Introduction The Major Salivary Glands: *Parotid-produces serous secretion containing alpha amylase enzyme (ptyalin) *Submandibular-produces serous and mucous secretion *Sublingual-similar to submandibular secretion
*The Minor Salivary Glands-buccal glands secret only mucus
Salivary Flow: *1-1.5 L/day **Major flow in unstimulated state comes from Submandibular **Major flow in stimulated state comes from Parotid
Innervation of salivary glands Excitation of parasympathetic nerve fibers (facial and glossopharyngeal nerves) causes: - Vasodilatation - Increased watery secretion Excitation of sympathetic nerve fibers (superior cervical ganglion) causes: -slight increase in viscid saliva -vasoconstriction
Basic saliva components • Water • Ions: Na+, K+, Ca2+, Cl–, HCO3– • Proline-rich proteins for protection of teeth enamel: • Enzymes: ptyalin (from salivary glands), **lingual lipase (secreted from glands on the tongue).
• Immunoglobolins: IgA • Mucin: glycoproteins for lubrication of food and protection of oral mucosa • Lysozyme, lactoferrin, thiocyanate ions • pH of saliva is about 7
Function of Saliva 1. Moistens oral mucosa. In fact, the mucin layer on the
oral mucosa is thought to be the most important nonimmune defense mechanism in the oral cavity .It facilitates speaking and chewing. 2. Moistens dry food, lubricates food to facilitate swallowing and cools hot food. 3. Provides a medium for dissolved foods to stimulate the taste buds. 4. Buffers oral cavity contents. Saliva has a high concentration of bicarbonate ions. 5. Digestion. Alpha-amylase, contained in saliva, breaks 14 glycoside bonds, while lingual lipase helps break down fats.
Function of Saliva (cont.) 6. Neutralizes any gastric acid that refluxes from stomach into the lower esophagus. 7. Mineralization of new teeth and repair of precarious enamel lesions. Saliva is high in calcium and phosphate. It helps to minimize tooth decay 8. Protects the teeth by saliva protein which contains antibacterial compounds. Thus, problems with the salivary glands generally result in dental caries . 9. Controls bacterial flora of the oral cavity Lysozyme, Secretory IgA, and Salivary Peroxidase play important roles in saliva’s antibacterial actions.
Function of Saliva (cont.) ***Lysozyme agglutinates bacteria and activates autolysins. ***IgA interferes with the adherence of microorganisms to host tissue. It neutralizes viruses, bacterial, and enzyme toxins ***Peroxidase breaks down salivary thiocyanate which, in turn, oxidizes the enzymes involved in bacterial glycolysis. ## Also saliva contains lactoferrin which binds free iron in the saliva causing bactericidal or bacteriostatic effects on various microorganisms requiring iron for their survival.
Some of intraoral complications of salivary hypofunction include 1. Candidiasis 2. Recurrent aphthous ulcers 3. Dental caries.
General structure of the salivary unit
Formation of saliva • ***Saliva contains more K+ , HCO3– and less Na+ , Cl– compared to plasma. • ** saliva produced by acinar cells has almost the same composition of the plasma. In the salivary ducts saliva composition is altered by absorption of Na+ and Cl– from the saliva and secretion of K+ and HCO3– into saliva. • ** Na+ absorption and K+ secretion is increased by aldosterone. i.e aldosterone increases K+ and reduces Na+ conc. in saliva.
Variation in osmolality and ionic composition of saliva with flow rates ***At resting condition flow of saliva
is slow so the the modification in composition will be more. In this state the conc. of ions as follows Na and Cl: 15 mmo/l, K: 30 HCO3: 50 ***When salivary glands are stimulated maximally and the flow is increased, the conc. of ions is less changed and conc. of Na and Cl is half or two third of plasma conc. and K conc. is four times of the plasma conc. HCO3 conc. is also increased *** the salivary ducts are relatively impermeable to water so saliva is hypotonic
Mastication (chewing) •
Chewing: is the first stage
• Chewing reflex:
of food ingestion
Presence of food bolus causes dropping of the lower jaw. This stretch the mastication muscles which causes reflex contraction of mastication muscles (Stretch reflex). Contraction of mastication muscle will elevate lower jaw so the bolus stimulates mouth lining and this initiates another reflex. This reflex repeats itself again and again until the bolus is swallowed.
