Acid base and GIT: part 2

The pancreatic secretion of electrolytes

The aqueous component of pancreatic cells is contributed by acinar cells ( isotonic, rich in Na, K, Cl and bicarbonates, stimulated by CCK and Ach; concentration similar to that in plasma), intralobular ductal cells (bicarbonates double and chlorides less of that in plasma, spontaneous secretion) and extralobular ductal secretion ( rich in Bicarbonates and poor in chlorides, stimulus is SECRETIN)

The basolateral transporters are called house keepers as they maintain the normal pH and maintain the cell  membrane volatage.

ref: Kim D, Steward MC. The role of CFTR in bicarbonate secretion by pancreatic duct and airway epithelia. J Med Invest. 2009;56 Suppl:336-42. Review

Secretin secretion from the duodenal S cells is stimulated by gastric distension and acid secretion of stomach  that signals the ductal cells to secrete bicarbonate-rich, clear, watery fluid ( hydraulic secretion).

The ''exocrine'' pancreas is an abdominal “salivary gland” and releases 1.5 l of pancreatic juice daily, with the pH increasing with increased secretion rate. The maximal secretion rate about 20-50 µl/min. The pancreatic juice is a clear fluid, isosmolar with plasma. Bicarbonates in the pancreatic secretion can approximate to the [H⁺] in gastric juice (150 mM). Pancreatic juice (pH 8) thus buffers the extremely acid gastric juice and protects the duodenal mucosa.

At high secretory rate bicarbonates increase and chloride decreases and vice-versa. Thus both share a reciprocal relationship.

This is because at low flow rates, the pancreatic juice which is rich in Na and Cl comes from the acinar and ductal cells whereas at high flow rates, the proportion of ductal cell secretion rises which has got a high HCO₃ concentration.

Thus Bicarbonate secretion can vary from 80 to 120 mEq/l depending on the secretory rate. Na and K secretion (unlike saliva) are similar to plasma and remain unaffected by the secretory rate.

A schema of transporters including the SKOU pump in pancreatic ductal cell

The secretion of HCO₃ being the primary process, can be understood as:

A: Entry of Bicarbonate in to the duct cell    

i.                    Through Na/ HCO₃ cotranspoter (NBC) located on the basolateral membrane.

ii.                  Through the H₂ CO₃  reaction inside the cell through Carbonic anhydrase catalysed reaction where CO₂ + H₂O  combine to form H₂CO₃ and then breaking into H⁺ and HCO₃^-. The H+ are extruded through either an active H+-ATPase pump or by Na/ H exchanger.

B: Release of HCO₃ into the lumen

1.         Depends on Cl- transport across the apical membrane (as seen to be defective in cystic fibrosis).
2.          Secretin opens the Chloride channels which is proved by 20- fold decrease in the resistance of the apical membrane to chloride ions. The chloride channels can be CFTR Cl^- channels or Ca ⁺² sensitive Cl^- channels.
3.    The chloride recycles through the Cl/ HCO₃ exchanger which extrudes the HCO₃ ions into the lumen.
4.     A rise in [Ca²⁺] opens up luminal chloride channels and a basolateral K channel through which these ions can leave the cell.
5.       The fall in intracellular Cl and K activates a basolateral Na/K/Cl cotransporter through which NaCl enters the cell.
6.      It is followed by paracellular transport of Na and accompanied by H₂O (the acinar lumen has  about -6mV potential)
7.     If the luminal [Cl-] concentration falls or there is a reduction in the activity of Cl/HCO₃ exchanger, then HCO₃ can be extruded from the CFTR channels directly into the lumen.

        i.           

C: Holding of HCO₃ in the lumen

Because of electrical gradient, HCO₃ has a tendency to go back in the cell at 145 mM concentration.The IC concentration of HCO₃ is about 10-15 mM and the cell membrane potential is about  -60mV (even at max stimulation??).Another important event which takes place during this instance is the inactivation/ closure of basolateral Cl/ HCO₃ exchanger ( I have not drawn in this figure). This decreases Cl concentration in the lumen and favors HCO₃ extrusion through the CFTR channel which otherwise shows only 25 % conductance for HCO₃ as compared to Cl conductance.

suggested reading:

1. secretin receptors

2. VIP and Secretin

3. Potassium ion in pancreatic secretion