Physiology Gastrointestinal
3 major roles of gastric acid?
Gastric acid has 3 major roles: 1. Bacteriostatic (stops bacteria from reproducing) 2. Convers pepsinogen into its active form of pepsin 3. Begins protein digestion
Pepsinogen is converted into pepsin by the action of?
Gastric acid.
Describe pepsinogen. What is it? What does it do?
Pepsin is an active form of pepsinogen. Pepsinogen is secreted by the peptic cells of the gastric gland. When pepsinogen is first secreted, it has no digestive activity. However, when it comes in contact with gastric juice (HCL) or by vagal stimulation as mediated by acetylcholine, it is activated and splits to form the molecule pepsin which actively digests proteins. NOTE: pepsinogen has a molecular weight of 42,500 and when split into pepsin has a molecular weight of 35,000. Pepsin is a proteolytic enzyme (digesting proteins) in a highly acidic environment ranging between 1.8-3.5. In an environment with pH around 5, it is reversibly inactivated (so when the pH becomes less acidic than 5, it can become active again) In a basic environment of 7-8, it is irreversibly inactivated so it loses its proteolytic activity.
What percentage of the saliva secreted by the respective glands makes up the total percentage of saliva secreted?
Parotid gland secretes serous secretions and submandibular secreted serous and mucus and this makes up 90% of total saliva secreted. Sublingual glands also secrete both serous and mucus secretions and this accounts for only 10% of total saliva excreted. The tiny buccal glands only secrete mucus secretions and account for 1% of total saliva secreted.
What is the pH of saliva?
pH of saliva is about 6-7
What is xerostomia?
Absence of saliva
What factors make the smooth muscle membrane less excitable?
Factors that make the smooth muscle membrane more negative will also make it less excitable. This is called hyper polarization and factors that cause this: 1. secretion of norepinephrine or epinephrine 2. stimulation of sympathetic nerve fibers that secrete norepinephrine at their endings.
Pancreatic lipase
Fats to fatty acids and monoglycerides
What causes release of histamines?
Gastrin and Ach cause release from cells in stomach
Are all GI hormones peptides?
Yes, all GI hormones are peptides.
What type of salivary secretion do parotid, submandibular and sublingual glands produce?
Parotid glands produce serous secretion, submandibular and sublingual glands produce both serous and mucus secretion.
What are stimuli that initiate peristalsis?
1. The law of gut which means distention and downstream receptive relaxation will initiate peristalsis. 2. irritation of gut epithelium 3. Parasympathetic stimulation
What causes somatostatin release?
its release is stimulated by the presence of acid and is inhibited by vagal stimulation (acetylcholine).
What is the pH of HCL produced by the parietal cells?
About 0.8, making it highly acidic and thus, the concentration of hydrogen ions inside the parietal cell is about 3 million times that of arterial blood.
Where are gap junctions present?
Between muscle bundles and layers of smooth muscle in the gastrointestinal tract.
What happens is saliva is depleted from the body?
Depletion of saliva will lead to loss of K+
What is the maximum rate of secretion of saliva?
About 4ml/min
Pancreatic Cholesterol esterase
Cholesterol esters to fatty acids
What signals stimulate activation of pepsinogen?
Gastric acid (HCL) contact Vagal stimulation by activation of acetylcholine
Which hormone is nature's antacid?
Secretin, it produces bicarbonate ion to neutralize acids.
Gastric acid stimulation can be initiated by what?
Gastric acid (HCL) secretion can be stimulated by endocrine, paracrine and neurocrine stimulation. The following play roles in secreting gastric acid: Acetylocholine- Hal secretion, mucus, pepsinogen, and gastrin Histamine Gastrin-HCl secretion (1500x more powerful compared to histamine)
What controls secretions of hormones from their respective glands?
1. Local Response: The presence of food in a particular region of the gastrointestinal cavity usually stimulates a response in that region or adjacent regions. Thus, this local response can be caused by tactile stimulation (the presence of food causing the glandular cells to become in contact with the food and begin secretion), distention of gut wall, local irritation (when food is present it obviously causes the entry of chemicals that that irritate the gut wall). As a result of local stimulation, the enteric nervous system (consisting of sympathetic and parasympathetic nerve fibers) is activated as a reflex. 2. Nervous Input: Due to local stimulation, nervous input increases. The activation of parasympathetic nerve fibers increases glandular secretion. This is especially true for secretions in upper regions of the tract as hormones and local neural stimuli act on the distal end. Note: Stimulation of sympathetic nerves going to GI tract causes slight or moderate increases in secretion by some of the local glands. However, do not forget that sympathetic nerves fibers inhibit GI activity and vasoconstrict blood vessels. Thus activation of these fibers can either increase or decrease glandular secretion. 3. Hormones: Hormones are secreted from the gastrointestinal mucosa in response to presence of food in the lumen of the gut. Hormones are then absorbed into the blood and carried to the glands where they stimulate secretion. This type of hormonal action is particularly useful in production of gastric juice and pancreatic juice when food enters the stomach.
Functions of saliva
1. Lubrication and binding of food 2. Provides wetness to dry food making it more soluble (easy to swallow) 3. Oral hygiene- flow of saliva wash away pathogenic bacteria (washes mouth at a secretion rate of 0.5ml/min). Saliva contains significant amount of anti-bodies that can destroy oral bacteria. at night during sleep, flow of saliva decreases and bacteria can build up in the mouth, destroying tissues and thus leading to dental carries. Thus saliva can help prevent dental carries.
