Salivary Glands - NPB114 MT2 PDF

SALIVARY GLANDS Oral cavity’s job ○ Mechanical digestion (chewing) ○ enzymatic /chemical digestion (salivary enzyme) ○ Chemosensation (taste of food) ○ Swallowing Saliva ○ Exocrine secretion Produce 500-600 mL/day ○ Job: enzyme...

SALIVARY GLANDS Oral cavity’s job ○ Mechanical digestion (chewing) ○ enzymatic /chemical digestion (salivary enzyme) ○ Chemosensation (taste of food) ○ Swallowing Saliva ○ Exocrine secretion Produce 500-600 mL/day ○ Job: enzyme for digestion of fats and starch ○ Has lots of proteins but 99% of H2O and 1% protein Lubricant Solubilizes taste molecule Speech Protective Proteins in saliva ○ Mucins Can polymerize to make mucus Job: lubricant Sticky Antibacterial Prevents enamel of teeth from going away ○ Histatins Lots of histidine Antibacterial Antifungal ○ Cystatins Lots of cysteine Antibacterial Prevents enamel loss ○ Salivary amylase Digests starch Salivary lipase/lingual lipase - digests triglycerides ○ Salivary immune bodies Antibacterial ○ Salivary lysozyme Targets bacterial walls antibacterial GLANDS Submandibular ○ Produces basal saliva Low volume Sticky proteins Sublingual ○ Stimulates slate saliva Submandibular + sublingual ○ Mixed cells -> serous (watery, ion rich) and mucous (protein content) Parotid gland ○ Produces 50% of stimulated state saliva ○ Serous cells -> parotid makes a watery ion rich secretion AUTONOMIC N.S INPUT PNS ○ Produce watery, large volume SNS ○ Biphasic = initially volume is low due to vasoconstriction but them volume goes up due to vasodilation SALIVA FORMATION Salivon = basic unit Acinar produce the initial/unmodified saliva Duct cells = modify the saliva by adding or removing ions Exocrine secretion = contents come from the blood Level of ions in blood from highest to lowest: ○ NA+ ~ 145 ○ Cl ~ 110 ○ HCO3 ~ 25 ○ K~4 Levels of ions in saliva during low (basal) and high food stimuli ○ Low: Na, HCO3, Cl are basically zero K+ is actually higher than that of blood ○ High: Na, HCO3, Cl are secreted to reach the level to that of the blood This shows that capillary ions diffuse into acinar cells K+ is Same as blood  ACINAR CELLS PRODUCE INITIAL SALIVA ○ Na+ travels from blood to acinus via paracellular transport Cl- ion transport ○ Cl- ions flow into acinar cells via Na+/K+/Cl- cotransporter (secondary active transport), and leave the cell via a Cl- channel In this cotransporter 2 Cl- ions enter along with one K+ ion directly K+ transport ○ K+ moves into the cell via Na+/K+ ATPase ○ K+ leaves the cell via an apical K+ channel ○ 3 Na+ go out and 2 K+ come in ○ K+ can also move parallel from basolateral to acinus (basically between the acinus cells) H2O ○ Crosses via paracellular transport ○ Following ions via osmosis ○ Blood flow Blood flow ○ Regulated by changes in SNS input to arterioles Increase in SNS input causes vasoconstriction -> blood flow drops -> causes a drop in salivary production (so drop in volume); also activates protein synthesis Decrease in SNS input -> increase in blood flow -> increase in salivary flow rate and volume Increased SNS activity to salivary glands stimulates salivary protein synthesis and secretion which increases metabolism ○ When protein synthesis is increased metabolites (ADP, lactate, H+) OVERRIDE SNS input and causes the arteriole to relax (even though SNS is saying it to contract), ultimately causing vasodilation DUCT CELLS Remove Na+ and Cl- Add K+ Na+ is removed from saliva at apical membrane via NHE NHE = sodium, hydrogen ion exchanger ○ Then after that Na+ is removed into the capillary via the Na/K ATPase K+ secretion = K+ enters at the basolateral membrane via Na/K ATPase, leaves the cell via H+ pump (K+ leaves the cell and H+ goes into the cell) Cl- reabsorption at the apical membrane uses anion exchanger antiporter ○ Moves Cl- into the cell and bicarbonate ions out of the cell  ○ Then at the basolateral