts of ENS (intrinsic) & extrinsic neurons are part of ANS. 7/29/2024 38 CONTROL OF GI FUNCTIONS Other classification: The GI activities can be regulated in three ways: 1. Reflexes that originate outside the digestive system (called long reflexes). 2. Reflexes that originate inside the digestive system (called the enteric nervous system or short reflexes ). 3. Gastrointestinal (GI) Peptides 7/29/2024 39  Initiated by stimuli inside or outside the GIT & involve CNS centers & extrinsic ANS nerves. Fig. 2: Neural control; controls all GI activities, including: muscle contraction, secretion, absorption & blood flow. 7/29/2024 40 ENTERIC NERVOUS SYSTEM (ENS) The enteric nervous system (ENS) is considered as the third division of the ANS. Another name for ENS is the mini brain. It is located within the wall of the digestive tract, all the way from the oesophagus to the anus. The myenteric plexus is located between longitudinal and inner circular layers of smooth muscle, and it is involved in control of digestive tract motility. The submucosal plexus located between the inner circular muscle and the luminal mucosa. It senses the environment of the lumen and regulates gastrointestinal blood flow and epithelial cell functions, including glandular secretion. 7/29/2024 41  The different layers of the wall of the GI tract. Starting from the lumen of the gut, the wall consists of mucosa with epithelial layer (1), lamina propria (2), and muscularis Fig. 3: (A) Three-dimensional cross mucosae (3); submucosa (4); a submucosal plexus (5); inner section of the gut wall. (B) Functional circular muscle layer (6); myenteric plexus (7); outer longitudinal layers of the wall of the intestine. muscle layer (8); and serosa (9). 7/29/2024 42 ENTERIC NERVOUS SYSTEM Enteric Nervous System (ENS) The GIT has a nervous system all on its own and it’s the Enteric Nervous System OR the intramural plexus. It lies in the wall of the gut, beginning in the oesophagus and extending all the way to the anus. Classification of ENS Anatomically, the ENS consists of two main ganglionated plexuses: 1. The submucosal (Meissner) plexus and 2. Myenteric (Auerbach) plexus There are about 100 million sensory neurons , motor neurons and interneurons. 7/29/2024 43 ENTERIC NERVOUS SYSTEM 1. Submucosal plexus (Meissner’s plexus): is located between inner circular layer and submucosal layer of the gut. Innervates: Glandular epithelium; intestinal endocrine cells; submucosal blood vessel. It controls mostly the gastrointestinal secretions and local blood flow. 2. Myenteric plexus (Auerbach’s plexus): is an outer plexus lying between the inner circular muscle layer and the outer longitudinal muscle layer. It controls mostly the GIT movements. The enteric plexuses communicate with each other through interneurons and with the CNS through vagal, pelvic, and splanchnic nerves. 7/29/2024 44  Fig. 4: The enteric nervous system. 7/29/2024 45 ENTERIC NERVOUS SYSTEM Receptors The receptors are: a. Mechanoreceptors- sense mechanical events (e.g., stretching) in the GIT wall & mesentery. b. Chemoreceptors/osmoreceptors detect the presence of nutrients and end products of digestion, osmolality, and pH in the GIT lumen. They can also respond to mechanical stimuli. c. pain receptors (nociceptors) and thermoreceptors. Though not well established in GI, it is confirmed in gall bladder. Stimulation of these receptors initiates reflexes that: (1) ↑ or ↓ glands that secrete digestive juices into the lumen or hormones into the blood. (2) stimulate the smooth muscle of the GIT walls to mix lumen contents & move them. The afferent fibers are sent to: - Plexuses of ENS - Sympathetic prevertebral ganglia - Spinal cord - Brain stem (Dorsal Vagal Complex of medulla). 7/29/2024 46  Dorsal Vagal Complex and its Location AP- Area postrema NTS- Nucleus Tractus Solitarius DMN- Dorsal Motor Nucleus DMN = DMV- Dorsal Motor nucleus of Vagus Regulation of GI motor & GIT secretory functions Fig. 5: Dorsal vagal complex of medulla. 