Basic Mechanism of Secretion
1. Substance to be secreted is produced (mitochondrion produce ATP and react with substrate provided by nutrients in blood to produce substance to be secreted, mainly this synthesis occurs in endoplasmic reticulum and Golgi complex. The substrate is then stored until hormones trigger their release through membrane permeability to calcium ions and the release of the substrate via exocytosis). 2. Secretion of sufficient water and electrolytes must also be carried out to make sure the secreted organic substance can pass through the cells in great profusion.
Why is saliva hypotonic?
A hypotonic solution is a solution with less concentration of solutes. Saliva is hypotonic because it has less Na and Cl which is reabsorbed by the body and only K+ is left. Thus less solute means it has less osmolarity than plasma because water will move out of it. Saliva also has aldosterone channels and remember aldosterone causes Na+ and Cl- to be reabsorbed by the body. Same thing happens here, Na+ and Cl- are reabsorbed by the body and K+ is secreted into the saliva.
Why is vasoconstriction of digestive system by sympathetic nervous system helpful?
A major importance of vasoconstriction by sympathetic nervous system is that it shuts off blood flow to digestive system in emergency situations when it is needed crucially by other parts of the body. Example: In circulatory shock, all other parts of the body need blood and this system comes into effect. Also during exercise, blood flow is needed by skeletal muscles. sympathetic stimulation also causes vasoconstriction of large intestinal and mesenteric veins to aid with this.
How much saliva is secreted per day?
About 800 and 1500 milliliters of saliva are secreted daily averaging about 1000ml.
Where do all the fats go?
Almost all the fats absorbed from the intestinal tract do NOT go to the portal vein to liver but are instead absorbed into intestinal lymphatics and then conducted to the systemic circulating by way of the thoracic duct.
Role of pancreas
As chyme passes from the stomach to small intestine, two things must happen: 1. Acid must be neutralized to prevent damage to the duodenum 2. Macromolecular nutrients-proteins, fats, starches must be broken down much further so their nutrients can be absorbed. The pancreas, which sits below the stomach plays roles in doing just that. Its pancreatic enzymes are secreted by pancreatic acini to break down macromolecules into its constituents and Its small ductules and large ductules leading from the acini produce bicarbonate ions for neutralization of acids. The combined product of enzymes and bicarbonate ions flows through the long pancreatic duct and empties into the duodenum.
Sensory Afferent Neurons and their Role in The Gut
As mentioned before many sensory afferent neurons innervate the gut (they are in the epithelium and provide branches to both the myenteric and submucosal plexuses and even pass branches to vagus, spinal cord and pre vertebral ganglion of sympathetic nervous system). These sensory nerves can be stimulated in the following ways: 1. Irritation of the gut mucosa 2. excessive dissension of the gut (outward expansion due to gas or air) 3. presence of specific chemical substances in the gut Signals transmitted through these fibers can cause excitation or under certain circumstances inhibit of intestinal movements or intestinal secretions.
Myenteric Plexus and Its Actions
As mentioned in my notebook, The myenteric or Auerbach's plexus spreads the entire length of the gastrointestinal tract and is composed of longitudinal and circular smooth muscle layers. It has excitatory and inhibitory roles. Excitatory:The myenteric plexus is mainly associated with controlling muscle activity along the length of the plexus. Thus, when stimulated, it is responsible for: 1. Increased tonic contraction of gut wall or tone 2. Increased intensity of rhythmical contractions thus increased propulsion 3. Slightly increased rate of rhythm of contraction 4. Increased velocity of conduction of excitatory waves along the gut wall causing more rapid movement of the gut peristaltic waves Some Functions of myenteric plexus are inhibitory: Some fiber endings of this plexus secrete an inhibitory transmitter possibly vasoactive intestinal polypeptide which is particularly important in inhibiting or decreasing the action of the gastrointestinal sphincters. the pyloric sphincter: which controls emptying of stomach into duodenum ileocecal sphincter: controls emptying of small intestine into cecum Thus the sphincters become relaxed.
Gastrointestinal Reflexes
As the enteric nervous system is supplied with the parasympathetic and sympathetic fibers, they work together to cause the following gastrointestinal reflexes: 1. Local Reflexes that are integrated entirely in the gut wall: These include gastrointestinal secretion, peristalsis, mixing contractions, local inhibitory effects and so forth. 2. Long Loop Reflex: Reflexes from gut to pre vertebral sympathetic ganglion and back to gut: These reflexes transit signals long distances to other areas of the gastrointestinal tract. Think of it as a signal going from one organ of the gastrointestinal system to the pre vertebral ganglion and coming back to another organ in the gastrointestinal system to cause an effect. Example: signals from the stomach reach the colon to evacuate the colon (gastrocolic reflex). Signals from colon and small intestine to inhibit stomach motility (enterogastric reflex). Signals from colon to ileum to stop the ileum from emptying its contents in the colon (colonial reflex). Basically, from gut to afferent nerves to pre vertebral ganglion to efferent nerves and back to gut 3. Reflexes from gut to spinal cord or brain stem and then back to gut. These are of 2 types: Vasovagal reflex: reflex from duodenum and stomach to brainstem and back to stomach by way of vagus nerves to control gastric motor and secretory activity. Stomach / duodenum Afferent Nerves brain stem Efferent Nerves stomach / duodenum Pain Reflexes that cause general inhibition of entire gastrointestinal tract Defecation reflexes that travel from colon and rectum to spinal cord and back to produce powerful cooling, rectal and abdominal contractions required fro defecation. Colon / rectum Afferent. Nerves. spinal cord Efferent Nerves colon / rectum
Possible pathology associated with Gastric malfunction
As we know that gastric plays a role in growing the mucosa in the stomach, duodenum and colon, patients with gastric secreting hormones can develop hypertrophy or hyperplasia due to overproduction of mucosa in these regions. On the contrary, removal of atrium of stomach, the site of G cells that produce gastrin can result in atrophy.
