Six

Question 1

How much salivary gland secretions are secreted each day? What is their tonicity like at low flow rates? High flow rates? What is their function? What percentage does each major salivary gland produce in the unstimulated state? In the stimulated state?

Answer 1

 Roughly 1.5 L fluid per day

 Secretions are hypotonic at low flow rates but isotonic at higher flow rates

 Protect mucosa of the upper GI tract & begin the process of digestion

 In unstimulated state, submandibular glands secrete 70% and parotid glands 25% of saliva

 With stimulation, parotid glands secrete 70% and submandibular secrete 25%

 Sublingual glands contribute only 5% each to the total daily salivary flow

Question 2

What are the components of salivary gland secretions?

Answer 2

 Enzymes: salivary amylase and lingual lipase

 Mucins: glycoproteins that lubricate food and protect the mucosa

 IgA: secretory immunoglobulin to defend against bacteria

 Lysozymes: breaks down bacterial cell walls to protect against pathogens

Question 3

Name 6 functions of salivary gland secretions.

Answer 3

 Maintain mouth moisture

 Protect oral and esophageal mucosa

 Destroy pathogens

 Protect dental enamel

 Begin the process of digestion

 Bathe the esophagus in an alkaline-rich fluid to combat reflux of gastric acid

Question 4

Describe the effects of both parasymp and symp stimulation on the synthesis of saliva.

Answer 4

Parasympathetic stimulation causes:

 Increase in the synthesis of watery saliva

 Secretion of kallikrein to increase blood flow to the salivary glands (increase salivation)

Sympathetic stimulation causes:

• Synthesis of viscous saliva rich in protein and bicarbonate
• Contraction of myoepithelial cells
• Constriction of blood vessels to decrease blood flow to the salivary glands (decrease salivation, the saliva that is produced is more viscous)

Question 5

What are the 3 functions of the stomach?

Answer 5

Secretory: intra-luminal secretions (exocrine)

Endocrine: hormones that regulate gastric acid secretion

Motor: storing, mixing, and emptying

Question 6

What cells are specific to the proximal stomach? What is their function?

Answer 6

Parietal cells

 Located in the fundus and body only (not found in antrum)

 Secrete acid (HCl) and intrinsic factor (IF)

 Intracellular canaliculi for acid secretion

Question 7

What cells are specific to the distal stomach? What is their function?

Answer 7

Enteroendocrine cells (G cells)

 Secrete hormones with endocrine & paracrine functions

 Found scattered in the neck/base of gastric glands

 Usually have broad base and basal concentration of secretory vesicles (vs. apical location of serous cells)

Question 8

Describe the location and function of gastric mucous cells and chief cells.

Answer 8

Gastric mucous cells

• Line the surface and gastric pits
• Apical mucous droplets
• Secrete specialized mucous to protect epithelial cells– resists acid and enzymatic digestion

Chief cells

 Secrete pepsinogen
 Pepsinogen: activated to pepsin & cleaves internal peptide bonds

Question 9

Describe what occurs in the activation of parietal cells. Describe the process of acid secretion in parietal cells.

Answer 9

 In the resting state the H-K pumps are stored in the tubulovesicles
 With stimulation the vesicles fuse and form secretory channels

 Fueled by hydrolysis of ATP, H+ is secreted in exchange for K+

 K+ & Cl- exit through luminal channels

 pH rises in the parietal cell stimulating basal uptake of CO2 & H2O

 Carbonic anhydrase converts CO2 & HO2 to H+ & HCO3-

 H+ is secreted & HCO3- is exchanged for Cl-

Question 10

Describe the direct and indirect stimuli for secretion of acid.

Answer 10

Direct: Acetylcholine (ACh), gastrin, & histamine bind directly to membrane receptors to stimulate acid secretion

Indirect: Acetylcholine (ACh) & gastrin stimulate histamine release from enterochromaffin-like cells (ECL)

Question 11

Describe the signal transduction elicited by the direct stimuli for acid secretion in the parietal cell.