7/29/2024 47 ENTERIC NERVOUS SYSTEM In general, the enteric neurons consist of sensory (afferent) neurons, interneurons, and motor (efferent) neurons. Sensory input comes from mechanoreceptors within the muscular layers and chemoreceptors within the mucosa. Mechanoreceptors monitor distention of the gut wall, whereas chemoreceptors in the mucosa monitor chemical conditions in the gut lumen. Enteric motor nerves supply vascular muscle, gut muscle, and glands within the gut wall. Efferent neurons of the ENS may be stimulatory or inhibitory. The nature of their action is largely determined by the type of neurocrine substance they secrete, and the nature of the receptors activated. Acetylcholine and substance P stimulate motility. Nitric oxide and vasoactive intestinal peptide (VIP) inhibit motility and cause hyperaemia that accompanies food digestion. 7/29/2024 48 REGULATION OF THE ENS FUNCTION 1. Local autonomic control: This is achieved by the intestinal cells of Cajal, the electrical pacemakers of the gut. These cells connect both with the smooth muscle and myenteric neurons. They modulate their activity for continuous and rhythmic peristalsis. 2. Vagal control: This is mediated through the central parasympathetic input from the vagus nerve. This allows the physiological state of the body to influence the activity of the gut. The preganglionic parasympathetic fibres consist of about 2000 vagal afferents and other efferents in the sacral nerves. They generally end on cholinergic nerve cells of the myenteric and submucosal plexuses. 7/29/2024 49 REGULATION OF THE ENS FUNCTION 3. The sympathetic fibres are postganglionic, but many of them end on postganglionic cholinergic neurons, where the noradrenaline (NA) they secrete inhibits acetylcholine secretion by activating α2 presynaptic receptors. Other sympathetic fibres appear to end directly on intestinal smooth muscle cells. 4. Other fibres also innervate blood vessels, where they produce vasoconstriction. It appears that intestinal blood vessels have a dual innervation: They have an extrinsic NA innervation and an intrinsic innervation by fibres of ENS (VIP and NO). 7/29/2024 50  Fig. 6: Overall neural interactions. Types of Afferents from GIT Types of Efferent to GIT Intrinsic Extrinsic Intrinsic efferent Vagal afferent - Afferent part of Extrinsic efferent: vagus Sympathetic – thoracolumbar Spinal afferent - Afferent splanchnic n (T5-L2) Parasympathetic 7/29/2024 Craniosacral (S2-S4) 51 REGULATION OF GI FUNCTIONS BY SNS SEGMENTAL DISTRIBUTION OF THE SYMPATHETIC NERVE FIBERS Sympathetic fibers from cord segment T1 generally pass from T7, T8, T9, T10, and T11 into the abdomen. The abdominal organs receive most of their sympathetic innervation from the lower thoracic spinal cord segments because most of the primitive gut originated in this area. Fig. 7: Sympathetic nervous system. REGULATION OF GI FUNCTIONS BY SNS Table 1: Adrenergic Receptors and Function. REGULATION OF GI FUNCTIONS BY PNS The vagus nerves supply parasympathetic nerves to the heart, lungs, oesophagus, stomach, entire small intestine, proximal half of the colon, liver, gallbladder, pancreas, kidneys, and upper portions of the ureters. Fibers from the seventh cranial nerve pass to the lacrimal, nasal, and submandibular glands, and fibers from the ninth cranial nerve go to the parotid gland The sacral parasympathetic fibers are in the pelvic nerves, which pass through the spinal nerve sacral plexus on each side of the cord at the S2 and S3 levels. These fibres (S2 and S3) then distribute to the descending colon, rectum, urinary bladder, and lower portions of the ureters. 7/29/2024 54  Fig. 8: Parasympathetic nervous system. 7/29/2024 55  REGULATION OF GI FUNCTIONS BY PNS Vagus Parasympathetic efferents to the small nerve intestine & large intestine musculature are predominantly stimulatory. This is due to their input to the ENS microcircuits that control the activity of excitatory musculomotor neurons. Fig. 9: Stimulatory & inhibitory parasympathetics. Signals from parasympathetic centers in the CNS are transmitted to ENS. They result in either contraction (+) or relaxation (−) of the digestive musculature. The (+) or (-) results from activation of the ENS circuits that control excitatory or inhibitory musculomotor neurons, respectively. 