Autonomic control of Gastrointestinal Tract
Autonomic System which is involuntary control is further divided into parasympathetic and sympathetic divisions. Parasympathetic Division that supplies the gut is divided into cranial and sacral divisions. REMEMBER: Parasympathetic stimulation increases activity of enteric nervous system. Cranial Parasympathetic nerve fibers are almost entirely in vagus nerves. These fibers supply extensive innervation to esophagus, stomach, pancreas and first half of gut (first half of large intestine). Sacral parasympathetic Nerve fibers are almost entirely in pelvic nerves which supply the distal half of the large intestine all the way down to the anus or second half of gut. Parasympathetic nerves also have afferent sensory fibers-about 80%
Nutrients stored by the liver
Blood that flows through gut, spleen, pancreas flows immediately into the liver by way of the portal vein. Here the blood goes to the liver sinusoids where the hepatic cells (reticuloendothelial cells and principal parenchymal cells of liver) absorb and temporarily store about 1/2 to 3/4 of nutrients. These nutrients are non-fat and water soluble such as carbohydrates and protein.
Which hormones are enterogasterones?
Both secretin and gastric inhibitory peptide inhibit gastric acid secretion and are thus enterogasterones.
Phases of gastric secretion
Cephalic Phase: Begins with the sight, smell and thought of food. The brain tells the body to start secreting gastric juice in preparation of a meal. Cephalic phase accounts for 30% of gastric acid secretion in response to a meal. Stimuli include: Mechanoreceptors Chemoreceptors: smell and taste Central pathway: thought Hypoglycemia (low sugar) These senses are transmitted via vagal nerve and thug a vagotomy would result in complete blockage of cephalic phase. Gastric Phase: (about 60% of gastric juice produced in response to a meal) When food enters the stomach, other factors come into play Distension causes vasovagal reflexex (reflexes travel from stomach to brain then back to stomach) as well as activation of local enteric nervous system. Other stimuli for gastric acid release include proteins peptides, coffee, caffeine, alcohol, calcium Intestinal Phase: (Accounts for 10% of gastric acid secretion in response to a meal) Stimuli include distention of small intestine and circulation of amino acids which have a direct effect on parietal cells.
Motilin
Chemistry of Motilin: It is a linear 22 Amino Acid Peptide that is unrelated to any other hormones. Stimuli: Motilin is secreted by the stomach and upper duodenum (upper small intestine) during fasting and the only known function of this hormone is to increase motility. When food is ingested, motion secretion is inhibited as it is ONLY secreted when a person is fasting. Physiological Effect: In a fasting person, it causes contractions in the upper GI every 100 minutes. It accounts for migrating motility complex thus known as "housekeeping contractions"
Cholecystokinin CCK
Cholecystokinin CCK is secreted by "I" cells mainly in the mucosa of the duodenum and jejunum in response to fats, fatty acids and monoglycerides NOT triglycerides in the intestinal content. Stimuli that cause release of CCK: Weak acids Faty acids or monoglycerides (not triglycerides) Peptides and Single amino acids Physiological Effects of CCK: 1. This hormone strongly contracts the gallbladder and relaxes the sphincter of Oddi, thus expelling bile into the small intestine which emulsifies fatty substances, allowing them to be digested and absorbed. 2. Inhibits Gastric Emptying: It inhibits stomach contraction moderately. Therefore, while contracting the gall bladder, it slows the movement of food from stomach to give adequate time for digestion of fats in the upper intestinal tract to occur. 3. It also controls appetite to prevent over eating. Role as Pancreatic Exocrine: Potent stimulator of enzyme secretion, thus secretes pancreatic enzymes Weak stimulator of bicarbonate secretion (but can potentiate secretin effects)
General Function of the GastroIntestinal Tract
Digestion- both mechanical and chemical Endocrine-production of hormones Expulsion- removal of wastes Protection- from bacteria and microorganisms Motility- smooth muscle contraction to propel chyme (the pulpy acidic fluid that passes from the stomach to the small intestine, consisting of gastric juices and partly digested food). Absorption-gets nutrients into the body, surface area and villi Secretion- mucus, buffers, hormones, enzymes Storage- retention of food as it is being passed through the system for digestion and absorption
What is the Law of Gut
Distention + downstream Receptive relaxation is called law of gut In other words, myenteric reflex or peristaltic reflex plus anal direction of movement is called law of gut
Main relationship between slow waves and spike potentials
Each time the slow waves temporarily becomes more than -40, a spike potential appears. The higher the slow wave potential rises, the greater the frequency of the spike potential and thus the greater the strength of contraction of the muscle.
What are structurally related hormones in the stomach?
