L1) General Principles of GIT physiology.pdf

L1 General Principles of GIT Physiology GNT Physiology Color Index: • Main text • Important • Female Slides • Male Slides • Notes • Extra Editing File Objectives Physiologic Anatomy of the Gastrointestinal Wall The General Characteristics of Smooth Muscle Smooth muscle cell classiﬁcations and types of contraction Muscle layers in GI wall Resources Only GI chapters included Electrical Activity of Gastrointestinal Smooth Muscle Slow Waves and spike potentials Calcium Ions and Muscle Contraction Neural Control of Gastrointestinal Function-Enteric Nervous System Diﬀerences Between the Myenteric and Submucosal Plexuses Types of Neurotransmitters Secreted by Enteric Neurons Autonomic Control of the Gastrointestinal Tract sherwood-human-physiology Hormonal Control of Gastrointestinal Motility Functional Types of Movements in the GI Tract Gastrointestinal Blood Flow-"Splanchnic Circulation" This is prof sultan meo! Eﬀect of Gut Activity & Metabolic Factors on Gastrointestinal Blood Flow. Click here for a helpful channel by the team! Introduction Female slides Let’s start with a story ❖ The foundations of what we now know about digestion came from a shotgun wound to the abdomen that created a window to the stomach. 1- What is the role of the Gl system in maintaining homeostasis? ❖ This internal environment contains contents which deﬁne how the cell will live. ❖ What essential elements do cells need from the internal environment? O2, Nutrients, pH, Temperature, waste products 2- What are the challenges facing the GI system while it is trying to do its job? 1-Autodigestion, 2-infection,3-transform Macromolecules to Micromolecules. 3- How do nutrients reach our internal environment? ❖ ❖ ❖ ❖ through the GI system. The main function of the GI system is transfer nutrients from external environment into the internal environment. Can our cells utilize nutrients immediately as they are in the food we consume? No. The GI system first need to break down the macromolecule into micromolecule then absorb it from the lumen of GI to blood so it can reach the cell. Ex: sugar → monosaccharide, protein → amino acid etc. Is it just enough to ingest food to make nutrients available for cells to use? Protein, meat, carbs, vitamins nutrients, fats. Ingest Macromolecules in food There are 4 basic processes that enable it do its job Micromolecules that cells can use The 4 Basic GI Processes: 1 Motility: movement of food The muscular contractions that mixes and moves GI contents forward through the GI tract. Secretion: 2 Along the way, digestive juices are secreted into the GI lumen by exocrine glands. Importance of secretion: contains enzymes that break down macromolecules, and lubrication, immunity Digestion: 3 4 As the contents move along the GI tract, complex foodstuﬀ gets broken down into smaller absorbable molecules. It mixes bolus of food with other secretions and makes it more accessible for enzymes and secretion. It’s a mechanical and a chemical process Absorption: The small units are transferred from GI lumen into blood or lymph. Female slides Gastrointestinal Processes Secretion: Deﬁnition: it is an active process in which the GI tract secretes digestive juices (ex: acids, enzymes) which may come from the exocrine glands that are attached to the GI system, or from specialized cells in the GI wall. Digestive secretions consist of: Water + electrolytes + speciﬁc organic constitutes (enzymes, bile salts, mucus..ect) each region will have its own juice Digestion: Three diﬀerent biochemical categories of foodstuﬀ Carbohydrates Main energy source Carbs that we ingest are polysaccharides (starch, glycogen, mono-disaccharides) Carbs that can be reabsorbed are monosaccharides (glucose, fructose, galactose) Protein Fat Imp. for everything Energy source Digestion will break down dietary proteins ↓ small polypeptides ↓ amino acids Dietary fats is usually triglycerides ↓ Monoglycerides Digestion will break down polysaccharides into monosaccharides. The end product of triglycerides is = monoglycerides + free fatty acid Absorption: Deﬁnition: The transfer of small absorbable units form the GI lumen into blood and lymph. ● How and where? It occurs by and in the splanchnic circulation. Motility: ● The importance of movement of the wall of the GI system is: 1. Mixing with digestive secretions 2. Propulsion 3. Exposure to absorptive surface ● The structure that is responsible for its ability to produce movement is the smooth muscle cells. Food Journey Along GIT Female slides 5) Liver & Biliary system 1) Mouth & Oropharynx 1. 2. 