** It is important for digestion of food because 1. It breaks the cellulose membrane of the fruits and vegetables. 2. It increases the surface area on which digestive enzymes work 3. It prevents excoriation of gatrointestinal tract.
Swallowing (deglutition) • • 1. 2. 3.
Is the second stage of food ingestion It consists of three stages Voluntary stage- initiation stage Pharyngeal stage Involuntary stages Esophageal stage
Bolus of food
Tongue presses the hard palate
forces the bolus to oropharynx
Tonsillar pillar areas
Swallowing is initiated by closing the mouth and pushing voluntarily the bolus by the tongue posteriorly and upward against the palate
Pharyngeal stage The second stage starts when the bolus reaches posterior part of the mouth and early parts of pharynx. It is involuntary
Reflexly Nasopharynx closed by elevation soft palate
action and reflex in nature. Presence of food in above places stimulates pressure receptors there specially on tonsillar pillars. Sensory impulses carried to swallowing center in brain stem.
Epiglottis closes the larynx
Bolus entering esophagus and UES relax
Pharyngeal stage (cont.) •
Impulses coming from swallowing center to pharynx and esophagus to finish stage 2 and 3 of the swallowing act. In pharyngeal stage, the following events occur: 1. pushing the soft palate upward to prevent reflux of food to nasal cavity. 2. to prevent passage of food into trachea. This done by: a. The vocal cords are approximated b. The larynx is pulled upward c. Epiglottis swing back over the opening of larynx. 3. Palatopharyngeal folds are pulled medially forming slit through which the good masticated food can pass easily. 4. Relaxation of upper esophageal sphincter 5. Pharyngeal muscle contraction starts (peristalsis) from upper parts and spreading downward
Pharyngeal stage (cont.) • At the beginning of stage two, inhibitory impulses from swallowing center to respiratory center to stop respiration at any point of respiratory cycle. • Pharyngeal stage lasts for less than two seconds • The upper esophageal sphincter (the upper 3 cm of esophagus) is closed all the time except during swallowing. • **the sensory information initiating swallowing reflex is carried by 5th and 9th cranial nerves. The motor orders from swallowing center to pharynx and esophagus are through 5th,9th,10th,12th cranial verves and few upper cervical spinal nerves.
(3) Esophageal stage • Movement of bolus through esophagus is through peristalsists: • Primary peristalsis is continuation of pharyngeal peristalsis which takes 8-10 second to travel along the esophagus. This peristalsis is capable to push the bolus down ward. Bilateral cervical vagotomy will abolish this peristalsis. • Secondary peristalsis starts if primary peristalsis fails to push the bolus downward and will continue until the esophagus is empty. This peristalsis is initiated by distention of the esophagus by retained food. It is due to stimulation of the myentric plexus in the wall of esophagus and it will continue after vagotomy
Esophageal stage (cont.) Lower esophageal sphincter (LOS) Is located 3 cm above the junction between esophagus and stomach . It remains contracted all the time except during esophageal stage of swallowing. The LOS is relaxed by receptive relaxation mechanism ( during peristaltic contraction the part in front of contraction part is relaxed by inhibitatory neurons in myentric plexus). *** LOS is important to prevent reflux of stomach content into esophagus. ** pressure in LOS is about 30 mm Hg. *** failure of LOS relaxation causes achalasia ** failure of LOS contraction causes reflux of stomach content to esophagus causing reflux esophagitis.
When intra-abdominal pressure is increased during coughing, the lower portion of the esophagus is closed by valve like action of this part
Bolus of food
LOS opens Due to wave of relaxation transmitted through Myenteric Inhibitory Neurons Relaxed muscles
Stomach
Relaxed muscles
Stomach
VOMITING CENTER **is found in reticular formation of medulla and pons. **receives sensory impulses from pharynx, esophagus, stomach and upper parts of small intestine. ** sensory impulses reaching it from GIT are carried by both afferent sympathetic and parasympathetic fibers. CHEMORECEPTOR TRIGGER ZONE ** is located on the floor of fourth ventricle of the brain.
** is stimulated by certain drugs like morphine, apomorphine, digitalis, circulating emetic substances for example substances accumulated in the blood of renal failure patients. ** it is also stimulated by impulses coming from vestibular apparatus.
