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Flashcards in Salivary/Gastric Secretion Deck (31)
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1
Q
A
2
Q

Parotid Glands

A
  • Parotid glands
  • 60% of saliva volume
  • serous acini
3
Q

Submaxillary Glands

A
  • mixed serous (protein) - mucus fluid
  • serpus and mucous acini
4
Q

Sublingual Glands

A
  • mixed serous (protein) - mucus fluid
  • mostly mucous acini, with serous cells present as cap like structures
5
Q

Glandular Structure - Acinus

A
  • bulbous portion
  • permeable to water, filters water and ionic components from blood
  • highly vascularized, flow of blood can increase dramatically upon activation
6
Q

Glandular Sturucture - Ducts

A
  • impermeable to water
  • secrete bicarbonate ions
7
Q

Composition of Saliva

A
  • water
  • ionic factors
  • Na+, K+, Cl-, HCO3 -
  • Ca2+, I-, H2PO4, F-, and SCN-

•organic components

  • alpha - amylase
  • lysozyme
  • lingual lipase
  • Proline Rich Proteins (PRP)
  • mucins
  • gylcoproteins
  • immunoglobulin A
  • lactoferrin
  • albumin
8
Q

Function of Saliva

A
  • protective
  • digestive
9
Q

Function of Saliva - Digestive

A
  • alpha-amylase initiates starch digestion, and lipase fat digestion. The pH optima of amylase is 7.0 while that of lingual lipase is 4.0.
  • Since the proximal stomach stores food with limited mixing, chyme in the proximal stomach can remain non-acidified for a variable period.
  • Although lipase and amylase can initiate nutrient digestion, normally their activity is not significant relative to that of the pancreatic and intestinal (brush border) enzymes.
  • However, liberation of micronutrients by the salivary enzymes is likely important in signaling meal status to regulate gastric secretion and motility (gastric emptying).
10
Q

Function of Saliva - Protective

A

•I - , SCN- , immunoglobulin A, lysozyme and lactoferrin all act to kill bacteria or retard bacterial growth in the mouth.

Proline Rich Polypeptides also have anti-microbial properties, and also can neutralize dietary tannins.

Secreted HCO3 - buffers pH and Mucus coats the exterior of chewed food (Chyme) and the oral cavity to prevent abrasion and aides in swallowing.

•Saliva also acts as a solvent and aids in taste sensation.

11
Q

Mechanism of Secretion

A
  • The acinus is where active secretion of fluid, HCO3 - and organic components take place.
  • The acinus produces saliva by filtering plasma and secreting HCO3 - and protein (including mucus).
  • Ductal cells modify the filtrate as it passes to the oral cavity, and secrete HCO3 - continuously adding it to saliva without gland activation.
  • Filtration through acinar cells is passive. Fluid movement is accomplished by increasing blood flow and thereby elevating hydrostatic pressure around the acinus.
  • The elevated interstitial pressure drives filtration through the acinar cells, thereby elevating net fluid flux between the acinar cells and into the lumen.
  • The large fluid flux ‘drags’ ions and some plasma protein into the lumen.
  • Deletion of the water channel AQP5 present in the apical membrane of acinar epithelial cells decreases agonist-stimulated saliva secretion indicating significant transcellular, in addition to paracellular, water movement.
12
Q

Regulation of Secretion

A
  • Acinar Cells
  • Sympathetic
  • beta-adrenergic receptors –> elevated protein secretion
  • alpha-adrenergic receptors –> vasoconstriction
  • Since increases in blood flow are required to increase salivary flow rate, sympathetic stimulation by itself leads to secretion of a very viscous saliva. This is observed in coincidence with the “fight or flight” and other stressful sympathetic mechanisms
  • Parasympathetic

-activate proetin secretion (Ach) and fluid flux by relaxation of vascular smooth muscle (Substance P)

13
Q

Other Peptides that Alter Saliva Composition

A

•Kallikrein

-The enzyme Kallikrein is produced in mesenchymal cells surrounding acini and ducts. Kallikrein is released into the extracellular space during gland activation where it catalyzes the production of bradykinin, which then acts to relax vascular smooth muscle.

•Aldosterone and ADH

-Aldosterone and anti-diuretic hormone influence the composition of saliva under low flow conditions only; (increase K+ content and reduce Na+ ) presumably through their ability to enhance expression of Na-K ATPase protein and/or activity within the ductal cells

•No other hormone including any of the primary GI hormones, have a significant influence on salivary secretion rate, or composition.

