Saliva PDF

II SALIVA 2.1 Introduction The digestive system consists of a gastrointestinal tract and accessory glands. Its roles40 are: 1. Secretion of digestive juices 2. Digestion of food 3. Movement of food 4. Absorption of digestive products 5. Excr...

II SALIVA 2.1 Introduction The digestive system consists of a gastrointestinal tract and accessory glands. Its roles40 are: 1. Secretion of digestive juices 2. Digestion of food 3. Movement of food 4. Absorption of digestive products 5. Excretion 6. Endocrine function41 The anatomical order of the digestive tract: 1. Mouth (oral cavity)42 2. Pharynx 3. Esophagus 4. Stomach 5. Small intestine (bowel) a. Duodenum b. Jejunum c. Ileum 6. Large intestine (bowel) a. Cecum b. Colon i. Ascendant ii. Transverse iii. Descendent 7. Sigmoid Colon43 8. Rectum a. Anal sphincter Accessory glands: 1. Salivary gland 2. Pancreas 3. Liver 40 One could argue there is an “accessory” role of information: it tells the body what is or isn’t good to eat. 41 The endocrine system refers to the collection of glands of an organism that secrete hormones directly into the circulatory system to be carried towards a distant target organ. Conversely, exocrine refers to any gland or cell releasing substances into a tube, a cavity or outside the body. 42 Oral or buccal are adjectives relating to the mouth. 43 Some medical sources consider the sigmoid colon, the rectum and the anal canal to be part of the large intestine. On Dr. Papacocea’s slides, however, they were presented as separate parts. 16 2.1.1 Digestive tube layers From outside to inside: 1. Serosa 2. Longtitudinal muscle layer 3. Circular muscle layer 4. Submucosa 5. Mucosa The submucosa contains the so-called Meissner plexus: thousands of networked neurons comprising the local nervous plexus. 17 The muscularis also contains the Auerbach plexus (not pictured) which controls muscle contraction (for example to move the food down the tract). 2.1.2 Digestive secretions Secretions occur in most places along the digestive tract. These secretions consist of mixtures of varying content and concentrations. Generally, enzymes, mucus, ions and other substances can be found. Regulation of secretion is normally both nervous and humoral.44 It is mainly parasympathetic45, but can sometimes also be conditioned.46 Secretion can depend on certain variables: quantity (eg. more saliva is secreted when eating), quality (the type of food will dictate the content of secretion) and biorhythm (persons with a strict regular diet can get conditioned to secrete in anticipation even if no food is yet present). 44 From, with or by hormones 45 Unconscious, “rest-and-digest”. The opposite is sympathetic, together they form the autonomous nervous system. 46 See Pavlov’s dog. 18 2.2 Saliva The target cell in salivary secretion is an exocrine cell, located in one of the salivary glands. The salivary glands are the parotid, submandibular and sublingual glands, as well as some smaller buccal glands.47 The secretory or exocrine cells in such gland consist of acini48 which contain both serous49 cells and mucus cells. The secretion is then excreted in the oral cavity through the ducts, which are made from striated cells and are myoepithelial.50 Depending on the gland, acini are serous in the parotid gland, mucous in the sublingual gland and both in the submandibular gland. 47 These secrete mostly mucus. 48 Clustered cells resembling a raspberry, sg. acinus 49 Secreting a body fluid that is not mucus 50 Cells usually found in glandular epithelium as a thin layer above the basement membrane but generally beneath the cells in the lumen. 19 20 The exocrine cells pictured above are typical cells found in salivary glands. They have an apical pole (at the level of secretion), rich in granules containing enzymes, and a basal pole which is in contact with the blood vessel. 2.2.1 Primary saliva Saliva secretion actually happens in two steps. Primary saliva is produced in the acini by an active secretion done by ionic pumps. This primary secretion contains ptyalin and mucin in a solution of ions in concentrations not too different from plasma – it is (nearly) isotonic. 