Saliva and gastric secretions Flashcards
Secretory cell locations
-lower part of crypts and submucosal glands along the GI
-salivary glands
-pancreas
-airways
-most mucous membranes
Secretory diarrhea
-heat labile enterotoxin and cholera toxins overactivate the secretory cells
-causes excessive ion secretion which pulls water into the GIT to cause diarrhea
Mechanism of secretory cells
-Driven by Na-K ATPase (charge separation and concentration differences)
1.activation of cell (by VIP or acetylcholine) increases either Ca and/or cAMP, which activates apical Cl channels AND/OR cystic fibrosis transmembrane regulator (CFTR)
2. K channel activation via Ca or CAMP further hyperpolarization of membrane increases force for driving Cl and bicarbonate out of the cell to mucosal side
3.Cl and bicarbonate move out of the cell into the lumen pulling Na paracellularly through incomplete tight junctions to maintain electroneutrality
4.Cl replenished by NKCC transporter; bicarbonate replenished by carbonic anhydrase and protons exiting the basolateral side of the cell through cation exchanger
5. water uses osmotic drive from movement of Na and Cl ions either paracellularly or through tight junctions
Saliva production
-produced by acinar cells (watery to mucous secretions) of 3 main glands (parotid, mandibular, and sublingual)
-innervated by parasympathetic pathways
pH of saliva
-when pH is low, duodenum secretes secretin which will increase alkalinity
Functions of saliva
-facilitate mastication, taste, swallowing
-dilution and cleaning of the oral cavity
-buffering
-protection of tooth enamel
-absorption of vit B12 through glycoprotein production that binds to it and protects it from the stomach acidity and releases in duodenum
-antibacterial
-cooling
Cat grooming
-cats grooming have hollow papillae filled with saliva
-put saliva on skin
-saliva evaporates on skin providing cooling capability
Salivary gland
-secretions from acinar cells are connected by a series of ducts that converge on intercalated duct. Then drain into striated ducts and then excretory ducts converging on the main duct
Composition of saliva
-main ions in saliva change as flow rate is increased
-has alpha-amylase (except carnivores and ruminants) and small amount of lipase, and lysozymes (antibacterial)
Tonicity of saliva
-Unstimulated (basal) secretion from submaxillary and parotid in non-ruminants=hypotonic
-as flow increases, becomes isotonic (increase in Na, Cl, HCO3)
**ruminant saliva is ALWAYS isotonic at any flow rate
Saliva and plasma
-saliva is always hypotonic to plasma at all flow rates because HCO3 concentration exceeds that of plasma (except at very low rates)
Composition of saliva-species differences
-Ruminant- higher Na, higher pH (alkaline) because higher HCO3 and PO4
-Dogs: low Na, Cl, HCO3 and PO4; electrolyte balance is very different than serum
Modification of plasma secretion
-saliva contents are originally amylase and electrolytes but the concentration of electrolytes changes as it passes through ducts that absorb Na and Cl, and secrete K and HCO3
Neural control of salivary secretion
-parasympathetic nervous system
4 secretory areas of stomach
1.esophageal stomach
2.cardia
3.Fundic
4. Pyloric stomach
Esophageal stomach (nonglandular)
-lined by stratified squamous epithelium
-no mucous, acid, or enzymes
-very small in dog, pig, cow
Cardia
-glandular
-invaginations in the submucosa form short glands lined by simple columnar cells that produce a thick mucus and buffer
-very large in pig; small in dog; absent in horse and cow
Fundic
-deep invaginations in the submucosa lined by cells that produce acid, proteolytic enzymes, hormones, and mucous
-present in all mammals
Pyloric stomach
-moderately deep glands lined by epithelial cells that produce mucus and buffers, BUT no acid or enzymes
-has enteroendocrine cells that for example, G cells produce gastrin in response to distention or increased pH
-sphincter at end
Parietal glands (oxyntic) cell types
-chief cells
-Parietal cells
-endocrine cells
-D cells
-mucus cells
-mucus neck cells
Endocrine cell function in parietal gland
-synthesize histamine via histidine decarboxylase
D cell function in parietal gland
-close to parietal cells
-secrete somatostatin
Mucus cell function in parietal gland
-found on top of gland, joining with gastric pit producing mucus
Mucus neck cell function in parietal cells
-precursors for all other cell types
Antral mucosa of parietal glands
-no chief or parietal cells
Parietal cells
-Secretes HCl (~150 mM)
-energy required to pump H+ out of parietal call into the lumen
>against concentration gradient 2.5 million fold
Chief cells
-produce pepsinogen
Parietal cell appearance during secretion vs resting
-Secretion: apical membrane is amplified by fusion of microvesicles and secretory canaliculi. Also includes increases H, K, and ATPase molecules
Gastric secretion from parietal cells
1.Cl actively transported from cytoplasm of parietal cell into the lumen of the canaliculus