14
Q

Receptor Coupled Second Messengers - Acinar Cell

A
  1. cAMP is elevated by Sympathetic Stimulation activating exocytosis of storage granules (protein secretion; e.g. mucopolysaccharides, digestive enzymes).
  2. Ca2+: Parasympathetic stimulation (Ach) and substance P elevate Ca2+ in acinar cells, which activates both exocytosis and HCO3 - secretion.
15
Q

Receptor COupled Second Messengers - Vascular Smooth Muscle

A
  • Substance P elevates cAMP in vascular cells that leads to vasodilation of feed arterioles to the acini. Coupled with increased metabolism by acinar and ductal cells, causing release of vasoactive metabolites, blood flow to Acini is dramatically increased during PS activation, and thereby filtration through the acini increases the flow of saliva.
  • Vasoactive intestinal peptide (VIP) also may be a neurotransmitter used for initiation vasodilation.
  • Bradykinin released by ductal cells may also play a role.
  • The bottom line: parasympathetic and metabolic activity elevate blood flow to acini, which leads to elevated acinar filtration and enhanced flow of saliva.
16
Q

Gastric Secretions - 3 Regions in the Stomach

A
  • Cardiac glands are mucus-secreting glands found primarily in proximal stomach.
  • Gastric (or Oxyntic) glands are located in the central 3/4 of the stomach and penetrate into the submucosa secreting primarily hydrochloric acid (HCl), and Pepsinogen. There are also mucus-secreting cells at the regions of the gland nearest the stomach lining.
  • The third type of gland is smaller in size and located in the terminal Antral region. These Pyloric glands secrete mucus into stomach and gastrin into the blood.
17
Q

Cellular Properties and Functions of Oxyntic Glands

A
  • Oxyntic (HCl secreting) glands protrude into the stomach lining.
  • In the non-activated state, the density of the glands make the surface of the stomach look like it is covered with small holes.
  • Lining the opening of these ‘gastric pits’ at the epithelial surface are mucus and HCO3 - secreting cells.
  • The cells within the oxyntic gland and stomach epithelia are connected by tight junctions making them impermeant. This feature together with secretion of mucus and HCO3 - provide the stomach surface with a protective barrier.
  • Anything that alters the coupling between cells leads to defects in the barrier and subsequent ulceration in the presence of HCl. Similar cells are found lining cardiac and pyloric glands.
  • Further down the gastric pits are pluripotential cells (mucus neck cells) which can migrate to the surface, or differentiate into secretory cells that remain within the gland.
  • There are two types of secretory cells within the gland.
  • Oxyntic (parietal) cells
  • Peptic (chief) cells
18
Q

Mucus Neck Cells

A
  • pluripotent cells down in the gastric pits of oxyntic glands
  • can migrate to the surface or differentiate into secretory cells within the gland
19
Q

Oxyntic (Parietal) Cells

A
  • secrete HCl and the vitamin B12 binding protein intrinsic factor.
  • Intrinsic factor is a glycoprotein, which is essential for normal absorption of Vitamin B12 in the intestine.
20
Q

Peptic (Chief) Cells

A
  • secrete pepsinogen and gastroferrin.
  • Pepsin is a proteolytic enzyme secreted in an inactive form (pepsinogen) and converted by stomach acidity via autocatalysis to pepsin. Pepsin expresses maximal activity at pH < 5.0.
  • Gastroferrin - binds iron, preventing formation of insoluble iron salts and phosphates.
21
Q

Basal Secretion of HCl

A
  • Basal (non-activated) secretion of HCl is relatively low, but significant.
  • Since the volume of the stomach is low during rest (no food buffers), resting stomach pH can be as low as 2.0. With maximal stimulation, luminal pH can reach 1.0 or lower, though during digestion of a meal, food buffers the pH to higher levels. However, the gradient between cell (pH 7.0) and lumen can be as high as 106 .
  • The hydrochloric acid secreted by oxyntic cells produces an acid environment in the stomach lumen, which helps to kill bacteria and to activate pepsin.
  • However, the primary digestive role for HCl is to solubilize connective tissue and dissociate ionic bonds between molecules
22
Q