2.2.2 Secondary or Final saliva Primary saliva is not left untouched by the gland: in the salivary ducts, it is adapted and reformed: the final composition of saliva is altered. The striate cells of the duct actively reabsorb Na and secrete K instead.51 This process is regulated by aldosterone. Also, Cl is reabsorbed (passively) and exchanged for HCO3 (bicarbonate). The result is that the final saliva is hypotonic52 and has a pH that is very slightly acidic (6.8-7).53 In conclusion: the first stage involves the acini, and the second, the ducts. 51 Antiport mechanism 52 Up to 10 times less Na and 7 times more K concentration than plasma. 53 Enables ptyalin to do its work in optimal conditions 21 Daily secretion of saliva is about 1000 to 1500 ml per day, but this can vary: Increased flow with: - Pregnancy - Psychological disorders (eg schizophrenia) - Nervous diseases (eg Parkinson’s) Decreased flow with: - Age - Dehydration - Sleep - Stress 2.3 Saliva composition You now know that final saliva will contain water, mucus and various ions. There is, of course, more. Thanks to Burger and Emmelin and their experiment, we know that saliva also contains some other organic substances such as urea54 and ptyalin.55 54 CO(NH2)2 -- Urea serves an important role in the metabolism of nitrogen-containing compounds by animals and is the main nitrogen-containing substance in the urine of mammals. 55 Salivary amylase 22 2.4 Roles of saliva Saliva has digestive and non-digestive roles. Digestive roles: 1. Moistens dry food and so increases solubilisation of food particles 2. Allows mastication, swallowing, helps stimulate taste buds and olfactory receptors56 3. Hydrolyses starch with ptyalin, generating dextrines and finally maltose 4. Lubricates and washes buccal cavity 5. Protects against mechanical injuries Non-digestive roles: 1. Talking 2. Excretion of viruses, heavy metals, ions 3. Promotes oral hygiene by excreting bacteria 4. Antiseptic role through thiocyanate57 ions, lysosime, IgA58 5. thermoregulation59 6. endocrine role: secretes EGF60 and NGF61 56 Olfactory receptors are responsible for the detection of odor molecules. 57 Technically an anion. Thiocyanate is an important part in the biosynthesis of hypothiocyanite by a lactoperoxidase. Thus the absence of thiocyanate in the human body, (e.g., cystic fibrosis) is damaging to the human host defense system. 58 Immunoglobuline A (antibody) – generally protects mucosa (also in the nasal cavity) 59 Not in humans, not really, but in dogs and rats – fun to know. 60 Epidermal growth factor or EGF is a growth factor that stimulates cell growth, proliferation, and differentiation: involved in wound healing. 61 Nerve growth factor (NGF) is a small secreted protein that is important for the growth, maintenance, and survival of certain target neurons (nerve cells). 23 2.5 Regulation In the previous chapter on body water we talked about the reflex arc. Salivary regulation works much in the same way as it is a reflex that is regulated by both nervous and humoral stimuli. To recap, the reflex arc consists of: - receptors - sensory fibers (afferent) - nervous center - motor fibers (efferent) - effectors 2.5.1 Nervous regulation In the case of saliva, the nervous regulation consists of both parasympathetic and sympathetic reflexes. Parasympathetic reflexes (picked up by receptors 5, 7, 9 and 10) stimulate a very watery salivary secretion that is low in enzymes and mucus. The sympathetic reflex, controlled by fibers originating in the cervical ganglia, stimulate62 the secretion of a saliva rich in mucus and ptyalin. There is a conditioned part to this reflex, too. A smell, sight, remembrance or even thought of a favorite food can stimulate the appetite area located in the anterior part of the hypothalamus. This in turn stimulates salivary centers as if food were actually ingested. We will discuss this mechanism in more detail in the next chapter on gastric secretion. 62 Via sympathetic nerves. 24 2.5.2 Humoral regulation The hormones that affect salivary secretion are: Increase secretion: 63 1. Bradikynin 2. VIP64 Decrease secretion:65 1. Angiotensin II 2. Substance P 3. Oxytocin *** 63 These are generally vasodilators, so they widen blood vessels and increase blood flow 64 Vasoactive intestinal peptide 65 Vasoconstrictors – decrease blood flow 25 III THE STOMACH: Gastric juice 3.1 Introduction In this part we will discuss gastric juice, its composition and secretion mechanism. Gastric juice is the body fluid found and secreted by cells in the stomach. The stomach has a vertical and a horizontal part. The horizontal part is represented by the cardial sphincter, the fundus and the body (corpus). The vertical part consists of the antrum, the pyloric channel. In previous chapters we discussed the various layers of the gastrointestinal tract, and we saw that it is roughly the same throughout the tract. The stomach, then, also consists of the same layers, as can be seen on the picture below – serosa, muscularis, submucosa, mucosa. 