7/29/2024 56 TABLE 2: EXCITATORY AND INHIBITORY ACTIONS OF SYMPATHETIC AND PARASYMPATHETIC STIMULATION. ORGAN EFFECT OF SYMPATHETIC EFFECT OF STIMULATION PARASYMPATHETI C STIMULATION Gut Lumen Decreased peristalsis and tone Increased peristalsis and tone Sphincter Increased tone (most times) Relaxed (most times) Liver Glucose released Slight glycogen synthesis Gall blader and bile Relaxed Contracted ducts EXCITATORY AND INHIBITORY ACTIONS OF SYMPATHETIC AND PARASYMPATHETIC STIMULATION SYMPATHETIC NERVOUS SYSTEM o PARASYMPATHETIC NERVOUS Systemic arterioles SYSTEM 1. Abdominal viscera: Constricted o NONE o NONE 2. Muscle: Constricted (adrenergic α) Dilated (adrenergic β2) Dilated (cholinergic)  HORMONAL CONTROL OF GI FUNCTIONS GI hormones coordinate GI activities together with neurons. Intrinsic hormones- Secreted by DS enteroendocrine cells. >20 secreted by the gut. All gut hormones are gut peptides, whereas not all gut peptides are gut hormones. Extrinsic- Secreted from external source. – The basic extrinsic hormone of the GIT is aldosterone. – In the GIT, it stimulates Na & H2O reabsorption from the gut & salivary glands. Some are secreted from both the GIT and other sources. Neurocrine? – from ENS neurons. Part of paracrine. 7/29/2024 59  Fig. 10: Mode of activity of GI hormones. 7/30/2024 60 HORMONAL CONTROL OF GI FUNCTIONS Classification The main GIT hormones are grouped into 3 categories: a. Gastrin family, e.g. Gastrin, Cholecystokinin b. Secretin family, e.g., Secretin, Glucagon-like intestinal polypeptide, Vasoactive intestinal Polypeptides (VIP) c. Polypeptides: Gastric Inhibitory Peptides, e.g. Neurotensin, Motilin. 7/29/2024 61 HORMONAL CONTROL OF GI FUNCTIONS A.) Cholecystokinin (CCK) It is secreted by the I cells in the mucosa of the duodenum and jejunum in response to digestive products of fat; fatty acids and monoglycerides in the intestinal contents. Also secreted by neurons in the brain and gut. There are various types: CCK 4, CCK 8, CCK 33 etc. Function 1. It stimulates gallbladder contraction for bile release. 2. CCK inhibits stomach contraction moderately, inhibiting gastric emptying. 3. It promotes intestinal motility. 4. It inhibits appetite to prevent overeating during meals by inhibiting the feeding centers. 7/29/2024 62 HORMONAL CONTROL OF GI FUNCTIONS B.) Secretin It was the first GIT hormone discovered by W.M. Bayliss and E.H. Starling in 1902. It is secreted by the S cells in the mucosa of the duodenum in response to gastric acid. Function 1. It inhibits gastric emptying. 2. Inhibits gastric acid secretion but stimulates CCK hormone 3. Promotes pancreatic secretion of bicarbonate which helps neutralize gastric acid in small intestine. 7/29/2024 63 HORMONAL CONTROL OF GI FUNCTIONS C.) Motilin: Is a hormone secreted by endocrine cells in the small intestine. It belongs to the group 3 polypeptides It is secreted by the endocrine cells in the stomach and upper duodenum during fasting. Function 1. It stimulates migrating motor complex. D.) Glucagon-Like Peptide I: Is a hormone secreted by endocrine cells in the small intestine. Function 1. It slows gastric emptying. 7/29/2024 64 HORMONAL CONTROL OF GI FUNCTIONS E) Gastric inhibitory peptide It contains about 43 amino acids. It is secreted by the mucosal cells of the upper small intestine mainly in response to fatty acids and amino acids. Functions: It inhibits gastric secretion and can be stimulated by glucose. It stimulates insulin secretion and for this reason it is called glucose dependent insulinotropic peptide. 7/29/2024 65 HORMONAL CONTROL OF GI FUNCTIONS F) Vasoactive intestinal polypeptide It has 28 amino acids in its chain. It is produced by the nerves of the GIT. Function: 1. It causes dilation of blood vessels which leads to increase in blood flow to the Gastro-Intestinal glands, leading to Gastro- Intestinal secretion. 7/29/2024 66  Table 3: Important Gut and neuroendocrine hormones 7/29/2024 67 SLOW WAVES AND SPIKES The smooth muscle of the gastrointestinal tract is excited by almost continual slow, intrinsic electrical activity along the membranes of the muscle fibres. The voltage of the resting membrane potential of the gastrointestinal smooth muscle can change to different levels. These may involve slow waves and spikes These can also have important effects in controlling motor activity of the gastrointestinal tract. 7/29/2024 68 Fig. 11: Membrane potentials in intestinal smooth muscle. 