46: Salivary/Gastric Function Flashcards
List the cells types of origin and functions of each of the major digestive enzymes, hormones, and paracrine factors in the salivary glands and stomach.
Paracrine control in the GI system is mainly exerted by 3 factors:
1. Serotonin: produced by enterochromaffic cells (EC) in intestine in response to distension; indirectly excites the ENS to increase motility and secretions.
- Somatostatin: produced by D cells and is a potent inhibitor of several processes (pancreatic & gastric secretions; motility); can act in an endocrine as well as paracrine manner.
- Histamine: released by EC-like cells in stomach; potently stimulates HCl secretion (H2 receptors)
Neuroendocrines: ACh, Norepi, VIP, gastrin-releasing peptide (GRP), and substance P.
Location and relative amounts of major GI hormones:
Gastrin: secreted by antral mucosa cells (G-cells in stomach) in response to food, distension, vagus; acts to increase acid secretion by parietal cells; stimulates growth of gastric mucosa.
Cholecystokinin/CCK: secreted by mucosa of intestine (I-cells in duodenum and jejunum) in response to fats and proteins/peptides/amino acids; acts to increase gall bladder contraction, and increase pancreatic enzyme & bicarbonate secretion (e.g., trypsin, chymotrypsin, lipases, amylases). Inhibits gastric emptying.
Secretin: secreted by mucosa of small intestine (S-cells in duodenum) in response to the arrival of acidic chyme from the stomach; acts to increase bicarbonate (HCO3-) and fluid secretion by pancreas; decreases gastric acid secretion in stomach by decreasing gastrin; inhibits gastric emptying.
Motilin; secreted by mucosa of small intestine (M cells in duodenum and jejunum) during the fasting period; promotes contractions in distal stomach and intestines to ‘clear’ the tract of indigestible materials.
Glucose-dependent insulinomic peptide (GIP): secreted by mucosa of small intestine (K-cells in duodenum and jejunum) in response to fat and carbohydrates; acts on pancreas to stimulate insulin secretion, inhibits HCl secretion by parietal cells.
For carbohydrates and lipids, digestion is initiated in the mouth by salivary and lingual enzymes: amylase for carbohydrates and also some lipases for lipids.
For proteins, digestion is initiated in the stomach by gastric proteases called pepsins. There is additional lipid digestion in the stomach due to swallowed lingual lipase, and some gastric lipase is also secreted. Gastric enzymes do not support any carbohydrate digestion.
In the small intestine, pancreatic enzymes such as lipase, chymotrypsin, and amylase are critical for the digestion of lipids, protein, and carbohydrates, respectively. Enzymes on the luminal surface of the small intestine (e.g., brush border disaccharidases and dipeptidases) complete the digestion of carbohydrates and proteins (a process referred to as membrane digestion).
Explain the major features of salivary secretions, how it is modified by flow rate, and its regulation by the ANS.
Acinar cells of the parotid glands secrete a serious watery substance rich in a-amylase. Acinar cells of the of the sub lingual and submandibular glands secrete a seuro-mucus product rich in glycoproteins
Lubrication functions of saliva depend on mucus secretion and include:
Moistening the mouth to prevent dehydration of the oral mucosa
Lubricating the food to aid in swallowing. It depends on the presence of mucous in saliva.
Protective functions reduce the adverse effects of oral bacteria:
Saliva flow across the teeth helps to clear bacteria
Saliva contains substances that reduce bacterial growth (lysozyme, IgA-binding protein)
Digestive functions are relatively minor: Salivary amylase (ptyalin) is identical to pancreatic amylase
Ptyalin converts starch to sugar at pH optimum of 7; denatured below pH 4 in stomach
Lingual lipase hydrolyzes triglycerides and is secreted by small salivary glands on the tongue surface.
At low (basal) flow rates, Na+ and Cl- are absorbed and K+ is secreted by the duct cells of most salivary glands. These transport processes generate a K+-rich, hypotonic salivary secretion at rest. Note that the ‘tightness’ of the ductal epithelium inhibits paracellular water movement contributing to the hypotonic product.
At high flow rates, saliva is more like plasma.
High [HCO3-] makes fresh saliva more alkaline than plasma and functions to neutralize gastric acid that refluxes into the esophagus as well as acid produced by oral bacteria.
Aldosterone is the only humoral agent to affect salivation, stimulating Na+ reabsorption and K+ secretion by the salivary glands.
Salivary Acinar Cells. During salivary secretion, blood flow to the acini is increased by PNS stimulation. Salivary acinar cells make alpha-amylase (ptyalin), creating the primary secretion. Lingual lipase (secreted from the Von Ebner’s glands of the tongue) is added to the saliva in the mouth.
Salivary secretion is unaffected by gastrointestinal hormones and is controlled by autonomic innervation. PMS stimulation promotes increased salivary secretion. SMS stimulation decreases salivary secretion. Activation of salivary glands causes release of kallikrein resulting in the potent vasodilator bradykinin vasodilation increases hydrostatic pressure and capillary filtration thereby supplying the fluid for secretion. The salivation reflects can be conditioned.
Describe the functional anatomy of the stomach, including the locations, functions, and regulation of secretory glands.
The oxyntic (acid-forming) glands are located on the inside surfaces of the body and fundus of the stomach in the proximal 80% of the stomach. There are 3 primary cell types:
(1) mucous neck cells secrete mainly mucus which protect the stomach. Erosive gastritis can result from chronic use of NSAIDS as they inhibit prostaglandin (PG) synthesis in the stomach. PG maintains the physicochemical barrier by stimulating the secretion of mucus and HCO3-.