26 In addition to mucus-secreting cells that line the entire surface of the stomach, the stomach mucosa has two important types of tubular glands: oxyntic glands66 and pyloric glands.67 The oxyntic glands secrete hydrochloric acid, pepsinogen, intrinsic factor and mucus. The pyloric glands secrete mainly mucus for protection of the mucosa from the acid. They also secrete the hormone gastrin. 3.2 Secretory glands Oxyntic glands have 3 types of cells: 1. Mucous neck cells a. Mucus producing cells which cover the inside of the stomach, protecting it from the corrosive nature of gastric acid. It prevents the stomach digesting itself. 2. Oxyntic or Parietal cells a. These secrete gastric acid (HCl, KCl, NaCl) and intrinsic factor.68 3. Peptic or Chief cells a. cells in the stomach that release mainly pepsinogen – the precursor of pepsin. Pyloric glands secrete mainly mucus to protect themselves and the stomach wall from HCl. They also have specialized cells called gastrin cells, or G-cells, which produce the hormone gastrin. Gastrin, as we will see later, plays an important role in stimulation of acid secretion. 66 Found in the fundus and the corpus 67 In the pyloric antrum 68 a glycoprotein produced by the parietal cells of the stomach. It is necessary for the absorption of vitamin B12 (cobalamin) later on in the small intestine (less acidic area). 27 3.3 Gastric juice composition 28 The composition of gastric juice is fairly straightforward and consists, like many other bodily secretions, mainly of water with a small amount of organic and inorganic substances. We will discuss the secretion of these substances in the next paragraphs. - HCO3 = bicarbonate, Na = sodium, K = potassium - Enzymes: digestive enzymes pepsin and rennin o Pepsin69 converts proteins into simpler, more easily absorbed substances o Hydrochloric acid provides the acid environment in which pepsin is most effective. o Rennin aids the digestion of milk proteins.70 - Mucus secreted by the gastric glands helps protect the stomach lining from the action of the acid. 3.4 Regulation of gastric juice secretion The secretion of gastric juice follows a similar reflex arc as discussed in the previous chapters on body water and saliva. For gastric juice, however, one may distinguish three separate 69 Activated form of pepsinogen 70 Namely casein. 29 phases of secretion: cephalic, gastric and intestinal (see picture above). The regulation is also both nervous and humoral. 3.4.1 The three phases As mentioned, the three phases of gastric juice secretion are: - Cephalic71 phase - Gastric phase - Intestinal phase Note that each of these phases depends on the position of the food. Sometimes food does not have to be present at all to stimulate secretion; indeed, we can say secretion starts in the head. Cephalic Phase - Before food even enters stomach - Sight, smell, taste, thought of food can be a stimulus - Cerebral cortex sends nervous impulse (using acetylcholine, or Ach) through (the dorsal nuclei of) the vagus nerve72 stimulating the stomach (parasympathetic process, accounts for 30% of gastric secretion while eating). - Increases hydrochloric acid (HCl) & pepsin73 secretion - Acetylcholine further stimulates gastrin, which is secreted by the endocrine G-cells and travels the bloodstream until it reaches the stomach again and stimulates yet more HCl secretion Gastric Phase - Food reaches and distends the stomach - Nervous mechanism o Distension receptors from the gastric wall transmit impulses to the dorsal motor nuclei of the vagus nerve, which, through acetylcholine: " stimulate an increase in HCl, pepsin, histamine and gastrin. " The latter two further stimulate secretion HCl & pepsin during several hours - Humoral mechanism o When the stomach mucosa comes into contact with proteins and peptides, G- cells are triggered to release gastrin, thus increasing HCl and pepsin secretion. - Accounts for 60% of secretion Intestinal Phase - Nervous mechanism 71 Greek Kefalos = head 72 Also known as nerve X, or nerve 10 73 Peptide acting on proteins 30  o Distension receptors from the duodenum transmit impulses to the dorsal motor nuclei of the vagus nerve, releasing acetylcholine to " Local enteric nervous system (plexi) and then to " Gastric glands; effecintg: DIRECTLY: HCl and pepsin increase INDIRECTLY: Histamine increase, thus increasing HCl and pepsin - Humoral mechanism o If proteins reach duodenum: Further secretion of gastrin from G-cells (thus more HCl en pepsin; stimulatory effect). o If lipids and sugars reach duodenum: inhibitory hormones74 release from intestinal endocrine cells, inhibiting gastric secretion. 3.4.2 Inhibitory hormones Secretin is a hormone that regulates water homeostasis throughout the body, and influences the environment of the duodenum by regulating secretions in the stomach and pancreas. Secretin is produced in the S cells of the duodenum. Secretin’s role is to help regulate the pH of the duodenum by: - inhibiting the secretion of gastric acid from the parietal cells of the stomach; - stimulating the production of bicarbonate from the centroacinar cells and intercalated ducts of the pancreas.75 Somatostatin (also known as growth hormone-inhibiting hormone (GHIH)) is a peptide hormone that regulates the endocrine system and affects neurotransmission. Its main role is to inhibit a number of hormones, but for our purpose it is important to know it inhibits gastrin secretion. 3.4.3 Secretion of hydrochloric acid (HCl) Hydrochloric acid is secreted solely by the parietal cells, which synthesize HCl extracellularly. This occurs in several steps: - First, H2O is dissociated inside the cell cytoplasm into H and OH o H is then actively secreted into the canaliculi76 in exchange for K, thanks to H/K ATP-ase (an ionic pump). - Pumping out H by H/K/ ATP-ase results in OH accumulation o OH then forms HCO3 with CO2, which was acquired from plasma o HCO3 is then exchanged for Cl from extracellular fluid and Cl is secreted in the canaliculi 74 Secretin, glucagon, somatostatin, CCK, GIP, VIP 75 See chapter IV 76 “Canals” formed by the cells where HCl is stored until secretion; important to realize this is extracellular 31  o In the canaliculi there is now a potent concentration of hydrochloric acid (HCl) at a pH of about 1-1.5 which finally is secreted through the open end of the canaliculus into the lumen of the gland To produce such a concentration of H ions requires minimal back leak into the mucosa. This is achieved first by the thin layer of alkaline mucus forming a barrier, but also thanks to the very tight junctions between the cells themselves. 3.4.4 Pepsinogen and pepsin Peptic or chief cells are mainly responsible for the secretion of pepsinogen. When pepsinogen comes in contact with HCl, it is activated to form pepsin. Pepsin, vital for protein digestion in the stomach, only functions in a highly acid environment. This environment is provided by the hydrochloric acid. It works on proteins by attacking the molecular chain inside the protein molecule. 3.4.5 Intrinsic factor The substance intrinsic facto is a glycoprotein and is essential for the absorption of vitamin B12 in the ileum. It is secreted by the parietal cells along with HCl. Without this factor vitamin B12 would not be absorbed and anemia could develop, because red blood cells cannot mature without this vitamin. 3.4.6 Mucus Gastric mucus exists in three types: 1. Free mucus – dissolved in gastric juice 2. Attached to the gastric epithelium – loosely attached at that, as it could be washed away 3. Dense mucus layer, not detachable, important in protection of the stomach. It is made up of neutral mucopolisaccharides. Mucus synthesis is stimulated by prostaglandins, but inhibited by every-day factors such as smoking, aspirin, adrenalin, cortisol, and so on. If mucus is chronically inhibited, there will be a high risk of ulcer development. 