2. Na actively transported out of canaliculus into the cytoplasm of the parietal cells
3. Water becomes dissociated into H+ and OH- in cytoplasm. H+ is actively secreted into canaliculus in exchange for K+
4. CO2 formed during metabolism or from the blood. Combines with OH- to form HCO3- (from carbonic anhydrase)
5. HCO3- diffuses out of the cell cytoplasm into the extracellular fluid in exchange for Cl coming into the cell
Control of HCl secretion in parietal cells
1.depends on H/K ATPase (depends on K out)
2.HCl concentration drives water into gastric contents to maintain osmolarity
3.during gastric acid secretion, amount of HCO3- in blood is equal to amount of HCl secreted
4.Alkaline tide= temporary increase in blood pH following meal
5.Omeprazole inhibits excretion of HCl
Omeprazole
-proton pump inhibitor that prevents excretion of HCl from parietal cells through H/K ATPase
-used in dogs and cats, horses
-prevents frequent heart burn/ulcers
-expensive
-short half life, but one dose decreases acid production for days
Neural control of gastric secretion
-reflexes contribute to stimulation and inhibition of secretion (Enteric NS)
>Distention of stomach wall is sensed by mechanoreceptors which activates reflexes that stimulate acid secretion from parietal cell
-Also, activation of primary afferents that travel through vagus nerve to the dorsal vagal complex which then triggers response that travels back to stomach and activates parietal cells
**Vagus only plays a small role (can be reduced by atropine)
Hormonal control of gastric secretion through parietal cells
-Parietal cells: produce gastric acid in response to histamine, acetylcholine, gastrin receptors
Hormonal control of gastric secretion through Enterchromaffrin-like cells (ECL)
-produce histamine which acts in H2R histamine receptors
-stimulated by gastrin (CCK2 receptors)
-inhibited by somatostatin
Neurohumoral control of ghrelin
-X cells of stomach corpus
-circulating levels have circadian rhythm
-increased by fasting
-inhibited by SCFA, LCFA, AA
Neurohumoral control of motilin
-same family as ghrelin
-released during interdigestive period
Hormonal control of gastric secretion through G cells
-secretes Gastrin in the antrum
-stimulated by vagus which passes information to stomach, and increased amino acids and Ca result in increased gastrin synthesis
Hormonal control of gastric secretion through D cells
-in the antrum and fundus producing somatostatin
-provides negative feedback on G cells and parietal cells reducing feeding or gastrin-stimulated gastric acid secretion
Neurohumoral control of GLP-1 and PYY
-glucagon -like peptide AND peptide tyrosine-tyrosine
-responsible for ileal brake that occurs in response to fatty acids in the lumen
Luminal regulators and gastrin
-stimulate gastrin secretion indirectly
-acid output increased by short peptides and amino acids (especially aromatic AA)
-decreased by dietary lipids
-increased secretion by alcohol, coffee, dietary Ca
Helicobacter pylori
-associated with gastric colonization
-chronic infection can lead to hypersecretion (duodenal ulcers) or hyposecretion (gastric cancers)
Non-parietal mucus secreting cells
-activated release by prostaglandins and ANS
-protect the wall of the stomach through mucus and bicarbonate (produced by these cells via carbonic anhydrase)
>mucus forms a layer adjacent to epithelium that traps the bicarbonate and allows it to neutralize the H+ ions
Chief Cells
-secrete pepsinogen (protein digestion) and rennin (proteolytic enzyme to digest milk)
>pepsinogen is cleaved to pepsin by HCl in gastric glands and lumen
Chief cell regulation
-located in pits of gastric glands
-contains zymogens (proenzymes) which are activated by acid created by parietal cells
-regulation of secretion/exocytosis through acetylcholine, gastrin, and low pH (similar to parietal cell)
Intrinsic factor secretion
-from parietal cells (humans and pigs) or exocrine pancreas (dogs and cats)
Three phases of secretion of gastric acid secretion
- Cephalic phase
- Gastric phase
- Intestinal phase
Cephalic phase
-30% stimulated by anticipation of eating (taste and smell)
-neuronal stimulation (acetylcholine and muscarinic receptors) and gastrin-releasing peptide
Gastric phase
-60% stimulated by stomach distention and digested proteins detected by G cells
Intestinal phase
-10% of acid is stimulated when chyme enters the small intestine, and is stimulated by small intestine distention (S cells)
-starts out stimulatory and then inhibits as gastrin levels increase (and cholecystokinin is released from I cells)
Anti-ulcer drugs
-receptor antagonists (histamine H2-receptor antagonists)
-receptor agonists (acting on prostaglandin E receptor or somatostatin receptor)
-pump inhibitors (H/K proton pump inhibitors; ex. omeprazole)
Octreotide
-somatostatin analog
-mimics natural somatostatin pharmacology
-injectable, long lasting
-inhibits the release of hormones including gastrin (impact on pancreas, insulin, glucagon, CCK)