(2) peptic (or chief) cells secrete pepsinogen and gastric lipase.
(3) parietal (or oxyntic) cells secrete hydrochloric acid and intrinsic factor (essential for absorption of vitamin B12 in the ileum).
The pyloric glands secrete mucus for protection of the pyloric mucosa from the stomach acid. They also secrete the hormone gastrin (G-cells) and the endocrine & paracrine factor somatostatin (D cells).
There are some mucus-secreting cardiac glands in a limited area near the esophageal orifice.
Explain the mechanisms, stimulators and inhibitors of HCl secretion by the stomach, and related disorders.
The main driving force for hydrochloric acid secretion by the parietal cells is a hydrogen-potassium pump (H+-K+ ATPase) in the luminal membrane. At the apical membrane, H+ is secreted into the lumen in exchange for K+, via an active exchange process that is catalyzed by H+-K+ ATPase. Cl- follows by diffusing through Cl- channels. At the basolateral membrane, HCO3- is absorbed from the cell into the blood via a Cl- -HCO3- exchanger. The apical H+/K+ ATPase (proton pump) causes the active secretion of H+ into the lumen of the gastric pits. This combines with secreted Cl- to form concentrated HCl. The H+/K+ ATPase is the target for proton pump inhibitors to decrease gastric acid release in patients with GERD or ulcers.
When parietal cells are destroyed (e.g., chronic gastritis) the individual develops achlorhydria (lack of stomach acid secretion), and often pernicious anemia due to failure of maturation of the RBCs in the absence of vitamin B12 stimulation of the bone marrow.
Prolonged vomiting typically causes dehydration, alkalosis, & hypokalemia.
Stimulators of acid secretion:
Histamine, from ECL cells, diffuses through the mucosa to act on adjacent parietal cells.
The vagus, via direct and indirect effects.
Gastrin, carried through the blood, acts directly on parietal cells + stimulates histamine release.
Insulin, carried through the blood, acts directly on parietal cells and promotes HCl secretion.
Caffeine (a phosphodiesterase inhibitor) increases cAMP in the parietal cells, increasing proton pump activity.
Stress, although not well understood, appears to increase acid secretion in certain people and may be a cofactor in ulcer formation (with Helicobacter pylori).
Inhibitors of acid secretion:
Somatostatin, released from endocrine cells in the gastric pit, acts in a paracrine manner on the parietal cells, as well as on G-cells to inhibit gastrin.
Glucose insulinotropic peptide or gastric inhibitory peptide (GIP), released from the duodenum and jejunum, acts directly on the parietal cells.
Secretin, released from the duodenum and jejunum, acts at the G-cells to suppress gastrin.
H2 receptor antagonists (e.g. cimetidine) are effective as OTC antacid agents because of the strong cooperativity of ACh, gastrin, and histamine in stimulating HCl production.
Proton pump inhibitors (e.g., omeprazole/prilosec) are even more effective than histamine receptor antagonists because they block the final common pathway.
Describe the neurohumoral regulation of gastric secretion during the cephalic, gastric and intestinal phases, including the pertinent reflexes.
Gastric HCl secretion is divided into 3 phases: cephalic, gastric, and intestinal (minor).
The stimuli for HCl secretion in the cephalic phase are smelling, tasting, and conditioned reflexes. HCl is secreted by direct stimulation of the vagus nerve (ACh receptor on parietal cell), and also indirect stimulation of the parietal cell by gastrin. In this pathway the vagus releases Gastrin Releasing Peptide (GRP) onto G-cells, releasing gastrin. Gastrin enters the circulation (hormone) and stimulates the parietal cells to produce HCl.
The stimuli for HCl release in the gastric phase are distension of the stomach and the presence of breakdown products of proteins (amino acids, small peptides). Same as above (direct and indirect vagus effects) plus distention of the antrum activates local reflexes to enhance gastrin release plus amino acids and small peptides stimulate G-cells to release gastrin. The intestinal phase accounts for only 10% of acid secretion and is mediated by products of protein digestion
HCl secretion is inhibited when it is no longer needed for activation of pepsinogen (when chyme has moved to small intestine and the pH of stomach contents decreases – due to removal from the stomach of food - a buffer). Pepsins (from pepsinogen) are proteolytic enzymes that attack the internal peptide bond in proteins.
The major inhibitory mechanism to reduce HCl secretion by parietal cells is through somatostatin via direct and indirect effects.
In the corpus of the stomach, the vagus directly stimulates parietal cells via ACh, and also stimulates ECL cells (increased histamine release) and D cells (decreased somatostatin release).
In the antrum of the stomach, the vagus stimulates both G cells and D cells:
- The vagus stimulates the G cells via GRP (gastrin-releasing peptide), promoting gastrin release. This gastrin promotes gastric-acid secretion by two endocrine mechanisms: directly via the parietal cell and indirectly via the ECL cell, which releases histamine.
- The vagal stimulation of D cells via ACh inhibits the release of somatostatin, which would otherwise inhibit - by paracrine mechanisms - the release of gastrin (stimulate HCl) from G cells and - by an endocrine mechanism-acid secretion by parietal cells.
Luminal H+ directly stimulates the D cells to release somatostatin, which inhibits gastrin release from the G cells, thereby reducing gastric-acid secretion (negative feedback).
In addition, products of protein digestion (i.e., peptides and amino acids) directly stimulate the G cells to release gastrin, which stimulates gastric-acid secretion (positive feedback).