3.4.7 Histamine and gastrin As stated earlier, HCl secretion is under continuous control by both nervous signals and humoral mechanisms (or, in other words, endocrine signals). Histamine plays an important role in the humoral system. Parietal cells operate in close association with so-called ECL cells (enterochromaffin-like cells), whose primary function is the secretion of histamine. Histamine is a chemical mediator and since the ECL cells lie deep in the oxyntic gland, histamine will make direct contact with the parietal cells. The rate and amount of HCl 32 secretion by parietal cells is directly related to histamine release: this is a paracrine77 mechanism. In fact, it is these cells that are stimulated by gastrin to in turn stimulate HCl release! When certain foods – mostly proteins – come into the antral end of the stomach, gastrin cells in the pyloric glands are stimulated to release gastrin into the blood. It then reaches the ECL cells in the corpus of the stomach, causing histamine release which acts quickly to stimulate HCl secretion. So: food!gastrin!circulatory system !ECL cells ! histamine ! parietal cells HCl! 3.4.8 Other gastric enzymes Gastric lipase is a weak lipase acting only on pre-emulsified fats. Rennin (also known as labferment) breaks down casein (milk proteins). 3.5 Roles of hydrochloric acid - Digestive roles o Protein denaturation (changing, or rather simplifying the structure of the molecules, making them ready for pepsin action) o Activating of pepsinogen to pepsin o Creating and maintaining an optimal pH for pepsin - Non-digestive roles o Antimicrobial (antiseptic protection due to destruction of microorganisms) o Chemical and mechanical protection due to mucus and HCO3 barrier o Antianemic role " By secreting intrinsic factor along with HCl, it prevents anemia caused by B12 deficiency – pernicious anemia.78 " It converts Fe3 to Fe2, the only absorbable form for the body, thus preventing anemia caused by iron deficiency 3.6 Receptors of parietal (oxyntic) cells By now we have learned that a variety of messengers and substances target oxyntic cells to secrete gastric acid and other substances. The three important ones are gastrin, histamine and the neurotransmitter acetylcholine. The oxyntic cell has receptors for all three: 77 Only stimulates neighboring cells 78 This can appear due to absence of intrinsic factor or during atrophic gastritis, whereby parietal cells are destroyed. 33  - H2 receptors for histamine o Blockers: ranitidine, cimetidine, famotidine o Prevents histamine from binding, reduces acid secretion - M3 receptor for acetylcholine o Blockers: atropine et al. - CCK-B Gastrin receptor o Blocker: proglumid " If no blockers help, a H-pump blocker may be prescribed (omeprazole), which blocks H-secretion altogether 3.7 Pathology: ulcers Ulcers represent a pathological state where there is a disturbance in the equilibrium between - Aggression factors: HCl and pepsin - Protection factors: o Gastric epithelium integrity o Gastric mucus o Gastric microcirculation o Cytoprotective prostaglandins Every time aggression factors increase or protection factors decrease (or both), the risk of ulcers rises. 34 3.7.1 Ulcer types Normally, the stomach produces enough mucus to protect the mucosa against HCl and pepsin action. Moreover, in the duodenum, pancreatic bicarbonate creates a pH of 7.5 at the luminal membrane of the mucosa. Still, mucosa ulceration may occur due to various causes. - Gastric ulcer o Decrease of protective factors o Aggression factors low, normal or high - Duodenal ulcer o Increase of aggression factors o Protective factors normal or low 3.7.2 Other risk factors HCl and pepsin secretion can be increased by caffeine, anti-inflammatory drugs, hyperparathyroidism, gastrin producing tumors (Zollinger-Ellison syndrome, tumor mostly located in pancreas). Aspirin and other drugs alike can decrease the protective factor of the mucosa as it depletes it of prostaglandins. Alcohol can damage the mucus barrier and further stimulate acid secretion. Addendum: HCl synthesis and secretion *** 35 IV PANCREAS 4.1 Introduction The pancreas is an abdominal organ and one of the accessory glands of the digestive system. It is a mixed gland, meaning that it has both exocrine and endocrine functions. In this chapter, we will focus on the exocrine secretions of the pancreas.79 5 ; 19 The pancreas is situated inferior and parallel to the stomach. It is a large, compound gland with a structure that is similar to salivary glands. The pancreatic secretion is called pancreatic juice and is released into the lumen of the duodenum via a duct (the Wirsung duct or channel).80 HCO3 secret ncini by The pancreatic juice secreted in the duodenum will contain HCO3 (bicarbonate) to counter the acidity of gastric juice, as well as many digestive enzymes. These enzymes are secreted by the acini.81 So-called centroacinar cells are responsible for fluid and electrolyte secretion. Duct cells will finally modify this secretion by adding HCO3. The exocrine glandular tissue mass comprises around 80% to 90% of the total mass of the pancreas. We will now have an in-depth look at the exocrine pancreatic secretion. 