Mechanism of HCl Secretion in Oxyntic Cell

A
  • Upon activation of the oxyntic cell, mitochondrial metabolism is elevated producing CO2. CO2 produced by cellular metabolism or entering the cell from the blood reacts with H2O under the influence of carbonic anhydrase to form carbonic acid, which then dissociates into H+ and HCO3 - .
  • H+ are actively secreted into the lumen in exchange for K+ by the H+ - K + ATPase while the HCO3 - diffuses out of the cell into the blood in exchange for Cl- via a HCO3 - / Cl- antiporter.
  • The release of HCO3 - to the blood raises venous pH. The rise in venous (blood) pH that accompanies luminal H+ secretion is referred to as the “alkaline tide”.
  • Electroneutrality must be maintained as the cell secretes H+ to the lumen and HCO3 - to the blood; in fact it is the electro-chemical gradient developed by the Na+ /K+ , and H+ -ATPases which drives the other passive processes.
  • During activation, several transporters in the basolateral membrane assure that cell Cl levels are elevated. These mechanisms include the basolateral Cl- / HCO3 - antiporter and Na+ /Cl- cotransporter.
  • Cl - is then secreted into the lumen through co-transport with K+ . Since the H+ -ATPase exchanges H+ to the lumen for K + back into the cell, and equimolar Cl is secreted with K+ to the lumen, there is no net K+ flux (K+ cycles between cell and lumen).
  • Therefore, during active secretion there is net secretion HCl to the lumen, and Na+ and HCO3 to the blood.
23
Q

Regulation of HCl Secretion

A

•Acid secretion from oxyntic cells is increased by Acetylcholine (parasympathetic), gastrin (endocrine) and histamine (paracrine; from Enterochromaffin-like cells, ECL’s).

24
Q

HCl Acid Secretion - Gastrin

A
  • Gastrin release from G cells is stimulated via GRP release from submucosal plexus neurons and presence of peptides in the stomach lumen and inhibited by somatostatin release (paracrine) in response to stomach pH lower than 3.
  • Gastrin release into the blood from G cells (in pyloric glands) is stimulated by peptides in the lumen and by the release of gastrin releasing peptide (GRP) from nerves whose cell bodies reside in the sub-mucosal plexus. Gastrin binds to receptors on the oxyntic cells causing an elevation of cell Ca2+ by releasing Ca2+ from intracellular stores.
25
Q

HCl Acid Secretion - Histamine

A
  • So-called Enterochromaffin cells (ECL) also are located within gastric pits, and secrete Histamine continuously.
  • This histamine diffuses through the extracellular space and binds Histamine-2 (H2) receptors on oxyntic cells elevating cellular cAMP which activates of Protein Kinase A which weakly activates HCl secretion, but sets the basal rate of HCl secretion.
  • Since gastrin and Ach elevate Ca2+ in oxyntic cells, histamine is the secretagogue that works via an independent pathway.
  • Prostaglandins and likely PGI2 (prostacyclin) specifically, block histamine induced cAMP formation, and therefore may play a significant role in regulating both basal, and activity stimulated (potentiated) acid secretion.
26
Q

Major Mechanisms for Stimulating Gastric Acid Secretion

A

•3 Phases

  • Cephalic
  • Gastric
  • Intestinal
27
Q

Cephalic Phase

A

The cephalic phase is initiated by central anticipatory signals like smell of food or time of day.

28
Q

Gastric Phase

A

The Gastric phase begins as food reaches the stomach eliciting distension and elevating the luminal pH by buffering its contents.

29
Q

Inhibition of Gastric Secretion

A
  • The strongest activator of Acid Secretion is gastrin.
  • G cells have receptors on their luminal surface, which can sample the contents of the gastric lumen (amino acids).
  • In addition to this primary sensory information, G cell secretion also is modulated by somatostatin released from cells located within the pyloric glands (paracellular regulation), as well as, neural input from the submucosal plexus.
30
Q

Somatostatin

A
  • Somatostatin secreting cells are located in proximity to G cells. Somatostatin inhibits gastrin secretion by the G cell.
  • In turn, Somatostatin secretion is regulated by both neural input and primarily by the acidity within the canal. Low pH (< 3) in the pyloric region of the stomach stimulates somatostatin secretion leading to inhibition of gastrin secretion.
  • At pH < 2, somatostatin secretion is maximal
31
Q

Neural Regulation

A
  • The network of nerves located in the wall of the alimentary canal integrate local inputs and central output to regulate gastrin secretion.
  • As the stomach empties, stretch is reduced thereby decreasing enteric stimulation of gastrin and oxyntic cell secretion.
  • Similarly, feedback from duodenal sensors (pH) also leads to decreased enteric stimuli for gastrin and oxyntic cell secretions.