Firstly, all GI hormones are peptides. Two structurally related families are: 1. Gastrin and cholecystokinin (CCK) 2. Secretin family: glucagon, Gastric inhibitory Peptide (GIP) aka Glucose-Dependent Insulinotropic Peptide, Vasoactive intestinal Peptide (VIP). Some effects in this family are shared
Anatomy of Gastrointestinal
From outside surface inward: 1. serosa- outermost layer surrounding the muscularis is the serosa 2. Longitudinal muscle layer- outer layer of muscle in the stomach right below serosa. Longitudinal muscle contraction causes esophageal shortening. 3. Circular smooth muscle layer- aids in peristalsis. Circular muscles make up the middle layer of the stomach. 4. submucosa- surrounds the submucosa and is made up of various blood vessels and nerves 5. mucosa- This is the innermost layer and is the mucous membrane layer and contains the gastric glands and pits. Additionally in the mucosa, sparse bundles of smooth muscle fibers: the mucosal muscle lie in the deep layers of the mucosa. Cardiac incisura- a deep notch between the esophagus and the funds of the stomach. The fundus stores undigested food and also the gases released from the chemical digestion of food.
What is motility of the stomach?
Gastric Motility: Contractions of gastric smooth muscle serves two basic functions: ingested food is crushed, ground and mixed, liquefying it to form what is called chyme. Chyme is forced through the pyloric canal into the small intestine, a process called gastric emptying.
Describe Gastrin
Gastrin is secreted by the "G" cells in the antrum of the stomach in response to stimuli of ingesting a meal. Examples of stimuli of ingesting a meal include distention of the stomach, release of products of protein, and gastrin-releasing peptide (which is released by nerves of gastric mucosa during vagal stimulation). Primary Functions of Gastrin: 1. Stimulation of gastric acid secretion 2. Stimulation of growth of the gastric mucosa (mucosal growth), duodenal mucosa and colonic mucosa Other functions: stimulates parietal cell HCL release either directly or via histamines (1500 time more potent than histamines) Site of G cell secretion: antrum of stomach, duodenum and jejunum
When asked what secretes gastric acid, don't get confused by what?
Gastrin. As it is simply a hormone that stimulates gastric acid or HCL secretion. it is not the only stimulant of gastric acid however and other factors can also cause HCL secretion (histamines, acetylcholine). Only difference is that gastrin secretion of HCL is 1500 times more potent than that of histamines.
In smooth muscles of gastrointestinal tract, what are true action potentials and what are they caused by?
In smooth muscles of the GI tract, spike potentials are true action potentials and are automatically created when the resting membrane potential becomes more positive than -40. the channels that trigger action potential are calcium-sodium channels allowing large amounts of calcium to enter and small amounts of sodium. These channels are slower to open and thus the action potential has a longer duration.
What are pre-ganglionic and post ganglionic fibers
In the autonomic nervous system (ANS), fibers from the central nervous system (brain and spinal cord) to the ganglion are known as preganglionic fibers. All preganglionic fibers, whether they are in the sympathetic nervous system (SNS) or in the parasympathetic nervous system (PSNS), are cholinergic—that is, these fibers use acetylcholine as their neurotransmitter—and are myelinated. In the autonomic nervous system, fibers from the ganglion to the effector organ are called postganglionic fibers.Postganglionic fibers in the sympathetic division are adrenergic and use norepinephrine (also called noradrenalin) as a neurotransmitter. By contrast, postganglionic fibers in the parasympathetic division are cholinergic and use acetylcholine as a neurotransmitter.
Chyme is formed where?
In the stomach and then propelled into the small intestine.
How are gastric ulcers produced?
In ulcers, there is a back leak H+ ion in exchange for Na+ ions. Thus the pH of the tissue that the H+ leaks into becomes very low (acidic) and results in cell death. Damage of mast cells causes histamines to release resulting in a vicious cycle: histamine, vascular damage, local ischemia. The more H+ leaks, the more cell death occurs
Gastric Inhibitory Peptide aka GLIP-Glucose Dependent Insulinotrophic peptide
It is secreted by the K cells in the duodenum and proximal jejunum (upper small intestine) in response to all major food stuff such as fats, proteins and carbohydrates. The fat must be hydrolyzed. Physiological effect: Inhibits gastric acid secretion as the name suggests and thus is a enterogasterone Produces insulin release as the other name also suggests glucose dependent insulinotrophic peptide
How is HCL secreted?
Main driving force of HCL secretion in parietal cells is the hydrogen-potassium ATPase pump. Water dissociates into H+ and OH- in the cytoplasm. The H+ then move into the canaliculi of the parietal cells in exchange for K+, an active exchange process catalyzed by the H-K-ATPase pump. The H+ ion concentration increases and eventually these are the sites where HCL is made and secreted.
Importance of Mucus in the Gastrointestinal Tract
Mucus is a thick secretion that is mainly water, electrolytes and a mixture of several glycoproteins that are composed of large polysaccharides bound with much smaller quantities of protein. 1. Adherent properties- This quality allows mucus to adhere tightly to the food particles and to spread as a thin film over the surface of the food. 2. Sufficient body- Mucus has sufficient body allowing it to spread on the wall of the gut and prevents actual contact of most food particles with the mucosa. 3. Low resistance for slippage- thus, particles can slide across the epithelium with great ease. 4. Causes fecal particles to adhere to one another- thus, feces are formed and expelled during bowel movement. 5. Mucus is strongly resistant to digestion by the gastrointestinal tract- thus while food is being digested by the action of enzymes and juices, the mucus will stay intact. 6. Buffering properties- The glycoproteins of mucus have amphoteric properties which means they are capable of buffering small amounts of both acids and alkalies, often containing large quantities of bicarbonate and thus specifically neutralizing acids.
Muscle layer functions as a SYNCYTIUM
Muscle bundle fibers are separated from each other by loose connective tissue but fuse with one another at many points, therefore each muscle layer functions as a syncytium. In this way, when an action potential is elicited anywhere within the muscle mass, it generally travels in all directions in the muscle and the distance it travels depends upon the excitability of the muscle. Note: since there are a few connections between longitudinal and circular muscle layers, excitation of one of these layers often excites the other as well.