membrane Cl- channel moves chloride out of the cell into the blood FLOW RATE High at stimulated state ○ Thinking, smelling, seeing food ○ Exposed to food ○ Chewing ○ When there is lots of volume or time -> saliva travels past duct cells VERY QUICKLY and has no time to be ionized or deionized Low flow rate ○ Saliva travels slowly past duct cells -> allows the duct cells enough time to modify the saliva HCO3 Saliva is relatively isotonic 290-300m osmol Bicarbonate neutralizes acidity in reflux in PHARYNX UES & LES protect from reflux When we swallow our saliva with bicarbonate, it neutralizes the stomach acid in reflux Production Occurs mainly in the stimulated state ○ In both acinar and duct cells ○ CO2 from blood goes into cell turns into bicarb and then can leave the cell and bring in Cl- via an anion transporter REGULATION IN SALIVARY SECRETIONS PNS input = stimulatory ○ Large volume, watery, HCO3 SNS input = biphasic ○ Initially, reduces blood flow which reduces salivary secretion rate and increases protein production which makes local metabolites which override the vasoconstriction and increase blood flow and increase salivary secretion Stimuli mainly occurring in two phases ○ Cephalic phase = see, smell, talking, thinking food ○ Oral phase = food in mouth, taste, chewing Sour > salty ~umami > sweet > bitter (production of saliva) Vagotomy = PNS efferrents are cut, which decreases saliva production significantly Acute fear = increases SNS, which decreases salivary production Lack of sleep = decrease production Depression = decrease production PHARYNX ANATOMY Pharynx = interior of throat and mouth; food and air passage ○ Surrounded by walls of skeletal muscle ○ Superior, middle, inferior pharyngeal constrictors = collapse the oropharynx and hypopharynx during a swallow 3 parts ○ Nasopharynx ○ Oropharynx = extension soft palate to the base of tongue ○ Hypopharynx Vocal cords/opening of the trachea ○ Then trachea and UES and esophagus right near below hypopharynx Vocal cords are voluntarily controlled during speech Larynx = during a swallow, musculature contracts and moves the trachea up and forward, which OPENS the UES DURING A SWALLOW Prevent food stuff from entering the airways (nasopharynx/nasal passage and trachea) More food bolus from anterior oral cavity -> pharynx -> past UES -> into esophagus Upper esophageal sphincter/UES ○ Made of skeletal muscle ○ High pressure (40-100 mmHg) ○ Closed ○ PNS input ○ Inspiration contracts in tighter Ex. cough or sneeze Lower esophageal sphincter/LES ○ Less defined ○ Weak (10-12 mmHg) ○ Smooth muscle ○ Surrounded by diaphragm ○ Inspiration, cough, sneeze increase tone which increase gastric load ○ PNS input ESOPHAGUS ANATOMY Esophagus = food passage Transit tube 10-12 inches Upper ⅓ is skeletal muscle Middle ⅓ is mixed  Lower ⅓ is smooth muscle SWALLOWING Starting it is voluntarily controlled Oral phase ○ After chewing food, tongue separates a small bolus of food, tongue presses the bolus of food against the food of the mouth, which activates touch receptors, which send info to brain stem, which activates the swallowing center ○ Tongue will do “peristalsis” to push the food ○ Touch info from the back of the tongue and rear of the roof will send signals to the swallowing center ○ Soft palate musculature will contract, which will block nasopharynx, and therefore no food will enter into the nasal passage and instead go into the oropharynx Since the nasopharynx is closed, you stop breathing during a swallow ○ Superior, middle, inferior pharyngeal constrictors contract in sequence, which moves the bolus downward The musculature of the larynx will constrict ○ Pharyngeal phase of swallowing ○ Muscles at the base of the tongue and those surrounding the trachea will contract ○ Contraction moves the trachea up and forward, which will open the UES ○ Voice box/vocal chords at the top of the trachea