3. Secretes bile for fat digestion Chop & lubricate food Initiate carb digestion Propels food into the esophagus 6) Pancreas Secretes digestive enzymes into duodenum (HCO3-) Mechanical breakdown of food occurs and the chemical digestion of carbs starts. Oropharynx will propel food into esophagus 7) Small Intestines 3 2) Salivary glands 1. 2. Lubrication Have enzymes for carb digestion (amylase) 3) Esophagus Conducts food to stomach It’s a path that allows food to reach the stomach. 1. 2. 2 1 5 4 6 7 8 Continues Digestion Primary site of absorption By the time the bolus of food leaves the stomach and reaches the intestine, it will be called chyme (more liquid). The intestine will continue digesting whatever had not been digested previously. It will start absorbing nutrients into the blood. There will be secretion of digestive enzymes coming from the pancreas as well as bile acids coming from biliary system and liver. 4) Stomach 1. 2. Stores food Initiates protein digestion When we eat a big meal in bouts which are large. Until the body breaks it down, it will be stored in the stomach. The stomach continues the process of digestion and breaking down (chemically and mechanically). 8) Large intestine 1. 2. Reabsorbs ﬂuid & electrolytes Stores fecal matter. Large Intestine is responsible for reabsorbing electrolytes and ﬂuid that have been secreted into the bolus. Lastly, stores feces until it's time to be excreted Gastrointestinal Function Male slides The alimentary tract provides the body with a continual supply of water, electrolytes & nutrients. To achieve this function, it requires: 1 Movement of food through the alimentary tract (Motility) 3 Absorption of water, various electrolytes, and digestive products 2 Secretion of digestive juices and digestion of the food 4 Circulation of blood through the gastrointestinal organs to carry away the absorbed substances The GI system The gastrointestinal system consists of the gastrointestinal tract (GIT) and associated organs that produce secretions Digestive Tract Accessory organs ● A hollow tube extending from mouth to anus. ● Each region is modiﬁed to serve its function. ● Regions are separated by sphincters (to control movement from one region to the other). Include: 1. Salivary glands (into mouth) 2. Liver and gallbladder (into duodenum & aid in digestion) 3. Pancreas These add secretions to the digestive tract. 1. 2. 3. 4. 5. 1 3 Upper esophageal sphincter (UES) : Between the pharynx & esophagus Lower esophageal sphincter (LES): Between esophagus and stomach Pyloric sphincter: Between stomach and duodenum Ileocecal valve: Between small intestine and cecum External and internal anal sphincter: Between GI system & External env. Total = 6 sphincters 2 In addition of “sphincter of Oddi”, that control secretion system coming from Accessory organs into the duodenum. 4 5&6 To help U remember, Oddi=Audi Physiologic Anatomy of the GI wall Anatomy of the GI wall: ● amazing drawing by Sara Alshahrani according to female doctor 4 main layers/ 5 layers (from outer surface inward): ○ ○ Serosa Muscularis Longitudinal muscle layer the contraction = shorten of the segment Circular muscles layer the contraction = constrict the lumen and decrease its diameter Submucosa (Denser CT) larger blood vessels, nerves and lymphatics pass through Mucosa (Loose CT) small capillaries, vessel and nerves pass through ■ ■ ○ ○ ● ● ● ● In addition, sparse bundles of smooth muscle ﬁbers, the mucosal muscle lies in the deeper layers of the mucosa. Movement is possible in the GIT because of the presence of smooth muscle layer. A cross section of the GIT will look the same from the esophagus to anus, because the structure and layers of the wall are the same. All contain 5 layers. However they are diﬀerent in cells, glands, length etc. Outside Inside Female slides Characteristics of Smooth & Skeletal Muscle Smooth muscles Skeletal muscle Spindle shaped, Non-striated Cylindrical muscle ﬁbers, Striated Single nucleus Multinucleated Smaller and shorter Long Involuntary Voluntary Contractile units arranged diagonally Contractile units arranged parallel to long axis of ﬁber Dense bodies actin ‫ﻟﺗﺛﺑﯾت‬ Z-lines actin ‫ﻟﺗﺛﺑﯾت‬ Cross bridges are present along the entire length of the thick ﬁlament Bare portion in the center of the thick ﬁlament. Side-polar myosin arrangement. Cross bridge is covering the whole thick ﬁlament (myosin) Bipolar myosin arrangement (no cross bridge in the middle) Ca+2 induces a chemical change in myosin (thick ﬁlament) Ca+2 induces a physical (mechanical) change in actin (thin ﬁlament) Contraction: thin ﬁlaments surrounding the thick ﬁlament will move into opposite directions Contraction: both thin ﬁlaments surrounding thick ﬁlament will move in the same direction