Salivary and gastric secretions Flashcards
What are the functions of saliva
Lubrication- aid swallowing, aids taste and facilitate movement
Protection- reduces adverse effects of bacteria
Digestion- beginning of breakdown of carbohydrates and fats via enzymes alpha amylase and lingual lipase
What is Sjögren’s syndrome?
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.
What is xerostomia?
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
List the 3 major salivary glands
The submandibular glands secrete approximately 70% of saliva (mixed).
The parotid glands secrete 25% (serous).
The sublingual glands secrete 5% (mucus).
What are the two types of secretions?
Serous secretions: the main type of protein secreted is ptyalin (hydrolizes starch)
Mucous secretions: main protein is mucin, acting as lubricant
Describe the structure of salivary glands
Salivary glands contain blind-ended acini connecting with ducts draining into major ducts
Describe how salvia is made to be hypotonic
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 2 stage model of salivary secretion
Fluid solution
NaCl reabsorption and K+ secretion
Describe the ionic movement in acinar cells
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 ionic movement in ductal cells
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.
State how the composition of saliva changes with flow rate
Principle component water
Electrolytes
Na+ and Cl- < plasma
HCO3- and K+ > plasma
Concentration of electrolytes varies with flow rate (high flow, higher Na+ and Cl-)
Saliva always HYPOTONIC (c.f. plasma)
low rate of secretion – maximum reabsorption of electrolytes
high rate – less time to reabsorb so higher osmolality
What is the only hormonal effect on salivary secretion?
The only hormonal effect on saliva secretion is from aldosterone, which increases ductal Na+ absorption and K+ secretion.
List things which decrease salivary secretion
Sleep, dehydration, fatigue, and fear all inhibit salivation.
List things which increase salivary secretion
Thought, smell, or taste of food by conditioned reflexes and by nausea
Give the nerve and neurotransmitter which stimulates salivary secretion
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.
Describe parasympathetic stimulation of salivary glands
promote watery secretion myoepithelial cells surrounding acini and ducts contract and eject preformed saliva
- also leads to increased blood flow
Describe the composition of gastric juice
Water, electrolytes to dissolve and dilute digested food HCl Pepsins Mucus Intrinsic factor(IF)
Why doe the stomach have HCl?
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
Why are pepsins important?
(endopeptidases, cleave peptide bonds-protein digestion)
- Secreted as inactive pepsinogens, away from stomach lining activated to form pepsins at low pH (<5)
Why is intrinsic factor important?
glycoprotein binds vitamin B12 necessary for vitamin B12 absorption in the ileum * the only indispensable substance of gastric juice
What is the importance of bicarbonate in the stomach?
Protect surface epithelial cells from acid/pepsin erosion
Describe the two major regions of secretion from 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
List the cells in the exocrine regions
Parietal (oxyntic) – acid secreting, IF
Histamine cells
List the cells in the endocrine regions
Very few parietal cells Endocrine cells –G cells that produce gastrin D cells (secrete somatostatin- regulator of gastrin release and gastric acid secretion)
How does the stomach prevent self digestion and mechanical damage?
Lumen
What do chief cells secrete?
Secrete pepsinogen
What is 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 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 acid secretion by parietal/oxyntic cells in gastric glands
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-)
H+ is pumped across the luminal membrane by H+/K+-ATPase. (H+ ions secreted by active transport by H+K+ ATPase with inward K+ movement, both against large concentration gradients )
Cl- leaves by diffusion (down gradient in Cl channel)
Cl-HCO3- exchanger in the basolateral membrane : provide Cl- ions for HCl and HCO3- exists in large quantities,
Describe how the H+-K+ pump works
The major component of acid secretion is the H+/K+-ATPase, or proton pump, which actively exchanges H+ for K+.
For vectorial H+ secretion to occur, conductance pathways for K+ and Cl- must exit for recycling of K+ ions and extrusion of Cl-, respectively
How is the proton pump in the oxyntic cell unique?
It has an enormous active secretory capacity, capable of secreting protons against large electrochemical gradients. As a consequence, luminal pH can approach the 1–2 range, representing a 5–6 log unit difference from intracellular pH values of approximately 7. No other part of the body can approach this level of acidification.
How are H+ and HCO3− produced?
Action of carbonic anhydrase
What are proton pump inhibitors?
Very potent inhibitors of the H+/K+-ATPase pump on the luminal surface of oxyntic (parietal) cells.
How does Omeprazole work?
Binds irreversibly to the H +/K+-ATPase pump, thereby inhibiting H + secretion until new H +/K+-ATPase protein is synthesized
Name the 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).
Give the names of two 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
How are gastrin, acetylcholine, histamine and prostaglandin secreted?
Gastrin 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.
How do NSAIDs affect gastric acid secretion?
NSAIDs inhibit prostaglandin formation and increase gastric acid secretion.
What is Autoimmune atrophic gastritis
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)
Name the 3 phases of regulation of gastric acid secretion
cephalic gastric(considered most important) intestinal.
Describe the cephalic phase
Sight
Smell
Taste
Thought
Describe the gastric phase
Protein content
Increased pH
Antral distention
Describe the intestinal phase
Intestinal gastrin
Amino acids
Describe gastrin and its effects
G cells of pylorus and duodenum
Endocrine effect
Release triggered by aa and peptides in stomach
Low pH inhibits release
Describe histamine and its effects
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.
Describe acetylcholine and its effects
Act on parietal and ECL cells to promote acid and histamine secretion
Acts on D cells to inhibit somatostatin release
Describe GRP from vagus and its effects
G cells to promote gastrin release
acts on D cells to inhibit release of somatostatin
Describe the vagal stimulation of the corpus of the stomach
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)
Describe the vagal stimulation of the antrum of the stomach
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
Food in the stomach stimulates gastric acid secretion by two major mechanisms. What are they?
Distention of the stomach by food
Digestion of protein
Digested protein fragments in the proximal small intestine stimulate gastric acid
secretion by three major mechanisms. What are they?
Gastrin
Absorbed amino acids
Entero-oxyntin