Answer 11

• ACh binds to receptor coupled to a G-protein
• G-protein activation leads to conversion of PIP2 to IP3 and DAG
• DAG activates protein kinase C (PKC)
• IP3 causes intracellular Ca2+ increase
• Gastrin binds to its receptor and activates the H-K pump in a similar fashion to

that of ACh (through IP3 & DAG stimulation of protein kinase C and increased

calcium)

• Histamine receptor is H2 receptor coupled to G protein
• G-protein activates adenylyl cyclase generating cAMP
• cAMP activates protein kinase A (PKA)
• PKA phosphorylates a number of parietal cell proteins (including the H-K pump)

Question 12

Describe the 4 phases of acid secretion. When do they occur? What mediates them? How much of total acid secretion do they account for?

Answer 12

Basal (interdigestive)
 pH in the interdigestive phase is high (3-7) and acid secretion is basal.
 pH with a meal and secretagogue stimulus decreases; pH decrease varies with the buffering capacity of the food, the rate of gastric emptying, and other factors

Cephalic phase
 Initiated by smell, sight, taste, and thought of food
 Accounts for nearly 30% of gastric acid secretion
 Mediated by vagus nerve (directly stimulates parietal cells; stimulates G cells; stimulates ECL cells; & inhibits D cells)

Gastric phase
 Vagal pathway
 Local ENS pathway
 Peptides & AAs stimulate G cells directly
 Accounts for 50-60% of total acid secretion

Intestinal phase
 Peptides stimulate duodenal G cells
 Absorbed AAs are hypothesized to stimulate parietal cells
 Accounts for 5-10% of total acid secretion

Question 13

Describe the mucous cell barrier. Describe specifically the functions and mechanisms of mucous-cell secretions. What are some regulating factors? Describe the same things for bicarb secreting surface cells.

Answer 13

 Relatively impermeable to acid
 Bicarbonate-rich microclimate (maintains high local pH)
 Composed of a mucous gel layer with varying thickness

Mucous-cell secretion
 Mucin (glycoprotein): serves as protective layer over gastric mucosa
 Mucin combines with water, electrolytes, & phospholipids to form a mucous gel layer
 Protects against noxious luminal contents (acid, bile, endopeptidases, etc.)
 Protects against abrasive effects of food
 Regulation is less well-understood than that of acid, but is thought to be mediated by vagal stimuli and local irritants
 PGE2 helps to maintain the mucous cell layer and therefore NSAIDs (which block PG formation can lead to gastric ulcerations and GI bleeding)

Gastric surface cells secrete HCO3
 Mucous-gel layer traps bicarb creating an “unstirred layer” where the pH is 7
 Stimuli for HCO3 secretion appear to be vagal and intraluminal acid(vs. intraluminal pH of 1-3)

Question 14

Describe the gastric endocrine function. What the most common regulatory peptides? What is their function? What cells secrete them? How are they regulated?

Answer 14

 Enteroendocrine cells secrete regulatory peptides into the blood stream to help control acid secretion

 The 2 best studied regulatory peptides secreted by enteroendocrine cells are: gastrin and somatostatin

 Gastrin: Secreted by G cells in the antrum
Stimulates acid secretion, and histamine release
Acts as a trophic factor for epithelial proliferation
ACh increases secretion
AA and peptide increase secretion
Somatostatin decreases secretion

 Somatostatin: Secreted by D cells
Primary function is to inhibit gastrin release and acid secretion
Luminal acid increases secretion
Gastrin increases secretion
ACh decreases secretion

Question 15

Describe gastric emptying. What size particles are retained in the stomach? What substances leave the stomach slowly?

Answer 15

Gastric emptying

 Processes of propulsion, grinding, and retropulsion repeat multiple times

 Particles larger than 2 mm are retained in the stomach initially (and then moved on by the MMCs)

 Acidic and caloric fluids leave the stomach slowly, but fats exit even more slowly

Question 16

Describe the process of B12 absorption.

Answer 16

B12 absorption

 Parietal cells secrete intrinsic factor

 Cyanocobalamin (B12) binds to R protein in stomach

 In the duodenum pancreatic proteases separate R protein and vitamin B12

 IF binds free B12 escorting it to the terminal ileum for absorption