Pancreatic Secretion

Question 1

Endocrine pancreas

Answer 1

The endocrine function is located in specialized cells called the Islets of Langerhans which are interspersed throughout the gland.

b cells —> insulin

A cells —> glucagon

Question 2

Exocrine pancreas

Answer 2

exocrine pancreas secretes approximately 1L of fluid (pancreatic juice) per day into the lumen of the duodenum where it plays an important role in the digestive process.

This juice contains two important constituents; (1) HCO3- containing aqueous component, and (2) digestive enzymes.

Question 3

Pancreatic acinar cells

Answer 3

These cells contain numerous zymogen granules and produce the digestive enzymes present in pancreatic juice.

Question 4

Pancreatic duct cells

Answer 4

elaborate the fluid and electrolyte secretion of the pancreatic juice and they contain carbonic anhydrase used to form HCO3-.

Question 5

Pancreatic juice secretion

Answer 5

Pancreatic juice is secreted into the duodenum via the duct of Wirsung, which joins the common bile duct.

Question 6

Secretion of bicarbonate

Answer 6

Carbon
dioxide diffuses into the ductal cells where, under the
influence of carbonic anhydrase, it is converted to H2CO3 then dissociates to form HCO3- and H+. Intracellular H+ is moved out of the cell across the basolateral membrane in exchange for Na+ by a Na+/H+ antiporter (i.e., the ions are transported in opposite directions. As the pancreatic juice flows along the duct Cl- is exchanged for HCO3-. The rate of HCO3- secretion depends on the availability of luminal Cl- which is dependent on the opening of the Cl- channel in the apical membrane.

Question 7

Electrolyte composition and their flow in pancreatic juice

Answer 7

In contrast to saliva, pancreatic juice is isotonic to plasma at all rates of secretion. This is the result of a free passive movement of water with solutes. The principal anions are Cl-, and HCO3-, and the principal cations are K+ and Na+.

While concentrations of cations are not affected by the rates of secretion the concentration of anions varies considerably with rates of secretion.

So….

Na+ and K+ stay the same.
Cl- and HCO3- change (Cl- decreases with flow, HCO3- increases)

Question 8

Secretion of pancreatic enzymes

Answer 8

Most of the enzymes are proteolytic and are secreted as inactive proenzymes because in the active form they would damage the cells that store them. Trypsin, chymotrypsin and carboxypeptidases are amongst the most important. Activation of
the proenzymes is initiated by a brush border peptidase enterokinase which is made by the enterocyte. This peptide converts trypsinogen to trypsin which autocatalyzes the conversion of more trypsin and also activates other proenzymes. Pancreatic juice also contains a trypsin inhibitor which binds to free trypsin preventing the activation of the proenzymes prior to their entry into the intestinal lumen.

Question 9

Autodigestion

Answer 9

When all of the available substrates have been utilized these pancreatic enzymes then digest each other in the intestinal lumen. This process of “autodigestion” forms a significant component of daily absorbed protein.

Question 10

Regulation of pancreatic secretion (hormones)

Answer 10

Secretin:
stimulates HCO3- and H2O secretion from the duct cells and is released by the entry of acid into the duodenum. Vasoactive intestinal polypeptide (VIP: a hormone in the secretin family) also increases HCO3- and fluid secretion but is less potent than secretin itself. Both work by binding to receptors on the duct cell membrane activating adenylate cyclase to increase intracellular levels of cAMP. Secretin and VIP are responsible for almost no stimulation of enzyme secretion.

CCK:
is released by the presence of amino acids and fats in the duodenum and stimulates enzyme secretion from the acinar cells. Gastrin released by the presence of protein digestion products in the stomach also increases pancreatic enzyme secretion but is less potent than CCK. Binding of these hormones at receptors on the acinar cells results in an increase in intracellular Ca2+. CCK and gastrin have only weak stimulatory effects on electrolyte and fluid secretion.

Question 11

REGULATION OF PANCREATIC SECRETION (nerves)

Answer 11

Vago-vagal reflexes are initiated by the entry of chyme into the intestine. Vagal efferent fibers cause the release of both acetylcholine and VIP from postganglionic fibers innervating the acinar and duct cells. Stimulation of the vagus increases enzyme secretion from the acinar cells (cholinergic) and, to a lesser extent, HCO3- and H2O secretion from the duct cells (VIP-ergic). Acetylcholine binds to muscarinic cholinergic receptors causing an increase in intracellular Ca2+. Sympathetic stimulation inhibits vagal- and secretin-induced secretion and may inhibit pancreatic secretion indirectly by reducing blood flow.

Question 12

REGULATION OF PANCREATIC SECRETION (Potentiation of stimulation)

Answer 12

There is a potentiation of the secretory response among
the various stimulants of pancreatic secretion such that the
response of the agents in combination is greater than the sum of their individual effects. This potentiation is able to occur because activation of receptors on the cell surface stimulates different intracellular pathways.

Question 13

Interdigestive phase

Answer 13

occurs during those times when eating is not taking
place and the intestine is essentially empty. Basal (fasting) enzyme secretion is about 10% and basal HCO3- secretion is 1-2% of maximal secretion. Basal secretion may be related to a low level of acetylcholine release from the vagus and by circulating secretin.

Question 14

Phases of pancreatic secretion (after meal)

Answer 14

1. The cephalic phase is activated by the central integration
   of the sight, smell, taste and act of eating food. This is mediated by the vagus nerve.
2. The gastric phase is initiated by the entry of food to the
   stomach. Stimulation of enzyme secretion induced by the vagus continues and is augmented by the action of gastrin.
3. The intestinal phase is initiated by the entry of food into the duodenum. It accounts for 70-80% of the pancreatic secretory response to a meal. It is mediated by the release of secretin from S-cells in the intestine in response to luminal acid. The HCO3- ions in pancreatic juice neutralize the HCl which leaves the stomach in association with the gastric contents. CCK is released from intestinal I-cells in response to
   the presence of fatty acids and peptides. The enteropancreatic reflex involves the vagal release of acetylcholine in response to the presence of fatty acid or amino acids in the duodenum.

Question 15

PANCREATITIS

Answer 15

is an inflammatory condition that can cause damage to the pancreas. It is most commonly associated with alcohol abuse or blockage of the papilla of Vater by gallstones. Pancreatic enzymes accumulate in the duct, overcome trypsin inhibitor and digest the pancreas. In some cases the underlying cause is never known.

Question 16

STEATORRHEA

Answer 16

results from a loss of pancreatic lipase causing malabsorption of lipid. Up to 70% of ingested fat may be excreted under these conditions because this is the only method for lipid metabolism and there is not enough lingual lipase to perform this function.

Question 17

CYSTIC FIBROSIS

Answer 17

is one of the most common lethal genetic diseases in Caucasians. It is characterized by decreased Cl-
secretion of many epithelial tissues and the inability of cAMP to regulate Cl- conductance. There is evidence that the ion channel for Cl- in the apical membrane of the duct cell is the cystic fibrosis transmembrane conductance regulator (CFTR) that is regulated by cAMP. If this protein is not synthesized correctly cystic fibrosis occurs because the apical transport processes of the duct cell are disrupted with a severe decrease in secretion of HCO3- and water. The protein rich secretions then thicken and cause blockage of the ducts, and tissue destruction results from autodigestion.