VOMITING (emesis) ACT The sudden and forceful expulsion of gastric and upper intestinal contents * It is controlled by neurons in medulla (the ‘vomiting centre’) *It is triggered by one or more of the following stimuli: - excessive gastric or duodenal distension - noxious substances in stomach - certain smells or sights - emotional factors - touch receptors at back of throat - reflexes involving semi-circular canals (‘motion sickness’) - stimulation of the ‘chemoreceptor trigger zone’ by circulating ‘emetics’
THE VOMITING REFLEX SEQUENCE OF EVENTS • It starts by salivation and sensation of nausea • Deep inspiration, respiration held in mid inspiration • Closure of glottis • Relaxation of lower esophageal sphincter • Contraction of diaphragm and abdominal muscles causes increased intra-abdominal pressure • Duodenal contraction (reverse peristalsis). • Rapid rise in intra-gastric pressure causes reverse expulsion of gastric and upper parts of small intestine contents ***Vomiting act is accompanied by generalized autonomic effects e.g: - sweating - tachycardia - Salivation *** Vomiting of gastric content alone for prolonged time (for example in pyloric stenosis) leads to metabolic alkalosis While vomiting of large amount from duodenum causes metabolic acidosis
Types of gastric glands and cells • Gastric cells
• Gastric glands
1. mucous neck cells (secrete mucus) 2. surface epithelial cells (secrete mucus) 3. chief cells (secrete pepsinogen) 4. G cells (secrete gastrin - in antrum) 5. parietal (oxyntic) cells (secrete HCl and intrinsic factor)
1. The oxyntic glands (80% of gastric glands)-body and fundus 2. Pyloric glands (20% of gastric glands)- antrum region
Structure of a gastric exocrine secretory gland oxyntic gland
GASTRIC SECRETION • approx. 2 L gastric juice per day • secretion is isotonic, pH 2-3 (in stomach lumen) Functions of gastric secretion 1. Intrinsic Factor: - from parietal cells, for vitamin B12 absorption in lower small intestine (terminal ileum). - It is indispensable substance in gastric juice. It’s absence leads to pernicious anemia 2. Mucus: protects gastric epithelium. It adheres to gastric surface and prevents H+ and pepsin eroding the mucosa; failure of this process leads to gastric ulceration
GASTRIC SECRETION (cont.) 3. HCl - from parietal (oxyntic) cells • Function of Gastric acid -to kill micro-organisms but H. pylori survives by making ammonia (alkaline) from urea using urease enzyme. -to activate pepsinogen (cleaved to form pepsin)
pepsin: initiates protein digestion -breaks down connective tissue in food -denatures protein 4. Pepsinogen - from chief (peptic) cells - conversion to pepsin (active enzyme) requires low pH; optimum pH 1-2
Mucosal Protection of gastric epithelium • mucus layer on gastric surface forms a mucosal barrier against damage to gastric epithelium – – – – –
a gel about 1 mm thick secreted by neck cells, surface epithelium can be cleaved by pepsin, so continual production is required release is stimulated by acetylcholine from nerve endings also rich in bicarbonate • HCO3- content creates a "micro-environment" around surface cells to prevent acid damage • HCO3- secretion is inhibited by adrenergic input (prominent in stress!)
• prostaglandins are protective agent (increase mucus production and blood flow) – inhibition of enzymes involved in prostaglandin production (cyclooxygenases =COX) by NSAIDs (non-steroidal anti-inflammatory drugs) such as aspirin, ibuprofen, etc. results in gastric damage
Gastric Mucous layer ***The surface epithelial cells of the stomach secrete thick insoluble, unstirred mucus that lines the surface of the stomach. •
• •
This mucus contains glycoproteins that form an almost gelatinous coating which contains relatively high concentrations of bicarbonate ion. This coating protects the stomach epithelium from gastric acid and pepsin. Glycosylation of mucin makes it relatively resistant to proteolysis by pepsin.
A second type of mucus (soluble) is secreted along with the gastric juice from the gastric pits to lubricate the food bolus and facilitate mixing. Soluble mucus restricts the access of gastric juice to the gastric pit epithelial cells.
Viscid mucus Soluble mucus
Parietal cells secret HCl and intrinsic factor
HCl secretion Three chemicals stimulate production of HCl from parietal cells:
1.