Contraction of Smooth Muscles ❖ ❖ ❖ ❖ Contraction is brought about by sliding of the thin ﬁlament over the thick ﬁlament. Myosin attaches to actin by its actin-binding site and then the power stroke causes sliding of the actin ﬁlament over myosin. The thin ﬁlament of smooth muscle does not have troponin. Tropomyosin does not block actin-binding site. What stops myosin from binding to actin at rest? The thick ﬁlaments are composed of myosin, and the thin ﬁlaments are predominantly actin. Myosin is prevented from binding to actin at rest by myosin light chain (MLC). When MLC is phosphorylated, myosin will form a cross bridge with actin and a contraction will occur ↑ [Ca+2] i Ca+2 binds to calmodulin Ca-CaM complex activates MLCK (Myosin light-chain kinase) Phosphorylates myosin head increasing the activity of ATPase Myosin head attaches to actin causing sliding of the ﬁlaments Smooth muscle cells use cross-bridge cycling between actin and myosin to develop force, and calcium ions (Ca+2) serve to initiate contraction. Thus, contractile activity in smooth muscle is determined primarily by the phosphorylation state of the light chain of myosin Classification of Smooth muscles Smooth muscles can be classiﬁed in many ways depending on the timing and means of increasing cytosolic Ca+2 Classiﬁcation of Smooth muscles Phasic VS Tonic Multi Unit VS Single unit Neurogenic VS Myogenic A smooth muscle of one organ may be multi unit, phasic and neurogenic While another organ it might be single-unit, tonic and myogenic. it can be classiﬁed by the 3 classiﬁcations at the same time. Phasic VS Tonic (depending on its contractile activity and how its cytosolic Ca+2 increases) Phasic Tonic ● Contracts in bursts “intermittently” ● ● Contraction → Relaxation a cycle of a contraction followed by a relaxation ● ● Contraction triggered by an action potential which increase [Ca+2] When an AP reaches cell, it will open Ca+2 channels. Ca+2 will ﬂow from ECF to ICF, and some will come from Sarcoplasmic reticulum -> trigger contraction process. ● ● ● 4. ● Associated with slow wave Examples: 1. GI tract Most of GI tract is phasic 2. Gastric antrum 3. Small intestine 4. Esophagus ● ● ● ● 1. 2. 3. 4. Muscle is usually partially contracted at all times. Continuous partial contraction = (Tone) they only relax when there’s an inhibitory signal coming from NS Causes of tonic contractions: 1. Repetitive spike potentials 2. Hormones 3. Continuous entry of Ca+2 ions Not associated with slow wave unlike phasic (often lasting several minutes or hours). This type has a low RMP (close to +ve than -ve) at which some voltage gated Ca+2 channels are open → entry of Ca+2→ partial contraction Examples: Blood vessels are always at a certain tone. This plays a role in BP regulation Airways Orad = upper part of Orad region of stomach stomach Lower esophageal, ileocecal, internal anal sphincters Focus its LOWER esophageal sphincter because the upper is made of skeletal muscle NOT smooth muscle Classification of Smooth muscles cont. Single unit vs. Multi-unit Based on how they get excited Multi Unit Single (Unitary) Composed of discrete, separate smooth muscle ﬁbers. Each ﬁber operates independently. Each is innervated by a single-nerve ending. ● ● ● Does not contract in response to stretch or without neural input (such as in esophagus & gallbladder) activated by hormones and neurotransmitters. ● Composed of many smooth muscle ﬁbers that become excited and contract as a single unit. Cells are connected by gap junction Function as a syncytium. Contracts spontaneously in the absence of neural or hormonal inﬂuence but in response to stretch (such as in stomach and intestine). The smooth muscles are connected to each other by gap junctions. So when a stimulus arrives it doesn't have to arrive at each muscle, it’s enough for it to arrive at one then the signal will spread to the rest of the muscle through gap junctions. ● ● ● ● ● Examples: -Ciliary muscle and iris of the eye (accomodation) -Piloerector muscle (goose bumps ‫)ﻗﺷﻌرﯾرة‬ Examples: Uterus, GI tract. Female slides Myogenic vs. Neurogenic Based on how contraction is initiated Neurogenic Myogenic ● ● ● Contraction is initiated in response to nerve ”signals” stimulation. Self-excitable Contraction is initiated intrinsically within the muscle without external nervous stimulus. They are specialized cells that act as pacemakers and generate an AP regardless of external innervation. Male slides Types of Smooth Muscles in GI The General Characteristics of Smooth Muscle in the Gut Longitudinal Characteristics Circular ● Thinner and weaker than circular ● Thicker and more powerful than longitudinal ● Contraction shortens the