close to allow food to pass across the epiglottis into the esophagus FOOD BOLUS ENTER THE ESOPHAGUS Esophageal phase ○ Soft palate relaxes, which will open passage from nasopharynx and oropharynx ○ Opens vocal cords ○ Epiglottis springs back to original position ○ Breathing is resumed ○ UES is closed = prevents reflux from the LES that opens ~ 1 second after UES opens Normally, esophagus exhibits background contraction ○ We need to relax it -> deglutitive relaxation/ deglutitive inhibition ○ Relaxes the tube of the esophagus to allow stuff to come down Liquids easily flow down to the stomach Peristalsis ○ In esophagus pushes solid foodstuff down into the stomach ○ Primary = usually pushes bolus down to the stomach  ○ Secondary = additional contractions to push bolus downward Guzzling = quick successive swallows of a liquid - temporarily delays primary peristalsis ○ After the very last swallow the primary peristalsis occurs and it is STRONG Control of swallowing is mediated by the brainstem ○ Swallowing center -> activates PNS output ○ Tone in the esophagus is mediated by PNS So is UES and LES but we are not too sure about that LES @ BOTTOM Low pressure Diaphragm contraction during inspiration increase the tone of LES When food enters the stomach, tone goes up Transient LES relaxation (TLESR) ○ Burp ○ If you increase frequency of TLESR you increase risk of reflux REFLUX Reflux = backward movement of contents Gastro-esophageal reflux = gastric contents are caustic (HCl) Reflux from the stomach damages the esophagus ○ Repairs quickly, no pain, no symptoms ○ Saliva HCO3 neutralizes reflux Sometimes the erosions actually cause damage and pain, which causes heartburn ○ Repairing might leave scarring ○ Sometimes might even get ulcers, which are non healed inflamed regions Gastroesophageal reflux disease (GERD) ○ Extensive ulcerations, unhealed regions in the esophagus ○ Inflammation ○ Can lead to esophageal cancer What induces relaxation of LES and therefore increases the risk of reflux? ○ High frequency of TLESR ○ Chocolate & Fatty meals ○ Coffee, Cola, Alcohol ○ Wearing tight clothing ○ Weight gain and pregnancy ○ Heavy lifting Treatments include: avoiding the food and drinks, trying to not burp for fun, antacids (malox or peptobismol) SWALLOWING PROBLEMS Dysmotility = lack of coordination in smooth muscle, which leads to uncoordinated peristalsis scleroderma = autoimmune disease that attacks upon smooth muscle ○ Rare ○ Lack of peristalsis in latter ⅔ of esophagus ○ LES loses its tone, which causes reflux Achalasia / chagas disease ○ No peristalsis in the esophagus ○ Esophagus is relaxed, dilated ○ LES is tightly closed ○ Bite from assassin bug/kissing bug trypanosomi cruzi Produces a toxin that affects the heart, enteric NS, and other neurons ○ Nitrates and botox can relax LES as treatment Neuromuscular diseases: ○ Stroke Uncoordinated contraction, which leads to aspirated food into nasal passage and trachea ○ Parkinson's patients ○ Polio patients STOMACH Stores ingesta (foodstuff) Digests foodstuff/ingesta by contractions and HCl and other enzymes Controls gastric emptying from chyme into the small intestine ○ Upper left (on paper) is cardia/cardiac stomach and upper right (on paper) is the fundus Rugal area before middle ○ Middle is the corpus/body ○ Then bottom, right before the pyloric sphincter is the antrum/pylorus ○ After the sphincter you have the duodenum It has less curvature on the left side (of the paper) and greater curvature on the right side Muscularis externa has 3 layers of muscle: ○ Inner oblique At the cardiac stomach, strip along the lesser and greater curvature ○ Middle circular Through the entire stomach ○ Outer longitudinal  At the very start of the stomach/proximal and distal/ last part of the stomach Neuronal control via the autonomic NS and enteric NS Neuronal afferents detect ○ Lumen pH and osmolarity ○ Calorie