Acetylecholine: released from cholinergic nerve fibres (parasympathetic) - acts on muscarinic receptors (M3 )
2. Gastrin: released from G cells of pyloric glands acts on G receptors 3. Histamine: released from enterochromaffin-like-cells (ECL) and mast cells acts on H2 receptors. inhibited by H2 receptor antagonists (eg. cimetidine) -ECL are stimulated by gastrin and acetylcholine ** each one of the three stimulants potentiates the effects of the others.
EFFECT of parietal stimulation by the three stimulants are: **more H+/K+-ATPase inserted in membrane **more Cl- channels inserted
PARACRINE HORMONES AND HCl RELEASE IN THE GASTRIC PHASE OF SECRETION Histamine: Released from mast cells in mucosa by Ach (from nerves) and gastrin (G-cells) Acts directly on parietal cells to stimulate HCl production. H2-receptor antagonists block action of histamine
Somatostatin: Released from D-cells in gastric epithelium by direct action of H+ (at lumen pH < 2). Reduces gastrin release â&#x2020;&#x2019; reduced HCl secretion
histamine
ECL cell
Mechanism of HCl formation 1. H+ ions are formed inside parietal cells from dissociation of carbonic acid which is formed from combination of CO2 and water under the influence of carbonic anhydrase enzyme (HCO3 conc. Increases inside parietal cell). 2. Cl- is pumped inside parietal cell in exchange of HCO3 (antiporter). 3. H+ ions are pumped into gastric lumen by K+/H+ pump. 4. Cl- moves out (by diffusion) of parietal cell into lumen through electrical gradients. ****H+/K+-ATPase (i.e. proton pump), located in the luminal membrane of parietal cells
Another version (Guyton) for Hydrochloric acid formation : Hydrogen ions are formed from the dissociation of water molecules. The enzyme carbonic anhydrase converts one molecule of carbon dioxide and one molecule of water to a bicarbonate ion (HCO3-) and a hydrogen ion (H+) The bicarbonate ion (HCO3-) exchanged for a chloride ion (Cl-) on the basal side of the cell and the bicarbonate diffuses into the blood. Potassium( K+ ions diffuse into the canaliculi. Hydrogen ions are pumped out of the cell into the canaliculi in exchange for potassium ions, via the H/+K +ATPase.
Extra points regarding HCL formation • During active secretion of HCl after a meal, the pH of the blood drained from the stomach is elevated (due to secretion of HCO3 ions). this increase in pH of the venous blood leaving the stomach is referred to as the alkaline tide. It raises the pH of systemic blood and make urine alkaline (postprandial alkaline tide). • * The K+/H+ pump is very powerful and requires appreciable amount of energy because H+ is pumped against more 1000000 concentration gradient (pH 7 to pH 1) ) - It can concentrate H+ 3 million times. - Inhibition of this pump by drugs called proton pump inhibitor (Omeprazole ) helps in reducing the amount of HCl secretion.
• The pH of parietal cell secretion into canaliculi is very low (about 0.8).
Intragastric pH after a meal
Stomach â&#x20AC;&#x201C; somatostatin Duodenum â&#x20AC;&#x201C; secretin, hyperosmotic chyme fatty acids
Inhibition of acid secretion
Phases of gastric secretion Cephalic phase: Occurs before food enters stomach ~30% of total secretion Direct vagal stimulation + gastrin release Gastric phase: Occurs while food is in stomach >60% of total secretion Involvement of: vagal and enteric nerves paracrine (local) hormones (histamine) endocrine hormones (gastrin) Gastrin secretion inhibited at lumen pH <2 Intestinal phase: Occurs after food enters small intestine Largely hormonal: - stimulatory effects (gastrin) - inhibitory effects (secretin, GIP etc)
Cephalic Phase of gastric secretion
1. The taste or smell of food, tactile sensations of food in the mouth, or even thoughts of food stimulate the medulla oblongata (green arrow).
Taste or smell of food Tactile sensation in mouth
2. Parasympathetic action potentials are carried by the vagus nerves to the stomach (pink arrow).
3. Parasympathetic vagus nerve
Medulla oblongata
1
fibers stimulate enteric plexus of the stomach.
4. Postganglionic neurons stimulate secretion of parietal and chief cells and stimulate gastrin secretion of endocrine cells.
5 Vagus nerves
2
Secretions stimulated
3 Gastrin
4 Circulation
5. Gastrin is carried through the circulation back to the stomach (purple arrow), where it stimulates secretion of parietal and chief cells.