segment of the intestine and expands the lumen ● Contraction reduces the diameter of the lumen and increases its length. ● The Ca+2 inﬂux from outside is important in the activity of this type of muscle. because the intracellular Ca++ storage is insuﬃcient ● Contraction shortens the distance that the food has to travel Contains Excitatory motor neurons Innervated by ● Intracellular release of Ca+2 is more important. ● More gap junctions are available. ● Contraction pushes food forward or backward Excitatory & inhibitory motor neurons because they sometimes need to relax Enteric Nervous System (ENS) Important The Speciﬁc Characteristics of Smooth Muscle in the Gut Gastrointestinal Smooth Muscle Functions as a Syncytium Numbers are not important Individual smooth muscle ﬁbers Length: 200 to 500 μm Diameter : 2 to 10 μm Electrical Activity of Gastrointestinal Smooth Muscle The smooth muscle of the GIT is excited by almost continual slow, intrinsic electrical activity along the membranes of the muscle ﬁbers. Arranged in bundles of ≤ 1000 parallel ﬁbers. Within each bundle, the muscle ﬁbers are electrically connected with one another through large numbers of gap junctions. Each muscle layer functions as a syncytium, that is when an action potential is elicited within the muscle mass, it generally travels in all directions in the muscle. The activity is divided into two types of electrical waves : Slow Waves (Resting) Spikes (Action potentials) Female slides Electrical Activity of Different Muscles Types Smooth muscle Skeletal muscle/Nerve Cardiac muscle RMP value -50mV to -60mV (More +ve) -70mV -90mV RMP behavior NOT stable (Fluctuating) Stable (Linear) Stable (Linear) Threshold: -40mV RMP is characterised by spontaneous gradual alternating (Fluctuations): Hyperpolarization (Far from threshold) & Depolarization (Close to threshold) swings in the potential Feature these ﬂuctuations are called Slow wave potentials (no contraction occurs) If the depolarization of slow waves reaches the threshold, spike potential appears (real AP) → causes contraction. -Why does this ﬂuctuating happen? Because GIT smooth muscles don’t have to be contracted all the time (e.g. during fasting) AP is generated by stimulus, which increases RMP to threshold level AP produced by Na+ inﬂux AP is generated by stimulus, which increases RMP to threshold level AP produced by Na+ inﬂux While plateau is caused by Ca+2 Graphs Guyton The slow waves usually do not by themselves cause muscle contraction in most parts of the gastrointestinal tract, except perhaps in the stomach. Instead, they mainly excite the appearance of intermittent spike potentials, and the spike potentials in turn actually excite the muscle contraction. Electrical Activity: Slow Waves Slow Waves waves ● Most GI contractions occur rhythmically, determined mainly by the frequency of slow waves of smooth muscle membrane potential. These waves are not action potentials. They are oscillating depolarization and repolarization in the resting membrane potential with unknown cause. Deﬁnition ● ● Intestinsity ● The Intestinsity of slow wave varies between 5-15mV ● The frequency of slow wave varies from one organ to the other in GIT: ○ Stomach = 3/min which is why gastric emptying is considered slow when compared to the rest of GIT ○ Duodenum = 12/min ○ Ilium = 8-9/min Frequency RMP is NOT stable. It is characterized by spontaneous alternating hyperpolarizing and depolarizing swings in potential slow wave potential. ● The level of RMP in smooth muscle can be modiﬁed by several factor:. 1- If it becomes less negative = depolarized muscle is more excitable. 2- If it becomes more negative = hyperpolarized muscle becomes less excitable. ● RMP ● Features Threshold Slow waves are not AP. They can not generate contractions. Slow waves can generate an AP that will generate a contraction. ● When the slow wave potential reaches threshold → true action potential is generated on the peak of slow wave = spike potential. Every action potential will have a depolarization followed by repolarization. ● ● ● Origin: No Ca entry (only Na) ● ● ● ● ● ● ● IMPORTANT: The ion that is responsible for the slow wave is Na+ inﬂux not Ca+2 They may originate in the interstitial cells of Cajal (ICC) Interstitial cells of Cajal (ICC): a specialized, non-contractile cell that can undergo cyclical changes in membrane potential. ICC is the pacemakers of the gut. ICC are abundant in the myenteric plexuses. These ICCs form a network with each other and are interposed between the smooth muscle layers, with synaptic-like contacts to smooth muscle cells. When we disconnect the GI system from CNS, the GI can work normally since it