69 REGULATION OF THE MOTOR FUNCTIONS Factors that depolarize the membrane—that is, make it more excitable— They are: (1) stretching of the muscle, (2) stimulation by acetylcholine released from the endings of parasympathetic nerves, and (3) stimulation by several specific gastrointestinal hormones. Gastrin, CCK, insulin, motilin, and serotonin enhance intestinal motility. Factors that stimulate muscular contractions of the small intestine: CCK, Bombensin, Opioid peptides (e.g. met-enkephalin), Tachykinins (e.g., substance P), Acetylcholine, Motilin (stimulates migrating motor complex) 70  REGULATION OF THE MOTOR FUNCTIONS Important factors that make the membrane potential more negative—that is, that hyperpolarize the membrane and make the muscle fibres less excitable— They are: (1) the effect of norepinephrine or epinephrine on the fibre membrane and (2) stimulation of the sympathetic nerves that secrete mainly norepinephrine at their endings. Secretin and glucagon inhibit small intestinal motility. Factors that inhibit muscular contractions of the small intestine: Sympathetic discharges, α-adrenergic agonist, Calcitonin gene-related peptide (CGRP), Nitric oxide, VIP, and Glucagon. 71 LOCAL REFLEXES Local reflexes are the most important regulators of contractions in the small intestine. This involves a variety of mechanisms that soften the food, propel it through the length of the gastrointestinal tract, and mix it with hepatic bile stored in the gallbladder and digestive enzymes. Some of these mechanisms depend on intrinsic properties of the intestinal smooth muscle. Others involve the operation of reflexes involving the neurons intrinsic to the gut, reflexes involving the central nervous system (CNS), paracrine effects of chemical messengers, and gastrointestinal hormones. 7/29/2024 72 LOCAL REFLEXES Gastrocolic reflex Distention of the stomach by food initiates contractions of the rectum and, frequently, a desire to defecate. The response is called the gastrocolic reflex. This may be amplified by gastrin's action on the colon. Because of this response, defecation after meals is the rule in children. In adults, habit and cultural factors play a large role in determining when defecation occurs. 7/29/2024 73 LOCAL REFLEXES Gastroileal reflex When food leaves the stomach, the cecum relaxes and the passage of chyme through the ileocecal valve increases (gastroileal reflex). This is presumably a vagal reflex. BER The movements of the colon are coordinated by the BER of the colon. The frequency of this wave, unlike the wave in the small intestine, increases along the colon, from about 2/min at the ileocecal valve to 6/min at the sigmoid. Others: Duodenocolic and enterogastric reflexes. 7/29/2024 74 CONCLUSION/SUMMARY The wall of the alimentary canal: mucosa, submucosa, muscular layer and serosa. Mucosa: epithelium, laminar propria and muscularis mucosa. Muscularis propria: inner circular smooth muscle, Myenteric plexus, outer longitudinal smooth muscle. Innervation: Enteric nervous system (ENS) and ANS ENS: Submucosal/Meissner’s plexus and Myenteric/Auerbach plexus Submucosal/Meissner’s plexus: GI secretion and blood flow. Myenteric/Auerbach’s plexus: Increased GI motility and sphincter relaxation. PNS stimulation (cholinergic activity): Increased GI motility and sphincter relaxation, increased GI secretion. Strong SNS stimulation (Noradrenergic activity): Decreased GI motility and Increased sphincter tonicity or contraction, decreased GI secretion. 7/29/2024 75 PATHOPHYSIOLOGY 1. Achalasia: This occurs due to damage to the myenteric plexus in the wall of the oesophagus, causing problem with swallowing. 2. Hirschsprung disease or congenital megacolon: It is a congenital disorder of the enteric nervous system characterized by failure to pass meconium at birth or severe chronic constipation in infancy. It is a polygenic disorder with characteristic mutations in at least three different classes of genes involved in neuronal development and differentiation. The typical features are absence of myenteric and submucosal neurons in the distal part of the colon and rectum. Loss of peristalsis associated with absence of the nerve plexus in the colon, causing obstruction in the colon and a condition termed toxic megacolon. 7/29/2024 76  THANK YOU FOR YOUR ATTENTION 7/29/2024 77