79 Endocrine secretions of the pancreas are glucagon and insulin (by the Lagerhans islets) into the blood. 80 Note that the pancreatic head is situated in the duodenal concavity 81 Much like the ones in salivary glands, see chapter 2 36 4.2 Pancreatic Juice The pancreas secretes digestive enzymes together with large volumes of HCO3 solution. The precise contents and characteristics of the juice are to some extent determined by the type of nutrients in the chyme.82 In other words: it adapts its secretion depending on what you just ate. 4.2.1 Pancreatic Juice: composition and secretion 9. 5 ( ---- Pancreatic secretion is 98% water and 2% dry substances. We saw earlier that pancreatic juice content can vary depending on the type of food you eat. This is thanks to the duodenal mucosa which contains a large variety of endocrine cells (much like G-cells in the stomach) which release various substances into the blood when triggered by certain nutrients. For example, starch from bread will stimulate S-cells, which release secretin, which in turn “tells” the pancreas to release pancreatic amylase. Proteins trigger CCK-cells, which release CCK into the blood, causing the pancreas to release proteases. 82 Chyme (/kaɪm/; from Greek χυμός khymos, "juice") is the semifluid mass of partly digested food expelled by the stomach into the duodenum. 37  simple, ugerous/glucose enzyme helps breakdown carbohydrates e > proteins amylase proteolytic : - /maltose & Salivary Amylase selivery > - gland-mouth as Good lipolytic - fate Pancreatic Amylase small intestine > carbohydrate glycolytice > sugars - - > - 4.2.1.1 Pancreatic juice composition: digestive enzymes Note that there are enzymes to digest just about anything: protelolytic enzymes for proteins, lipolytic enzymes for fats, glycolytic enzymes for sugars. The enzymes are synthesized in the endoplasmic reticulum of the acinar cells and packaged in the zymogen granules. The glycolytic enzyme is pancreatic amylase, which we remember from saliva. The pancreatic variety is much stronger than the ptyalin found in saliva. Unlike the other pancreatic enzymes, amylase is released in active form.83 Pancreatic amylase hydrolyzes starches, glycogen and most other carbohydrates to form mostly disaccharides,84 oligosaccharides85 and a few trisaccharides.86 It functions optimally at a pH of 7 Pancreatic lipase is responsible for the digestion of lipids. 87 It acts together with a co-factor (co-lipase) to attack and break the bonds of triglycerides, resulting in monoglycerides and free fatty acids, and sometimes free glycerol and fatty acids.88 Free glycerol is readily absorbed Finally, the pancreatic enzymes for digesting proteins are trypsin, chymotrypsin and carboxypolypeptidase. These are released in inactive form, as they would otherwise digest the pancreas itself (as we will see, this happens with acute pancreatitis). 4.2.1.2 Protease activation Trypsin, chymotrypsin and carboxypolypeptidase are secreted as trypsinogen, chymotrypsinogen and procarboxypolypeptidase respectively. These inactive forms become activated only after they are secreted into the duodenum. Trypsinogen is the first to be activated by enterokinase, an enzyme released from duodenal mucosa when chyme comes in contact with the mucosa.89 Trypsin then activates all the other proteases. 90 4.2.2 Secretion The pancreatic digestive enzymes are released by the pancreatic acini. Large volumes of sodiumbicarbonate solution are secreted by cells in the small ducts leading from the acini. This mixture then travels through the pancreatic duct (Wirsung duct) and joins the common 83 It does not form a danger to pancreatic tissue 84 Eg. maltose (2 glucose) 85 Dextrins 86 Eg. maltotriose 87 Other enzymes for fat digestion that were not mentioned in the lecture are cholesterol esterase, which hydrolyzes cholesterol esters; and phospholipase, which splits fatty acids from phospholipids. 