has its own pacemaker. Electrical Activity: Spike Potential Important Spike potential are true action potentials. They occur automatically when the resting membrane potential of the gut smooth muscle is more positive (<-40mV) Threshold: <-40mV Normal RMP in smooth muscles: between -50 and -60 mV The resting membrane potential averages about -56 mV ● ● ● ● ● RMP= resting membrane potential ● The higher the slow wave potential rises, the greater the frequency of the spike potential, ranging between 1 - 10 pikes per second. ● They last 10 - 40 times as long in gastrointestinal muscle as the action potentials in large nerve ﬁbers, each garoeintenal spike lasting as long as 10 - 20 msec. Increases in the spikes’ frequency → increase in the strength of contraction. ‫اﻟدﻛﺗور ﻗﺎﻟﮭﺎ ﺑﺎﻟﺣرف ودي اﺟﯾﺑﮭﺎ‬ More rises in the slow wave ->increase in the frequency of the spikes. ‫ﺗﻛﻣﻠﺔ‬ ‫ﻟﻠﻣﻼﺣظﺔ اﻟﻲ ﻓوق‬ ● ● When the slow waves reach the threshold, it causes a spike which is an AP that causes contractions Auscultating membrane potential Entry of Ca2+ through Calcium-Sodium channels Entry of Na+ These factors cause hyperpolarization Threshold point These factors cause depolarization Guyton The precise cause of the slow waves is not completely understood, although they appear to be caused by complex interactions among the smooth muscle cells and specialized cells, called the interstitial cells of Cajal, which are believed to act as electrical pacemakers for smooth muscle cells. These interstitial cells form a network with each other and are interposed between the smooth muscle layers, with synaptic-like contacts to smooth muscle cells. The interstitial cells of Cajal undergo cyclic changes in membrane potential due to unique ion channels that periodically open and produce inward (pacemaker) currents that may generate slow wave activity. Female slides The AP of the smooth muscle is similar to the AP pacemaker of cardiac muscle “SA node”. The diﬀerence it that the SA node is unstable but it’s regular. It always reaches the threshold, unlike muscle contraction. Signiﬁcance: we don't need the GIT to work while we’re asleep, unlike the cardiac muscle. we need our heart to pump through out our whole life. Slow-Wave potential Pacemaker potential Smooth Muscle Electrical Activity ● In GI smooth muscle ﬁbers, the channels responsible for the action potentials are somewhat diﬀerent; they allow especially large numbers of calcium ions to enter along with smaller numbers of sodium ions and therefore are called calcium-sodium channels. ● These channels are much slower to open and close than the rapid Na channels of large nerve ﬁbers. Ca++ ions & Muscle Contraction: ● ● ● Smooth muscle contraction occurs in response to entry of calcium ions into the muscle ﬁber. The slow waves do not cause calcium ions to enter the smooth muscle ﬁber (only sodium ions). Therefore, the slow waves by themselves usually cause no muscle contraction (except in the stomach). Instead, it is during the spike potentials, generated at the peaks of the slow waves, that signiﬁcant quantities of calcium ions do enter the ﬁbers and cause most of the contraction. Tonic Contraction of Some GI Smooth Muscle: ● ● Some smooth muscle of the GI exhibits tonic contraction as well as or instead of rhythmical contractions. Tonic contraction is continuous, not associated with the basic electrical rhythm of the slow waves but often lasting several minutes or even hours. They don’t depend on slow wave because a slow wave may and may not generate an AP. They are controlled by: repetitive spike potentials, hormones and continuous entry of Ca++ ions. 1 Intracellular Ca2+ concentrations increase when Ca2+ enters cell and is released from sarcoplasmic reticulum. 2 Ca2+ binds to calmodulin (CaM) 3 Ca2+ - calmodulin activates myosin light chain kinase (MLCK) 4 5 MLCK phosphorylates light chains in myosin heads and increases myosin ATPase activity. Activate myosin crossbridges slide along actin and create muscle tension. Smooth muscle electrical activity cont. Important 1- The eﬀect of norepinephrine or epinephrine on the ﬁber membrane Factors that hyperpolarize the membrane potential 2- Stimulation of the sympathetic nerves that secrete mainly norepinephrine at their endings. Sympathetic stimulation decrease number of spike potentials Important 1- Stretching of the muscle 3- Stimulation by several speciﬁc gastrointestinal hormones Factors that depolarize the membrane potential 2- Stimulation by acetylcholine released from the endings of parasympathetic nerve it is considered as an excitatory NS for the GI Female slides Slow or myogenic wave (oscillating depolarization and repolarization; “basic