GI secretion: salivary glands, stomach, exocrine pancreas

Question 1

Saliva secretion 1

Answer 1

• As saliva secretion rate increases, so does the concentration of Na, HCO3-, and Cl (K concentration remains constant)
• In the acinus of the salivary gland there are NaCl cotransporters that transport NaCl into the lumen, and AQPs which allow water to follow

Question 2

Saliva secretion 2

Answer 2

• In the ducts there are K and HCO3- transporters that secrete these two substances into the lumen
• There are also NaCl transporters that allow for NaCl reabsorption along the ducts
• When saliva needs to be made at a faster rate there is less NaCl reabsorption and more HCO3- secretion along the ducts to increase the osmotic pressure and pull more water into the acinus

Question 3

Pancreatic juice secretion

Answer 3

• As the secretion rate increases Na and K concentrations remain constant, where as HCO3- concentrations increase then plateau and Cl- concentration decrease then plateau
• The mechanism of secretion is similar to salivary glands, however there are 2 main differences
• In the ducts of the pancreas there are more NaHCO3 channels to allow for a higher bicarb concentration in the secretion
• Also there are AQP pores in the ducts of the pancreas, allowing for more secretions to be made at a faster rate

Question 4

Gastric juice secretion

Answer 4

• As secretion rate increases Cl and K concentration remain constant, where as H+ concentration increases then plateaus and Na concentration decreases then plateaus
• In the gastric pit there are AQPs and proteins that generate HCl
• There are NaHCO3 cotransporters on the apical membrane (not within the pit)

Question 5

Cellular mechanisms of NaCl secretion (salivary glands) 1

Answer 5

• Cl in the cell uses the Cl channel (CFTR and Ca-activated) to diffuse down its gradient into the lumen
• This causes paracellular Na movement from basal to apical side in order to balance charges and maintain the membrane potentials
• The Cl gradient (higher in the cell compared to lumen) is produced by the action of NKCC and HCO3-/Cl- anti porter-anion exchanger (both on basal membrane)
• These move Cl into the cell, down the concentration gradient (much higher Cl in ISF), but against its electrical gradient (cell is more negative than ISF)
• Overall the movement of Cl from AE and NKCC is uphill

Question 6

Cellular mechanisms of NaCl secretion (salivary glands) 2

Answer 6

• Together this sets up the Cl electrochemical gradient that the Cl channels on the apical membrane use
• The HCO3-/Cl- anion exchanger moves Cl into cell and HCO3- out of cell
• It is driven by the NHE causing depletion of H+ (by moving it out of the cell) and thus promoting further formation of HCO3-/H+ (from H2O+CO2) and increasing the gradient and thus activity of AE
• The capacity of maximally-stimulated acinar cells to secrete NaCl is greater than ductal cells’ capacity to reabsorb NaCl (via CFTR and ENac), so final NaCl concentration increases as flow rate increases

Question 7

HCO3- secretion (pancreas)

Answer 7

• HCO3- enters the cell on the basal side by NBC symporter (uses Na gradient to transport HCO3-)
• The HCO3- then uses the CFTR channel to diffuse down its gradient into the lumen
• Capacity of maximally-stimulated ducts to secrete NaHCO3 is greater than capacity of maximally-stimulated acini to secrete NaCl

Question 8

HCl secretion (stomach)

Answer 8

• On the apical membrane of the parietal cell there is an HKA (H+/K+ exchanger), analogous to Na/K ATPase
• HKA pumps H+ into lumen and K into cell, K is then recycled via leaky K channels into lumen
• Flow of H+ out of cell leaves HCO3- in cell elevated, allowing for anion exchanger to pump HCO3- out of cell (basally) for Cl- into cell
• This increases the Cl- gradient and allows for Cl to flow thru Cl channels on apical membrane, downhill into lumen (transcellular Cl movement)
• Omeprazole blocks the HKA nz

Question 9

The gastric barrier bicarb pump

Answer 9

• NBC (HCO3-/Na+ cotransporter) on basal membrane allows HCO3- to enter cells to neutralize H+
• NBC action dependent on pH: its action will increase as pH falls, indicating an increase in H+
• A pH sensor activates COX which creates prostaglandins
• The PGs activate the NBC
• COX will be inhibited by ASA
• The unstirred layer slows H+ diffusion toward the mucosa, and slows HCO3- diffusion away from mucosa (reduces H+ damage to mucosa and reduces HCO3- neutralization of H+ in lumen)