88 Guyton & Hall make no mention of free glycerol + fatty acids, though it is mentioned in Dr. Papacocea’s book. I have found no other source confirming or disproving this, but as was also discussed in the Biochemistry lectures, lipase can in principle only cleave two fatty acids off a triglyceride, resulting in a monoglyceride + 2 free FA. 89 Trypsinogen may also be activated by previously formed trypsin still found in the duodenum: autocatalytic 90 Two other proteases are collagenase and elastase (digesting collagen and elastic proteins resp.); they are released and activated in a similar manner. 38 bile duct (or hepatic duct) before it empties in the duodenum through the papilla of Vater, surrounded by the sphincter of Oddi. The main (Wirsung) duct runs the entire length of the pancreas. An accessory duct, known as the Santorini duct, empties from the superior part of the pancreatic head either directly into the duodenum or in the Wirsung duct. As previously stated, the pancreatic juice is collected in the acinar ducts before being transported through a network of branches to the Wirsung duct. 39  secretion nervous pancreatic G hormonal mechanism 4.3 Regulation of pancreatic secretion nervous mechanism parasympathetic mechanism Not unlike salivary and gastric secretion, pancreatic secretion is regulated by both a nervous and a hormonal mechanism. The nervous mechanism consists of a - - parasympathetic mechanism, with the vagus nerve releasing acetylcholine. The hormonal part is represented by - - CCK, Secretin, VIP, GIP91 and somatostatin and enteroglucagon. 4.3.1 Stimuli causing secretion So The basic stimuli causing pancreatic secretion are: 1. Acetylcholine cetylcholine - > nervous parasympathic i. Representing the nervous parasympathetic mechanism, it is released -> nerve vague - from the vagus nerve endings and other nerves in the enteric nervous - system 2. Cholecystokinin (CCK) 92 cholecystokinin : fuodenal mucosa i. Secreted by the duodenal mucosa when food93 enters the small intestine. It stimulates a pancreatic secretion rich in enzymes. 3. Secretin94 Secretin-Guonal mucosa Amys ③ Proteases i. Secreted by duodenal mucosa in response to highly acid chyme. It - stimulates a watery, alkaline95 secretion. Another stimulus is VIP (vasoactive intestinal peptide), a hormone which stimulates secretion of water and electrolytes. It also stimulates contraction of enteric smooth muscle, dilating peripheral blood vessels, pancreatic bicarbonate secretion, and inhibits gastrin-stimulated gastric acid secretion. Acetylcholine and CCK both stimulate a secretion rich in pancreatic enzymes but with relatively small quantities of water and electrolytes. Most of the enzymes remain in the acinar ducts until the watery secretion, stimulated by secretin, washes them out. 4.3.2 Phases of pancreatic secretion Pancreatic secretion occurs in three phases which are the same for gastric secretion: the cephalic phase, gastric phase and the intestinal phase. 91 In Dr. Papacocea’s book this hormone is listed as a stimulus, however it is now believed that the (sole) function of GIP is to induce insulin secretion. 92 CCK, like secretin, passes through the circulatory system to the pancreas, but unlike secretin, CCK causes secretion of pancreatic enzymes by the zymogen granules of the acinar cells. This effect is similar to the nervous, vagal stimulation, but is actually stronger. 93 Mostly fats and proteins; to a lesser extent glucose. 94 Secretin is mainly responsible for the watery secretion in the duodenum.. At the level of the stomach, it inhibits the secretion of gastric acid from the parietal cells. 95 Large volumes of HCO3 40  - Cephalic phase o Before food enters stomach o 10% of total secretion AfferentIs o Sight, smell, taste, thought of food can be a stimulus (conditioned reflex) 57910 o Cerebral cortex sends a nervous impulse, releasing acetylcholine from the vagal nerve endings in the pancreas o Unconditioned reflex: oral cavity receptors release impulses transmitted by afferent nerves V, VII, IX and X (vagus). These impulses reach the pancreatic center of the medulla oblongata. The efferent (or motor) fibers are vagal (X) and they release acetylcholine, stimulating pancreatic secretion and gastrin secretion in the stomach o Hormonal: gastrin can stimulate acinar cells (zymogen granules) as well, via the CCK receptor. - Gastric phase o Food is in the stomach o Nervous stimulation continues o