electrical rhythm”) fail to induce contraction because Em is below threshold with Parasympathetic input, the membrane at the plateau of the slow wave depolarizes all the way to threshold; action potentials occur “on top of” the slow wave, and these set oﬀ contractions. the contraction /tension follows slightly after the electrical response If resting potential is shifted to more negative values (from sympathetic input) spikes and contractions will not occur - The level of RMP in smooth muscle can be modiﬁed by several factors, it averages about -56mV. which is less negative than other cells making it easily excitable - If it becomes less negative = depolarized → muscle is more excitable. - If it becomes more negative= hyperpolarized → muscle becomes less excitable. Female slides Migratory motor complex (MMC) Please be familiar with the abbreviation Important ● ● ● ● ● ● Rhythmic contractions of the small intestine during the fasting state. To clear intestine from it’s contents. Allows particles > 2mm to pass from stomach to duodenum. Starts at the stomach and moves down to terminal ileum. At intervals of 90 - 120 min. Motilin is thought to play a role in their generation. 4 Main Phases 1 2 Prolonged quiescent period Period of increasing AP and contractility 3 Period of peak electrical & mechanical activity 4 Period of declining activity Migratory motor complexes Disappear upon feeding Control of the GIT system 1 2 Neural Hormonal Local External Brain of gut Embedded in the wall of the GIT (Enteric Nervous System) -Sympathetic Innervation ( Thoracolumbar Outﬂow ) -Parasympathetic Innervation ( Craniosacral Outﬂow ) Connections of the Enteric nervous system (ENS): Autonomic Output Connections ● Sympathetic Innervation (Thoracolumbar outﬂow): the sympathetic ﬁbers originate in the spinal cord between segments T5 and L2. The sympathetic innervate all GIT and Secret norepinephrine mainly. ● Its stimulation inhibits activity of the GI system. ● strong Stimulation of SNS can Inhibit motor movements of the gut so greatly that this literally can block movement of food through the GI tract. ● Parasympathetic Innervation (Cranial and Sacral outﬂow): Vagus nerves(cranial division) innervate esophagus, stomach,pancreas and intestines down to the ﬁrst half of the large intestine. The pelvic nerves (sacral division) Innervate the distal half of the large intestine and the anus ( to execute the detection reﬂex ). Its stimulation Increase in activity of the entire enteric nervous system. ● ● ● Sensory Input Connections 1. Stimulus: Stretch,Distention ,Irritation ,Chemicals. 2. Receptors stimulated 3. Signal Relayed 4. Signal Transmitted: Prevertebral ganglia ,Spinal Cord, Brainstem 5. Type of signal transmitted: Inhibitory or Excitatory. Sympathetic Parasympathetic Control of the GIT system cont.. Enteric Nervous System: ● Enteric Nervous System (ENS) is the nervous system of GI tract. ● It’s a part of autonomic nervous system as sympathetic and parasympathetic. ● It lies entirely in the wall of the gut, beginning in the esophagus and extending all the way to the anus. ● It has as many neurons as the spinal cord (about 100 million). Neural Control of Gastrointestinal Function-Enteric Nervous System The enteric nervous system can function on its own, independently of the parasympathetic and sympathetic systems, however, these extrinsic nerves can greatly enhance or inhibit gastrointestinal functions. The sensory nerve endings send aﬀerent ﬁbers to both plexuses of the enteric system and then to: (1) (2) (3) The prevertebral ganglia of the sympathetic nervous system The spinal cord The vagus nerves all the way to the brainstem. These sensory nerves can elicit local reﬂexes within the gut wall Components of the enteric nervous system Important It is composed mainly of two plexuses (interconnected) The Myenteric (Auerbach’s) Plexuses The Submucosal (Meissner's) Plexuses ● An outer plexus ● It lies in between the longitudinal and circular muscle layers. ● Control mainly the gastrointestinal movements ( motility ) ● Consists mainly of a linear chain of many interconnecting neurons. ● When stimulated, its principal eﬀect is to: 1. Increase tonic contraction 2. Increase intensity and rate of the rhythmical contractions. 