Lecture 9 - Physiology of the Mouth and Oesophagus and Tummy PDF

Overall learning outcomes To know how saliva is produced and the role it plays in digestion To know how absorption through the mouth works and understand the barriers to oral delivery To know basic dental problems  Mouth Food mixed with saliva as it is chewed T...

Overall learning outcomes To know how saliva is produced and the role it plays in digestion To know how absorption through the mouth works and understand the barriers to oral delivery To know basic dental problems  Mouth Food mixed with saliva as it is chewed Three pairs of salivary glands (parotid, submandibular, sublingual) Around 1500ml saliva secreted each day Saliva contains – mucous to help lubricate food – -amylase to initiate breakdown of carbohydrate –  Parotid salivary gland mouth (watery saliva/ a-amylase) sublingual pharynx salivary gland trachea (thick saliva/mucus) oesophagus submandibular salivary gland (watery saliva/ a-amylase)  Formation of saliva Isotonic fluid produced by acinar cells – secrete electrolytes & water Fluid modified as it flows along salivary duct Final composition depends upon flow rate & neuronal input  Regulation of saliva secretion Controlled by Conditioned Fear reflexes? Dehydration reflexes mediated via ANS Parasympathetic Higher centres of brain – watery saliva – rich in amylase & mucous Taste Salivatory Chewing – increased blood flow nucleus in Brainstem to glands Smell Sympathetic – Promotes increased output of thicker mucous Duct – reduces blood flow to Acinus glands Salivary gland  Swallowing (deglutition) Voluntary stage soft palate – Tongue pushes bolus hard palate pharynx backwards to orthopharynx Pharyngeal stage » Reflex action › controlled by deglutition centre in medulla and pons of brain food » Soft palate and uvula move up to seal off nasopharynx » Larynx raised, glottis sealed » Epiglottis covers glottis & breathing tongue suspended for 1-2 s epiglottis oesophagus glottis trachea Oesophageal phase of swallowing & digestion Tube connecting laryngopharynx to stomach Muscularis layer striated for first third to assist in swallowing Middle third is mixture of striated and smooth muscle Lower third is all smooth muscle Digestion and transit in G.I. Tract Segmentation - occurs largely in small intestine to facilitate mixing of food Peristalsis - concerned mainly with propulsion of food along tract bsorption through the mouth Absorption of drugs Buccal or Sublingual delivery – drug needs to cross epithelium (oral mucosa). Enters bloodstream directly & typically results in greater bioavailability. Does not need to go through the digestive system so avoids first pass metabolism (loss of drug during absorption via gut wall). Good if rapid action is required! However, Solubility in saliva – needs to be considered passive diffusion – only small lipophilic  Oral Mucosa Surface area is limited Stratified squamous Epithelium ~200cm2 Passive Basement membrane diffusion Lamina propria Rich blood supply – rapid onset Buccal administration of drugs - considerations Drug must dissolve in saliva so hydrophobicity is an issue Need to consider swallowing reflex for buccal delivery – retention in mouth is important Surface area for absorption is limited ~200cm2 v’s 20,000cm2 (skin) or 350,000cm2 (GI tract)  Barriers to absorption/oral delivery Drug must diffuse across lipophilic cell membrane and hydrophilic interior of cell. These barriers must be taken into consideration. Enzymatic barrier (aminopeptidase) in buccal tissue also exists causing rapid degradation of peptides and proteins – limits transport across epithelium. Challenge – suitable delivery systems. Challenges for buccal delivery Barriers Drug (dose) must be kept in place for absorption. Excess saliva could reduce this. Surface area is limited Taste of drug must be bland Drug must be a non-irritant to mouth or teeth Oral/Dental problems Dry mouth – Xerostomia Oral ulcers Oral thrush  Oral/Dental problems Dry mouth can lead to oral ulcers and dental caries and can affect both digestion and drug absorption. This can be a side effect of certain drugs and can be treated with artificial saliva preparations (lozenge/spray/gel). Oral ulcers – usually clear up without treatment but in some cases require  Oral/Dental problems Oral thrush – yeast infection Caused by: over-use of antibiotics, poor immune system, underlying disease, smoking, dentures... Treatment aimed at reducing fungal infection using oral anti-fungal gel e.g. miconazole, nystatin  Oral/Dental problems Some examples of medications that may cause tooth decay Antacids - may contain sugar or artificial sweeteners. Chewable antacids can get stuck between your teeth and over time, can result in decay. Pain medications - opioids can cause dry mouth and the consequent erosion of tooth enamel. Antihistamines – can block the release of saliva, resulting in dry mouth.  