content and type of macronutrient ○ Stretch of the wall ○ Temperature and pain stimuli ANATOMY AND MOTOR ACTIVITY Two parts ○ oral/proximal/upper stomach Accommodates a food load Food storage can last as long as 1 hour Food is stored in layers Bottom is first consumed Prior to loading the upper stomach (fasting) muscle is contracted (Em = -40 mV, depolarized past threshold -50 mV) ~ 13 mmHg Start eating a meal and swallowing causes the relaxation at upper stomach ~9.8 mmHg, which lasts 20-30 minutes Receptive relaxation = act of swallowing induces oral stomach relaxation; vagus/PNS input mediates Gastric accommodation = stretching at stomach wall causes relaxation ○ caudad/distal/lower stomach Peristalsis (grinds foodstuff mixing with HCl and enzymes) causes gastric emptying Smooth muscle cells prior to foodstuff entry are hyperpolarized (-70 mV), which means no contraction When food enters the cells depolarize, which will cause muscle cells to contract (up PNS and down SNS) FED MOTOR ACTIVITY Peristalsis starts at top of the caudad stomach and progresses towards the pyloric sphincter which is tightly closed The peristaltic contraction does not have a tight contraction Food stuff gelstiturated via tiny bore in contraction and is retropulsed back up Duration ○ Tougher food = longer duration ○ More calories = longer duration  ○ More viscosity = longer duration Lag phase Regulation ○ Size of particles in chyme detected by touch sensitive neurons -> brainstem -> increase PNS activity ○ Chemicals from food also detected sensory input goes to brain stem and enteric NS which increases gastrin and CCK secretion ○ Stimuli in duodenum Wall stretch inhibits fed motor activity fats , proteins/aa acidity inhibits fed motor activity L-tryptophan inhibits fed motor activity No lag phase is seen with baby food and applesauce FASTED MOTOR ACTIVITY/MIGRATING MOTOR COMPLEX MMC Three phases ○ 1: motor quiescence 75-90 minutes ○ 2: contractions (peristalsis) irregular 15 minutes ○ 3: strong rhythmic contractions; peristalsis starts as high as the fundus progresses through the stomach and enters the small intestine to mid jejunum; pyloric sphincter is open 5-10 minutes ○ Motilin induced ○ Eat a meal to stop it PYLORIC SPHINCTER At the distal end of the stomach Regulated gastric emptying Prevents reflux from small intestine into the stomach Antrum – sphincter – duodenum Structure: all circular muscle, lots of PNS input Tightly closed during fed motor activity, majority of fasted motor activity Opens during gastric emptying Largest opening during phase 3 fasted motor activity Regulation ○ Hormones: CCK, GLP1 – cause contraction which means slow gastric emptying High fat and aa in duodenum = closes Secretin = ? High H+ in duodenum = closes High osmolarity = closes via unknown signal factor ○ Same stimuli are detected by sensory neurons (extrinsic) vagal, spinal afferents  Information is sent to brain stem and spinal cord Increase SNS = contraction Low frequency PNS = closes High frequency PNS = opens ○ Electrically stimulate duodenum to contract causes the pyloric sphincter to contract too ○ Electrically stimulating the antrum causes the pyloric sphincter to relax GASTRIC EMPTYING Empty stomach contents during fed motor activity into the duodenum ~ 200 kcal/hour In general, liquids empty fastest because there is no lag phase Solid emptying rate depends on toughness of food stuff (lag phase) Fats Indigestible solids empty out fast Liquids = rate of emptying is dependent on ○ Calories: more calories = longer emptying ○ Volume: large volume empty faster than small volume ○ Fat: slows emptying ○ osmolarity/tonicity: hyperosmotic/hypertonic = empty slower ○ L tryptophan: slows emptying ○ pH: acidity slows emptying ○ Gravity: no effect ○ Milk, 1M glucose solution = empty fast Emptying of solids ○ Lag phase breaks apart foodstuff to 1mm in diameter ○ Particle size