3. Increase velocity of conduction of excitatory waves along the gut wall. ● The myenteric plexus has excitatory and inhibitory motor neurons. ● An inner plexus ● It lies in the submucosa beneath the circular muscle layer ● Controls mainly GI secretion and local blood ﬂow ● Controls : (1) Local intestinal secretion, (2) Local absorption (3) Local contraction of the submucosal muscle that causes various degrees of enfolding of the gastrointestinal mucosa. Smooth muscle electrical activity cont. Types of Neurotransmitters Secreted by Enteric Neurons The speciﬁc functions of many of GI neurotransmitters are not well known, but some research have discovered the eﬀects of some of these substances as following: 2. Inhibitory Motor Neurons: 1. Excitatory Motor Neurons: Suppress Muscles contraction Evoke Muscle Contraction & Intestinal Secretion ● ● Neurotransmitters of motor neurons: (increase motility) ○ Substance P ○ Ach Neurotransmitters of secretomotor neurons: (from glands) (releasing of water, electrolytes and mucus from crypts of Lieberkuhn) ○ Ach ○ Vasoactive intestinal peptides (VIP) ○ Histamine (decrease motility and secretion) ● Adenosine tri-peptide (ATP) ● Nitric oxide (NO) ● VIP A. B. Notice that VIP has dual action Released near glands → Gland activation Released near muscle → Muscle inhibition Male slides Many aﬀerent sensory nerve ﬁbers innervate the gut. Some of them have their cell bodies in the enteric nervous system and some in the dorsal root ganglia of the spinal cord. ● ● ● These sensory nerves can be stimulated by a. Irritation of the gut mucosa b. Excessive distention of the gut c. Presence of speciﬁc chemical substances in the gut. Signals transmitted through the ﬁbers can then cause excitation or inhibition of intestinal movements or secretion. Other sensory signals from the gut go all the way to multiple areas of the spinal cord and even the brain stem. For example, 80% of the nerve ﬁbers in the vagus nerves are aﬀerent rather than eﬀerent. These aﬀerent ﬁbers transmit sensory signals from the GI tract into the brain medulla, which in turn initiates vagal reﬂex signals (vagovagal reﬂexes). GI reflex 1- Short Reﬂexes Reﬂexes that are integrated entirely within the gut wall (enteric nervous system): ● GI Movement: Peristalsis/Mixing ● GI Secretions ● Inhibitory Eﬀects 2- Long GI reﬂexes: A- Prevertebral sympathetic ganglia: ● ● ● Important Reﬂexes from the gut to the prevertebral sympathetic ganglia and then back to the GIT A way for organs to communicate with each other These reﬂexes transmit signals long distances to other areas of the GI tract, such as: Gastrocolic Reﬂex: Signals from stomach causes evacuation of colon (increase motility of the colon) When eating breakfast: Stomach Tells the Colon to start emptying, so it’s ready for the upcoming bolus of food Enterogastric Reﬂex: Colonoileal Reﬂex: Signals from intestine inhibit emptying of stomach (inhibit gastric motility & secretions) When you are full: Intestine Tells the Stomach to stop emptying, so it can reabsorb the bolus of food Signals from colon inhibit emptying of ileal contents When you want to defecate: Colon Tells the Ilium to stop emptying, so it can eject feces into anus without interruptions B- Spinal Cord & Brain Stem Important Reﬂexes from the gut to the spinal cord or brain stem and then back to the GIT, such as: Gastric control: Reﬂexes from the stomach & duodenum to the brain stem and back to the stomach (by way of the vagus nerves) to control gastric motor and secretory activity. Pain reﬂexes: Pain reﬂexes that cause general inhibition of the entire GI tract after the area of pain. Defecation reﬂexes: Defecation reﬂexes that travel from the colon and rectum to the spinal cord and back again to produce the powerful colonic, rectal, and abdominal contractions required for defecation innervated by: pelvic nerves (sacral division of parasympathetic) GI reflex cont.. Gastrocolic reﬂex Signals from stomach causes evacuation of food signals from stomach to colon and large intestine to get rid of the the storaged feces because there’s a new day and a new food will arrive Will be discussed in colon physiology lecture later Enterogastric reﬂex Signals from intestine inhibit emptying of stomach stimulates mass movements after a meal. Will be discussed in detail in stomach secretion lecture Colonileal reﬂex Signals from colon inhibit emptying of ileal contents Hormonal control Male slides Actions Hormone Site of secretion Stimuli for secretion Stimulates: Gastrin(M) G cells of the: - Antrum - Duodenum - Jejunum Cholecystokinin (CKK) I cells of the: - Duodenum - Jejunum - Ileum Secretin S cells of the: - Duodenum - Jejunum p - Ileum (Acid inhibit its release) - Protein - Distention of the stomach - Vagal stimulation - (GRP) - Gastric H+ secretion - Growth of gastric mucosa - Protein - Fatty acids - Acids - Pancreatic enzyme secretion - Pancreatic HCO-3 secretion - Gallbladder contraction - Growth of the exocrine pancreas - Relaxation of sphincter of Oddi - Acids & fat in the duodenum - Pepsin secretion - Pancreatic HCO-3 secretion - Biliary