Are gastrin and gastric acid the same?
No, gastrin is a hormone produced by G cells which stimulates production of gastric acid (HCL) by the parietal cells.
Does pyloric gland have parietal cells?
No, only the gastric gland has parietal cells that produce HCL more potently than histamines and also these parietal cells also produce intrinsic factor for vitamin B12 absorption.
Can peristalsis occur without myenteric reflex
No. Thus in congenital absence of myenteric plexus, there is no peristalsis. The effects of myenteric plexus and the consequent peristalsis is also blocked by the drug atropine which paralyze the cholinergic nerve endings (parasympathetic nerve endings) which otherwise stimulate all gastrointestinal activity. `
What is the ionic composition of saliva?
Normally, the following are the concentrations of the ions that make up saliva: Na+: 15mEq/L -1/10th its concentration in plasma Cl-: 15mEq/L-about 1/15th its concentration in plasma K+: 30mEq/l -about 7 times its concentration in plasma HCO3+ 50-70mEq/L- about 3 times its concentration in plasma Ionic concentration of saliva depends upon the rate of reabsorption. Sodium ions are actively reabsorbed from the salivary ducts and potassium is actively secreted into the saliva. Thus the concentration of sodium ions in saliva is very low and that concentration of potassium in saliva is very high.
Nervous Regulation of Salivary Secretion
Parasympathetic Nervous Pathway for Regulating Salivary Secretion: salivary glands are controlled mainly by the parasympathetic nervous signals by way of the superior and inferior salivary nuclei in the brainstem. These salivary nuclei are located at the junction of the medulla and pons. When they are excited, the parasympathetic nervous system, cranial nerves IX -glossopharyngeal and X-vagus are activated and acetylcholine is released which causes salivary secretion from salivary glands Sympathetic: sympathetic stimulation can also increase salvation, much less than parasympathetic stimulation. The sympathetic stimulation originates from superior cervical ganglion. Norepinephrine is secreted which influences the salivary glands.
Nervous control of blood flow
Parasympathetic nervous system slows down flight or fight and activates the digestion. Thus, stimulation of the parasympathetic nerves will increase blood flow to the digestive system. This happens at the same time as the parasympathetic system stimulates glandular secretion and thus increased blood flow by parasympathetic stimulation probably occurs secondarily due to glandular secretion. Sympathetic system however decreases blood flow to digestive tract by vasoconstriction.
What is peristalsis and what causes it?
Peristalsis is the contractions that take place to move food from pharynx to stomach and this is controlled entirely by esophagus. There are two kinds of peristalsis: 1. Primary peristalsis: Continuation of the wave that starts in the pharynx runs through the esophagus and goes all the way into the stomach. 2. Secondary peristalsis: If primary peristalsis fails, secondary peristalsis brought about by distention of the esophagus by food retained in it takes over. These secondary peristaltic waves continue until food is propelled into the stomach. Myenteric nervous system is required for this secondary peristalsis to take place.
Pancreatic Phospholipase
Phospholipids to fatty acids
Neurons of parasympathetic division
Preganglionic Neurons of parasympathetic system are longer than preganglionic neurons of sympathetic system as they are further away from the spinal cord. Postganglionic neurons of gastrointestinal parasympathetic system are located mainly in myenteric and submucosal plexus and their stimulation causes an overall stimulation of entire enteric system which in turn enhances most gastrointestinal functions. postganglionic fibers in the parasympathetic division are cholinergic and use acetylcholine as a neurotransmitter.
Neurons of sympathetic division
REMEMBER: SYMPATHETIC STIMULATION INHIBITS GASTROINTESTINAL ACTIVITY Preganglionic fibers of sympathetic system leave the cord between T5-L2 and enter the sympathetic chain that lies lateral to the spinal cord and many of these fibers pass to outlying ganglion such as celiac and mesenteric ganglion (and synapse with pre vertebral ganglion according to the professor). Postganglionic neuron bodies of the sympathetic division mostly originate from celiac ganglion and various mesenteric ganglion and then spread to all parts of the gut. Sympathetic fibers innervate mostly all of the gut instead of just oral cavity and anus (as is true for parasympathetics). Sympathetic nerve endings mainly secrete norepinephrine.
What can cause a change in resting membrane potential of smooth muscle in gastrointestinal tract?
Resting membrane potential of smooth muscles in gastrointestinal tract ranges between -50 and -60 millivolts averaging at -56 millivolts. There are factors that can cause a change in this baseline resting membrane potential and they are described as: 1. Depolarization: when the membrane becomes less negative. This usually occurs when the resting membrane potential reaches -40 and thus the fibers are more excitable and more likely to contract such as seen in spike potentials. 2. Hyperpolarization- When the membrane becomes more negative, making the fibers less excitable.
How can saliva destroy bacteria?
Saliva contains several factors that destroy bacteria: 1. Thiocyanate ions 2. Proteolytic enzymes the most important being lysozyme Proteolytic enzymes attack the bacteria and aid the thiocyanate ions in entering bacteria where they become bactericidal by functioning as antibodies. These proteolytic enzymes also digest food particles thus further helping to remove bacteria.
Saliva and its types
Saliva is produced by 3 types of glands: parotid, submandibular and sublingual. In addition there are many tiny buccal glands Saliva has two types of protein secretions: 1. Serous secretion: contains ptyalin an alpha-amylase which is an enzyme for digesting starches. it is a watery secretion 2. Mucus secretion- contains mucin for lubricating and for surface protective purposes.
