Lecture 5 Flashcards
Describe the three functions of saliva
Lubrication -moistening the mouth lubricating the food to aid swallowing. - facilitates movements of the mouth and tongue for speech
- helps to dissolve chemicals within food for its presentation to the taste receptors.
Protection - reduces the adverse effects of oral bacteria (e.g., dental caries).
- the alkalinity of fresh saliva neutralizes acid produced by oral bacteria;
- the flow of saliva across the teeth also helps to wash away bacteria.
- contains additional substances that reduce bacterial growth (e.g. Lysozyme attacks bacterial cell walls; Lactoferrin chelates iron, which is needed by many bacteria for replication, immunoglobulin A (IgA)-binding protein is required for the immunologic activity of IgA.)
Digestion - begin the breakdown of carbohydrates and fats via the enzymes α-amylase and lingual lipase. (e.g. α-Amylase (ptyalin) hydrolyzes starches. It has a pH optimum of 7 but remains active in the stomach because a high proportion of a meal remains unmixed for many minutes in the stomach. α-Amylase can break down up to 75% of the starch in a meal before the enzyme is denatured by gastric acid. Lingual lipase hydrolyzes triglycerides and is secreted by the small salivary glands present on the surface of the tongue. It has an acidic pH optimum and remains active in the stomach.
Name and describe two dysfunctions of salivary secretion
Sjögren’s syndrome is an autoimmune disease that destroys the exocrine glands and most commonly affects tear and saliva production. The hallmark manifestations of Sjögren’s syndrome are dry eyes and dry mouth, known as sicca symptoms.
Patients with xerostomia (dry mouth) lack adequate saliva. They typically have dental caries and halitosis due to bacterial overgrowth and have difficulty speaking or swallowing solid food due to inadequate lubrication
State the three major salivary glands and its percentage of secretion in terms of mucus
The submandibular glands secrete approximately 70% of saliva (mixed).
The parotid glands secrete 25% (serous).
The sublingual glands secrete 5% (mucus).
Describe the composition of saliva
Primary saliva secreted by the acinus is an isotonic solution resembling interstitial fluid; the duct reabsorbs NaCl (but not water), causing saliva to become hypotonic.
Describe the role of acinar cells in the secretion and modification of saliva
Cl-via uptake by a basolaterally located Na+, K+, 2Cl– cotransporter (CO) and release through the calcium-activated apical chloride channel (Cl).
The process is sustained by Na+/K+/ATPase (ATP). Na+ enters the acinar lumen paracellularly through leaky tight junctions (TJL)
H2O follows via aquaporin 5 (W) or paracellularly.
Describe the role of ductal cells in the secretion and modification of saliva
removal of Na+ from saliva is via an apical sodium channel (Na) and a basolateral Na+/K+/ATPase.
Cl- removal from saliva occurs via different chloride channels in the apical and basolateral membranes of ductal cells.
**Removal of salt is not accompanied by water since ductal cell tight junctions (TJT) are not leaky and aquaporins are not expressed in apical membranes.
Ductal cells can secrete bicarbonate and potassium via unidentified apical bicarbonate chloride (BCE) and potassium proton (KHE) exchangers.
How does the flow rate affect the composition of saliva
Concentration of electrolytes varies with flow rate (high flow, higher Na+ and Cl-) i.e. at high flow rates, there is less time for the ducts to absorb NaCl, and final saliva more closely resembles the primary isotonic solution produced by the acini.
The salivary ducts reabsorb NaCl without water, causing saliva to become hypotonic. Saliva is more hypotonic at slow flow rates because ducts have more time to reabsorb NaCl.
Saliva always HYPOTONIC (c.f. plasma)
low rate of secretion – maximum reabsorption of electrolytes
high rate – less time to reabsorb so higher osmolality
Describe the central control of salivary secretions
Salivation is stimulated by the thought, smell, or taste of food by conditioned reflexes and by nausea. Sleep, dehydration, fatigue, and fear all inhibit salivation. Stimuli are integrated by the salivary nuclei in the pons, and salivation is determined by the resulting parasympathetic tone.
Efferent nerves reach the salivary glands via the glossopharyngeal and facial nerves. Acinar secretion is stimulated by the release of acetylcholine, which acts via the muscarinic receptors.
Parasympathetics stimulation
- promote watery secretion myoepithelial cells surrounding acini and ducts contract and eject preformed saliva
- also leads to increased blood flow
Sympathetic stimulation variable:
- does increase output of amylase but blood flow reduced (vasoconstriction) and fall in rate of secretion e.g. in dry mouth associated with fear
What is the only hormonal effect on saliva secretion
aldosterone, which increases ductal Na+ absorption and K+ secretion.
Describe the composition and function of gastric juice
Water, electrolytes to dissolve and dilute digested food
HCl, (pH 1-3) - Hydrolysis fat and starch;
- Antiseptic, kills contaminating microorganisms,
- Converts pepsinogens to pepsin (important digestive enzyme, which breaks down the proteins). Provides optimum pH for pepsin
Pepsins - (endopeptidases, cleave peptide bonds-protein digestion)
- Secreted as inactive pepsinogens, away from stomach lining activated to form pepsins at low pH (<5)
Mucus (water + glycoprotein Mucin) bicarbonate barrier
- protect surface epithelial cells from acid/pepsin erosion
Intrinsic factor(IF) – glycoprotein binds vitamin B12 necessary for vitamin B12 absorption in the ileum
Describe the origin of secretions in the stomach
an exocrine or glandular portion that consists of the fundus and body or acid-secreting area
- an endocrine or hormone secreting area portion that is located in the antrum or gastrin-secreting area
Describe the structure and function of gastric (oxyntic) gland
Mucous cell- secrete protective barrier
Endocrine cells – D cells (secrete somatostatin- regulator of gastrin release and gastric acid secretion)
Chief Cells- secrete pepsinogen(converted by gastric acid to active form pepsin)
In exocrine region:
Parietal (oxyntic) – acid secreting, IF
Histamine cells
In endocrine region:
Very few parietal cells
Endocrine cells –G cells that produce gastrin
How does the stomach protect against self digestion and mechanical damage?