HCO-3 - Growth of the exocrine pancreas Inhibits: - Gastric emptying Gastric H+ secretion GlucoseDependent Insulinotropic Peptide (GIP) K cells of the: - Duodenum - Jejunum - Protein - Fatty acids - Oral glucose - Insulin secretion from pancreatic β cells Motilin M cells of the: - Duodenum - Jejunum - Fat - Acid - Nerve - Gastric motility - Intestinal motility - GI movement Propulsive “Peristalsis” ● Moves food forward along the tract. ● Usual stimulus is distention. ● Distension→stimulates the proximal portion to contract and the distal portion to relax ● Organizes propulsion of material over variable distances within the GI lumen. ● Other stimuli that can initiate peristalsis include chemical or physical irritation of the epithelial lining in the gut. ● Myenteric plexus is important. ● Atropine (cholinergic blocker) depresses propulsion. (ADR: constipation) ● Propulsive segment: (contracts) 1.contraction (circular M.) 2.relaxation (longitudinal M.) ● Receiving segment: (relaxs) 1.contraction (longitudinal M.) 2.relaxation (circular M.) ● propagated , rhythmical. Peristaltic reﬂex & the Law of the Gut: Important Mixing “Segmentation” ● Provides mixing of intestinal contents with digestive juices. ● Segment of bowel contracts at both ends. ● A second contraction occurs in the center of the segment ● Blend diﬀerent juices with the chime. ● Bring products of digestion in contact with absorptive surfaces ● Segmental contractions are responsible for mixing. ● Alternate segments contract, and there is little or no net forward movement. ● Contraction happens at the middle of chyme ● It’s not propagated Orad=upper part = mouth direction Caudad=lower part= Anal direction When a segment of the intestinal tract is excited by distention and thereby initiates peristalsis, the contractile ring causing the peristalsis normally begins on the Orade side of the distended segment, pushing the intestinal contents in the anal direction (Caudad direction) for 5 to 10 cm before dying out. Control of the GI blood flow Male slides 1) Neural: Parasympathetic stimulation: ↑ Local blood ﬂow ↑ Glandular secretion Sympathetic stimulation: Intense vasoconstriction of the arterioles ↓ Local blood ﬂow (greatly) The local metabolic vasodilator mechanisms override the sympathetic eﬀects, returning the normal blood ﬂow to GI muscle and glands 2) Gut activity & metabolic factors: Possible causes of the increased blood ﬂow during gut activity ● Most of the peptide hormones 1) CCK 2) VIP 3) Gastrin 4) Secretin ● Some of the GI glands release into the gut wall two kinins (vasodilators): 1) Kallidin 2) Bradykinin 3) kinins ● ↓ O2 conc. in the gut wall → ↑ intestinal blood ﬂow at least 50 - 100%. The Splanchnic Circulation Vena Cana Hepatic Veins Liver Gut Spleen Pancreas ‫اﻟﺻورة ﻣوﺟودة ﻋﻧد‬ ‫اﻟﺑﻧﺎت واﻷوﻻد‬ • Splanchnic circulation includes the blood ﬂow through the gut, spleen, pancreas, and liver. The design of this system is such that all the blood that courses through the gut, spleen, and pancreas then ﬂows immediately into the liver by way of the portal vein. In the liver, the blood passes through millions of minute liver sinusoids and ﬁnally leaves the liver by way of hepatic veins that empty into the vena cava of the general circulation. TEST YOURSELF ! MCQ: Q1) which one of the following is not considered as one of the accessory organs? A) gallbladder B) spleen C)liver D)pancreas Q2) What is the frequency of slow-wave potential in the ileum? B) 6 A) 3 C) 9 D) 12 Q3) Which one of the following increase blood ﬂow during GI activity? B) bradykinin A) CCK C) decrease O2 concentration D) all Q4) Which of the following is an example of tonic contraction A) GI tract B) Gastric antrum C) small intestine D) blood vessels Answers: Q1:B | Q2:C | Q3:D | Q4:D SAQ: Q1) List three factors that cause increase blood ﬂow during Gl activity. ● ● ● Gastrin Bradykinin Decrease oxygen concentration Q2) Brieﬂy explain the mechanism of the Contraction of Smooth Muscles. 1- ↑ [Ca+2] 2- Ca+2 binds to calmodulin 3- Ca-CaM complex activates MLCK (Myosin light-chain kinase) 4- Phosphorylates myosin head increasing the activity of ATPase 5- Myosin head attaches to actin causing sliding of the ﬁlaments Team Leaders Rafan Alhazzani Fahad Almughaiseeb Ghaida Aldossary Faisal Alzuhairy Team Members Sarah Alshahrani Hamad Alziyadi mansour Alotaibi Melaf Alotaibi Nazmi A Alqutab Layan aldosary Raghad Almuslih Nazmi M Alqutab Norah alhazzani Layla Alfrhan khalid Alanezi Jouri Almaymoni Lama Almutairi Abdulaziz abahussain Salma Alkhlassi Remas mohammed Yousof Badoghaish Shoug Alkhalifa

L1) General Principles of GIT physiology.pdf

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