Secretin
Secreted by S cells in the mucosa of the duodenum in response to gastric juice being dumped in from the pylorus of the stomach as well as fat. Thus stimuli for secretin secretion: Gastric acid from duodenum pH less than 4.5 Fat from duodenum Secretin has little action on the motility of the stomach and acts to promote pancreatic secretion of bicarbonate and bile secretion of bicarbonate which in turn helps to neutralize the acid in the small intestine. Thus, it is known as "Nature's Antacid" Stimulation of secretin further inhibits gastric acid secretion (thus it acts as enterogasterone-any hormone that prevents further movement of chyme by inhibiting gastric acid secretion). Stimulates pepsin secretion (pepsin breaks down protein into smaller components) Has a trophic effect on exocrine pancreas (as it stimulates pancreas to produce bicarbonate).
What does bicarbonate do to acid chyme?
Secretin induced bicarbonate acid neutralizes chyme coming from stomach. Thus secretin is said to be natures antacid.
What are factors that help strengthen the gastric mucosal barrier?
Secretion of bicarbonate ion HCO3-, prostaglandins, gastrin (which regulates gastric acid production), epidermal growth hormone. As a result, ulcers are avoided.
Causes of Activity Induced Blood flow: Vasodilators and Decrease in Oxygen Concentration
Several Vasodilators are secreted from the mucosa of the intestinal tract during digestion (this increases blood vessel surface and thus increased blood flow). 1. Most of these substances are peptide hormone: cholecystokinin, vasoactive intestinal peptide, gastrin, secretin. 2. Secretion of two kinins by gastrointestinal glands: kallidin and bradykinin. these kinins are powerful vasodilators believed to cause much of the mucosal vasodilation. 3. Decreased oxygen concentration in the blood can increase blood by 30-50 fold. Decreased oxygen also leads in an increase of the vasodilator adenosine that can be responsible for much of the increased blood flow.
Types of Secretory Glands
Several types of glands provide the different types of alimentary tract secretions: 1. Single Cell Mucous Glands-aka mucous cells or goblet cells because they look like goblets. Found on the surface of the epithelium in most parts of the gastrointestinal tract and function mainly in response to local irritation of the epithelium. They secrete mucus directly on the surface of the epithelium to prevent excoriation and digestion. 2. Simple cells or Pits: Many surfaces of the gastrointestinal tract are lined by pits that represent invaginations of the epithelium or INDENTATIONS of the epithelium into the submucosa. In the small intestine, these pits are called Crypts of Lieberkuhn. They are deep and contain specialized secretory cells to secrete intestinal juice. 3. Tubular Glands- in the stomach and upper duodenum are large numbers of tubular glands. These are acid secreting oxyntic gland. 4. Complex glands- Also associated with the alimentary canal here several complex glands such as the salivary glands and those in the pancreas and liver. They provide secretions for digestion and emulsification of food.
Rhythmical changes in membrane potential are caused by?
Since rhythm is determined by slow waves, thus these slow waves will also control rhythmical changes in membrane potential. Recall that slow waves do NOT cause action potentials which are caused by spike potentials (due to influx of calcium ions). Thus, rhythmic changes will occur only by changes in conductance of sodium as slow waves only cause entry of sodium ions.
Bundling together of smooth muscle fibers
Smooth muscle fibers are about 200-500micrometers in length and about 2-10 micrometers in diameter. They are bundled together, about 1000 fibers in a bundle. In longitudinal muscles fibers, they extend down the intestinal tract and in circular muscle fibers, they extend around the gut. What allows electrical signals to move readily across the muscle fibers? Within each muscle bundle, muscle fibers are electrically connected with one another through large number of GAP JUNCTIONS which have low resistance to ions and allow their movement from one muscle cell to another. Therefore, electrical signals that initiate muscle contraction can travel readily from one fiber to another within each bundle and always more rapidly along the length of the bundle than sideways.
Electrical Activity of Gastrointestinal SMOOTH MUSCLE
Smooth muscle of gastrointestinal tract is excited by almost continual, slow, intrinsic electrical activity along the membranes of the muscle fibers. This activity has two types of electrical waves: slow waves and spikes 1. Slow waves- Gastrointestinal contractions occur rhythmically and this rhythm is mainly determined by the frequency of the slow waves. (Rhythmical changes in membrane potential are caused by variations in sodium conductance. )Slow waves ARE NOT ACTION POTENTIALS. They are slow changes in the resting membrane potential (resting membrane potential is usually between -50 and -60 millivolts and these slow waves causes the potential to change between 5-10 millivolts). The frequency of the slow waves varies between 3-12 per minute in different parts of the gastrointestinal tract. For example, in the stomach, duodenum and ileum the rhythm of contraction is about 3/min, 12/min and 8-9/minute respectively. Slow waves themselves do not cause muscle contraction in most parts of the gastrointestinal tract except perhaps in the stomach. They mainly excite the spike potentials which in turn excite muscle contraction. 2. Spike Potentials- Are true action potentials. They occur automatically when resting membrane potential of smooth muscles becomes more positive than -40millivolts. This is usually referred to as depolarization. In the graph in the notebook, each time the slow waves temporarily becomes more than -40, a spike potential appears. The higher the slow wave potential rises, the greater the frequency of the spike potential and thus the greater the strength of contraction of the muscle. The channels responsible for action potentials in smooth muscles of gastrointestinal tract are calcium-sodium channels which allow a LARGE number of Calcium ions to enter along with a small number of sodium ions. These channels are much slower to open and thus accounts for the longer duration of action potentials. The greater the frequency of spike potentials, the stronger the muscle contraction. However, increasing frequency does not increase the maximum frequency of contraction,
What are tonic contractions and what causes them?