Mucus layer of mucopolysaccharides and mucoproteins prevents from mechanical/physical damage
Mucus viscosity generates unstirred layer or mucosal barrier - a local protective environment
Mucin has basic side chains.
HCO3- secreted from surface epithelial cells.
Both neutralise H+ ions
Tight junctions between cells stop acid entry into underlying tissue
Net result - pH of unstirred layer is ~7.0 and therefore pepsinogen not activated - preventing enzymatic and chemical damage
Continual replacement by stem cells
State and describe a dysfunction of gastric mucosa
Gastritis (inflammation of the gastric mucosa) has many causes, but it is most commonly caused by an infection by the bacteria Helicobacter pylori. Other common causes include smoking, use of alcohol and nonsteroidal anti-inflammatory drugs (NSAIDs), and chronic stress.
What is the process restitution
if the surface epithelium of the stomach is acutely damaged, it rapidly regenerates in a process called restitution. This repair results from rapid division of stem cells, which are located in the neck of gastric glands.
Describe the role of oxyntic cells in acid secretion
Tubulovesicular membrane contains H+-K+ pump (H+/K+ ATPase) responsible for acid secretion
Upon stimulation tubulovesicular membrane fuses into canalicular membrane.
The fusion is accompanied by
Insertion of H+/K+ ATPase and K+ and Cl- ion channels into canalicular membrane
Dense mitochondria to support high metabolic activity of cell
H+ and HCO3− are generated inside the cell by the action of carbonic anhydrase. (H+ ions from dissociation of water; OH- ions converted to HCO3-)
Cl-HCO3- exchanger in the basolateral membrane : provide Cl- ions for HCl and HCO3- exists in large quantities, that the gastric venous blood becomes alkaline, known as postprandial alkaline tide
Name a proton pump inhibitor and its mechanism
omeprazole are very potent inhibitors of the H+/K+-ATPase pump on the luminal surface of oxyntic (parietal) cells. Omeprazole binds irreversibly to the H +/K+-ATPase pump, thereby inhibiting H + secretion until new H +/K+-ATPase protein is synthesized
Explain the control of acid secretion
Three major stimulators of acid secretion:
(1) gastrin (predominantly secreted by antral G cells),
(2) histamine (in humans probably arising from mast-like cells)
(3) acetylcholine (secreted from postsynaptic vagal fibers innervating the gastric mucosa).
Major paracrine inhibitors of gastric acid secretion.
(1) Somatostatin, secreted from antral and oxyntic gland D cells as well as pancreatic islet cells,
(2) prostaglandins from mucosal cells
in and acetylcholine stimulate secretion via an increase in intracellular Ca2+.
Histamine stimulates secretion via an increase in cyclic adenosine monophosphate (cAMP).
Prostaglandin E2, which is produced locally in the stomach, is a physiologic antagonist of histamine at the oxyntic cell and acts by inhibiting the production of cAMP. NSAIDs inhibit prostaglandin formation and increase gastric acid secretion.
Name a explain a gastric parietal cell dysfunction
Autoimmune atrophic gastritis is an antibody mediated destruction of gastric parietal cells, which causes hypochlorhydria (insufficient acid secretion), and a deficiency of IF. The loss of IF results in vitamin B12 mal-absorption and pernicious anemia)
What are three phases of gastric secretion
Cephalic, gastric and intestinal
Explain the direct and indirect actions of gastrin
G cells of pylorus and duodenum
Endocrine effect
Release triggered by aa and peptides in stomach
Low pH inhibits release
Explain the direct and indirect actions of histamine
ECL cells close to parietal cells
Paracrine effect by local diffusion
ECL cells themselves stimulated by gastrin and acetylcholine
Ach/gastrin thus has direct and indirect route of stimulation which amplify /potentiate the signal
Histamine also leads to local vasodilation of arterioles.
Explain the direct and indirect actions of Ach
act on parietal and ECL cells to promote acid and histamine secretion
Acts on D cells to inhibit somatostatin release
Describe the regulation of gastric acid secretion
Vagal stimulation –
Corpus:via Ach, increases acid secretion via directly parietal cells, and indirectly via ECL and D cells (ECL increases acid secretion via histamine release, D cells inhibit somatostatin)
Antrum: via GRP, stimulates both G and D cells (increase gastrin, inhibit somatostatin)
Gastrin from antrum promotes acid secretion by two endocrine mechanisms:
Directly via parietal cells
Indirectly via ECL cells
CHANGE:
High luminal H+ directly stimulates D cells to release somatostatin , which inhibits gastrin release from G cells (NEGATIVE feedback)
High luminal products of protein digestion (peptides, aa) directly stimulate G cells to release gastrin, which stimulates gastric acid secretion (POSITIVE feedback)