Stomach
**Peptides in stomach cause also secretion of gastrin
***Inhibition of HCl secretion by low luminal pH. A local effect to prevent gastric damage by very acidic gastric contents
Vagus nerves
Medulla oblongata
Gastric Phase 1. Distention of the stomach activates a parasympathetic reflex. Action potentials are carried by the vagus nerves to the medulla oblongata (green arrow).
1 Secretions stimulated
2
Distention
2. The medulla oblongata stimulates stomach secretions (pink arrow).
3
3. Distention of the stomach also activates local reflexes that increase stomach secretions (purple arrow). 4. Peptides in stomach cause secretion of gastrin
Stomach
Local reflexes stimulated by stomach distention
Intestinal phase of gastric secretion - occurs when chyme enters small intestine - largely hormonal: 1. Initial stimulatory effects on gastric secretion (via enteric gastrin) 2. Feedback inhibitory effects (secretin, gastric-inhibitory-polypeptide)
Intestinal Phase **Chyme in the duodenum with a pH less than 2 or containing fat digestion products (lipids) inhibits gastric secretions by three mechanisms.
Vagus nerves
1. Sensory vagal action potentials to the medulla oblongata (green arrow) inhibit motor action potentials from the medulla oblongata (pink arrow).
2. Local reflexes inhibit gastric secretion (orange arrows).
3. Acid, fat, protein breakdown products, hyperosmotic or hypo-osmotic or any irritating factor in duodenum and upper small intestine cause secretion of Secretin, gastric inhibitory polypeptide, and cholecystokinin produced by the duodenum (brown arrows) inhibit gastric secretions in the stomach.
Medulla oblongata Decreased gastric secretions
Vagus nerves
2
Local reflexes
1 pH<2 or lipids
Secretin, gastric inhibitory peptide, cholecystokinin
3
4 Circulation
Secretion from other parts of GIT Esophygeal secretion: entirely mucus and it’s function is; to prevent mucosal excoriation by newly entering food. To protect the lower esophagus from the effect of refluxed gastric juice.
Duodenal secretion: alkaline (containing large amount of HCO3 ions) mucus secretion from compound mucous glands called Brunner’s glands which are found in large no. in duodenal wall in area between pylorus and papilla of Vater. Brunner’s glands secretion is stimulated by: 1. Tactile or irritating stimuli on duodenal mucosa 2. Vagal stimulation 3. Secretin hormone Their secretion is inhibited by sympathetic stimulation Function of Brunner’s gland secretion is to protect duodenal mucosa against the destructive effects of acidic chyme coming from the stomach.
Secretion from other parts of GIT (cont.) Secretion of small intestine 1.8 liter/day Intestinal epithelium (crypts of Lieberkuhn) has two types of cells a. Goblet cells- secrete mucus (mucin) for lubrication and protection and also bind some bacteria and Immunoglobulins. Secretion of mucus is increased by parasympathetic stimulation and by chemical and physical irritation. b. Entrocytes- secrete alkaline watery fluid similar to extracellular fluid. This helps in absorption of different substances by intestinal villi.
mechanism of intestinal watery secretion: Cl- and HCO3- ions are actively secreted. Sodium diffuse because of electrical gradient. Water will follow ions by osmosis.
Paneth cell provide defense against microbes
Secretion from other parts of GIT (cont.) â&#x20AC;˘ Secretion of the large intestine ***The epithelium of large intestine consists mainly mucous cells that secret mucus * this mucus contains HCO3- ions secreted by non-mucus secreting epithelial cells). * mucus secretion is increased by: - tactile stimulation of epithelium lining the intestine. - Local nervous reflexes - Stimulation of parasympathetic nerve fibers Functions of Mucus a. Protection b. Neutralization of acids formed in large intestine
If you are using Adobe Reader....to rotate the page>> click view then rotate view then click counterclockwise
Scanned by M-R-O for HAYAT Group 2008 Class Summarizing Group Oct.25th.10
Physio Lec #4 A
Scanned by M-R-O for HAYAT Group 2008 Class Summarizing Group Oct.25th.10
If you are using Adobe Reader....to rotate the page>> click view then rotate view then click counterclockwise
Scanned by M-R-O for HAYAT Group 2008 Class Summarizing Group Oct.28th.10
If you are using Adobe Reader....to rotate the page>> click view then rotate view then click counterclockwise
Scanned by M-R-O for HAYAT Group 2008 Class Summarizing Group Nov.3rd.10