Some smooth muscles of the gastrointestinal tract exhibit tonic contractions in addition to or in some cases, instead of rhythmical contractions of the slow waves. Tonic contractions is not associated with basic rhythmical contractions of slow waves but often last several minutes to even hours. Tonic contractions are sometimes caused by: 1. Repetitive spike potentials-the greater the frequency of spike potentials, the greater the degree of contraction. 2. Tonic contractions may also be brought about by hormones or other factors that cause continuous partial depolarization of smooth muscle membrane without causing an action potential. 3.Tonic contractions are also caused by influx of calcium ions brought about in ways not associated with changes in membrane potential.
Are spike potentials effected by changes in the nervous system and or hormonal stimuli?
Spike potentials are basically caused by depolarization (when the smooth muscle membrane potential becomes more positive than -40) and thus when depolarized, the muscle fibers are more excitable. Other ways that the membrane can be depolarized thus making it more excitable are: 1. Stretching of the muscle 2. Stimulation by acetylcholine (released by the endings of parasympathetic nerves) 3. Stimulation by specific gastrointestinal hormones Since all these factors are either hormonal or influenced by nervous system, depolarization or sake potentials are affected by nervous/hormonal stimuli.
Defecation reflexes go from colon/rectum to what?
Spinal cord and return via efferent nerves to stimulate powerful abdominal, colonic and rectal contractions necessary for defecation.
Function of pancreatic amylase?
Starch and glycogen to disaccharides
Submucosal plexus and its action
Submucosal segment in contrast with the myenteric plexus is concerned with controlling function of the inner wall of each minute segment of the intestine. Example: many sensory signals originate from the gastrointestinal epithelium and are then integrated in the submucosal plexus to help control local intestinal secretion, local absorption and local contraction of the submucosal muscle that causes various degrees of folding of the gastrointestinal mucosa.
Arteries of Splanchnic Circulation
Superior mesenteric artery- supplies walls of small intestine, pancreas and proximal colon Inferior mesenteric artery- supplies walls of large intestine and majority of colon
Hoe do sympathetic fibers inhibit the gastrointestinal system?
Sympathetic nerve fibers inhibit gastrointestinal activity in two ways: 1. For a slight effect but direct effect these sympathetic fibers secrete norepinephrine to inhibit intestinal smooth muscle except to mucosal muscle as it becomes excited and 2. For a major effect by secretion of norepinephrine to all the neurons of the entire enteric nervous system.
Functions of the stomach
Temporary reservoir for food Production of intrinsic factor (also known as gastric intrinsic factor, is a glycoprotein produced by the parietal cells and important for absorption vitamin B12) Chemical and enzymatic digestion, especially for proteins Liquefaction of food Slow release of food into small intestine for further processing
What is the antrum of the stomach?
The antrum of the stomach begins right before the stomach empties into the duodenum of small intestine and is lined by G cells (Gastrin Cells)
The Splanchnic circulation
The blood vessels of gastrointestinal system are part of a more extensive system called the splanchnic system. They include the blood flow through the gut (GI), pancreas (sits below liver), spleen and liver. How does blood flow through splanchnic system? The design of this system is that all the blood that flows through gut, spleen, pancreas flows immediately into the liver by way of the portal vein. In the liver this blood passes through many liver sinusoids and then leaves the liver by way of the hepatic veins and empty into the vena cava of general circulation. First Pass Effect: When blood is passed into the liver sinusoids, special cells that line the liver sinusoids called reticuloendothelial cells remove bacteria and other particular matter from the blood that might have entered from the gastrointestinal tract before this blood is allowed to move in the vena cava after leaving the hepatic veins. Thus, this prevents movement of potentially harmful substances from moving into the rest of the body.
What can block peristalsis from taking place?
The drug atropine can weaken the enteric nervous system, inhibit myenteric plexus and thus decrease peristalsis.
What are factors that weaken the gastric mucosal barrier?
The gastric mucosal barrier can be damaged by: H. pylori, NSAIDS (non-steroidal anti-inflammatory drugs), aspirin, ethanol, bile salts. A weakened gastric mucosal barrier can lead to gastritis and ulcers.
What is the gastric mucosal barrier?
The gastric mucosal barrier prevents the back flow of H+ ions. It has two parts that help prevent this back flow: Anatomic part: the cell membranes and tight junctions Physiological Part: the H+ that diffuse out are transported back into the lumen
What causes slow waves?
The interaction between smooth muscle and specialized cells called Cajal Cells is believed to bring about these slow waves. Again, Cajal cells do not bring about action potentials, they set up the baseline rhythm for the slow waves. (Death of Cajal cells can cause one to lose the ability of peristalsis since it is caused by a baseline rhythm and Cajal cells establish this baseline rhythm). Cajal cells are called "pacemaker cells" of smooth muscle aka they fix the frequency for smooth muscle slow waves. Canal cells form a network with each other and are present between smooth muscle layers with synaptic like contacts to smooth muscle cells.
Structure of pancreas
The pancreas is a compound gland with internal structure similar to that of the salivary glands Acini- grape like structures that store and secrete digestive enzymes Ducts- They secrete bicarbonate ions for neutralization of acids The ducts are of two types: Intercalated ducts: receive secretions from acini Interloper ducts: receive secretions form intercalated ducts
Describe the structure of parietal cells and how they are involved in HCL production.