Oral/Dental problems Inhalers for asthma contain an ingredient, (beta-adrenergic agonist), that is slightly acidic and this can be harmful to tooth enamel causing susceptibility to tooth decay.  Oral/Dental problems Advice for dental hygiene Drink plenty water Brush your teeth twice a day and get regular dental check-ups Use a moisturising mouth spray Reduce or give up smoking Reduce intake of caffeinated and dehydrating drinks like coffee, tea and alcohol Use a hydrating mouth rinse Overall learning outcomes To know the physiology of the stomach To know the cell types and key receptors found in the gastric glands of the stomach To understand how gastric acid is produced and hormones are released Functions of the stomach Temporary storage of food Mechanical digestion by stomach movements Chemical digestion of proteins Regulation of passage of chyme into small intestine Secretion of intrinsic factor - essential for absorption of vitamin B12 Digestion in the stomach - mechanical Muscularis enables food to be churned – particularly in the antrum where the muscle wall is thicker (more powerful contractions) Food mixed with gastric juice to produce chyme Chyme passes through pyloric sphincter to duodenum  Gastric glands Stomach mucosa composed of epithelium containing many (pits/glands) gastric lumen surface epithelial cells gastric pit gastric duct goblet (neck) cells oxyntic peptic (chief) cells (gastric) gland oxyntic (parietal) cells mucosa muscularis mucosa Secretory cells in gastric glands 3 key types of cells together produce gastric juices – Zymogenic (chief/peptic) cells secrete pepsinogen – Parietal (oxyntic) cells secrete HCl (and intrinsic factor) – Goblet (neck) cells secrete mucous Additional cells in gastric glands – G cells secrete gastrin – Enterochromaffin- (mast like) cells secrete histamine – D cells secrete somatostatin  Parietal cell distributio n More parietal cells are located in the body of the stomach – note the absence in the antrum Digestion in the stomach - chemical Proteins broken down by pepsin – only active in acid environment – Converted from pepsinogen by HCl Gastric lipase breaks down fat at higher pH (5-6) – Limited initiation of fat digestion – Plays an important role in lipid digestion in infants from breast milk Formation of stomach acid Proton pump Parietal Cell HCl secretion activates pepsin y doesn't the stomach digest itse Mucosal barrier! Tight junctions between mucosal epithelial cells prevents leakage of gastric juice onto underlying tissue Mucous secreted by epithelial/goblet cells has higher pH, providing localised neutralisation and physical barrier to acid Prostaglandins increase mucosal thickness and stimulate bicarbonate Three phases of gastric secretion Cephalic phase (increased secretion) Stimulated by sight, smell, taste, thought of food or  blood glucose Gastric phase (increased secretion) Stimulated by stomach distension due to presence of food Intestinal phase (decreased secretion) Stimulated by digested proteins/fat in the duodenum. Presence of fat or low pH in duodenum inhibits gastric secretion. Cephalic phase (increased secretion) Stimulated by sight, smell, taste, thought of food or  blood glucose Nerve impulses to the medulla oblongata cause parasympathetic neurones via the vagus nerves to increase HCl and pepsin in the stomach Gastrin secretion is also promoted in the antrum of the stomach and this stimulates further HCl and pepsin secretion Gastric phase (increased secretion) Stimulated by stomach distension due to presence of food Stomach distension triggers parasympathetic reflex leading to further HCl, pepsin and gastrin secretion Intestinal phase (decreased secretion) Stimulated by digested proteins/fat in the duodenum. Presence of fat or low pH in duodenum inhibits gastric secretion. Chyme entering the duodenum containing fat or enough HCl to lower the pH to below 2 will trigger inhibition of gastric secretion via three main routes: (i) Neuronal impulses are sent to the medulla to decrease parasympathetic stimulation of gastric glands. (ii) Local reflexes in the gut wall lead to decreased secretion. (iii) Release of three local hormones (secretin, gastric inhibitory peptide and cholecystokinin) travel via the bloodstream to the gastric glands and inhibit secretion.  Inhibition of HCl secretion Occurs once food has left the stomach Neuronal inhibition – partially digested protein and presence of fat in duodenum, combined with lower pH from gastric acid inhibits secretion by “enterogastric reflex” – Reflex mediated by medulla oblongata – leads to  parasympathetic stimulation Hormonal inhibition – Secretin and cholecystokinin released from duodenum – Other inhibitors include GIP (gastric inhibitory peptide), gastrone, glucagon, VIP (vasoactive intestinal peptide)