The parietal or oxyntic cells are found in the gastric gland which makes up about 80% of the proximal stomach. These cells are involved in HCL and intrinsic factor secretion. In terms of HCL secretion, it is formed at the canaliculi, villus like intracellular projections of the parietal cells that line the lumen and then conducted to the secretory end of the cell. The pH of the HCL is about 0.8 demonstrating extreme acidity and thus, hydrogen ion consecration is about 3 million times that of arterial blood.
Control of Gut Blood Flow
When Local Activity Increases: Blood Flow Increases (during active absorption of nutrients, blood flow in the villi and adjacent regions of the submucosa increases as much as 8 fold). Blood flow in the muscle layers of the intestinal wall also increases with increased motor activity in the gut. After a meal, blood flow will increase by 2-3 fold for up to 3-6 hours.
What is auto regulatory mechanism of sympathetic system?
The sympathetic system decreases blood flow to the digestive system by vasoconstriction. After a few minutes of vasoconstriction, the flow returns to about normal by the local metabolic vasodilator mechanism that are elicited by ischemia to override the vasoconstriction. This is the auto regulatory mechanism or auto regulatory escape.
Which Glands produce Gastric Secretions in the stomach?
There are 2 glands that produce gastric secretions in the stomach: Gastric gland (oxyntic) and pyloric gland. Gastric gland covers about 80% of the proximal stomach and is made up of three types of cells: 1. Mucus neck cells- mostly secrete mucus 2. Peptic or chief cells- secrete large quantities of pepsinogen and rennin. 3. Parietal or Oxyntic Cells- secrete HCL, about 1500 times more potently than histamines. Parietal cells in gastric gland also produce intrinsic factor which is necessary for absorption of vitamin B12. Pyloric Gland This gland contains no parietal cells and makes up 20% of the distal half of the stomach. It mainly has two types of cells: 1. G cells which secrete gastrin and control gastric secretions 2. Mucus neck cells- secrete large amount of thin mucus that helps lubricate food movement. Also secrete small amounts of pepsinogen
Endocrine (GI Hormones), Paracrine, and Neurocrines (neurotransmitters)
Think of an endocrine cell which is found in the GI mucosa. This endocrine cell produces GI hormones known as endocrine hormones and paracrine hormones. The endocrine (GI hormones) are secreted into portal circulation, pass to general circulation and effect the target cells, thus they travel long distances to have an effect. All GI hormones are peptides. Examples are gastrin, CCK, Secretin and motilin. The paracrine hormones are also produced by the endocrine cell but they simply diffuse within the GI tract to cause an effect on the target cell. Examples of paracrine cells are: Somatostatin and Histamines. 1 Somatostatin: (Growth hormone inhibiting hormone). its release is stimulated by the presence of acid and is inhibited by vagal stimulation (acetylcholine). It inhibits all GI hormones as well as gastric acid secretion by parietal cells. Inhibits gastrin release by inhibiting acid. 2. Histamine Gastrin and Ach cause release from cells in stomach Stimulates acid secretion Histamine H2 receptor blockers decrease acid production (Cimetidine (Tagamet), Ranitidine (Zantac)
Regulation of pancreatic secretion
Three basic stimuli are important in causing pancreatic secretion: 1. Acetylchloine from vagal nerve stimulation causes pancreatic stimulation 2. Cholecystokinin stimulates pancreatic secretion in response to fats and amino acids 3. Secretin causes pancreatic secretion as a result of presence of acids in the walls of the duodenum (remember it is an antacid).
In the absence of vitamin B12, what would happen?
Vitamin B 12 is essential for the proper maturation of red blood cells and thus since it is produced by the intrinsic factor of parietal cells in the gastric gland of the stomach, failure of the parietal cells in the gastric gland to produce intrinsic factor will result in anemia. (Lack of stomach secretion-achlorhydria).
Describe myenteric reflex
When a segment of the intestinal tract is excited by distention (expansion when food is present and attempting to pass), peristalsis is initiated and the contractile ring contracts in the direction of the distention thereby pushing the food from the oral to anal side. At the same time, the gut relaxes several centimeters downstream towards the anus which is called "receptive relaxation" thus causing food to be propelled to the anal side rather than oral. This complex pattern does not occur in the absence of the myenteric plexus and thus the complex is called the myenteric reflex or peristaltic reflex. The peristaltic reflex plus the anal direction of movement of peristalsis is called the law of gut.
Do you have preganglionic and postganglionic neurons in both parasympathetic and sympathetic divisions of the autonomic nervous system?
Yes, the preganglionic neurons of parasympathetic division are longer than those in the sympathetic division since they are further away from the central nervous system. Preganglionic fibers of sympathetic system leave the cord between T5-L2 and enter the sympathetic chain that lies lateral to the spinal cord and many of these fibers pass to outlying ganglion such as celiac and mesenteric ganglion (and synapse with pre vertebral ganglion according to the professor). Postganglionic neuron bodies of the sympathetic division mostly originate from celiac ganglion and various mesenteric ganglion and then spread to all parts of the gut. Sympathetic fibers innervate mostly all of the gut instead of just oral cavity and anus (as is true for parasympathetics). Sympathetic nerve endings mainly secrete norepinephrine. Sympathetic nerves also contain afferent sensory fibers (50%)
Vasovagal reflexes go from stomach/duodenum to what?
brain stem and back vie efferent nerves
